In vitro evaluation of meropenem-vaborbactam against clinical CRE isolates at a tertiary care center with low KPC-mediated carbapenem resistance

Kinn, Patrick; Chen, Derrick J.; Gihring, Thomas M.; Schulz, Lucas T; Fox, Barry C.; McCreary, Erin K; Lepak, Alexander J.

doi:10.1016/j.diagmicrobio.2018.09.017

Cited by 10 publications

(7 citation statements)

References 10 publications

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“…The authors also highlighted that vaborbactam significantly decreased meropenem MIC in both non-KPC-producing and KPC-producing CRE despite that previous studies have demonstrated decreased vaborbactam activity in non-KPC-producing CRE. The authors assume that this finding is due to the absence of NDM and OXA-48 isolates in the study sample population (181).…”

Section: Meropenem-vaborbactam Spectrum Of Activitymentioning

confidence: 92%

“…Vaborbactam lowered the MIC 90 of meropenem from Ͼ32 to 1 mg/liter (180). Kinn et al (181), assessing in vitro activity of MER-VAB against carbapenem-resistant Enterobacterales (CRE) isolates, reported that MIC decreased by 128-fold on average compared with that for exposure to meropenem alone. The authors also highlighted that vaborbactam significantly decreased meropenem MIC in both non-KPC-producing and KPC-producing CRE despite that previous studies have demonstrated decreased vaborbactam activity in non-KPC-producing CRE.…”

Section: Meropenem-vaborbactam Spectrum Of Activitymentioning

confidence: 99%

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New β-Lactam–β-Lactamase Inhibitor Combinations

et al. 2020

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SUMMARY The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam–β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa. Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, and some class D β-lactamases (OXA-48) in addition to carbapenem-resistant Pseudomonas aeruginosa. Ceftolozane-tazobactam is a treatment option mainly for carbapenem-resistant P. aeruginosa (non-carbapenemase producing), with some activity against ESBL-producing Enterobacterales. Meropenem-vaborbactam has emerged as treatment option for Enterobacterales producing ESBL, KPC, or AmpC, with similar activity as meropenem against P. aeruginosa. Imipenem-relebactam has documented activity against Enterobacterales producing ESBL, KPC, and AmpC, with the combination having some additional activity against P. aeruginosa relative to imipenem. None of these drugs present in vitro activity against Enterobacterales or P. aeruginosa producing metallo-β-lactamase (MBL) or against carbapenemase-producing Acinetobacter baumannii. Clinical data regarding the use of these drugs to treat MDR bacteria are limited and rely mostly on nonrandomized studies. An overview on eight BLBLIs in development is also provided. These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam).

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Section: Meropenem-vaborbactam Spectrum Of Activitymentioning

confidence: 92%

Section: Meropenem-vaborbactam Spectrum Of Activitymentioning

confidence: 99%

New β-Lactam–β-Lactamase Inhibitor Combinations

et al. 2020

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“…In preclinical studies, vaborbactam was shown to restore meropenem activity against KPC-producing CPE, including isolates that were also resistant to ertapenem. 11,36,38,39 It also significantly increased bacterial killing when combined with meropenem versus untreated controls, meropenem alone, or meropenem in combination with other antibacterial agents. 38,40-45 An in vitro study 46 separately demonstrated MIC lowering in 99 cUTI-derived CPE and ESBL isolates by meropenem-vaborbactam versus meropenem alone.…”

Section: Meropenem-vaborbactammentioning

confidence: 93%

Review of Ceftazidime-Avibactam, Meropenem-Vaborbactam, and Imipenem/Cilastatin-Relebactam to Target Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales

Hayden

White

Bennett

2020

Journal of Pharmacy Technology

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Objective: To provide a review of 3 novel antimicrobial agents—ceftazidime-avibactam, meropenem-vaborbactam, and imipenem/cilastatin-relebactam—regarding treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC). Data Sources: A literature search of PubMed and OVID (MEDLINE) was performed up to March 2020 using the following search terms: Vabomere, meropenem-vaborbactam, vaborbactam, RPX7009, Klebsiella pneumoniae carbapenemase, KPC, carbapenem-resistant Enterobacteriaceae, CRE, relebactam, imipenem-relebactam, MK-7655, ceftazidime-avibactam. Abstracts from conferences, article bibliographies, and product information were also reviewed. Study Selection and Data Extraction: Articles were first screened by English language, then title, then abstract, and finally by review of the full article. Fifty-five clinical and preclinical studies were included. Data Synthesis: These 3 novel β-lactam/β-lactamase inhibitor combinations have shown considerable improvement in safety and efficacy as compared with traditional polymyxin-based combination therapy for the treatment of KPC infections. While meropenem-vaborbactam has not shown improved activity against Pseudomonas aeruginosa, it has shown decreased rates of resistance to KPC versus ceftazidime-avibactam. Conclusions: With increasing incidence of KPC infections on a global scale, pharmacists should be aware of the notable similarities and differences between these 3 agents, and the current data supporting their use. Pharmacists may want to consider meropenem-vaborbactam over ceftazidime-avibactam for KPC infections due to decreased likelihood of resistance.

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“…The formulation of vaborbactam was tested with cephalosporins and aztreonam, but carbapenems produced the most potent combination, and meropenem with vaborbactam proved to be the most effective with the maximum potentiation [12,17,18]. Meropenem-vaborbactam was specifically designed to be effective against multidrug-resistant organisms, Enterobacterales-producing extended spectrum beta lactamases (ESBL), and carbapenemase-producing bacteria, such as (KPC) [16,[19][20][21][22]. This meropenem-vaborbactam combination maintains the broad spectrum of activity of meropenem, which includes many antibioticresistant gram-negative bacteria, and also utilizes the potent carbapenemase and b-lactamase inhibitor actions of vaborbactam, enhancing its range and potency of antimicrobial activity [16,19].…”

Section: Introductionmentioning

confidence: 99%

Microbiology of Meropenem-Vaborbactam: A Novel Carbapenem Beta-Lactamase Inhibitor Combination for Carbapenem-Resistant Enterobacterales Infections

Bhowmick

Weinstein

2020

Infect Dis Ther

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Vaborbactam is a novel boron-based beta-lactamase inhibitor developed to be effective against Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. This enzyme is a key driver in the global spread of β-lactam resistance among carbapenem-resistant Enterobacterales. Alone, vaborbactam has no antibacterial activity; however, the combination of meropenem-vaborbactam has enhanced activity against gram-negative organisms, particularly Enterobacterales with class A and C carbapenemases. Multiple in vitro studies evaluating isolates from various geographic regions, and over different time periods, have demonstrated the high potency of meropenem-vaborbactam against organisms containing KPC2 and KPC3. However, meropenem-vaborbactam does not have activity against OXA-48 or metallo-beta lactamases. This review covers the in vitro studies of meropenem-vaborbactam performed to date, which evaluated both large cohorts of clinical isolates and engineered isolates, to determine efficacy in various settings, including the presence of porin mutations and efflux pump upregulation.

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In vitro evaluation of meropenem-vaborbactam against clinical CRE isolates at a tertiary care center with low KPC-mediated carbapenem resistance

Cited by 10 publications

References 10 publications

New β-Lactam–β-Lactamase Inhibitor Combinations

New β-Lactam–β-Lactamase Inhibitor Combinations

Review of Ceftazidime-Avibactam, Meropenem-Vaborbactam, and Imipenem/Cilastatin-Relebactam to Target Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales

Microbiology of Meropenem-Vaborbactam: A Novel Carbapenem Beta-Lactamase Inhibitor Combination for Carbapenem-Resistant Enterobacterales Infections

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