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Meropenem/vaborbactam

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Meropenem/vaborbactam
Combination of
MeropenemBeta-lactam antibiotic
VaborbactamBeta-lactamase inhibitor
Clinical data
Trade namesVabomere, Vaborem, others
AHFS/Drugs.comMonograph
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
KEGG

Meropenem/vaborbactam, sold under the brand name Vabomere (by Melinta Therapeutics) among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia.[1][2][3] It contains meropenem, a beta-lactam antibiotic, and vaborbactam, a beta-lactamase inhibitor.[3] It is given by injection into a vein.[3]

Common side effects include headache, inflammation at the site of injection, nausea, diarrhea, liver inflammation, and low blood potassium.[3] Severe side effects may include anaphylaxis, seizures, and Clostridioides difficile-associated diarrhea.[3] It is unclear if use during pregnancy is safe.[4] Meropenem works by blocking the construction of the bacterial cell wall while vaborbactam blocks the breakdown of meropenem by some beta-lactamases.[3]

The combination was approved for medical use in the United States in 2017, and in the European Union in 2018.[3][2] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

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It is used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia.[3][2]

Side effects

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The most common adverse reactions were headache, infusion site reactions and diarrhea. Serious risks include allergic reactions and seizures and Meropenem/vaborbactam should not be used in people with severe allergic reactions to penicillins.[6]

Antimicrobial activity

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Meropenem/vaborbactam retains antimicrobial activity against class A and class C β-lactamase-producing Enterobacterales, especially those producing ESBL, KPC, and AmpC determinants. Meropenem/vaborbactam is also active against strains of Enterobacterales producing other types of class A serine carbapenemases (e.g. SME and NMC-A enzymes). Resistance to meropenem/vaborbactam in KPC-producing Enterobacterales is currently very rare and mostly due to porin inactivation. Interestingly, meropenem/vaborbactam retains activity also against strains producing KPC mutants that confer resistance to ceftazidime/avibactam (e.g., KPC-8, KPC-31). The activity of meropenem/vaborbactam against P. aeruginosa and A. baumannii was found to be similar to that of meropenem alone. In fact, in these species, meropenem resistance is largely mediated by mechanisms that are not antagonized by vaborbactam (e.g., outer-membrane impermeability, upregulation of efflux systems, and production of class B or class D β-lactamases). No antimicrobial activity has been reported for MBL-producing Gram-negatives and OXA-48-producing Enterobacterales.[7]

History

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In a study of 545 adults with complicated urinary tract infections, 98 percent of adults treated with meropenem/vaborbactam compared with about 94 percent of adults treated with piperacillin/tazobactam were cured defined as improvement in symptoms and a negative urine culture. About seven days after completing treatment, roughly 77 percent of adults treated with Vabomere compared with about 73 percent of those treated with piperacillin/tazobactam had resolved symptoms and a negative urine culture.[6]

In August 2017, the US Food and Drug Administration approved the combination to treat complicated urinary tract infections and pyelonephritis.[6]

Research

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Successful bacteremia clearance in a child has been reported using a meropenem-vaborbactam dose of 40 mg/kg every 6 hours given over 3 hours. It attained 100% of meropenem serum concentrations above the minimum inhibitory concentration for at least 40% of the dosing interval.[8]

References

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  1. ^ a b "Vabomere- meropenem-vaborbactam injection, powder, for solution". DailyMed. 19 October 2023. Retrieved 26 July 2024.
  2. ^ a b c d "Vaborem EPAR". European Medicines Agency. 24 September 2018. Retrieved 6 November 2019.
  3. ^ a b c d e f g h "Vabomere (combination) Monograph for Professionals". Drugs.com. Retrieved 6 November 2019.
  4. ^ "Meropenem / vaborbactam (Vabomere) Use During Pregnancy". Drugs.com. Retrieved 6 November 2019.
  5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ^ a b c "FDA approves new antibacterial drug" (Press release). U.S. Food and Drug Administration (FDA). 29 August 2017. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ Principe L, Lupia T, Andriani L, Campanile F, Carcione D, Corcione S, et al. (April 2022). "Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians". Pharmaceuticals. 15 (4): 463. doi:10.3390/ph15040463. PMC 9028825. PMID 35455461.
  8. ^ Hanretty AM, Kaur I, Evangelista AT, Moore WS, Enache A, Chopra A, Cies JJ (December 2018). "Pharmacokinetics of the Meropenem Component of Meropenem-Vaborbactam in the Treatment of KPC-Producing Klebsiella pneumoniae Bloodstream Infection in a Pediatric Patient". Pharmacotherapy. 38 (12): e87–e91. doi:10.1002/phar.2187. PMID 30300440. S2CID 52948188.