Talk:Adverse effects of fluoroquinolones/Archive 3

Archive 1

Archive 2

Archive 3

regarding the current intro

May I suggest we use the full names rather than hyphenate them? i.e. : levofloxacin (levaguin), ciprofloxacin (cipro) and moxifloxacin (avelox) This would make it easier on the reader to then go to the seperate article for each drug. Not everyone reading the article would be aware that avelox and moxifloxacin are one and the same, or levofloxacin and levaquin. Davidtfull (talk) 04:55, 19 February 2009 (UTC)

Fair idea.--Literaturegeek | T@1k? 17:40, 20 February 2009 (UTC)

Garbage

This article is currently garbage. The references due not support what is written in the lead. Will start working on getting it to some semblance of reality. What the references refer to are adverse events rather than true toxicities but that is a side point.

We start by talking about all the severe events this drug can cause and then the references talk about tendon problem! THIS IS DISHONEST and whoever added this should be ashamed. Will fix some of the most gross errors.--Doc James (talk · contribs · email) 08:19, 19 February 2009 (UTC)

Doc, it was me who wrote it, I haven't added very much data to this article, mainly I have been playing piggy in the midddle between the two disputing parties. I will explain why I added those refs, Steve put "citation needed" beside is the

"syndrome of long term[5] adverse effects."

soooo I provided a citation of a long term effect,,,,, tendon damage

Steve put citation needed beside this sentence

Adverse reactions may manifest during, as well long after fluoroquinolone therapy has been discontinued.[8]

sooooo I provided a citation of delayed tendon rupture as an example.

There was absolutely nothing that I can see dishonest in those edits or are you talking about some other part I am missing?

I don't think accusations of people being dishonest and being shamed is the right way to approach things especially as I think that you are wrong in your accuations (unless you are talking about a different part of the article)?--Literaturegeek | T@1k? 08:54, 19 February 2009 (UTC)

My apologizes literature. What was there needed to be removed. You did not add it so my accusations are not directed at you. The line I have serious concerns with is "serious adverse reactions (including blindness, psychosis, brain damage and death) which can occur from use of fluoroquinolone antibacterial drugs" and than the references refer to tendon problems.

The wording as it was misleads the reader. Hope the new changes are acceptable to people.--Doc James (talk · contribs · email) 09:08, 19 February 2009 (UTC)

Okie dokie no problem. Blindness, psychosis and death are possible adverse reactions of fluoroquinolones but having them in the lead as the first sentence worded like that was causing neutrality issues. One of your recent edits I disagree with. Your addition of overdose data now makes it sound like seizures occur only in overdose. Firstly especially as the article is now adverse events I don't think that overdose info is relevant to this article, perhaps relevant to the drug overdose article as a small entry. At the moment it is misleading as Government medical guidelines (MHRA) give a UK equivalent of a black box warning for seizures which can occur in people with or without a history of them. It appears in the British National Formulary. I think that needs changing. If you trust my editing (I feel I have been reasonably neutral on editing this article) I can start working on this article with you. I do have a moderate knowledge of the literature on quinolones and antibiotics in general.--Literaturegeek | T@1k? 09:22, 19 February 2009 (UTC)

Yes I agree that probably eventually acute overdose info should be moved to it owns article. Goldfrank's is the leading book of medical toxicology. You can get access to a limited view thru google books.

Happy to have your help editing. Uptodate is also a great source which I can get you access to if you are interested. This article needs a complete rewrite. It make it seem that all these exceeding rare events are common place with floroquinolones. The biggest concern with this drug group is its interaction with warfarin ( I have had one person die from this complication ). But that is a drug reaction and the death was due to human error rather than an intrinsic property of the drug. I see hundred of people on these drug and almost never see complications. I have seen one tendenopathy that resolved sponaneously.--Doc James (talk · contribs · email) 09:30, 19 February 2009 (UTC)

Well here are my honest views, I do not believe that 5% of people are getting tendon tears or 20% or whatever go psychotic on fluoroquinolones or whatever. I do not believe they have a mild side effect profile. They are 2nd behind clindamycin for causing C difficile for one and some hospitals and antimicrobial experts recommend now avoiding them whenever possible. I do think the type of adverse effects can be severe and for some people causing mental or physical disability lasting months or in severe cases years or even permanent, how common this is I dunno. I believe probably aminoglycosides would have "uncommon" severe adverse effects (ototoxicity, nephrotoxicity) of 1 or 2% perhaps(?) but they are severely restricted due to the fact they can cause long term or permanent damage. So I dispute the adverse effect profile more because of the severe consequences uncommon or not of fluoroquinolones. I do believe that often adverse effects are not connected to the patient, eg misdiagnosed with fibromyalgia, insomnia, anxiety, old age etc etc rather than FQ adverse effect. If you had an old lady and she developed muscle pain, insomnia and anxiety, you might diagnose flu symptoms and age related anxiety being in hospital environment. I have a next door who was on steroids and prescribed antibiotics and soon after his tendons or ligaments blew apart in his ankles and the doctors just said "they have no idea why it happened", they didn't attribute it to his antibiotic use. I have another neighbour who just finished a course of them and is perfectly fine. I know others who got CNS adverse effects. If the adverse effects were all acute and not potentially long lasting I wouldn't do anything more than add a list of adverse effects and move on editing elsewhere. We previously had a good secondary review article saying mild to moderate with uncommon severe adverse effects, then had a couple of sentences citing allegations of patient groups. I think we should add that back. Anyway time for me to join you editing. I do admit they are an important therapeutic tool and an effective antibiotic though. :=)--Literaturegeek | T@1k? 09:52, 19 February 2009 (UTC)

First of all, this article is NOT garbage. If you want to add something, REFERENCE it. DO NOT remove something just because you do not believe it. Of course these reactions are uncommon, but they obviously exist. I have to agree with Literaturegeek. Unless you see what these drugs can do in person, you will not believe it. JamesLockson (talk) 10:24, 19 February 2009 (UTC)

You have removed a number of good faith edits without justification. I have provided lots of reasons. Much of what I removed is unreferenced as it is untrue. Therefore I have removed it. Will leave what is here and we can wait for the editing community to decide which of the two versions is better.--Doc James (talk · contribs · email) 10:44, 19 February 2009 (UTC)

Moved

Moved the page to Adverse effects of fluoroquinolones. This is how Goldfrank's toxicology describe them. Less emotionally charge than toxicity and more NPOV.--Doc James (talk · contribs · email) 08:42, 19 February 2009 (UTC)

Also adverse events at therapeutic doses of a medication is not in clinical practice referred to as toxicity, it is referred to as an adverse event. see uptodate http://www.uptodate.com/online/content/topic.do?topicKey=antibiot/8621&selectedTitle=1~150&source=search_result#24

Otherwise the title would limit the discussion to acute overdose and two very rare complications: acute renal failure and seizures.--Doc James (talk · contribs · email) 08:59, 19 February 2009 (UTC)

I don't mind the name change and was neutral on this.--Literaturegeek | T@1k? 09:01, 19 February 2009 (UTC)

Delayed reactions

This section was bashing physicians without proper reference. Was misrepresenting reference and was OR.--Doc James (talk · contribs · email) 09:48, 19 February 2009 (UTC)

This concern has been addressed, it is deleted, I think by you.--Literaturegeek | T@1k? 03:15, 25 February 2009 (UTC)

Mortality

This section referred to the FDA If someone could find the actually reference maybe but we have no context.--Doc James (talk · contribs · email) 09:48, 19 February 2009 (UTC)

David has uploaded the scanned originals for verification. I can and mostly likely will link directly to them. I don't think that the figures are suspect or fraudulent. I think that is or will be resolved soon.--Literaturegeek | T@1k? 03:16, 25 February 2009 (UTC)

Case reports?

This article says that MSK problems are one of the most common side effects THAN back up the statement with a CASE report!!! Common on. This is enough to make a guy pull out his hair. Case reports are NOT a reflection of a common disease. And quoteing a bunch of case report is OR.--Doc James (talk · contribs · email) 10:11, 19 February 2009 (UTC)

I believe that I have deleted this one and other such misuses of case reports from the article. I have removed the majority of the original research from the article.--Literaturegeek | T@1k? 03:17, 25 February 2009 (UTC)

Next concern

"multiple skeletal events have been reported since 1972" and when is the ref from 1972. Therefore this statement does not muiple events since 1972 only events in 1972 from one fluoro that is not longer used.--Doc James (talk · contribs · email) 10:14, 19 February 2009 (UTC)

That statement was based upon the following citations. Indicative of the fact that spontaneous tendon ruptures had been associated with the fluoroquinolones since 1965 and for the most part a significant number of articles were published in the medical journals concerning this event just about every year since then. There has not been one year between 1992-2009 without such reports being published. Though the initial association began in 1965 in relation to nalidixic acid.

This is far from being an all inclusive list of such medical journal entries and other such main stream documentation I had relied upon in making that statement. Starting in 1965 and ending in 2009, almost forty years worth of such reports and the treating physician as well as the patient have no prior knowledge concerning such events, or if they do they consider them too rare to be given serious consideration. The most striking example is this 2002 report:

U.S. ARMED FORCES "Spontaneous Ruptures of the Achilles Tendon, US Armed Forces, 1998-2001 Methods. The Defense Medical Surveillance System was searched to identify all incident ambulatory visits of active duty servicemembers with a primary diagnosis of non-traumatic rupture of the achilles tendon (ICD-9- CM code 727.67) and other tendon ruptures (ICD-9- CM codes 727.60-727.66, 727.68-727.69) between January 1998 and May 2001. The most striking finding of this analysis is the sudden and significant increase in rates of achilles tendon ruptures beginning in calendar year 2000. The increase was manifested across all Services and in most demographic subgroups (table 1). Rates of non-traumatic ruptures of several other tendons also increased during the period; and increases in ruptures of the rotator cuff were comparable to those of the achilles tendon." Source: http://amsa.army.mil/1Msmr/2002/v08_n01.pdf

In the calender year 2000 levaquin was added to the forumulary and to the best of my knowledge the investigators did not give any serious consideration to the fact that this may have played a role. It would seem to me that logic would dictate that this be the very first thing to consider. It is my understanding that there was an investigation regarding this but I have not been able to access the results. Rumor has it though that the involvement of the quinolones was dismissed out of hand within that report. But since I do not have possesion of that report I do not know if that was true or not.

It would seem to me that this many reports for a "rare" disorder would indicate that it is anything but:

Perrot S, Ziza JM, De Bourran-Cauet G, Desplaces N, Lachand AT. [A new complication related to quinolones: rupture of Achilles tendon] Presse Med. 1991 Jul 6-13;20(26):1234. French. No abstract available. PMID 1831902 [PubMed - indexed for MEDLINE]

Blanche P, Sereni D, Sicard D, Christoforov B. [Achilles tendinitis induced by pefloxacin. Apropos of 2 cases] Ann Med Interne (Paris). 1992;143(5):348. French. No abstract available. PMID 1482040 [PubMed - indexed for MEDLINE]

Lee WT, Collins JF. Ciprofloxacin associated bilateral achilles tendon rupture. Aust N Z J Med. 1992 Oct;22(5):500. No abstract available. PMID 1445042 [PubMed - indexed for MEDLINE]

[3 cases of Achilles tendinitis caused by pefloxacin, 2 of them with tendon rupture] Rev Rhum Mal Osteoartic. 1992 Feb;59(2):162. French. No abstract available. PMID 1604233 [PubMed - indexed for MEDLINE]

Ribard P, Audisio F, Kahn MF, De Bandt M, Jorgensen C, Hayem G, Meyer O, Palazzo E. Seven Achilles tendinitis including 3 complicated by rupture during fluoroquinolone therapy. J Rheumatol. 1992 Sep;19(9):1479-81. PMID 1433021 [PubMed - indexed for MEDLINE]

Boulay I, Farge D, Haddad A, Bourrier P, Chanu B, Rouffy J [Tendinopathy caused by ciprofloxacin with possible partial rupture of Achilles tendon] Ann Med Interne (Paris). 1993;144(7):493-4. French. No abstract available. PMID 8141519 [PubMed - indexed for MEDLINE]

Dekens-Konter JA, Knol A, Olsson S, Meyboom RH, de Koning GH. [Tendinitis of the Achilles tendon caused by pefloxacin and other fluoroquinolone derivatives] Ned Tijdschr Geneeskd. 1994 Mar 5;138(10):528-31. Dutch. PMID 8139714 [PubMed - indexed for MEDLINE]

Royer RJ, Pierfitte C, Netter P. Features of tendon disorders with fluoroquinolones. Therapie. 1994 Jan-Feb;49(1):75-6. No abstract available. PMID 8091374 [PubMed - indexed for MEDLINE]

Prantera C, Kohn A, Zannoni F, Spimpolo N, Bonfa M. Metronidazole plus ciprofloxacin in the treatment of active, refractory Crohn's disease: results of an open study. J Clin Gastroenterol. 1994 Jul;19(1):79-80. No abstract available. PMID 7930441 [PubMed - indexed for MEDLINE]

Donck JB, Segaert MF, Vanrenterghem YF. Fluoroquinolones and Achilles tendinopathy in renal transplant recipients. Transplantation. 1994 Sep 27;58(6):736-7. No abstract available. PMID 7940700 [PubMed - indexed for MEDLINE]

Van Linthoudt D, D'Oro A, Ott H. [What is your diagnosis? Bilateral Achilles tendinitis associated with quinolone treatment] Schweiz Rundsch Med Prax. 1994 Feb 22;83(8):201-2. German. No abstract available. PMID 8134743 [PubMed - indexed for MEDLINE]

Huston KA. Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics. N Engl J Med. 1994 Sep 15;331(11):748. No abstract available. PMID 8058092 [PubMed - indexed for MEDLINE

Hernandez MV, Peris P, Sierra J, Collado A, Munoz-Gomez J. [Tendinitis due to fluoroquinolones. Description of 2 cases] Med Clin (Barc). 1994 Sep 10;103(7):264-6. Review. Spanish. PMID 7934295 [PubMed - indexed for MEDLINE]

Mirovsky Y, Pollack L, Arlazoroff A, Halperin N. [Ciprofloxacin-associated bilateral acute achilles tendinitis] Harefuah. 1995 Dec 1;129(11):470-2, 535. Hebrew. PMID 8846955 [PubMed - indexed for MEDLINE]

Szarfman A, Chen M, Blum MD. More on fluoroquinolone antibiotics and tendon rupture. N Engl J Med. 1995 Jan 19;332(3):193. No abstract available. PMID 7800023 [PubMed - indexed for MEDLINE]

Pierfitte C, Gillet P, Royer RJ More on fluoroquinolone antibiotics and tendon rupture. N Engl J Med. 1995 Jan 19;332(3):193. No abstract available. PMID 7800022 [PubMed - indexed for MEDLINE]

Castagnola C, Suhler A. [Tendinopathy and fluoroquinolones] Ann Urol (Paris). 1996;30(3):129-30. French. PMID 8766149 [PubMed - indexed for MEDLINE]

Maki T, Heinasmaki T, Riutta J, Tikkanen T, Laasonen L, Eklund K. [Bilateral Achilles tendon rupture caused by oral fluoroquinolones] Duodecim. 1996;112(19):1818-20. Finnish. No abstract available. PMID 10596182 [PubMed - indexed for MEDLINE]

Pierfitte C, Royer RJ. Tendon disorders with fluoroquinolones. Therapie. 1996 Jul-Aug;51(4):419-20. No abstract available. PMID 8953821 [PubMed - indexed for MEDLINE]

Skovgaard D, Feldt-Rasmussen BF, Nimb L, Hede A, Kjaer M. [Bilateral Achilles tendon rupture in individuals with renal transplantation] Ugeskr Laeger. 1996 Dec 30;159(1):57-8. Danish. PMID 9012076 [PubMed - indexed for MEDLINE]

Hugo-Persson M. [Rupture of the Achilles tendon after ciproxine therapy] Lakartidningen. 1996 Apr 17;93(16):1520. Swedish. No abstract available. PMID 8667750 [PubMed - indexed for MEDLINE]

McGarvey WC, Singh D, Trevino SG. Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report and literature review. Foot Ankle Int. 1996 Aug;17(8):496-8. Review. PMID 8863030 [PubMed - indexed for MEDLINE]

