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Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals.
Int J Antimicrob Agents. 2021 Nov; 58(5):106439.IJ

Abstract

We investigated the prevalence, resistance mechanisms and activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparator agents against carbapenem-resistant Enterobacterales (CRE) that did not carry carbapenemase genes. Among 304 CRE isolates collected in US hospitals during 2016-2018 (1.1% of the overall Enterobacterales), 45 (14.8%) isolates did not carry carbapenemases. These isolates were mainly Klebsiella aerogenes (n = 11), Enterobacter cloacae (n = 11) and Klebsiella pneumoniae (n = 10). Isolates harboured one to six β-lactam resistance mechanisms (median, three mechanisms). Acquired β-lactamase genes were detected in 21 isolates; blaCTX-M-15 was the most common acquired β-lactamase gene found (14 isolates). All 11 K. aerogenes and 6 E. cloacae isolates overexpressed AmpC. Only one isolate belonging to these species carried acquired β-lactamase genes. Disruptions or reduced expression of both outer membrane proteins (ompC/ompK36 and ompF/ompK35) were detected among 20 isolates. AcrAB-TolC was modestly expressed or overexpressed among 19 isolates from six species. One E. coli isolate produced a CTX-M-15 variant that displayed an increased meropenem minimum inhibitory concentration (MIC) when expressed in a clean background. Most β-lactam agents had limited activity against CRE isolates that did not carry carbapenemases. Ceftazidime/avibactam inhibited all isolates, while imipenem/relebactam and meropenem/vaborbactam inhibited 93.0% (88.9% if Proteus mirabilis is included) and 93.3% of tested isolates at current breakpoints. The resistance mechanisms among CRE isolates that did not produce carbapenemases are complex; β-lactam/β-lactamase inhibitor combinations might have different activity against these isolates depending on their resistance mechanisms and the bacterial species.

Authors+Show Affiliations

JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA. Electronic address: mariana-castanheira@jmilabs.com.JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34547421

Citation

Castanheira, Mariana, et al. "Activity of Ceftazidime/avibactam, Meropenem/vaborbactam and Imipenem/relebactam Against Carbapenemase-negative Carbapenem-resistant Enterobacterales Isolates From US Hospitals." International Journal of Antimicrobial Agents, vol. 58, no. 5, 2021, p. 106439.
Castanheira M, Doyle TB, Deshpande LM, et al. Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals. Int J Antimicrob Agents. 2021;58(5):106439.
Castanheira, M., Doyle, T. B., Deshpande, L. M., Mendes, R. E., & Sader, H. S. (2021). Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals. International Journal of Antimicrobial Agents, 58(5), 106439. https://doi.org/10.1016/j.ijantimicag.2021.106439
Castanheira M, et al. Activity of Ceftazidime/avibactam, Meropenem/vaborbactam and Imipenem/relebactam Against Carbapenemase-negative Carbapenem-resistant Enterobacterales Isolates From US Hospitals. Int J Antimicrob Agents. 2021;58(5):106439. PubMed PMID: 34547421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals. AU - Castanheira,Mariana, AU - Doyle,Timothy B, AU - Deshpande,Lalitagauri M, AU - Mendes,Rodrigo E, AU - Sader,Helio S, Y1 - 2021/09/20/ PY - 2021/05/26/received PY - 2021/08/31/revised PY - 2021/09/12/accepted PY - 2021/9/22/pubmed PY - 2022/1/27/medline PY - 2021/9/21/entrez KW - CRE KW - Carbapenem-resistant Enterobacterales KW - Non-carbapenemase-producing KW - β-Lactam resistance mechanisms KW - β-Lactam/β-lactamase inhibitor combinations SP - 106439 EP - 106439 JF - International journal of antimicrobial agents JO - Int J Antimicrob Agents VL - 58 IS - 5 N2 - We investigated the prevalence, resistance mechanisms and activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparator agents against carbapenem-resistant Enterobacterales (CRE) that did not carry carbapenemase genes. Among 304 CRE isolates collected in US hospitals during 2016-2018 (1.1% of the overall Enterobacterales), 45 (14.8%) isolates did not carry carbapenemases. These isolates were mainly Klebsiella aerogenes (n = 11), Enterobacter cloacae (n = 11) and Klebsiella pneumoniae (n = 10). Isolates harboured one to six β-lactam resistance mechanisms (median, three mechanisms). Acquired β-lactamase genes were detected in 21 isolates; blaCTX-M-15 was the most common acquired β-lactamase gene found (14 isolates). All 11 K. aerogenes and 6 E. cloacae isolates overexpressed AmpC. Only one isolate belonging to these species carried acquired β-lactamase genes. Disruptions or reduced expression of both outer membrane proteins (ompC/ompK36 and ompF/ompK35) were detected among 20 isolates. AcrAB-TolC was modestly expressed or overexpressed among 19 isolates from six species. One E. coli isolate produced a CTX-M-15 variant that displayed an increased meropenem minimum inhibitory concentration (MIC) when expressed in a clean background. Most β-lactam agents had limited activity against CRE isolates that did not carry carbapenemases. Ceftazidime/avibactam inhibited all isolates, while imipenem/relebactam and meropenem/vaborbactam inhibited 93.0% (88.9% if Proteus mirabilis is included) and 93.3% of tested isolates at current breakpoints. The resistance mechanisms among CRE isolates that did not produce carbapenemases are complex; β-lactam/β-lactamase inhibitor combinations might have different activity against these isolates depending on their resistance mechanisms and the bacterial species. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/34547421/Activity_of_ceftazidime/avibactam_meropenem/vaborbactam_and_imipenem/relebactam_against_carbapenemase_negative_carbapenem_resistant_Enterobacterales_isolates_from_US_hospitals_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(21)00720-2 DB - PRIME DP - Unbound Medicine ER -