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Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae.
Antimicrob Agents Chemother. 2017 09; 61(9)AA

Abstract

We determined imipenem, imipenem-relebactam, ceftazidime, and ceftazidime-avibactam MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six isolates carried extended-spectrum β-lactamases (ESBLs). With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against metallo-β-lactamase (MBL) producers. Ceftazidime-avibactam (but not imipenem-relebactam) was active against OXA-48-like producers, including a strain not harboring any ESBL. Major OmpK36 porin mutations were independently associated with higher imipenem-relebactam MICs (P < 0.0001) and showed a trend toward independent association with higher ceftazidime-avibactam MICs (P = 0.07). The presence of variant KPC-3 was associated with ceftazidime-avibactam resistance (P < 0.0001). In conclusion, imipenem-relebactam and ceftazidime-avibactam had overlapping spectra of activity and niches in which each was superior. Major OmpK36 mutations in KPC-K. pneumoniae may provide a foundation for stepwise emergence of imipenem-relebactam and ceftazidime-avibactam resistance.

Authors+Show Affiliations

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA cjc76@pitt.edu. VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA. XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28630202

Citation

Haidar, Ghady, et al. "Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam Against Carbapenem-Resistant Enterobacteriaceae." Antimicrobial Agents and Chemotherapy, vol. 61, no. 9, 2017.
Haidar G, Clancy CJ, Chen L, et al. Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(9).
Haidar, G., Clancy, C. J., Chen, L., Samanta, P., Shields, R. K., Kreiswirth, B. N., & Nguyen, M. H. (2017). Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae. Antimicrobial Agents and Chemotherapy, 61(9). https://doi.org/10.1128/AAC.00642-17
Haidar G, et al. Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam Against Carbapenem-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(9) PubMed PMID: 28630202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae. AU - Haidar,Ghady, AU - Clancy,Cornelius J, AU - Chen,Liang, AU - Samanta,Palash, AU - Shields,Ryan K, AU - Kreiswirth,Barry N, AU - Nguyen,M Hong, Y1 - 2017/08/24/ PY - 2017/03/28/received PY - 2017/05/19/accepted PY - 2017/6/21/pubmed PY - 2018/5/10/medline PY - 2017/6/21/entrez KW - CRE KW - Enterobacteriaceae KW - KPC KW - ceftazidime-avibactam KW - drug resistance mechanisms KW - imipenem-relabactam KW - mechanisms of resistance KW - porins JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 61 IS - 9 N2 - We determined imipenem, imipenem-relebactam, ceftazidime, and ceftazidime-avibactam MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six isolates carried extended-spectrum β-lactamases (ESBLs). With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against metallo-β-lactamase (MBL) producers. Ceftazidime-avibactam (but not imipenem-relebactam) was active against OXA-48-like producers, including a strain not harboring any ESBL. Major OmpK36 porin mutations were independently associated with higher imipenem-relebactam MICs (P < 0.0001) and showed a trend toward independent association with higher ceftazidime-avibactam MICs (P = 0.07). The presence of variant KPC-3 was associated with ceftazidime-avibactam resistance (P < 0.0001). In conclusion, imipenem-relebactam and ceftazidime-avibactam had overlapping spectra of activity and niches in which each was superior. Major OmpK36 mutations in KPC-K. pneumoniae may provide a foundation for stepwise emergence of imipenem-relebactam and ceftazidime-avibactam resistance. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/28630202/Identifying_Spectra_of_Activity_and_Therapeutic_Niches_for_Ceftazidime_Avibactam_and_Imipenem_Relebactam_against_Carbapenem_Resistant_Enterobacteriaceae_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&amp;pmid=28630202 DB - PRIME DP - Unbound Medicine ER -