Jagose JT, McGregor DR, Nind GR, Bailey RR. Achilles tendon rupture due to ciprofloxacin. N Z Med J. 1996 Dec 13;109(1035):471-2. No abstract available. PMID 9006634 [PubMed - indexed for MEDLINE]

Movin T, Gad A, Guntner P, Foldhazy Z, Rolf C. Pathology of the Achilles tendon in association with ciprofloxacin treatment. Foot Ankle Int. 1997 May;18(5):297-9. PMID 9167931 [PubMed - indexed for MEDLINE]

Benizeau I, Cambon-Michot C, Daragon A, Voisin L, Mejjad O, Thomine JM, Le Loet X. Tendinitis of the tibialis anterior with histologic documentation in a patient under fluoroquinolone therapy. Rev Rhum Engl Ed. 1997 Jun;64(6):432-3. No abstract available. PMID 9513620 [PubMed - indexed for MEDLINE]

Poon CC, Sundaram NA. Spontaneous bilateral Achilles tendon rupture associated with ciprofloxacin. Med J Aust. 1997 Jun 16;166(12):665. No abstract available. PMID 9216589 [PubMed - indexed for MEDLINE]

Shinohara YT, Tasker SA, Wallace MR, Couch KE, Olson PE. What is the risk of Achilles tendon rupture with ciprofloxacin? J Rheumatol. 1997 Jan;24(1):238-9. No abstract available. PMID 9002057 [PubMed - indexed for MEDLINE]

West MB, Gow P. Ciprofloxacin, bilateral Achilles tendonitis and unilateral tendon rupture--a case report. N Z Med J. 1998 Jan 23;111(1058):18-9. No abstract available. PMID 9484431 [PubMed - indexed for MEDLINE]

Stafford L, Bertouch J. Reactive arthritis and ruptured Achilles tendon. Ann Rheum Dis. 1998 Jan;57(1):61. No abstract available. PMID 9536827 [PubMed - indexed for MEDLINE]

Petersen W, Laprell H [Insidious rupture of the Achilles tendon after ciprofloxacin-induced tendopathy. A case report] Unfallchirurg. 1998 Sep;101(9):731-4. German. PMID 9816984 [PubMed - indexed for MEDLINE]

Blanco Andres C, Bravo Toledo R. [Bilateral tendinitis caused by ciprofloxacin] Aten Primaria. 1998 Feb 28;21(3):184-5. Spanish. No abstract available. PMID 9607242 [PubMed - indexed for MEDLINE

Gabutti L, Stoller R, Marti HP. [Fluoroquinolones as etiology of tendinopathy] Ther Umsch. 1998 Sep;55(9):558-61. German. PMID 9789471 [PubMed - indexed for MEDLINE]

Schwald N, Debray-Meignan S. Suspected role of ofloxacin in a case of arthalgia, myalgia, and multiple tendinopathy. Rev Rhum Engl Ed. 1999 Jul-Sep;66(7-9):419-21. PMID 10526383 [PubMed - indexed for MEDLINE

Lewis JR, Gums JG, Dickensheets DL. Levofloxacin-induced bilateral Achilles tendonitis. Ann Pharmacother. 1999 Jul-Aug;33(7-8):792-5. PMID 10466906 [PubMed - indexed for MEDLINE]

Harrell RM. Fluoroquinolone-induced tendinopathy: what do we know? South Med J. 1999 Jun;92(6):622-5. Review. PMID 10372859 [PubMed - indexed for MEDLINE]

Gibbon WW, Cooper JR, Radcliffe GS. Sonographic incidence of tendon microtears in athletes with chronic Achilles tendinosis. Br J Sports Med. 1999 Apr;33(2):129-30. PMID 10205697 [PubMed - indexed for MEDLINE]

van der Linden PD, van de Lei J, Nab HW, Knol A, Stricker BH. Achilles tendinitis associated with fluoroquinolones. Br J Clin Pharmacol. 1999 Sep;48(3):433-7. PMID 10510157 [PubMed - indexed for MEDLINE]

Casado Burgos E, Vinas Ponce G, Lauzurica Valdemoros R, Olive Marques A. [Levofloxacin-induced tendinitis] Med Clin (Barc). 2000 Mar 4;114(8):319. Spanish. No abstract available. PMID 10774524 [PubMed - indexed for MEDLINE]

Casparian JM, Luchi M, Moffat RE, Hinthorn D. Quinolones and tendon ruptures. South Med J. 2000 May;93(5):488-91. Review. PMID 10832946 [PubMed - indexed for MEDLINE

Malaguti M, Triolo L, Biagini M. Ciprofloxacin-associated Achilles tendon rupture in a hemodialysis patient. J Nephrol. 2001 Sep-Oct;14(5):431-2. No abstract available. PMID 11730281 [PubMed - indexed for MEDLINE]

Butler MW, Griffin JF, Quinlan WR, McDonnell TJ. Quinolone-associated tendonitis: a potential problem in COPD? Ir J Med Sci. 2001 Jul-Sep;170(3):198-9. PMID 12120977 [PubMed - indexed for MEDLINE]

van der Linden PD, van Puijenbroek EP, Feenstra J, Veld BA, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH. Tendon disorders attributed to fluoroquinolones: a study on 42 spontaneous reports in the period 1988 to 1998. Arthritis Rheum. 2001 Jun;45(3):235-9. PMID 11409663 [PubMed - indexed for MEDLINE]

Nuno Mateo FJ, Noval Menendez J, Suarez M, Guinea O. [Achilles pain and functional impotence in a patient with chronic obstructive pulmonary disease with pneumonia. Tendon rupture caused by levofloxacin] Rev Clin Esp. 2001 Sep;201(9):539-40. Spanish. No abstract available. PMID 11692412 [PubMed - indexed for MEDLINE]

Chhajed PN, Plit ML, Hopkins PM, Malouf MA, Glanville AR. Achilles tendon disease in lung transplant recipients: association with ciprofloxacin. Eur Respir J. 2002 Mar;19(3):469-71. PMID 11936524 [PubMed - indexed for MEDLINE]

Hersh BL, Heath NS. Achilles tendon rupture as a result of oral steroid therapy. J Am Podiatr Med Assoc. 2002 Jun;92(6):355-8. PMID 12070236 [PubMed - indexed for MEDLINE]

No authors listed] Side effects of levofloxacin. Prescrire Int. 2002 Aug;11(60):116-7. No abstract available. PMID 12199267 [PubMed - indexed

Hatori M, Matsuda M, Kokubun S. Ossification of Achilles tendon--report of three cases. Arch Orthop Trauma Surg. 2002 Sep;122(7):414-7. Epub 2002 May 03. PMID 12228804 [PubMed - indexed for MEDLINE]

Pouzaud F, Rat P, Cambourieu C, Nourry H, Warnet JM. [Tenotoxic potential of fluoroquinolones in the choice of surgical antibiotic prophylaxis in ophthalmology] J Fr Ophtalmol. 2002 Nov;25(9):921-6. French. PMID 12515937 [PubMed - indexed for MEDLINE]

Mazzone MF, McCue T. Common conditions of the achilles tendon. Am Fam Physician. 2002 May 1;65(9):1805-10. Review. PMID 12018803 [PubMed - indexed for MEDLINE]

Schepsis AA, Jones H, Haas AL. Achilles tendon disorders in athletes. Am J Sports Med. 2002 Mar-Apr;30(2):287-305. Review. PMID 11912103 [PubMed - indexed for MEDLINE]

Greene BL.Physical therapist management of fluoroquinolone-induced Achilles tendinopathy. Phys Ther. 2002 Dec;82(12):1224-31. PMID 12444881 [PubMed - indexed for MEDLINE]

Breck RW. "Ciprofloxacin: a warning for clinicians". Conn Med. 2002 Oct;66(10):635. No abstract available. PMID 12448217 [PubMed - indexed for MEDLINE]

van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH. Fluoroquinolones and risk of Achilles tendon disorders: case-control study. BMJ. 2002 Jun 1;324(7349):1306-7. No abstract available. PMID 12039823 [PubMed - indexed for MEDLINE]

Aros C, Flores C, Mezzano S.[Achilles tendinitis associated to levofloxacin: report of 4 cases] Rev Med Chil. 2002 Nov;130(11):1277-81. Spanish. PMID 12587511 [PubMed - indexed for MEDLINE]

Shah P.[Do tendon lesions occur during quinolone administration?] Dtsch Med Wochenschr. 2003 Oct 17;128(42):2214. German. No abstract available. PMID 14562223 [PubMed - indexed for MEDLINE]

Tomas ME, Perez Carreras M, Morillasa JD, Castellano G, Solis JA. [Rupture of the Achilles' tendon secondary to levofloxacin] Gastroenterol Hepatol. 2003 Jan;26(1):53-4. Spanish. No abstract available. PMID 12525331 [PubMed - indexed for MEDLINE]

Melhus A, Apelqvist J, Larsson J, Eneroth M. Levofloxacin-associated Achilles tendon rupture and tendinopathy. Scand J Infect Dis. 2003;35(10):768-70. PMID 14606622 [PubMed - indexed for MEDLINE]

Cebrian P, Manjon P, Caba P. Ultrasonography of non-traumatic rupture of the Achilles tendon secondary to levofloxacin. Foot Ankle Int. 2003 Feb;24(2):122-4. PMID 12627618 [PubMed - indexed for MEDLINE]

Bernacer L, Artigues A, Serrano A. [Levofloxacin and bilateral spontaneous Achilles tendon rupture] Med Clin (Barc). 2003 Jan 25;120(2):78-9. Spanish. No abstract available. PMID 12570920 [PubMed - indexed for MEDLINE]

de La Red G, Mejia JC, Cervera R, Llado A, Mensa J, Font J. Bilateral Achilles tendinitis with spontaneous rupture induced by levofloxacin in a patient with systemic sclerosis. Clin Rheumatol. 2003 Oct;22(4-5):367-8. No abstract available. PMID 14579169 [PubMed - indexed for MEDLINE]

Haddow LJ, Chandra Sekhar M, Hajela V, Gopal Rao G. Spontaneous Achilles tendon rupture in patients treated with levofloxacin. J Antimicrob Chemother. 2003 Mar;51(3):747-8. No abstract available. PMID 12615887 [PubMed - indexed for MEDLINE]

Othmani S, Battikh R, Ben Abdallah N. [The myo-tendinopathy caused by levofloxacin] Therapie. 2003 Sep-Oct;58(5):463-5. French. No abstract available. PMID 14682197 [PubMed - indexed for MEDLINE]

Gutierrez E, Morales E, Garcia Rubiales MA, Valentin MO. [Levofloxacin and Achilles tendon involvement in hemodialysis patients] Nefrologia. 2003 Nov-Dec;23(6):558-9. Spanish. No abstract available. PMID 15002793 [PubMed - indexed for MEDLINE]

[No authors listed] Tendon abnormalities and hypersensitivity of levofloxacin. Prescrire Int. 2003 Feb;12(63):20. No abstract available. PMID 12602391 [PubMed - indexed for MEDLINE]

Schindler C, Pittrow D, Kirch W. Reoccurrence of levofloxacin-induced tendinitis by phenoxymethylpenicillin therapy after 6 months: a rare complication of fluoroquinolone therapy? Chemotherapy. 2003 May;49(1-2):90-1. No abstract available. PMID 12756981 [PubMed - indexed for MEDLINE]

Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis. 2003 Jun 1;36(11):1404-10. Epub 2003 May 20. Review. PMID 12766835 [PubMed - indexed for MEDLINE]

Gold L, Igra H. Levofloxacin-induced tendon rupture: a case report and review of the literature. J Am Board Fam Pract. 2003 Sep-Oct;16(5):458-60. Review. No abstract available. PMID 14645337 [PubMed - indexed for MEDLINE]

Mathis AS, Chan V, Gryszkiewicz M, Adamson RT, Friedman GS. Levofloxacin-associated Achilles tendon rupture. Ann Pharmacother. 2003 Jul-Aug;37(7-8):1014-7. PMID 12841810 [PubMed - indexed for MEDLINE]

Filippucci E, Farina A, Bartolucci F, Spallacci C, Busilacchi P, Grassi W.[Levofloxacin-induced bilateral rupture of the Achilles tendon: clinical and sonographic findings] Reumatismo. 2003 Oct-Dec;55(4):267-9. Italian. PMID 14872227 [PubMed - indexed for MEDLINE]

Kowatari K, Nakashima K, Ono A, Yoshihara M, Amano M, Toh S. Levofloxacin-induced bilateral Achilles tendon rupture: a case report and review of the literature. J Orthop Sci. 2004;9(2):186-90. Review. PMID 15045551 [PubMed - indexed for MEDLINE]

Gomez Rodriguez N, Ibanez Ruan J, Gonzalez Perez M. [Achilles bilateral tendonitis and levofloxacin] An Med Interna. 2004 Mar;21(3):154. Spanish. No abstract available. PMID 15043504 [PubMed - indexed for MEDLINE]

Burkhardt O, Kohnlein T, Pap T, Welte T. Recurrent tendinitis after treatment with two different fluoroquinolones. Scand J Infect Dis. 2004;36(4):315-6. PMID 15198194 [PubMed - indexed for MEDLINE]

Kahn F, Christensson B. [A rapid development of Achilles tendon rupture following quinolone treatment] Lakartidningen. 2004 Jan 15;101(3):190-1. Swedish. No abstract available. PMID 14763088 [PubMed - indexed for MEDLINE]

Mehra A, Maheshwari R, Case R, Croucher C. Bilateral simultaneous spontaneous rupture of the Achilles tendon. Hosp Med. 2004 May;65(5):308-9. No abstract available. PMID 15176150 [PubMed - indexed for MEDLINE]

Vergara Fernandez I. [Muscle and tendon problems as a side-effect of levofloxacine: review of a case] Aten Primaria. 2004 Mar 15;33(4):214. Spanish. No abstract available. PMID 15023326 [PubMed - indexed for MEDLINE]

Fama U, Irace S, Frati R, de Gado F, Scuderi N. Is it a real risk to take ciprofloxacin? Plast Reconstr Surg. 2004 Jul;114(1):267. No abstract available. PMID 15220615 [PubMed - indexed for MEDLINE]Davidtfull (talk) 23:49, 20 February 2009 (UTC)

All this references to the FDA

Show me the evidence so that I may verify. Removed till than.--Doc James (talk · contribs · email) 10:15, 19 February 2009 (UTC)

David has emailed me scanned originals, I think it is verified.--Literaturegeek | T@1k? 03:19, 25 February 2009 (UTC)

Lots more case reports removed

This is NOT good enough evidence.--Doc James (talk · contribs · email) 10:18, 19 February 2009 (UTC)

I have removed a lot of case reports from this article. I think that the article is much better now. Certainly it is not a good article status or a featured article status but for an article that is only a few weeks old, I think that we have made good progress.--Literaturegeek | T@1k? 03:21, 25 February 2009 (UTC)

Another mislead ref

There has not been one year since 1983 Self explanatory.--Doc James (talk · contribs · email) 10:18, 19 February 2009 (UTC)

This article is about human not rabbits

Reports of tendonopathy occurring hours after a single dose further suggest direct cytotoxicity.--Doc James (talk · contribs · email) 10:24, 19 February 2009 (UTC)

I have deleted a lot of animal studies from the article.--Literaturegeek | T@1k? 03:22, 25 February 2009 (UTC)

Admin help

Well we definitely are going to need some help here. I have asked for further eyes. Currently this does not even come close to representing a balanced view of the topic. I shall continue editing over at Adverse effects of fluoroquinolones if anyone wishes to join. The editing community can than decide once I am done which version we wish to go with. Cheers.--Doc James (talk · contribs · email) 10:38, 19 February 2009 (UTC)

Another bad ref

The fluoroquinolones have been associated with fatal hepatitis,Zaidi SA (2003). "Hepatitis associated with amoxicillin/clavulanic acid and/or ciprofloxacin". Am. J. Med. Sci. 325 (1): 31–3. doi:10.1097/00000441-200301000-00006. PMID 12544082. {{cite journal}}: Unknown parameter |month= ignored (help). One case, not necessarily due to a floroquinoline and patient recovered with conservative treatment.--Doc James (talk · contribs · email) 11:30, 19 February 2009 (UTC)

1. “Treatment with moxifloxacin is associated with a risk of developing fulminant hepatitis potentially leading to life threatening liver failure and risk of potentially life threatening bullous skin reactions like Stevens-Johnson-Syndrome (SJS) or toxic epidermal necrolysis (TEN).” Bayer European Dear Doctor Letter February 2008

2. BMJ 1997;314:869 (22 March) Drug points Quinolones may induce hepatitis

3. “With regards to liver disorders, from Jan. 1, 1997, to June 30, 2006, Health Canada received 44 domestic reports of liver and biliary disorders suspected of being associated with levofloxacin. Of these 44 cases, there were 5 cases of hepatic failure, 9 of hepatitis and 1 of hepatorenal syndrome. Five of these 15 cases of liver disorders were fatal. The remaining 29 reports included ARs of increased liver enzyme levels, cholestatic hepatitis and jaundice. The median time to onset of the 44 ARs was 5 days (range 1-39 days), which can be considered a short to intermediate time to onset. The median age (for all cases that reported an age) was 48.5 years (range 19-84 years).” Health Canada - Note to editors - January 3, 2007

4. Ann Pharmacother. 2005 Oct;39(10):1737-40. Epub 2005 Aug 16. Levofloxacin-induced acute fulminant hepatic failure in a patient with chronic hepatitis B infection. Coban S, Ceydilek B, Ekiz F, Erden E, Soykan I. Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey.

