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Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018.
Antimicrob Agents Chemother. 2020 01 27; 64(2)AA

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 bla KPC-3, 51 isolates carrying bla KPC-2, 4 isolates carrying bla NDM-1, 3 isolates carrying bla SME-4, 2 isolates carrying bla VIM-1, 1 isolate carrying bla OXA-232, and 1 isolate carrying bla KPC-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 bla KPC-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.

Authors+Show Affiliations

JMI Laboratories, North Liberty, Iowa, USA mariana-castanheira@jmilabs.com.JMI Laboratories, North Liberty, Iowa, USA.JMI Laboratories, North Liberty, Iowa, USA.JMI Laboratories, North Liberty, Iowa, USA.JMI Laboratories, North Liberty, Iowa, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31712207

Citation

Castanheira, Mariana, et al. "Meropenem-Vaborbactam Activity Against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals During 2016 to 2018." Antimicrobial Agents and Chemotherapy, vol. 64, no. 2, 2020.
Castanheira M, Doyle TB, Kantro V, et al. Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. Antimicrob Agents Chemother. 2020;64(2).
Castanheira, M., Doyle, T. B., Kantro, V., Mendes, R. E., & Shortridge, D. (2020). Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. Antimicrobial Agents and Chemotherapy, 64(2). https://doi.org/10.1128/AAC.01951-19
Castanheira M, et al. Meropenem-Vaborbactam Activity Against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals During 2016 to 2018. Antimicrob Agents Chemother. 2020 01 27;64(2) PubMed PMID: 31712207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. AU - Castanheira,Mariana, AU - Doyle,Timothy B, AU - Kantro,Valerie, AU - Mendes,Rodrigo E, AU - Shortridge,Dee, Y1 - 2020/01/27/ PY - 2019/09/25/received PY - 2019/10/24/accepted PY - 2019/11/13/pubmed PY - 2021/1/5/medline PY - 2019/11/13/entrez KW - CRE KW - Enterobacterales KW - outer membrane protein JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 64 IS - 2 N2 - 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 bla KPC-3, 51 isolates carrying bla KPC-2, 4 isolates carrying bla NDM-1, 3 isolates carrying bla SME-4, 2 isolates carrying bla VIM-1, 1 isolate carrying bla OXA-232, and 1 isolate carrying bla KPC-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 bla KPC-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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/31712207/Meropenem_Vaborbactam_Activity_against_Carbapenem_Resistant_Enterobacterales_Isolates_Collected_in_U_S__Hospitals_during_2016_to_2018_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=31712207 DB - PRIME DP - Unbound Medicine ER -