Abstract
The activities of meropenem-vaborbactam and comparators against 152 (1.1%) carbapenem-resistant Enterobacterales (CRE) isolates identified among 13,929 Enterobacterales isolates collected from U.S. hospitals during 2016 to 2018 were evaluated. CRE rates were higher in the Middle Atlantic census division (3.5%) than in the other divisions (range, 0.0% for the West North Central division to 1.4% for the West South Central division). Among the CRE isolates, 134 carried carbapenemase genes, and these included 72 isolates carrying blaKPC-3, 51 isolates carrying blaKPC-2, 4 isolates carrying blaNDM-1, 3 isolates carrying blaSME-4, 2 isolates carrying blaVIM-1, 1 isolate carrying blaOXA-232, and 1 isolate carrying blaKPC-4 Meropenem-vaborbactam was active against 95.4% of the CRE isolates and 94.8% of the carbapenem-producing Enterobacterales (CPE) isolates when applying the CLSI breakpoints. All isolates producing serine carbapenemases were inhibited by meropenem-vaborbactam at ≤8 mg/liter. One Citrobacter freundii isolate carrying blaKPC-3 had a meropenem-vaborbactam MIC of 8 mg/liter and was resistant according to CLSI breakpoints (the isolate was susceptible when the EUCAST criterion of an MIC of ≤8 mg/liter for susceptible was applied), had disrupted OmpC and OmpF sequences, and overexpressed AcrAB-TolC. All carbapenemase-negative CRE isolates (n = 18) were inhibited by meropenem-vaborbactam at ≤4 mg/liter, and the MIC values of this combination ranged from 0.25 to 4 mg/liter. Among 7 isolates carrying metallo-β-lactamases and/or oxacillinases with carbapenemase activity, meropenem-vaborbactam susceptibility was 14.3% and 57.1% when applying CLSI and EUCAST breakpoints, respectively. CRE isolates were resistant to many comparator agents, and the most active agents were tigecycline, colistin, and amikacin (to which 63.2% to 96.7% of the isolates were susceptible). Understanding the epidemiology of CRE isolates in U.S. hospitals and the resistance mechanisms among these isolates is important to form guidelines for the treatment of infections caused by these organisms, which have high mortality rates.
Highlights
The activities of meropenem-vaborbactam and comparators against 152 (1.1%) carbapenem-resistant Enterobacterales (CRE) isolates identified among 13,929 Enterobacterales isolates collected from U.S hospitals during 2016 to 2018 were evaluated
The analysis of that study concluded that meropenemvaborbactam monotherapy showed significant improvement in clinical cure rates, lower nephrotoxicity, and lower mortality rates compared to the best available therapy, which consisted of multiple agents combined and included tetracyclines, aminoglycosides, colistin, and high carbapenem doses [16]
The authors highlighted that meropenem-vaborbactam considerably improved mortality rates among immunocompromised patients, who can be at a higher risk of these infections and who are rarely addressed in clinical trial studies [16]
Summary
The activities of meropenem-vaborbactam and comparators against 152 (1.1%) carbapenem-resistant Enterobacterales (CRE) isolates identified among 13,929 Enterobacterales isolates collected from U.S hospitals during 2016 to 2018 were evaluated. Serious infections caused by CRE organisms have a higher attributable mortality rate than those caused by isolates susceptible to carbapenems [3, 4]. Despite the good in vitro activity of ceftazidime-avibactam [8], no randomized trials specific for CRE were performed for this combination agent, and shortly after its approval, KPC-producing Enterobacterales isolates resistant to ceftazidime-avibactam emerged during therapy [9,10,11]. The analysis of that study concluded that meropenemvaborbactam monotherapy showed significant improvement in clinical cure rates, lower nephrotoxicity, and lower mortality rates compared to the best available therapy, which consisted of multiple agents combined and included tetracyclines, aminoglycosides, colistin, and high carbapenem doses [16]. The authors highlighted that meropenem-vaborbactam considerably improved mortality rates among immunocompromised patients, who can be at a higher risk of these infections and who are rarely addressed in clinical trial studies [16]
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