5. Adverse events associated with pyrazinamide and levofloxacin in the treatment of latent multidrug-resistant tuberculosis Tina Papastavros*, Lisa R. Dolovich*, Anne Holbrook**, Lori Whitehead and Mark Loeb From *the Faculty of Pharmacy, University of Toronto, Toronto, Ont.; the Centre for Evaluation of Medicines and the Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ont.; the Departments of Family Medicine and Medicine and the **Division of Clinical Pharmacology, McMaster University, Hamilton, Ont. Correspondence to: Dr. Lisa Dolovich, Centre for Evaluation of Medicines, Level P1, 105 Main St. E, Hamilton ON L8N 1G6; fax 905 528-7386; ldolovic@mcmaster.ca “There were 5 cases of hepatocellular injury.”

6. European Journal of Clinical Microbiology & Infectious Diseases Publisher: Springer-Verlag GmbH ISSN: 0934-9723 (Paper) 1435-4373 (Online) DOI: 10.1007/s10096-003-0914-6 Issue: Volume 22, Number 5 Date: May 2003 Pages: 294 - 296 Non-Fatal Acute Liver Injury Possibly Related to High-Dose Ciprofloxacin M. Goetz, P. R. Galle, A. Schwarting A1 Medical Clinic I, University of Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany “Reported here is a case of severe liver injury associated with ciprofloxacin administered for treatment of a gram-negative infection in a 79-year-old female. The patient presented with metabolic acidosis 48 hours after the first ciprofloxacin intake.”

7. Acute hepatitis associated with oral levofloxacin therapy in a hemodialysis patient. CMAJ 2003 Apr 1;168(7):847-8 (ISSN: 0820-3946) Schwalm JD; Lee CH Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON. “We present a case of levofloxacin-associated severe hepatocellular injury.”

8. Ciprofloxacin-induced acute liver injury: case report and review of literature Annette Zimpfer1, Albert Propst2, Gregor Mikuz3, Wolfgang Vogel2, Luigi Terracciano1 and Sylvia Stadlmann3 (1) Institute of Pathology, University of Basel, Schoenbeinstrasse 40, 4003 Basel, Switzerland (2) Department of Gastroenterology and Hepatology, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria (3) Institute of Pathology, University of Innsbruck, Muellerstrasse 44, 6020 Innsbruck, Austria Received: 18 July 2003 Accepted: 19 September 2003 Published online: 8 November 2003 Abstract Ciprofloxacin is a fluorinated quinolone antibiotic with relatively low occurrence of adverse side effects. However, increasing evidence suggests that ciprofloxacin may cause severe liver damage.

9. Hepatitis Associated with Amoxicillin/Clavulanic Acid and/or Ciprofloxacin. American Journal of the Medical Sciences. 325(1):31-33, January 2003. Zaidi, Syed A. MD Abstract: We describe an elderly patient with normal pre-existing liver functions who was treated with amoxicillin/clavulanic acid and later ciprofloxacin for acute bronchitis. He developed a pattern of liver dysfunction consistent with hepatocellular injury

10. BRIEF REPORT Possible Levofloxacin-Induced Acute Hepatocellular Injury in a Patient with Chronic Obstructive Lung Disease Anita Karim,1 Shahid Ahmed,1 Leonard J. Rossoff,1 Rina K. Siddiqui,2 and Harry N. Steinberg1 1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, Long Island Campus of the Albert Einstein College of Medicine, Bronx, and 2Department of Pathology, St. Luke'sRoosevelt Hospital, New York, New York

Again this is just a few references out of hundreds that I have on this specific adr. No doubt failing to meet the bar you have set, but an association has been established none the less. Davidtfull (talk) 15:12, 20 February 2009 (UTC)

Number 8 might be ok to use as it reviews the literature on liver disorder. The others looking at titles are just a case report.--Literaturegeek | T@1k? 18:00, 20 February 2009 (UTC)

I have read several abstracts and there does seem to be an agreement in the literature that fluoroquinolones as a class do sometimes cause hepatic problems, sometimes life threatening. Some quinolones do appear to be more toxic than others with some being removed due to this concern but it does seem to be a class effect with most authors urging caution in use of fluoroquinolones as a class in people with hepatic problems.--Literaturegeek | T@1k? 03:25, 25 February 2009 (UTC)

DNA damage

These are all studies of tissue culture. Any clinical significance? Does it increase ones risk of cancer? I do not treat cell cultures I treat people thanks.--Doc James (talk · contribs · email) 11:35, 19 February 2009 (UTC) Nalidixic acid, upon which all these drugs are based, is listed as a cartigen. Several veterinary drugs within this class has also been associated with being a cartigen. So perhaps it does. Do you wish for me to provide references to those two statements? If so I will.Davidtfull (talk) 14:58, 20 February 2009 (UTC)

Find me a review which shows increases cancer rates in humans.--Doc James (talk · contribs · email) 22:35, 20 February 2009 (UTC)

Hypothesis: is antibiotic use associated with breast cancer? Journal Cancer Causes and Control Publisher Springer Netherlands ISSN 0957-5243 (Print) 1573-7225 (Online) Issue Volume 14, Number 8 / October, 2003 DOI 10.1023/A:1026323424792 Pages 739-747 Subject Collection Medicine SpringerLink Date Saturday, October 30, 2004

“A recent cohort study in Finland reported an increased risk of breast-cancer associated with antibiotic use for UTI” This is a pay to view article so I have not read the full text, but I would assume since it refers to antibiotics used to treat UTI, it was referring to the quinolone class. Don't know for sure and not willing to shell out forty bucks to find out.

Skin cancer rates have been climbing in the U.S. at roughly 3% a year since the late eighties. One of the first fluoroquinolone approved for clinical use in the U.S. was Cipro, October 22, 1987. Coincidence, or yet another overlooked association? The three main types are basal-cell carcinoma (BCC), squamous-cell carcinoma (SCC), and malignant melanoma. All the fluoroquinolones are associated with phototoxicity. Exposure to quinolones with excessive sunlight causes phototoxicity and well-differentiated squamous cell carcinoma of the skin in animals.

Still looking for a review invloving humans that addresses this. But looking for reviews for a lot of the issues we are discussing, and this one is not all that important at the moment. If I stumble across one I will add it here for you, but more than likely all I will find is animal studies. Doubt that physicians would even think to associate increased rates of skin cancer with an antibiotic so more than likely there is nothing to be found concerning this in a review. But do you have a review that disputes the theory presented above? If so I would like to read it and see their evidence. Thanks.Davidtfull (talk) 07:23, 23 February 2009 (UTC)

A case report

A case report does not give an association: Hypoglycemia-induced anoxic brain injury has been associated with this class.Lawrence KR, Adra M, Keir C (2006). "Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin". J. Infect. 52 (6): e177–80. doi:10.1016/j.jinf.2005.08.024. PMID 16269178. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)--Doc James (talk · contribs · email) 11:43, 19 February 2009 (UTC)

I've run out of time this morning to fool with this further. But will provide additional references to this as well. Foolish of me to think that one reference that supported a statement was sufficient. How was I to know that hundreds would be required? Anyhow I have the hundreds so no problem doing so. Just a time constraint at the moment. But I did make the lists of these 4000 citations that I had relied upon when writing the article available to all who cared to read them. But apparently nobody cared to prior to trashing the article.Davidtfull (talk) 15:18, 20 February 2009 (UTC)

I only want review article. Case studies are not sufficient for wikipedia. By the way a case study does not prove an association. Thanks --Doc James (talk · contribs · email) 22:34, 20 February 2009 (UTC)

"Case studies are not sufficient for wikipedia". Wish someone had bothered to mention that before I wrote the article. Could have avoided a ton of problems. I was told that I had to cite anything that would be contraversial. Did not know that I was limited to using reviews written or financed by the various manufacturers, or by those beholding to them, instead. Independent reviews are harder to find then hen's teeth, but I will dig through my archives and see what I can find and cite to those instead. Some case studies may not prove an association but it presents sufficient evidence that such an association is within reason and should not be dismissed out of hand as to being irrelevant.Davidtfull (talk) 08:26, 21 February 2009 (UTC)

Well known association

is a well-known ADR to fluoroquinolone therapy and what is the support? THANK IS RIGHT ONE CASE. Well known is ONE CASE. Winrow AP, Supramaniam G (1990). "Benign intracranial hypertension after ciprofloxacin administration". Arch. Dis. Child. 65 (10): 1165–6. doi:10.1136/adc.65.10.1165. PMC 1792342. PMID 2248512. {{cite journal}}: Unknown parameter |month= ignored (help)--Doc James (talk · contribs · email) 11:43, 19 February 2009 (UTC)

This is than followed by a couple more case studies of one and a couple studies of cats.--Doc James (talk · contribs · email) 11:49, 19 February 2009 (UTC)

1. “Many drugs, including antibiotics, have been implicated in the aetiology of benign intracranial hypertension. We report the development of benign intracranial hypertension after the use of ciprofloxacin in a teenager with cystic fibrosis.” Arch Dis Child 1990 Oct;65(10):1165-1166 Benign intracranial hypertension after ciprofloxacin administration. Winrow AP, Supramaniam G. Department of Paediatrics, Watford General Hospital, Herts. PMID 2248512 [PubMed - indexed for MEDLINE]

2. “We report the occurrence of idiopathic intracranial hypertension in a patient treated with ofloxacin, a fluoroquinolone antimicrobial agent, for 16 months. The withdrawal of ofloxacin and acetazolamide therapy were followed by a complete recovery of visual function.” Idiopathic intracranial hypertension after ofloxacin treatment. Acta Neurol Scand 1993 Jun;87(6):503-4 Getenet JC, Croisile B, Vighetto A, Grochowicki M, Goudable B, Aimard G, Trillet M. Neurology Service, Neurological Hospital, Lyon, France. PMID 8356883 [PubMed - indexed for MEDLINE]

4. "Causes: Many conditions are associated with pseudotumor cerebri in children, none of which are convincingly causative, with the exception of medications. The following medications may be associated with pseudotumor cerebri: ...Antibiotics - Tetracycline, nitrofurantoin, fluoroquinolones”

Pseudotumor Cerebri: Pediatric Perspective William C Robertson Jr, MD, Professor, Departments of Neurology, Pediatrics, and Family Practice, Clinical Title Series, University of Kentucky Maria-Carmen B Wilson, MD, Medical Director of Pain Management, Department of Neurology, Tampa General Hospital; Associate Professor, Department of Neurology, Assistant Professor, Department of Pediatrics, University of South Florida College of Medicine; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital http://emedicine.medscape.com/article/1179733-overview

5. “Usual and common associations are excessive doses of tetracycline, vitamin A, administration of phenothiazine, estrogen, amiodarone and , quinolones...” Pankaj Kumar, R. Raja, Vineet Chauhan, Madhukar Rai, Shyam Sunder: Pseudotumor Cerebri As A Manifestation Of Addison's Disease. The Internet Journal of Endocrinology. 2007. Volume 3 Number 1. http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijen/vol3n1/addison.xml

6. “...the case for it having an aetiological role in PTCS { Pseudotumor Cerebri Syndrome } is at least relatively strong. First as Lesse (1992) points out, it is not a frequently used drug {refering to nalidixic acid} so particularly in children the number of case reports linking it with PTCS is rather high. Second there is the finding reported in two separate studies of resolution of PTCS after cessation of the drug followed by recurrences of PT CS after re exposure and again resolution with cessation (Boreus Sundstrom. 1967, Fisher 1967) ...Mukherjee et all 1990 ...of 12 infants developing PTCS within 24 – 48 hrs of starting a very high dose of Nalidixic acid...in the collected series of 1013 cases there were eight cases of PTCS attributed to nalidixic acid (Johnson 1992)... combined Glasgow and Sydney series of 270 case there was one case...”(sic) The Pseudotumor Cerebri Syndrome By Ian Johnston, Brian Owler, John Pickard pg 124 (in reference to nalidixic acid)

7. “However, quinolones are now emerging as causative agents of pseudotumor cerebri in infants and young children (30).” http://www.icddrb.org/images/jhpn181_isolation_discussion.pdf

8. “Quinolone derivatives (ciprofloxacin) were reported as an associated factor in one patient, while OCP was reported in two patients...”Acta Neurologica Scandinavica Volume 112 Issue 5, Pages 298 - 302 Published Online: 10 Oct 2005

9. “...tetracycline, nalidixic acid, nitrofurantoin, sulfamethoxazole, amiodarone, and indomethacin. Our patient was taking a quinolone, pefloxacin, of which nalidixic acid is a member, until the onset of her illness.”African Health Sciences, Vol. 2, No. 3, December, 2002, pp. 124-126 A 14-year-old Nigerian female with idiopathic intracranial hypertension (Pseudotumor cerebri or benign intracranial hypertension) A.C Onwuchekwa*, C.N. Nwankwo**, E.N. Chapp-Jumbo*

• Neurology Unit, Department of Medicine, University of Port Harcourt & University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria.
  • Department of Radiology, University of Port Harcourt & University of Harcourt Teaching Hospital, Port Harcourt, Nigeria.

Code Number: hs02053

Not conclusive by your standards but sufficient to prove an association does exist. I have numerous other citations I could reference but these were the ones most readily available. With these few additions we are up to ten already I believe. Not ONE.Davidtfull (talk) 14:51, 20 February 2009 (UTC)

The old FQ are no longer on the market because everyone agreed they were to toxic. We can have a section on the older FQ but they must be distinquished and not lumped togerther.--Doc James (talk · contribs · email) 22:33, 20 February 2009 (UTC)

Now I am really confused as most of the reviews you sent me includes the old quinolones. One in particular stated that: "For 2 decades {1979-1999}fluoroquinolones have been found to be generally well-tolerated and safe." (Lipsky 1999: one the citations most often referred to in support of the safety profile of the quinolones) and you noted above most of those quinolones everybody had since agreed were toxic and dangerous. But it is ok to cite to this review when stating "generally well-tolerated and safe?" Even though this author had lumped them all together to state that they were "generally well-tolerated and safe"? Yet a few years down the line everyone agreed that they were too toxic to remain in clinical use? Yet this is still to be considered a valid citation? And what I had state above cannot be used to contradict it because it refers to the same older quinolones that were removed because they were too toxic? What am I missing here as this is truly baffling me. The rules cannot change depending on which view you wish to support, or do they? Any number of these reviews include drugs that are stated to be safe and effective, minimum side effects, etc., that have been since been removed from clinical use due to toxicity issues and fatalities. Yet these very same reviews are being cited to prove how safe the drugs are. I think I need a more detail description of what kind of reviews you are looking for here as for the life of me I cannot grasp this concept. And I am not being argumentative here in the least. I am truly baffled by this.Davidtfull (talk) 08:46, 21 February 2009 (UTC)

Doc he has a good point. This is quite common with controversial drugs. The literature will praise the drugs for years or even decades before slowly gradually the literature condemns them increasingly. Although typically the full truth never comes out especially regarding long term effects. Another example is roaccutane, which has become condemned and is now a "drug of last resort" for severe acne due to being condemned in the medical literature as having serious adverse effects but the long term effects or possibly permanent effects are reported very little if at all in the literature.--Literaturegeek | T@1k? 14:31, 21 February 2009 (UTC)

Starting over

I have decided to start over rather than going thru each case study and animal experiment one by one.--Doc James (talk · contribs · email) 12:02, 19 February 2009 (UTC)

Private emails

Both user Davidtfull and talk have taken time to write me personal email. I have added discussion of a number of items above which I would like you guys to address rather than comparing the current scientific consensus to that or holocaust deniers. Currently this article is WP:FRINGE. --Doc James (talk · contribs · email) 17:30, 19 February 2009 (UTC)

That is getting crazy. I hope they calm down and apply some rational thought.--Literaturegeek | T@1k? 22:04, 19 February 2009 (UTC)

Yes but I do not take offense easily so no worries. I still believe in wikipedia and sometimes even refer patients here. We have a moto in medicine it goes "Show Me The Evidence" This applies to all sides. I truly do sit in the middle. No one who knows me would say I in any way protive the phrama industry. I do not see reps I do not take gift. I do not arrange CME events that have there sponsorship. I DO NOT write brand name, but always generic. I have tried to get nursing, pharmascists and government to do the same. Everything I have added is refernced to recent good quality refences which I am happy to send to anyone who does not have access.

But we have to support what we write and this has not been done at all at Fluoroquinolone toxicity. This is a couple of people who have taken it upon themselves because they have had an adverse event to demonize the use of this class of drugs.

It is amazing I have had a similar problem on the ADHD page, but from the opposite spectrum. There I was removing drug company propaganda and replacing it with peer review reviews published in good journals. I was called name, etc --Doc James (talk · contribs · email) 22:23, 19 February 2009 (UTC)

I don't believe you work for the drug companies, you just don't want to see wiki used for an agenda. I recall reading the ritalin page and found it highly biased in how it was written very promotional, dunno what the page is like now. I guess on wiki it depends on the editors who get involved whether an article becomes biased toward a drug company or toward people who are opposed to the drug. Who knows depending on how the fluoroquinolone community respond maybe a reasonable compromise can be reached. Stranger things have happened.--Literaturegeek | T@1k? 00:38, 20 February 2009 (UTC)

These other editors DO NOT represent the fluoroquinolone community. I believe I do and I thought we had already agreed to a reasonable compromise. That being I had declared a COI and left the editing to you and steve and offered any assistance you may require of me other than actively editing. I do NOT support what these other editors have been doing, and they have been doing it on their own with no influence or encouragement from me whatsoever. Somehow I think they are trying to destroy whatever goodwill you and I have developed in an effort to get this article deleted. I do NOT condone their current actions in the least as they are counter productive and frivolous and for the most part assisine and juvenile. Purile I believe the word to be.Davidtfull (talk) 04:20, 20 February 2009 (UTC)

Yes ADHD is another area with a lot POV pushing. I improved the ADHD page but did not have a chance to do the same for many of the sub pages. The problem is conscientious editors who base what they write on the scientific literature are out numbered. We have people pushing steroid use, people pushing fad diet, people blaming the worlds problems on a supposidely hidden infection cause of IBS that hasn't yet been discover.--Doc James (talk · contribs · email) 01:08, 20 February 2009 (UTC)

They may not be representatives from your organisation but I reckon there probably has been some talk about wikipedia on the various support groups and they have come onto wikipedia. Nothing is wrong with that, I am just saying.--Literaturegeek | T@1k? 08:49, 20 February 2009 (UTC)

No doubt there has been, as this article is of great interest and concern to the quinolone community. And those who are rational and reasonable, as well as responsible had asked that the nutjobs stay the hell away and not come to wikipedia and start anything. Those who are irrational, unreasonable and irresponsible appear to have given them the finger and did exactly that. I can only be responsible for my own actions, and will accept responsability for whatever they may be. But it is unreasonable and unfair to think I can take responsability for the actions of others I have no control over. Everybody has an opinion and are free to express whatever that opinion may be. But I do not and did not encourage people to make life miserable on wikipedia just to because they disagree with the changes to the article. They had done so with NO encouragment from me and without my knowledge or consent. In fact they were told SPECIFICALLY on some of the forums NOT to do this. And then did it anyhow. Seems they do this all the time and screw up any progress being made deliberately. Frustrating.Davidtfull (talk) 13:54, 20 February 2009 (UTC)

Reviews

If anyone would like a copy of some of the reviews please let me know and I would be happy to email you one. --Doc James (talk · contribs · email) 17:44, 19 February 2009 (UTC)

Please send me whatever you have, provided it was not authored by Ball or Tillitson. I have no interest (for personal and private reasons I do not wish to get into here) in what they have to say. Just send it to fqresearch@aol.com as an attachment.

More than likely I already have some of these articles you are willing to share, but I will add those that I do not to the site. Thanks for the offer, it is appreciated very much.Davidtfull (talk) 13:30, 20 February 2009 (UTC)

Feel free to send your reviews to me at fqhelp(at)gmail.com. I too would be interested to have a look at them. JamesLockson (talk) 11:04, 21 February 2009 (UTC)

Pediatric review, clinical study and review of the study to consider

A pediatric review to consider: http://www.fqresearch.org/kids_text/kids_10_text.doc Fluoroquinolones in Complicated Pediatric Urinary Tract Infections: A Review of the Literature Raffaella Mormile, MD, Laura Cuzzolin, MD, Vassilios Fanos, MD Infect Urol 15(3):3-8, 2002. © 2002 Cliggott Publishing, Division of SCP Communications Posted 09/10/2002

“The most frequent adverse effects in pediatric patients involve the GI tract and skin, but arthralgia and arthropathy are the main concerns.[5,6]”

“To date, however, the experimentally induced cartilage damage has not been confirmed in human juvenile joints”

(Comment: I have one case of a pediatric patient who sufferd severe cartilage damage in both knees resulting from levaquin that required surgery to repair in my archives. Patient has not yet fully recovered. Treatment was for a nail infection)

A clinical study to consider: http://download.veritasmedicine.com/PDF/CR002392_CSR.pdf

Comments:

712 evaluable for safety (533 levofloxacin, 179 comparator) Of the 712 subjects evaluable for safety, 275 (52%) levofloxacin-treated subjects and 94 (53%) comparator-treated subjects experienced 1 or more adverse event. Most adverse events were mild or moderate in severity. Seventeen subjects had 23 adverse events of marked severity. Most of the marked events were considered doubtfully related or not related to study drug. Twenty-three subjects experienced MS adverse events. The frequency of MS disorders was comparable in levofloxacin- and comparator-treated subjects (1.69% vs. 1.12%).

712 evaluable for safety (533 levofloxacin, 179 comparator) Levaquin 533 x 52%= 277.16 (rounded to 277) Actual percentage should be 51.25% (274.495 rounded to 275) Compactor 179 x 53%= 94.87 (rounded to 95) Actual percentage should be 52.5% (93.975 rounded to 94) study says 94 Percentages used would indicate 372 patients. Study states 369.

MS adverse events. Levaquin 533 x 1.69% = (9.0077) rounded to 9 Compactor 179 x 1.12% = 2.0048) rounded to 2 Study says: “Twenty-three subjects experienced MS adverse events” Percentages would indicate 11 patients. Study stated 23, twelve patients missing.

Serious adverse events were reported in 33 (6%) levofloxacin-treated subjects and 8 (4%) comparator-treated subjects. Most of the serious adverse events were considered doubtfully related or not related to study drug. Two serious adverse events in levofloxacin-treated subjects resulted in fatal outcomes. Neither death was considered related to levofloxacin.

Serious adverse events 533 x 6%= 31.98 (rounded to 32) study says 33 Actual percentage should be 6.25% (33.3125 rounded to 33) 179 x 4% = 7.16 (rounded to 7) study says 8 Actual percentage should be 4.5% (8.055 rounded to 8) Percentages would indicate 39 subjects. Study says 41.

Adverse events leading to treatment discontinuation occurred in 12 (2%) levofloxacin-treated and 2 (1%) comparator-treated subjects.

Adverse events leading to treatment discontinuation 533 x 2% = 10.66 (rounded to 11) but study says 12 subjects. Actual percentage should be 2.25% (11.9925 rounded to 12) 179 x 1% = 1.79 (rounded to 2) study says 2 subjects. Actual percentage should be 1.25% (2.2375 rounded to 2) Percentages would indicate 12 subjects. Study says 14 subjects.

A review of this study to consider: http://www.ncbi.nlm.nih.gov/pubmed/17901791?dopt=Abstract

Pediatr Infect Dis J. 2007 Oct;26(10):865-7. Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia. Bradley JS, Arguedas A, Blumer JL, Sáez-Llorens X, Melkote R, Noel GJ. Children's Hospital and Health Center, San Diego, CA, USA.

It was stated that “Levofloxacin was as well tolerated as comparators, with similar type and incidence of adverse events.”

Comments:

Yet the adverse events leading to discontinuation was 100% higher in the levaquin group (2% v 1%) and 50% more serious adverse events were found in the levaquin group, compared to the compactor. (6% v 4%) MS adverse events excluded 12 patients (which I would strongly suspect were related to levaquin MS adverse events.) How then is this to be considered “similar type and incidence of adverse events”?Davidtfull (talk) 11:56, 21 February 2009 (UTC)

Thanks for these.--Literaturegeek | T@1k? 21:18, 22 February 2009 (UTC)

Additional reviews to consider

1. “Although Achilles tendon rupture has been the most common injury with over 200 cases reported other joints may also be affected. Injury has been noted up to 90 days out after completion of therapy.” “Effects such as insomnia, dizziness, and anxiety have been reported in 0.9% to 11% of patients” “Crystaluria has been associated with the fluoroquinolones,” “In an 18-month post approval follow up study by the FDA for trovafloxacin 140 cases of liver toxicity were found” “Supportive rational is not seen for, lomefloxacin, sparfloxacin, moxifloxacin, and trovafloxacin, based on spectrum, safety and kinetic profile, in the clinical setting.”

Source: http://pharmacy.oregonstate.edu/drug_policy/pages/dur_board/reviews/articles/fluroquinolone-lit.html

2. Clinical Use of Fluoroquinolones in Children Abdullah A Alghasham and Milap C Nahata O B J E C T I V E: To review the pharmacokinetics, efficacy, and safety of fluoroquinolones in children. D A T A S O U R C E S: A MEDLINE search (January 1966–March 1998) was conducted for relevant literature. Excerpts:

"Quinolone-induced arthropathy and arthralgia has been rarely reported in children without cystic fibrosis. The first report was a case of destructive polyarthropathy in a 17-year-old boy after administration of Pefloxacin 800 mg/d for three months. The patient initially presented with joint pain and swelling, which deteriorated over three months and resulted in progressive difficulty in walking. X-ray findings showed severe destructive polyarthropathy. Microscopic examination of the cartilage and synovial biopsies revealed fibrosis of the synovial tissue and articular cartilage. Total bilateral knee and right hip replacements were needed.” “Nonetheless, FQ use in pediatric patients has increased as shown in the United States, where 8.4 million prescriptions for ciprofloxacin were written for patients 18 years and younger in 1996”

3. Ciprofloxacin Use in Children: A Review of Recent Findings from Pediatric Pharmacotherapy it is stated that: “Renal disease, including interstitial nephritis and RENAL CALCULI, has been reported in adults taking ciprofloxacin”

4. “FQ misuse was a common phenomenon in the teaching hospital studied” Eur J Clin Microbiol Infect Dis. 2006 Oct 28 Prospective assessment of fluoroquinolone use in a teaching hospital. Mean M, Pavese P, Vittoz JP, Foroni L, Decouchon C, Stahl JP, Francois P. Maladies Infectieuses, Departement de Medecine Aigue et Specialisee, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043, Grenoble (38) Cedex 9, France, PPavese@chu-grenoble.fr. http://cat.inist.fr/?aModele=afficheN&cpsidt=18318869

5. “On published clinical evidence, it offers no compelling advantages over established treatments for these conditions. In our view, claims that oral moxifloxacin provides “rapid relief from chest infections” are unsubstantiated, may mislead prescribers and should be withdrawn.” http://www.fqresearch.org/pdf_files/moxi.pdf original available here: http://dtb.bmj.com/cgi/content/abstract/42/8/61

6. “The new fluoroquinolones are rarely first-line agents and should be employed judiciously” Quinolones: a comprehensive review. Oliphant CM, Green GM. University of Wyoming School of Pharmacy, Casper, USA. coliphant@wmcnet.org http://www.aafp.org/afp/20020201/455.html

7. “The authors reviewed reported cases of antibiotic-induced manic episodes by means of a MEDLINE and PsychLit search for reports of antibiotic-induced mania. Unpublished reports were requested from the World Health Organization (WHO) and the Food and Drug Administration (FDA). Twenty-one reports of antimicrobial-induced mania were found in the literature. There were 6 cases implicating clarithromycin, 13 implicating isoniazid, and 1 case each implicating erythromycin and amoxicillin. The WHO reported 82 cases. Of these, clarithromycin was implicated in 23 (27.6%) cases, ciprofloxacin in 12 (14.4%) cases, and ofloxacin in 10 (12%) cases.” Antimicrobial-induced mania (Antibiomania): A review of spontaneous reports http://cat.inist.fr/?aModele=afficheN&cpsidt=13442254

MISC:

1. Jamaica Hospital Medical Center 8900 Van Wycjk Expressway Mamaica NY 11418 The Pharmacy, Therapeutics and Nutrition Committee reviews and evaluates all ADRs reported at the institution. The following is a summary of ADRs reported in 2002: A total of three hundred (300) ADRs were reported. Two hundred and fifty-three (253) were reported by the Pharmacist Thirty-four (34) were reported by the Physician Twelve (12) were reported by the Nurse One (1) was reported by the Nurse Practitioner The following Antibiotics accounted for 51 such events (17.0%): Augmentin - oral Ciprofloxacin (Cipro) - parenteral Ceftriaxone (Rocephin) - parenteral Gatifloxacin (TEQUIN) - parenteral Adverse drug reactions to antibiotics was the third leading cause of adverse reactions for the third year in a row.

2. Surge in Use of Cipro Spurs Concerns About Side Effects October 26, 2001 Health Journal Surge in Use of Cipro Spurs Concerns About Side Effects By TARA PARKER-POPE Staff Reporter of THE WALL STREET JOURNAL

3. Anthrax ills mirror Cipro side effects By MARK BENJAMIN and DAN OLMSTEDPublished: April 26, 2002 at 4:33 PM http://www.upi.com/Top_News/2002/04/26/Anthrax_ills_mirror_Cipro_side_effects/UPI-57501019853197/

4. Safety of the Fluoroquinolone Antibiotics: Focus on Molecular Structure CME Stacy J. Childs, MD, University of Colorado Health Sciences Center, Denver [Infect Urol 13(1):3-10, 2000. © 2000 Cliggott Publishing Co., Division of SCP/Cliggott Communications, Inc.] Abstract The excellent activity of fluoroquinolones against a broad range of gram-negative pathogens has made them mainstays of treatment of patients with uncomplicated and complicated urinary tract infections and prostatitis. But because safety profiles of the various fluoroquinolones differ, they cannot be considered interchangeable or of equal tolerability and safety. In recent years, several fluoroquinolones have had to be withdrawn or limited in use. To get at the heart of the safety problem requires a look at the molecular structure and pathophysiologic mechanisms of toxic effects of the fluoroquinolones in current use. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2094848 Davidtfull (talk) 13:45, 21 February 2009 (UTC)

When we shorten the article we can use these reviews to strengthen or expand the article.--Literaturegeek | T@1k? 21:18, 22 February 2009 (UTC)

I intend to resolve neutrality

I am going to try and resolve neutrality over the coming days and weeks, doing one section per day until finished. I will start with the introduction today.--Literaturegeek | T@1k? 15:05, 21 February 2009 (UTC)

Side effects

I would agree with many of David's points. Physicians and patients have a very poor understanding of side effects of drugs in general. Flip open any CPS and you will find large numbers of side effects listed for every drug. Drug reps never mention them. Ads mention them a top speed. On my rewriting of the article at Adverse effects of fluoroquinolones I learned about many side effects of this class of drugs which I was not aware of before.

Most of the side effects belonged to the older ones but many still do occur with the newer ones. They are rare on the basis of frequency but if one of these side effects hits you than of course it is common to you. I still insist on the use of review rather than case studies. --Doc James (talk · contribs · email) 03:19, 22 February 2009 (UTC)

I have to agree that reviews would be the best weapon for us to use for dueling over these issues. I will abide by that concensus and use them to support my arguments regarding statements made within the articles I feel are bias in support of the argument that the incident rate is comparative to other antibiotics, rather than use case studies or clinical studies. Then as a side note we can discuss whether or not the findings within the reviews are indeed truthfull and support the statements or b.s. and should not be used within the article based upon case studies and the like. Fair enough?Davidtfull (talk) 22:44, 22 February 2009 (UTC)

No harm in learning something new. Most if not all of the side or adverse effects of the older compounds are the same as the newer ones as it is largely a class effect. A better way of putting it is some of the side effects are more rare or very rare with the newer compounds or less common. I believe that we should be able to confirm all of the main adverse effects in a review of some sort.--Literaturegeek | T@1k? 03:24, 22 February 2009 (UTC)

This is not my take of the literature. Do you have support for the above statement. I can find support for mind if you wish.--Doc James (talk · contribs · email) 03:29, 22 February 2009 (UTC)

Depends on which adverse effects you are talking about? This review shows differences between the quinolones for the propensity to cause toxicity to certain organs or body systems. I can't clarify my statements unless I know which adverse effects we are talking about. I did say "most,,, if not all,,, leaving room that some adverse effects may be unique to an individual quinolone so we are not totally disagreeing.--Literaturegeek | T@1k? 18:27, 22 February 2009 (UTC)

I fully agree that the rate of adverse effects (certainly CNS, nerve injury, muscular, joint symptoms) are far more common and persisting with quinolones than other antibiotics. However, being far more common does not mean they are common adverse reactions. Severe adverse reactions may only be occasional or some of them rare but so to are probably severe adverse reactions to aminoglycosides and they are used sensibly by the medical profession as second line drugs with safety proceedures in place. David do you have the FDA adverse reactions myalgia, tendon etc which is cited in the article. Do you have those stats scanned and on your site or somewhere on the web for verification? What about the death rate you got from FDA, do you have the data scanned and on your site for verification? Would be more ideal if it could be linked to. They are good stats for the article. Sounds fair to me what you say David. I think though the thing is we can only go as far as what the author of a review goes. If they say rare, we can't say occasional. If they say occasional we can't say common etc. But I think that we have already established that anyway. I think we are making proogress here.--Literaturegeek | T@1k? 22:51, 22 February 2009 (UTC)

I will scan the responses to my FOI request and email them to you as attachements to the email. I did not publish them on my site as of yet as I had not had a chance to scan them. This gets me off my lazy butt to do so. Feel free to share them with anyone involved in this article with my blessings. I paid for them so I own them. They will be sent as jpg files and just be the summaries. The actual data included with the summaries is tens of thousands of pages long. The summaries may be too large for one email so I will send them drug by drug. I am confused once again here though (I get confused easily :) when you suggested linking to them. When I tried linking to the data on my site I was told that is a "no no" here. I was told that I can't be linking to my own site due to its negative POV.Davidtfull (talk) 23:10, 22 February 2009 (UTC)

I don't need them emailed to me, but would be better if they were on the web somewhere to link to for other wiki readers to see, so they don't get challenged down the road. I trust that the are legitimate. Yea that is because you own your site. I am not involved with your site so it might be ok to link to some stuff on your site as long as it is reliable stuff we are linking to. Are the summaries your summaries or the FDA's summaries?--Literaturegeek | T@1k? 23:20, 22 February 2009 (UTC)

Sorry, I had already sent them to you via your request. They are not ready to be posted on my site as of yet as I normally just post the summaries like I did in the comparision analysis I sent you. I sent you the actual documents recieved from the FDA unaltered. I have the same documentation for the summaries that ended in 2007 that I am comparing them to. A point to keep in mind while reviewing this data is the fact that the FDA uses the trade names to store the data. Hence ciprofloxacin, with hundreds if not thousands of different trade names would not merge that data. You have to generate a AER report for each and every trade name and then manually merge the data found for each drug name. Our cost for doing this we had estimated to exceed 150K in FDA fees. Money better spent elsewhere. Additionally everything reported prior to 1997 has been excluded from this data base. So information concerning nalidixic acid for instance would not contain anything reported between 1962-1996. Thirty four years worth of AER reports would not show up in the search. Just anything reported after 1996. Yet another problem as lot of the fluoroquinolones has been on the market in the States since 1982. Again 14 years worth of history excluded from the summaries I had sent you. I will however upload what I had sent you on my server and then send you the link.Davidtfull (talk) 02:37, 23 February 2009 (UTC)

Here are the links to the scans of the original documents being discussed here. I have the originals in my physical possesion.

Avelox AER December 2008

• fqresearch.org/jpegs/AVEL_1.jpg
• fqresearch.org/jpegs/AVEL_2.jpg
• fqresearch.org/jpegs/AVEL_3.jpg

Cipro AER December 2008

• fqresearch.org/jpegs/CIPRO_1.jpg
• fqresearch.org/jpegs/CIPRO_2.jpg
• fqresearch.org/jpegs/CIPRO_3.jpg

Factive AER December 2008

• fqresearch.org/jpegs/FACTIVE1.jpg
• fqresearch.org/jpegs/FACTIVE2.jpg
• fqresearch.org/jpegs/FACTIVE3.jpg

Floxin AER December 2008

• fqresearch.org/jpegs/FLOX_1.jpg
• fqresearch.org/jpegs/FLOX_2.jpg
• fqresearch.org/jpegs/FLOX_3.jpg

Levofloxacin AER December 2008

• fqresearch.org/jpegs/LEVO_1.jpg
• fqresearch.org/jpegs/LEVO_2.jpg
• fqresearch.org/jpegs/LEVO_3.jpg

Original FOI request letter November 2008

• fqresearch.org/jpegs/FOI_08_1.jpg
• fqresearch.org/jpegs/FOI_08_2.jpg

Davidtfull (talk) 02:50, 23 February 2009 (UTC)

Thanks for scanning the FDA documents David I have added them as references.--Literaturegeek | T@1k? 08:41, 26 February 2009 (UTC)

Old very new

I think we need to distinquish old vs new FQ when discussing side effects.--Doc James (talk · contribs · email) 03:20, 22 February 2009 (UTC)

I agree, certain quinolones for example had a much higher incidence of certain effects (or perhaps even unique side effects?), so we have to be careful not to misuse statements condemning one fluoroquinolone for having a high incidence of a certain adverse effect by then implying that other quinolones are the same. I have done a bit more deleting today, removing original research and case reports. I have shrunk the page by over 10 kb, the past couple of days. I think that slowly but surely we are making progress. :--)--Literaturegeek | T@1k? 21:02, 22 February 2009 (UTC)

Can we agree that if the older ones state a specific adr, and the same adr is present in ALL of the drugs found within this class, that this is to be considered a class effect? Or are we to judge each drug on its own merits, or lack thereof? I am seeking guidance as to when it would be considered proper to label something a class effect within the article. Nalidixic acid is still in use today here in the U.S. it is used on Indian reservations out West because it is cheap and readily available. Factive, though at one time denied approval in Europe is available in Mexico and the United States. A lot of the older drugs, if the manufacturer had not stopped production are still in use in Third World countries, or if they did stop production the excessive inventory is being sold off there as well. As such thier profile is still relavant I would believe to this article as physicians are still employing them today. As far as clinical trials go you might want to take a look at what went on over in Nigeria concerning Trovan years ago, yet another reason why I have so little faith in the use of reviews based upon clincial trials. Pfizer is being sued for billions of dollars by the Nigerian government regarding Trovan and illegal and utethical pediatric clinical trials. Trials that were being performed while activist were trying to get Trovan pulled from clincal use here in the States due to its toxic safety profile. We are also finding such trials seeking new indications as well as new drugs within this class being performed more and more in India, South America, Mexico and other such impoverished countries to avoid the oversite that more advanced countries employ to prevent false trials.Davidtfull (talk) 23:00, 22 February 2009 (UTC)

If an adverse reaction occurs with all fluoroquinolones, certainly those that are used in clinical practice I think that it is a safe bet and ok to call it a class effect. A review article should mention such adverse reactions. 99% of the people who will be coming across this article will be from english speaking countries or close to 99%. People using google.de will bring up de.wikipedia.org (german wikipedia) or french wikipedia fr.wikipedia.org so I don't think that we need to worry too much about drugs used in obscure countries. I know all about such trials and had heard about the nigerian one, I think on your site or on one of your youtubes. I have been discussing the problems and limitations of clinical trials with "The Doc".--Literaturegeek | T@1k? 23:16, 22 February 2009 (UTC)

citation request

In response to: Only limited research has been conducted into the long term effects of fluoroquinolones making epidemiology statistics of the incidence of fluoroquinolone toxicity difficult to ascertain.[citation needed]

“The reason long term effects aren't studied in the test group is that Levaquin is a short term therapy and does not include a requirement for long term post treatment evaluations.” Date: July17, 1999 Response received from: Celia A. DeLawter, Executive Operations Staff (HFD-6), Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857.

• Side-effects of quinolones: Comparisons between quinolones and other antibiotics

European Journal of Clinical Microbiology & Infectious Diseases 10.1007/BF01967014 “Few systematic and large scale comparisons between quinolones and other antibiotics has been performed.”

• Fluoroquinolones and risk of Achilles tendon disorders: case-control study

“Fluoroquinolones have been associated with tendon disorders, usually during the first month of treatment, but the epidemiological evidence is scanty. “ http://www.bmj.com/cgi/content/full/324/7349/1306

• Research Article

Tendon disorders attributed to fluoroquinolones: a study on 42 spontaneous reports in the period 1988 to 1998 Paul D. Van Der Linden 1 2, Eugène P. Van Puijenbroek 3, Johan Feenstra 4 5, Bas A. In T Veld 4 5, Miriam C. J. M. Sturkenboom 6, Ron M. C. Herings 7, Hubert G. M. Leufkens 7, Bruno H. Ch. Stricker 4 5 *

“surprisingly little is known about the epidemiology of fluoroquinolone-induced tendinitis and tendon rupture. Epidemiologic evidence is limited to one cohort study” http://www3.interscience.wiley.com/cgi-bin/fulltext/84002079/HTMLSTART

• Floxin Otic package insert (Daiichi Pharmaceutical Corporation—US), Issued 12/14/97, Rec 2/3/98; Rev 1/29/98, Rec 8/98

“Long-term studies have not been done”Davidtfull (talk) 06:38, 23 February 2009 (UTC)

In response to: "As a result of the efforts of The Fluoroquinolone Toxicity Research Foundation[citation needed] and Public Citizen the FDA ordered black box warnings on all fluoroquinolones warning consumers of the toxic effects of fluoroquinolones on tendons.[14]

• The text of my own petition regarding these issues filed 2-20-2004

http://fqresearch.org/letters_to_the_fda_8.htm

• Response recieved from the FDA March 12, 2004 in regards to this petition:

“This is in response to your emails to Dr. McClellan, Dr. Sherman, and Dr. Galson of February and March, 2004 regarding Quinolone post marketing reports. They have forwarded your emails to the Center for Drug Evaluation and Research's Office of Executive Programs to respond... there have been several labeling supplements added as well as adding new indications since the original approval in 1996."

NOTE: Cipro was approved in 1987, almost a decade earlier. Somehow the FDA is under the impression that the original approvals for the quinolones was 1996.

http://fqresearch.org/letters_to_the_fda_13.htm

• My response to the FDA response received above. The FDA never responded to this rebuttal.

http://fqresearch.org/letters_to_the_fda_14.htm

Other letters and petitions filed by members of the forum:

• http://fqresearch.org/letters_to_the_fda_5.htm
• http://fqresearch.org/letters_to_the_fda_4.htm
• http://fqresearch.org/letters_to_fda_1.htm

In addition the letters sent to the media:

• http://fqresearch.org/media_wizard.htm

Press releases:

• http://fqresearch.org/press_release_wizard.htm

Letter sent to EVERY attorney general asking them to support the tendon petitions:

• http://fqresearch.org/attorney_general_letter.htm

Their responses:

• http://fqresearch.org/attorney_general_responses.htm

Is this sufficient or do we need more documentation? Davidtfull (talk) 07:46, 23 February 2009 (UTC)

It is important to state when this conclusion was made. One could say as of "so and so a year" little evidence of long term evidence is available. Because it might become available at some point.

Than we need to specify what long term means. "In this prospective study of 276 pediatric patients who were exposed to relatively high FQ doses for long durations, no severe or persistent musculoskeletal lesion was observed."http://pediatrics.aappublications.org/cgi/content/full/111/6/e714

However, long-term therapy (> 28 days) during a clinical study of chronic prostatitis was associated with asymptomatic increases in liver enzyme levels of 3 times or higher than normal values in 9% of 140 patients.[27] http://www.medscape.com/viewarticle/418295_2

Medicine is hard to write about as it is so nuanced. Yes drugs can cause bad side effects but what they are supposed to be used to treat can also be fatal.

--Doc James (talk · contribs · email) 13:42, 23 February 2009 (UTC)

"What they are supposed to be used to treat can also be fatal". Do you know of any case(s) of otis media proving to be fatal? That is what some of the pediatric trials were for. Or perhaps chronic prostatitis, or non bacterial sinustis, a head cold, or perhaps even chronic bronchitis? Perhaps it would be better to state that "due to the lack of a significant number of long term studies (greater than one year follow up) available at this time, the idemiology statistics used to report the incidence of fluoroquinolone toxicity may not be accurate, or possibly even misleading."Davidtfull (talk) 15:01, 23 February 2009 (UTC)

I see lots of deaths from chronic bronchitis. I have 3 people dieing from it right now to tell you the truth. Otis media can lead to meningitis. I have had one such case. The rest I agree. All antibiotics are overused. This is well know. It is not just the fault of physicians but patients play a role. You would not believe the numbers who insist on antibiotics for the viral infections. And the ones with bacterial infections who do not want something relatively safe like amoxicillin but insist on either a macrolide or a FQ. I frequently tell people that they are not the physician and therefore do not get to decide on the treatment. But I know many docs would just give the patient what they want.--Doc James (talk · contribs · email) 16:32, 23 February 2009 (UTC)

Wasn't being sarcastic with my above questions Doc, gotta remember you guys are a lot more educated than I, and have a lot more clinical experience. I've never heard of kid suffering a fatal ear ache is all. Meningitis yes, have heard of that many times. The only way to level the playing field here is for me to ask stupid questions concerning certain things I am confused about or don't quite understand. Getting me on the same page will avoid a lot of misunderstandings and needless debates. Not looking lay blame on ANYONE here, neither the drug companies, the physicians, the patients, etc. Who is to held ultimately to blame is irrelevant and counter productive to what we are trying to accomplish here. That being providing high quality, and properly cited informational article regarding the true and known safety profile of this class. Everything else is distracting bs that can wait for another day. And yes indeed I would not challenge for a minute how ignorant patients are and how they demand an antibiotic for every visit. Seems they feel cheated if you don't write a script for something. Whether they need it or not. They are their own worse enemy in that regard. Sorry to hear about those patients that are struggling. You do the best you can and hope God is willing to do the rest. Ain't enough money in this world for me to spend one day in your shoes Doc. You're caught between a rock and hard place the moment you step out of bed each morning.

Are we in agreement here then that we will only use "class effect" to describe an ADR, or any other common element that is found within ALL of the drugs commonly in use today? And the other guideline being that only "reviews" are to be considered "trump"? If so then we have resolved two of the major issues amicably. That's making some positive progess in a very short time.Davidtfull (talk) 03:31, 24 February 2009 (UTC)

The reason long term effects aren't studied in the test group is that Levaquin is a short term therapy and does not include a requirement for long term post treatment evaluations.” Date: July17, 1999 Response received from: Celia A. DeLawter, Executive Operations Staff (HFD-6), Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857.

Is the above on your website, the scanned original document/correspondance with the FDA? If it isn't, is it possible to upload it?--Literaturegeek | T@1k? 15:06, 24 February 2009 (UTC)

Will try and trace down the original doc. Gotta remember that was ten years ago so that will take some time and effort. Reference to it is on my website via a copy of an email that refers to it, but the actual document is not. Let me try and find it for you. It is here somewhere as I throw nothing away. Just got to put my finger on it is all. When I do I will scan it and upload it to my server for you and provide a link. I believe that ALL of the stuff I referenced to regarding the FDA I have original docs for, just don't know where in my file cabinets they are hiding at the moment is all. Davidtfull (talk) 22:16, 24 February 2009 (UTC)

Thanks David. It would be great if you could because it verifies that long term testing is not done for antibiotics.--Literaturegeek | T@1k? 03:38, 25 February 2009 (UTC)

Major issues fixed

I think that he major issues have been fixed. I have removed original research, misuse of references, misrepresentation of references, removed unneutral wording and the like. Also removed data which was talking about one quinolone rather than quinolones as a drug class.--Literaturegeek | T@1k? 03:41, 25 February 2009 (UTC)

The introduction (which is far as I got) still contains at least one misrepresenation of references, to wit:

The references used to support this statement fail to do so, and grossly misrepresents the contents of the citations being used:

“The FDA and other health authorities have investigated case reports they have received for certain aspects of fluoroquinolone toxicity including tendon rupture and peripheral neuropathy. Based on their analysis of case reports they have concluded that fluoroquinolones rarely cause long term damage.”

The first reference used:

Hedenmalm K, Spigset O (April 1996). "Peripheral sensory disturbances related to treatment with fluoroquinolones". J. Antimicrob. Chemother. 37 (4): 831–7. doi:10.1093/jac/37.4.831. PMID 8722551 Division of Clinical Pharmacology, Norrland University Hospital,

Once again an editor is attempting to use an antiquated study to support a controversial statement made within the article. This study was done in 1995, fourteen years ago, and excludes about 15 of the drugs found within this class. The National Board of Health and Welfare (Sweden’s health authority) did not investigate these case reports as implied by this statement. This review was based on 37 reports submitted to the Swedish Adverse Drug Reactions Advisory Committee. This committee did not conduct this investigation or write this report. Hedenmalm et al did, and this article does not support the statement made “rarely cause long term damage”.

The study was done in Sweden so would have only included quinolones that were on the Swedish market at that time. It was not an international study.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

In fact this citation refutes this within the abstract itself where it was stated that “Seventy-one per cent of the patients recovered within 2 weeks after drug discontinuation.” Logic would dictate that 29% did not. The duration of symptoms in the 28 cases (where information was provided) was stated within the article to have varied from a ”few hours to over a year”.

The article stated that “In two patients on fluoroquinolones (Aoun et al., 1992; Rollof & Vinge, 1993), EMG showed indications of toxic axonal neuropathy, but the causative role of the fluoroquinolone was not established in one of these cases (Rollof & Vinge, 1993).” And goes on further to state that: “Similar changes may have been present in most of our patients, although patient no. 11 had normal EMG and nerve conduction velocity despite continuing symptoms.” A continuation of symptoms even though the patient had a normal EMG, would also indicative of long term damage induced by the drug of an unknown etiology.

Since most neuropathies are axonal neuropathies, recovery would have to be considered long term extending over months and years. The article even goes further and states that “As the number of patients treated with fluoroquinolones is growing, it can be expected that the number of patients who experience such reactions will increase.” “Will increase” would indicate that the authors did not believe this to be rare, but soon to be a common event.

I find it very difficult if not impossible to accept this citation as being valid being used in this fashion. This study is relying solely upon 36 case studies of which only 28 were used to determine duration. The investigators excluded 20% of these cases from this determination. Yet an all inclusive statement is being made based upon spontaneous reports received over fourteen years ago by the Swedish Adverse Drug Reactions Advisory Committee. Of these four drugs found within this class, one that was pulled from the market as it was too toxic, and the other two rarely even used at all these days.

I see that they did make an approximate guess at the incidence rate, or epidemiology and stated this in the article.

If the 14 reported cases for norfloxacin in 1988-89 are related to the 147, 438 and 218,357 packages sold in the same years, a risk of one case for every 1250 to 2500 treatments could be expected (if it is assumed that only 5-10% of cases are reported).

I have reworded the introduction accordingly.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

The fluoroquinolones studied were norfloxacin, ciprofloxacin, ofloxacin and temafloxacin. The article states that Norfloxacin was introduced in 1986, when in fact it was patented in 1978, eight years earlier. Cipro in 1986, when in fact it was patented in 1983, three years earlier. Ofloxacin in 1990, though it was patented in 1982, eight years earlier and Temafloxacin in 1991, though it was patented in 1982, nine years earlier. No where within this study did it state anything comparative to having “concluded that fluoroquinolones rarely cause long term damage”. Long term damage was not even mentioned.

The study assigned the incident of PSD as follows: Norfloxacin 31 Ciprofloxacin 5 Temafloxacin 1

They are probably talking about when the drugs were introduced onto the Swedish market rather than when they were patented. Remember it is a Swedish study not an international or US study.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

Dr. Cohen’s study in 2001 (Peripheral Neuropathy Associated with Fluoroquinolones Jay S Cohen) refutes this as well, and it was done six years later and included four other fluoroquinolones that were not used in the Swedish study, that being:

Levofloxacin (n=33) Ciprofloxacin (n=11) Ofloxacin (n=6) Lomefloxacin N-1) Trovafloxacin (n=1)

There has been an argument put forth that Dr. Cohen’s study is somehow defective as the case studies he had used were obtained from the Internet. I would consider this assertion to be frivolous, as the cases were required to provide information that equaled or exceeded the standards of the FDA’s MedWatch program. Hence the cases are to be considered to be as valid as the ones used in the Swedish study.

They are defective in drawing epidemiology evidence from it. You could do a case study on nvCJD analysing 30 or whatever cases of nvCJD but that wouldn't mean that you could then say such in such disorder occurs commonly. Case studies are not epidemiology. If it was possible to make an epidemiological calculation I am sure that Dr Cohen would have applied a rough guess statistic for his results but he couldn't. The standards for FDA MedWatch inclusion were not to do with epidemiology. It met the standards for a case study under medwatch guidelines. A case study does not prove nor disprove whether a cases are common it just gives a picture of what is common amongst the cases. All the cohen study does is show that quinolones are capable of doing long term damage in an undetermined percent of people.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

Of the 52 cases studies, 41 (91%) presented with a PNS injury. The study stated that “Based on the severity scale defined in the Methods section, two cases were mild (4%), seven moderate (16%), and 36 severe (80%). The duration of symptoms exceeded one month in 41 of 45 cases (91%), three months in 32 cases (71%), one year in 26 cases (58%), and 12 (27%) have exceeded two years’ duration. One case has continued more than four years and another more than six years. These numbers are not final because some cases were relatively new and are still evolving...Although many newer cases are still evolving, symptoms had lasted more than three months in 71% of cases and more than one year in 58%. These cases suggest a possible association between fluoroquinolone antibiotics and severe, long-term adverse effects involving the PNS as well as other organ systems.”

This data is discussed in the controversy section of the adverse effects of fluoroquinolones and also later on in the fluoroquinolone toxicity article. It has not been left out.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

The second reference used was a newspaper article entitled “FDA orders 'black box' label on some antibiotics” and the comments made within that article make no mention of PNS injuries. Bayer defended the drugs as being "well-tolerated and effective in all approved indications." Which is Bayer’s standard frivolous response to any negative article concerning their products. The ridiculous statements made the FDA's Dr. Renata Albrecht that “ fluoroquinolones drugs can increase the risk of tendonitis and tendon rupture -- which is about 1 in 100,000 -- by three to four times” has been so soundly refuted it does not require further discussion. The FDA also stated within this article that it has received "hundreds" of reports of tendon problems linked to fluoroquinolones and that, (without being more specific, citing the ongoing lawsuit) "the FDA continues to receive a considerable number of reports on tendon adverse effects."

No mention of the PNS events to be found within this newspaper article. Regarding the tendon issues (which is but ONE of the many long-term events associated with this class) the FDA stated that is has received hundreds of such reports and continues to receive a considerable number of such reports. As Doc had stated in an earlier discussion “This is enough to make a guy pull out his hair” (No wonder I have been going bald over the past decade after starting to do this research)

There are two refs there, one is the peripheral neuropathy and the other is the tendonopathy. The refs you provided a week or so ago actually backed up the FDA. The refs you provided you had mistaken relative risk ratio and odds ratio etc as percent but when correctly interpreted they actually agree wiith the FDA if not actually suggesting an even lower risk. There were studies showing higher rather in the elderly and heart and lung transplant patients and those on corticosteroids but the FDA acknowledge that tendon damage is increased in these groups. So I have not seen a paper which contradicts the FDA yet. I am not denying that the risks of tendon damage are downplayed by the FDA or that their methodology of the FDA or other papers may not have flaws but you need to provide a citation to refute the FDA stats. So far all the papers you have provided agree with the FDA that I have seen.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

These two references do not support the statement: “Based on their analysis of case reports they have concluded that fluoroquinolones rarely cause long term damage” As neither citation makes any mention of any conclusions being reached regarding long term damage, this is a fraudulent statement and needs to be revised. Dr. Cohen’s review soundly refutes it and the statement should be changed to reflect the conclusions of Dr. Cohen. If a review can be found that supports it then we would have to state that it is controversial and not conclusive, as the two reviews would be in conflict. I have yet to review any investigation by any health authority that would support this. But this is what the statment is claiming to be fact, without citing to any such investigations.

I changed the peripheral neuropathy statement as they do give an approximate calculations which is not rare but more occasional. The FDA statement of 4 per 100,000 is rare by anyones judgement and need a citation to refute it. You know what you would be best doing, the only way I think that you are going to be able to reword the introduction is to get that FDA official letter scanned where they acknowledge that there is no long term study done on teh drugs because they are meant for short term use. That would really help to sort the introduction out. Other than that I don't know what you can do unless you can refute the FDA stats with papers.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

I think it best that we arrive at some kind of consensus and formulate some guidelines regarding the use of antiquated studies to support current events. This is going to take forever if I have to refute each and every use of antiquated data and engage in the numerous discussions we will end up having as a direct result. Particularly if the reviews fail to even address the drugs that are currently in use today. Or are refuted by newer studies.

It would be unethical of us to support one point of view over another based upon irrelevant an antiquated data just because someone does not take the time to properly research the citation used. Of even a greater concern would be the deliberate use of such citations knowing full well that they do not support the statement being made, in the hopes that they would be taken at face value and not researched or even read.

Inadvertent errors we all will make, and I made a ton of them within the original article being unaware of the standards we were required to apply. Mea Maxima Culpa. But are we not required to have at least to have read the citations we are using before citing to them? Or are we only to read the abstracts and go from there? Would it not be fair that we add to the guidelines being employed here that we must first read the papers before citing to them, (and not just the abstracts), and the citation must, in some fashion, support the assertions being made? Or am I once again to be considered being unreasonable and difficult here?Davidtfull (talk) 06:34, 25 February 2009 (UTC)

I recommend if you can finding that FDA official letter, getting it scanned and then we can acknowledge that there has been no or little research done into the long term effects. If you can get that letter upload I think that would make a great citation and would resolve everyone battling to prove the other side as incorrect.--Literaturegeek | T@1k? 08:29, 25 February 2009 (UTC)

I have edited comments into your post.--Literaturegeek | T@1k? 08:30, 25 February 2009 (UTC)

Your edits resolved all the issues I had concerning the way in which those citations were used. I appreciate you doing that. They now reflect the content of the references correctly. I have sent an email to Chicago, as we are still working with the Attorney General there, and asked my associates to look and see if that document we are looking for might be included in the research that they have. So I was not blowing that off to question these citations. I was multitasking.  :)

On a side note I don't understand the difference between the Cohen study and the Hedenmalm study as they both used spontaneous reports, they are both studies, not reviews, and the only difference is one made a guess as to frequency and the other did not. The FDA also used spontaneous reports to formulate their guess as well. Be that as it may, my immedate concern was addressed correctly (as well as promptly) and we can move forward from there and talk about Cohen at another time. At the moment his study is no longer relevant. Finding that doc however is and I am working diligently on doing that.Davidtfull (talk) 09:36, 25 February 2009 (UTC)

Good, no problem, you are welcome David. The Hedenmalm study used reports to a regulatory body and they were able to make an approximate guess based on knowledge that approximately 5 - 10% of notable drug adverse reactions get reported to the drug regulatory body in Sweden. A case study by simply asking members of an online support group to complete a structured questionaire and giving medical history etc could not possibly be used to say what percent or number per thousand experienced those adverse reactions out of the general population. That is the difference. Also Cohen doesn't give any approximate statistic of how many people per say 1,000 people he reckons suffered adverse reactions in the general population so we would be doing original research by applying any epidemiology to his study.--Literaturegeek | T@1k? 15:04, 25 February 2009 (UTC)

Thanks for explaining this.Davidtfull (talk) 02:29, 26 February 2009 (UTC)

Suggested addition to the intro

This is just a suggestion that may help put some of qoutes used in the articles concerning the fluoroquinolones being as comparatively safe as other antibiotics as well as such side effects being mild or rare in its proper context. This can be accepted or rejected or even modified by the other editors. I am just making a suggestion here that may help to resolve any lingering issues, if there are any such issues, after FG's outstanding edits.

Suggested text:

In spite of this ongoing controversy, in 2005 Owens et al opinioned that “...The currently marketed quinolones have safety profiles similar to that of other antimicrobial classes...” Ball et al back in 1999 (Ball had an affiliation with Bayer at that time), had opinioned that the “...Fluoroquinolones are generally well tolerated with most side effects being mild and serious adverse effects being rare...” Several of these drugs (grepafloxacin, temafloxacin, trovafloxacin) had already been removed from clinical use at the time that Ball et al was published, (or soon thereafter), due to toxicity issues.Davidtfull (talk) 10:14, 27 February 2009 (UTC)

Merging Adverse effects of fluoroquinolones to Fluoroquinolone toxicity

The proposal is to merge Adverse effects of fluoroquinolones to here (i.e., Fluoroquinolone toxicity). There is no good reason for a content fork here, and maintaining one article well is tough enough. SD (talk) 19:50, 26 February 2009 (UTC)

I would support this idea to merge the adverse reactions article into this article.--Literaturegeek | T@1k? 03:12, 27 February 2009 (UTC)

Support Kevin McCready (talk) 03:16, 27 February 2009 (UTC)

We have reached the point now that we should remove the dispute tags and merge the two articles. As such I would also support a merger.Davidtfull (talk) 06:24, 27 February 2009 (UTC)

I am also in Support of merging Adverse effects of fluoroquinolones here. JamesLockson (talk) 09:16, 27 February 2009 (UTC)

STRONG NO SUPPORT I do not support the merging of ADR into toxicity. First of all Adverse effects of fluoroquinolones is the usual scientific term to describe what is being described. Fluoroquinolone toxicity would be used for acute toxicity by the medical community however it is also the term used by a small group who wishes to demonize their use. Will make a larger community aware. I would support merging some of the content from toxicity into ADRs. Cheers--Doc James (talk · contribs · email) 14:49, 27 February 2009 (UTC)

I can be swayed either way on the title of the article. If it were merged into adverse effects we could have a section where it discusses when the medical community refer to it as toxicity, eg cardiotoxicity, neurotoxicity etc and how it is referred to such as by the quinolone groups. I support merging still though, the articles do need to be merged.--Literaturegeek | T@1k? 18:53, 27 February 2009 (UTC)

Scope of two articles

Toxicity states that this page is about the "long term or serious physical and mental adverse reactions". That mades Adverse effects of fluoroquinolones a much broader article into which Fluoroquinolone toxicity could potentially be combined as a subsection. Adverse effects of fluoroquinolones discusses mild side effects aswell. --Doc James (talk · contribs · email) 15:04, 27 February 2009 (UTC)

Most drugs can have adverse effects, but fluoroquinolone is the only drug X that has its own Wikipedia article "Adverse effects of X". There are a few other articles "X toxicity" where X is a drug (Digoxin toxicity, Gentamicin toxicity, Paracetamol toxicity); these are significantly shorter than Fluoroquinolone toxicity. This is unbalanced; the prominence given to fluoroquinolone is not justified.

Would it be a solution to have one separate article "Controversies surrounding fluoroquinolones", similar to Thiomersal controversy, for which it is clear from the start that any claims reported on concerning toxicity are the subject of a controversy? "Adverse effects" should confine itself to what is significant and generally accepted in the professional medical community. Hopefully "Adverse effects" can be reduced then to no more than a section of the article Quinolone. SD (talk) 19:12, 27 February 2009 (UTC)

An adverse effects article could be written for acetaminophen and digoxin. The above are discussing acute or chronic overdoses not side effects seen at normal doses. We could have an article on FQ toxicity that would discuss acute overdoses of FQ. But that is not what we have here and therefore this article is named wrong.

We already have a section called controversies surrounding FQ in the AE article.

Here is a list of ADRs for digoxin and there is a seperate article called digoxin toxicity. These are the reactions at normal doses when blood levels are in the therapeutic range:

ADVERSE REACTIONS SIGNIFICANT — Incidence not always reported.

Cardiovascular: Heart block; first-, second- (Wenckebach), or third-degree heart block; asystole; atrial tachycardia with block; AV dissociation; accelerated junctional rhythm; ventricular tachycardia or ventricular fibrillation; PR prolongation; ST segment depression

Central nervous system: Visual disturbances (blurred or yellow vision), headache (3.2%), dizziness (4.9%), apathy, confusion, mental disturbances (4.1%), anxiety, depression, delirium, hallucinations, fever

Dermatologic: Maculopapular rash (1.6%); erythematous, scarlatiniform, papular, vesicular, or bullous rash; urticaria; pruritus; facial, angioneurotic, or laryngeal edema; shedding of fingernails or toenails; alopecia

Gastrointestinal: Nausea (3.2%), vomiting (1.6%), diarrhea (3.2%), abdominal pain

Neuromuscular & skeletal: Weakness

<1% (Limited to important or life-threatening): Abdominal pain, anorexia, eosinophilia, gynecomastia, hemorrhagic necrosis of the intestines, increased plasma estrogen and decreased serum luteinizing hormone in men and postmenopausal women and decreased plasma testosterone in men, intestinal ischemia, palpitation, sexual dysfunction, thrombocytopenia, unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy), vaginal cornification

Any arrhythmia seen in a child on digoxin should be considered as digoxin toxicity. The gastrointestinal and central nervous system symptoms are not frequently seen in children. From uptodate.com--Doc James (talk · contribs · email) 19:24, 27 February 2009 (UTC)

I actually spoke to a doctor I know who has been a doctor for decades and uses gentamycin fairly often and says that he has never seen a case of ototoxicity from aminoglycosides, but that is probably because it is usually reserved for severe infections and/or as a second line drug and have safety measures eg measuring blood levels etc.--Literaturegeek | T@1k? 19:49, 27 February 2009 (UTC)

Problems with the mortality section

Even though literature has done a lot of work improving this article there is a lot more to do. Lets look at the mortality section it says: "2,298 total death outcomes by case, 806 attributed to Levofloxacin" now lets look at the ref. It says "944 death outcomes 51128 total reactions. But on the first page it says these cannot be scientifically established and does not indicate a cause and effect relationship."

Therefore the reference does not say that 944 deaths are attributed to levo it says attributable CANNOT be determined.

For example if someone has sepsis is put on a FQ and dies you cannot say they died from the FQ.

Also this states ADR reporting support the name change. There is a lot more work that needs to be done before I would support merging toxicity into Adverse effects of fluoroquinolonesDoc James (talk · contribs · email) 19:06, 27 February 2009 (UTC)

The only info you get in the summaries is outcome by cases. You have to plow through each individual record to determine whether it was the primary drug, secondary drug, the exact circumstances, etc. Since these are calls being made by the attending physician you see that disclaimer. How then do you suggest we indicate that x number of "outcome by cases" come from the levaquin summaries, Y number of "outcome by cases" come from the cipro summaries, etc., and all of these numbers combined equal Z? If you use the words "associated" as in X number of outcome by cases is "associated" with levaquin (as those numbers are derived from the levaquin summaries, hence are associated with the levaquin summaries) you are giving the wrong impression. Same thing with using attributed. As they are being attributed to being derived from that summary. It is a matter of symatics here, using the proper verbage to let the reader know "here is where these numbers came from". We had already informed them that these numbers are outcomes by cases. X number of people have died while on these drugs. Whether the drug was the cause of death, who knows for sure. But somebody reported this death and had stated that a drug from this class was somehow involved. Maybe it was involved because it failed to work. Maybe it was involved because it was one of a dozen different drugs the patient was on. Maybe it was involved because it actually killed the patient. And without actually reviewing the medical records and the autopsy you do not have an answer. But all we are trying to state here is that the FDA recieved x number of reports and within this x number of reports we have a significant number of deaths being reported. We are citing to a fact, and where this fact was derived from. Not citing to the actual meaning of the fact, as we do not know what that might be without doing OR.Davidtfull (talk) 06:11, 28 February 2009 (UTC)

Yea but the doctors who reported death as an ADR, reported it because they believed that the quinolone was responsible and not another cause such as infection. If there was doubt in the clinician's mind then he/she probably wouldn't have reported it. What reliability then are clinical trials which are "the opinion of the clinican observing", setting aside bias? What you have just said from my interpretation casts doubt on the entire of medicine. You are sounding worse than us now with your lack of trust in medicine and clinical judgement by physicians. :) Or have I made a mixup, like I mixed up what statistical significant meant? I am not trying to be rude, just poking a bit of friendly fun to lighten up the situation, as well as make a point.--Literaturegeek | T@1k? 19:29, 27 February 2009 (UTC)

I do not know how the American reporting system works. That would be an interesting question to look at. Before this type of info would be relevant it would need to be put into context. ie how many deaths and ADRs occur with other broad spectrum antibiotics perportional to their frequency of us.Doc James (talk · contribs · email) 19:35, 27 February 2009 (UTC)

Here is an interesting page: http://www.fda.gov/medwatch/how.htm It looks like anyone can report ADRs in the USA.--Doc James (talk · contribs · email) 19:36, 27 February 2009 (UTC)

Go ahead a try downloading one of those quarter reports you find on the FDA site. You will find that they are totally inacessable unless you have the antiquated software they were created with loaded on your computer. I am a computer tech by profession and I have yet to be able to locate that software. It is about thirty years out of date from what I understand. It use to be available through the colleges but that was back in the seventies. Additionally the FDA reviews these reports and only enters about one out of four into the database. It has been estimated that only about 1-3% of these reactions are reflected by this database. As such 97% of the reactions that have taken place are missing.Davidtfull (talk) 05:52, 28 February 2009 (UTC)

Indeed I did make a bit of a mixup, as anybody can report an ADR to the FDA. That can be done in the UK as well. I think the problem is also people die of infections as well more commonly than they die of quinnolones but then again I think that the controversy is using quinolones as first line drugs and/or for simple infections or misusing them by patient (demanding) and or doctor (prescription happy) for virus's.--Literaturegeek | T@1k? 19:40, 27 February 2009 (UTC)

Yes, I agree they should not be first line and should be reserved for severe infections. Support for this shouldn't be hard to find.--Doc James (talk · contribs · email) 23:43, 27 February 2009 (UTC)

Not too sure what planet you live on Doc, but finding support for not using the fqs as a first line agent here in the States will prove to be an exercise in futility. Just about all of the guidelines here recommend them as first line agents. You will find pretty much the same in all those reviews you are so fond of. Got into a knock down drag out fight about this a few years ago with one of your peers. He loves the damned things and produced evidence that indeed they are recommended as first line agents for just about anything you can think of. Things might of changed since then but I highly doubt it.

And from my own experience dealing with these survivors RARELY if ever did they suffer from a serious infection. I would venture to say about 75% or more of those on my forum did not even have ANY kind of bacterial infection to begin with. Maybe that is why they got hit so hard. Just like my case, 24 and 48 hour cultures showed no bacterial growth. Given a 1000 mg a day of levaquin (for two weeks) to treat a "suspected" bladder infection when in fact I had a kidney stone and was pissing blood from it. When the cultures came back negative he then insisted I had chronic bacterial prostatitis. Even though about nine months earlier my prostate was just fine. (As well as when I changed urologists down the road)

The stone was on the xray but the radiologist missed it. I was on these drugs for almost two months. Started out with floxin, switched to cipro and finally levaquin. Complained the WHOLE time about most of these adrs we are discussing and the urologist told me flat out they had NOTHING to do with the fluoroquinolones. Safe and effective, well tolerated, etc., etc., just like you have stated within your article. Might be the reason he blew off my concerns and crippled me for life instead of stopping the drugs. May have believed they may not help, but certainly could not hurt, based upon such information as you are presenting. I have met only ONE doctor who has treated me in the past twenty years that had any idea regarding these reactions. And that was because she suffered them herself. Not bitching here, just explaining the current situation here in the States is all.

Oh and the FDA AERS system? What a joke. They excluded ANY REPORTS prior to 1997. So you are handicapped right from the get go. Thirty five years worth of data is missing. Anything prior to 1997 resides on another database and the two are not linked and the second database is no longer available. Takes specialized software to even access it. Play around with it a bit and you will see what I mean. Here is the link: http://www.fdable.com/aers/advanced Davidtfull (talk) 05:41, 28 February 2009 (UTC)

Many sources outside of the USA recommend avoiding fluoroquinolones (and clindamycin) wherever possible, mainly due to high rates of C. Difficile infections.--Literaturegeek | T@1k? 06:41, 28 February 2009 (UTC)

The U.S. is decades behind everyone else when it comes to the proper use of this class:

Development of Fluoroquinolones as First-line Drugs for Tuberculosis—at Long Last!

At the present time, fluoroquinolones or doxycycline are advocated as first-line agents for prophylaxis or treatment following exposure to spores,1 in combination with additional agents for therapy of inhalational or other serious forms of anthrax

Due to antimicrobial resistance fluoroquinolones may be the antimicrobial of choice for empiric treatment of urinary tract infections. For this indication, based on safety, efficacy and price ciprofloxacin is the fluoroquinolone of choice. Source: Fluoroquinolone Criteria for Use VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel

the Infectious Diseases Society of America (IDSA) guidelines and some studies have suggested that fluoroquinolones may be used as first-line therapy for treatment of uncomplicated bacterial cystitis in woman

Since fluoroquinolones had been used as first line antimicrobial agents for N gonorrhoeae infections in Japan

The information collected will optimize the management of patients with urinary tract infections with secondary bacteremia, primarily with gram negative bacteria especially Escherichia coli. The current IDSA guideline endorses the use of fluoroquinolones and trimethoprim-sulfamethoxazole as the first line agents

On the other hand, fluoroquinolones are recommended as first-line agents in the empirical treatment of community-acquired pyelonephritis.

The article states that levofloxacin is an effective first-line agent for the treatment of prostatitis

All of the fluoroquinolones are effective in treating urinary tract infections caused by susceptible organisms. They are the first-line treatment of acute uncomplicated cystitis

However, in hospitalized patients with CAP, the fluoroquinolones are first line agents.

Trimethoprim-sulfamethoxazole has been the mainstay of therapy for UTIs, but fluoroquinolones have now become first-line empirical therapy

Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever

This is just a sample of what I am referring to.Davidtfull (talk) 07:17, 28 February 2009 (UTC)

David sounds like you were see by a doc who likes drug reps too much. From the Stanford guild 2006 (my 2008 is a work): Pneumonia 1st azithro 2nd FQ Simple UTI 1st: septra or nitro 2nd:FQ Phaygitis 1st Penicillin 2nd azithromycin FQ not mentioned Bacterial sinusitis 1st penicillin family 2nd Amp/Clav or FQ Cellulitis: 1st Cephalozprorine 2nd Azithro. Will writ emore latter.--Doc James (talk · contribs · email) 16:53, 28 February 2009 (UTC)

"David sounds like you were see by a doc who likes drug reps too much." Guess there is an epademic of that lately, as just about all the patients I have talked to over the years, and we are talking tens of thousands, say pretty much the same things. Over and over ad nausem. Personally I have been treated by dozens of specialists who have worked in vain to put me back together since 2000. And they were no different. Maybe I should move to Canada or maybe Sweden. Got relatives in Sweden. Don't know a soul in Canada except you at the moment. Do I have to learn French first? I know German, Polish, Swedish, a little Arabic as well as Spanish and Mexican. But alas, can't speak French. But neither can most of the French, so that shouldn't be a real problem. Not doubting that other countries have different standards when it comes to first line agents. A majority of our members are American, and as you can see by my precious post, the quinolones are considered first line agents for just about everything here in America. Just another strange coincidence I guess. The country that uses the quins the most is the country that has the largest community of folks who have suffered severe reactions. But we have members of this elite community from every country in the world that has unrestricted access to the Internet, and where these drugs are prescrbibed. Far too many to even begin to count. Davidtfull (talk) 01:03, 1 March 2009 (UTC)

Doc lives on planet Canada. I think the USA has a different policy when it comes to quinolones, or antibiotics. From my moderate knowledge of quinolones most countries use quinolones as 2nd or even 3rd line drugs and there are some eminent microbiologists and other specialists at least in the UK who increasingly advising avoiding quinolones wherever possible to minimise C.Difficile infections. I might actually try and track down the name of the professor of microbiology who has been giving lectures around the UK about avoiding quinolones.--Literaturegeek | T@1k? 17:20, 28 February 2009 (UTC)

Some of the info in not encyclopedic

Dear Doctor Letters and Advisories are not encyclopedic and therefore do not belong. One could say many dear doctor letters have been sent out regarding this drug similar to every other drug on the market. Have you guys all see the dear doctor letters regarding metoclopramide for example?--Doc James (talk · contribs · email) 19:06, 27 February 2009 (UTC)

I was thinking that when it comes to merging there is going to need to be some pruning to make the two articles fit and I thought that the least notible section was this one and it was on my sites for deletion anyway. I can support this.--Literaturegeek | T@1k? 19:20, 27 February 2009 (UTC)

Proposal

My proposal would be to rename this article Controversies surrounding fluoroquinolones. Link to it from the AE article section and than edit things further so that it better explains the POV of the anti FQ group and explains the controversy: such as concerns over lack of long term evidence, court cases that this group has brought forth, etc. One could even talk about the more theoretical evidence such as death reported. One would need to see if other broad spectum antibiotics get as many death reported perpotional to the frequency of their use. It wouldn't be easy but on such a page one have a little more leway with evidence inclusion.--Doc James (talk · contribs · email) 19:29, 27 February 2009 (UTC)

Now their's an idea Doc. That might resolve things, I know there are several articles with such names, adhd controversy, fluoride controversy, aspartame controversy etc.--Literaturegeek | T@1k? 19:35, 27 February 2009 (UTC)]]

Excellent if no one objects lets go with this, I will leave it to you.--Doc James (talk · contribs · email) 19:42, 27 February 2009 (UTC)

I would support this as well. You have the same kinds of problems within your article as you have just commented on here. Statements being made without context, etc. So such a divorce may resolve all of these issues and still leave the patient and the physician with a reasonable view of the safety profile and allow compliance with the restrictions being imposed upon us by the rules of wikipedia. I say go for it.Davidtfull (talk) 06:21, 28 February 2009 (UTC)

References

I need this one in full text please dave or James I would appreciate it very much.

A quote from a news article regard the study I am requesting above,

"A study of ADRs in Italy, published in 2005, found that among more than 50 types of drugs, fluoroquinolones accounted for 11 percent of all adverse events and were involved in the largest number of serious problems, edging out antidepressants."

Now that is pretty significant as that paper sounds like one that is independent of drug company data which is alledgedly fraudulent.--Literaturegeek | T@1k? 07:57, 20 February 2009 (UTC)

Serious adverse CNS effect occur in 4 per 100,000 patients treated with levofloxacine.[19]

CNS side effects have been found to occur with fluoroquinolones 1.12 times more frequently than with other classes of antibiotics.[1]

I have reviewed the article, made a few small tweaks. Ok firstly, where did the statistic which I find very doubtful for 4 per 100,000 patients treated come from? What was classed as a severe CNS adverse reaction? Just status epilepticus and psychosis? What was the exclusion criteria? Is this from case reports from the FDA or similar? If so it is the drug companies abusing case report data and using it for epidemiology, or they have done in the past and the author is rereferencing it. Case reports are not epidemiology.

The next part is also very dubious again, basically the reader of the article is meant to believe that fluoroquinolones are only 0.12% more likely than something like amoxycillin or erythormycin to cause CNS adverse effects? How was that statistic determined? Maybe I need to see the full text. Also how do you explain the Italy study finding more neuropsychiatric adverse reactions with fluoroquinolones than even antidepressants? Even if there were methodology issues with the italian study, there is no reason to explain drug company data saying you are no more likely to get CNS effects from quinolones than taking a tetracycline but yet a survey of doctors finding it the most problematic drug in their practice for causing neuropsychiatric problems. Why such a huge difference in opinion between the survey of doctors and peer review of drug company clinical trials?--Literaturegeek | T@1k? 08:39, 20 February 2009 (UTC)

I also removed this statement "For example only one case report of seizures possibly due to gatifloxacin exsists." from the article body as I felt it was suggestive of "how rare" seizures are. Case reports are not epidemiology studies. Medical journals will only publish a paper if it is something new to the current literature, so you would expect to not find lots of case reports saying the same thing as journals will not rehash what has already been published. That is how peer reviewed journals work.--Literaturegeek | T@1k? 09:35, 20 February 2009 (UTC)

Looked at the study abve. FQ as a class had 31 reports of neuro psyc NSAIDs 32, SSRI30, opoids 30, PPIs21 Lipid lowerers 23, ACEI 10, macrolids 11 etc. Not large numbers by any means. Serious cases are not common and could fit the 4:100000. 2 cases hallucinations, 2 hyperkinesia, 2 amnesia. None of the other catergories. NSAIDS were the most common. This fits with the rest of the literature which lable this group the most dangerous drug class. I see more people harmed by NSAIDS than anything else by far. A megnatude greater.--Doc James (talk · contribs · email) 21:35, 20 February 2009 (UTC)

Strange, I have never really thought of NSAIDs as causing neuropsychiatric effects. I guess I learnt something new. I knew they could affect the stomach and kidneys. I know they can cause tinitus (probably GABA antagonism especially in overdose).--Literaturegeek | T@1k? 21:59, 20 February 2009 (UTC)

NSAIDs combined with fluoroquinolones causes neuropsychiatric effects. One has to then wonder how many of these patients that reported an adr to NSAIDs were also taking a quinolone at the same time and of course the quinolone never considered to be part of the equation. Just speculating here. But with so many of the adrs of the quinolones overlooked or denied by the medical community this could be yet another manifestation that is being ignored as such an association is far from intutive. Be interesting to study the history of the NSAID reactions and see if there was a significant increase after the quinolones came on the market. There has been significant increases in joint problems, some skin cancers, fibromyalgia, chronic fatique, and a whole host of other disease states since they were first introduced. Coincedence? Possibly, but then again possibly not. But we got enough on our plate at the moment without dealing with things of a speculative nature. This can wait for another time to dig deeper into. I just know from experience that taking Motrin with Levaquin put me in ER having seizures. And even though an AER report was made, Motrin, rather than levaquin, was the primary suspect drug. Even though I had taken it for years prior without a problem. Levaquin was not even mentioned in the report.Davidtfull (talk) 01:23, 3 March 2009 (UTC)

contravesery stub

“led to a class action lawsuit by these groups”

These groups did not file a class action lawsuit. There were two class action lawsuits filed on behalf of the postal workers after the anthrax scare in 2001 in regards to Cipro. The one filed by Sheller, Ludwig and Bady was withdrawn allegedly due to the insurmountable cost of proceeding. The other class action lawsuit I had not been following and I am not too sure if it is still pending or had been withdrawn as well. A number of members of the forums may have joined the Sheller suit, after it had already been filed. But they did not instigate it. Others signed on with the Sheller firm and filed individual lawsuits, only to be suddenly dropped like hot potatoes and then finding themselves in a position of not being able to secure replacement counsel before the statute of limitations would run out on their cases. There are a number of lawsuits filed by individuals that have been consolidated, but the groups we are referring to here are not involved in that litigation, though perhaps some of their members are. There were two petitions filed, one by the Attorney General of the State of Illinois, that I was involved in, as well as the petition filed by Public Citizen, to whom I had provided the research found on the fqresearch site. Public Citizen filed a lawsuit in Federal Court (1-2008) to compel the FDA to respond to their petition. The Attorney General is still awaiting a response from the FDA, and has been for a number of years now (petition was filed in 2005). It is my understanding that they too may be filing a Federal Lawsuit to compel the FDA to respond to their petition as well.

There is a third petition in the works that the Foundation is working on concerning the peripheral neuropathy issues, but that has not been filed as of yet.

“Partly as a result of the efforts of Public Citizen the FDA ordered a black box warnings on all fluoroquinolones advising consumers of the potentially toxic effects of fluoroquinolones on tendons”

I would believe that it was a direct result of the lawsuit filed by Public Citizen in January of 2008 that resulted in this. The responses I had received from the FDA clearly indicated to me that they were NOT willing to add these warnings. They had stated to me that they did not feel that they were warranted and they would continue the ongoing review that had started back in 1996 as they felt this needed more study even though they had been studying it for almost thirteen years. The FDA did not order a black box warning. They suggest it and the various manufacturers could have very well refused to co-operate. The FDA did not mandate this addition. The same applies to the issuing of Dear Doctor Letters. This too was voluntary. Only those fluoroquinolones taken orally or injected received the black box. Eye drops, ear drops, ect., did not. Nor did the generic manufacturers comply with this request to date.

“and has been collecting research on them for over 10 years”

I have been researching this since 1998. But I have not been collecting this research and compiling it for over ten years. That would be an exaggeration. I did not start physically collecting the data until 2000, so it would only be correct to state the past nine years, not ten, in that context. But in regards to actually doing the research, for over ten years would be correct, as it has been eleven years now.

“should be used only as a last resort antibiotic”

Though this is my personal view, the official view of the Foundation is that they should not be considered a first line agent for any disease state that a safer and equally effective alternative exist for the patient. It is my personal view that they should only be used when the patient has a proven need and there is a confirmed bacterial infection, that if not treated by this class, puts the patient at risk of losing life or limb. If there is a viable alternative, then that should be employed first before turning to this class.

“scripting abuse of fluoroquinolones needs to be urgently curtailed to reduce the incidence of severe adverse reactions”

As well as reduce the risk of this class no longer being a viable alternative due to bacterial resistance. I fully understand, and support the need for this nuclear bomb to be available to the physician. There are indeed cases where this drug MUST be used. There is no other option available. You prescribe the drug and retire to the chapel and pray that it works. But physicians MUST be instructed in its proper use. We cannot afford to be without this class. Even I understand and support this. That is a no brainier. But we can well afford to educate both the patient and the physician in its proper use and remove those that have proven to outweigh the perceived benefits.

You will have to check with Jeanne over at Lariam USA regarding any pending legal action concerning lariam. I do know that last year they produce a commercial video concerning these reactions and the video has been released for sale. One has also been produced concerning the fluoroquinolones, which I believe is schedule for commercial release within the coming months, but this had been relayed to me verbally and not in writing. It was produced, directed and paid for out of pocket by a Hollywood director who suffered horribly from these reactions.

On a side note, I always go by Mr. David T. Fuller in any official capacity, rather than just David T. Fuller. I do this deliberately for in the past people have added “Dr.” to my name, without my knowledge or consent, even though I do not have a doctorate degree or a medical degree. I graduated from the school of hard knocks with honors, not a school of higher learning. Recently a publication of mine was published on the CDC site, in regards to the issues concerning Cipro being used in children and they too had added “Dr.” to my name, and it has been proving rather difficult to get this corrected. Another written response of mine was recently accepted by JAMA AT THE CROSSROADS: QUESTIONS FOR READERS and is scheduled to be published in the March 4, 2009, issue of JAMA and there too I had signed the response Mr. David T. Fuller. Within the Journal of Medical Case reports my comments were published on February 13, 2009 (Death following bilateral complete Achilles tendon rupture in a patient on Fluoroquinolone therapy: A case report. http://www.jmedicalcasereports.com/content/3/1/1/comments) and they too had left off the Mr. in the heading, but included it where I had signed the comment. As you can see I go to great lengths to avoid ANY possible confusion regarding this. I have been published (and then plagerised) for years now on the Internet. Do a google search and you will get about 500 or so hits. Whenever I am published on a website I make damn sure that nobody confuses me with a physician. Just as I am doing here. As such I would rather not have such mistakes take place here by having another editor added a title to my name that I have not earned, desire nor deserve.

Other than a critical fact checking regarding the activities of Lariam USA and making the suggested changes, this outta do it. Davidtfull (talk) 17:44, 21 February 2009 (UTC)

To help maintain a fair balance here, I believe the statement "These groups of people claim to have suffered serious long term harm and sometimes permanent injury to their health from using fluoroquinolones." To be too harsh. This should be changed. As it all too inclusive. Though I have stated that I will not be editing the article, may I suggest the following to be a better fit:

"Certain members of these groups (not all) have alleged to have suffered non-abating injury, or long term medical complications as direct result of fluoroquinolone therapy. Other have alleged to have suffered serious long term harm or even permanent injury to their health, as a result of fluoroquinolone therapy. With the remainder stating that their recovery from these adverse reactions took months to years, but was eventually obtained to a certain degree."

Not all members of the forum are a medical mess. Some just have a rough time of it for a while and recover completely within a reasonable amount of time. Others never do, with the remainder falling somewhere in the middle. We also have members who have not even suffered a reaction, whackos and nut cases, the curious, and those simply looking for valid information. We also have posers and fakes, but they do not last long as most moderators vet the new members and keep a doisere on the members and are always checking for this. Lie on these forums and you will be banned for life within a very short time. There are also some forums that are way, way out there and cause far more harm as they are basically a free for all with no moderation whatsoever, and anybody with a keyboard becomes an instant expert on these issues. I believe we had recently been visited by a couple of these flying monkeys here.

To the best of my knowledge the Foundation and Lariam USA is the only organized group here in the States that does more than just host a forum. I may be mistaken here, but if they are out there I am not aware of thier existance. So I cannot address whatever claims they may be making. But for the most part these groups are basically just asking for fair warnings and proper use. As well as acknowledgment of thier plight. At the moment they feel like the lepers outside the city gates. To be ignored until they perish and not scare the children anymore. Davidtfull (talk) 18:15, 21 February 2009 (UTC)

Thank you for the suggestions. I am not sure how you think we should word the law suit sentence or if you think it should be removed. We could add a couple of citations regarding the cipro lawsuits and reword the sentence if you provide citations regarding the lawsuits. I have reworded the controversy section according to your suggestions. I added the /commentsletter you got published in the medical journal as a citation as it confirms your activism and also mentions you as head of your organisation. Do you have any further suggestions for the rewording? Lariam is worth a mention due to its similarity with long term effects and the fact it is a quinolone antibiotics and lariam are both quinolone derivative but I think that any further addition of adverse effects and damage of lariam should go on the lariam wiki page. I would like to watch that video about fluoroquinolones when it comes out. The lariam video would be good as well. Do you have to order it or is it watchable online? I could imagine what it is like running a forum full of people who are a physical and psychiatric mess due to adverse drug reactions let alone those that want to intentionally disrupt the place.

Is the controversy section close to being finished?--Literaturegeek | T@1k? 19:26, 21 February 2009 (UTC)

I am very pleased with the way it turned out. You have NO idea what it has been like dealing with people in such horrible shape for the past eight years, 24/7, when you yourself are not a whole lot better. You really cannot get angry with them for they know not what they do for thier brains are not exactly firing on all cylinders. Add in the adrs of narcotic pain meds, psych drugs, etc., well you get the idea. You could imagine, but you would not even be close. (LOL) The lariam video can be ordered either from my site, you will find it listed under "Current News" or directly from Lariam USA. I think it cost about 20-30 dollars. Not sure. The fluoroquinolone video has not been released to me yet. But that one I was told was set for theatrical release nationwide. I will work on the lawsuit part of this as I have citations to both cipro lawsuits as well as the levaquin multidistrict. I will suggest the text, provide citations, and you and doc can edit the article as you see fit. This system seems to be working out the best for all concerned. Please do not cite the publication on the CDC site until I get that DR title removed. I may fight hard and relentlessly, but I do not do so unethically. Citing to the CDC article when the DR title is still there would be unethical in my mind and as such totally unacceptable. Right now I got a washing machine tore apart so I am going to log off until later. Just taking a break and caught your note. On a side note where would it be best to post the links to the reviews I have? My talk page, yours, docs, or the article talk page? Please provide a preference. Thanks...Davidtfull (talk) 21:05, 21 February 2009 (UTC)

I made a few changes to controversy section as it was repetative but glad that it was satisfactory. I may just order that video. You should find some more volunteers to help you running your group, otherwise you will burn yourself out. I will not use the CDC citation until you give the ok. I would say probably on the relevant article talk page would be best.--Literaturegeek | T@1k? 21:36, 21 February 2009 (UTC)

Recently added references to the class action lawsuits that have been filed concerning tequin, trovan, and ciprofloxacin. The statement: "Professor Cohen and Dr Flockhart are doctors who have expressed concern about the adverse effect profile of fluoroquinolones" should be amended to read "since the mid nineties", as this is when the book Bitter Pills was published and Dr. Flockhart is quouted extensively in that book. Just a suggestion.Davidtfull (talk) 08:10, 25 February 2009 (UTC)

Added more information concerning the qualifications of Dr. Cohen and Dr. Flockhart, by including their full titles. Feel free to revert this edit if this was inappropriate, or unneccassary. But "Professor Cohen and Dr. Flockhart" seemed a bit vague to me considering their higher status in the medical community. Or perhaps it was the original intent to downplay this aspect of their qualifications and I just messed that up.Davidtfull (talk) 10:35, 27 February 2009 (UTC)

citation requests

In response to: The distinction between a quinolone drug and a fluoroquinolone drug is the addition of the fluorine atom to the pharmcore, resulting in a fluorinated drug. The terms fluoroquinolone and quinolone are often used interchangeably, without regard to this distinction.[citation needed]

Reduced Fluoroquinolone Susceptibility in Salmonella enterica Serotypes in Travelers Returning from Southeast Asia Antti Hakanen,*† Pirkko Kotilainen,† Pentti Huovinen,* Hans Helenius,‡ and Anja Siitonen§

• National Public Health Institute, Turku, Finland; †Turku University Central Hospital, Turku, Finland; ‡Turku University, Turku, Finland; and §National Public Health Institute, Helsinki, Finland

http://www.cdc.gov/ncidod/EID/vol7no6/hakanen.htm “Thus, the terms reduced fluoroquinolone susceptibility and quinolone resistance are used interchangeably hereafter.”

http://books.google.com/books?id=bd0R7RCuvdwC&pg=PA1043&lpg=PA1043&dq=%22fluoroquinolones+and+quinolone+are+often+used+interchangeably%22&source=bl&ots=6jwDDXNML4&sig=FtRL0hk42b6_Hq-PibsQMbLCxrg&hl=en&ei=1VaiSefDM9G3twegu8iTDQ&sa=X&oi=book_result&resnum=6&ct=result

Reese and Betts' a Practical Approach to Infectious Diseases: Edited by Robert F. Betts, Stanley W. Chapman, Robert L. Penn By Robert F. Betts, Stanley W. Chapman, Robert L. Penn, Richard E. Reese Edition: 5, illustrated Published by Lippincott Williams & Wilkins, 2003 ISBN 0781732816, 9780781732819 1202 pages “In this chapter the terms "fluoroquinolones" and "quinolones" are used interchangeably. I. An overview of the fluoroquinolones”Davidtfull (talk) 08:03, 23 February 2009 (UTC)

In response to: The most widely used fluoroquinolones include ciprofloxacin, levofloxacin and moxifloxacin.[citation needed]

“Currently, ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin are the most widely used fluoroquinolones. “

POLICY STATEMENT PEDIATRICS Vol. 118 No. 3 September 2006, pp. 1287-1292 doi:10.1542/peds.2006-1722) This Article The Use of Systemic Fluoroquinolones Committee on Infectious Diseases http://aappolicy.aappublications.org/cgi/content/full/pediatrics;118/3/1287Davidtfull (talk) 08:07, 23 February 2009 (UTC)

Thanks for that David, have added the reference.--Doc James (talk · contribs · email) 13:25, 23 February 2009 (UTC)

Another ref concerning researchers interchanging fluoroquinolone and quinolone:

"All isolates with reduced ciprofloxacin susceptibility were uniformly resistant to nalidixic acid (MIC > 32 µg/mL). Thus, the terms reduced fluoroquinolone susceptibility and quinolone resistance are used interchangeably hereafter." http://www.cdc.gov/ncidod/EID/vol7no6/hakanen.htm —Preceding unsigned comment added by Davidtfull (talk • contribs) 08:30, 25 February 2009 (UTC)

Thanks David, I used it as a citation.--Literaturegeek | T@1k? 09:02, 25 February 2009 (UTC)