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Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals from 2012 to 2015.
Antimicrob Agents Chemother. 2017 03; 61(3)AA

Abstract

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying blaKPC collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC50/90, 0.5/1 μg/ml; 98.9% susceptible at ≤2 μg/ml) were the most active agents. Only 80.5% and 59.0% of isolates were susceptible to colistin and amikacin, respectively. All three isolates (0.7%) displaying resistance to ceftazidime-avibactam (K. pneumoniae; MICs, ≥16 μg/ml) were evaluated using whole-genome sequencing analysis and relative quantification of expression levels of porins and efflux pump. Two isolates carried metallo-β-lactamase genes, blaNDM-1 or blaVIM-4, among other β-lactam resistance mechanisms, and one displayed a premature stop codon in ompK35 and decreased expression of ompK36 Ceftazidime-avibactam was active against 100.0 and 99.3% of isolates carrying blaKPC-3 (n = 221) and blaKPC-2 (n = 145), respectively. Isolates carrying blaKPC were more commonly recovered from pneumonia (n = 155), urinary tract (n = 93), and skin/soft tissue (n = 74) infections. Ceftazidime-avibactam (97.8 to 100.0% susceptible) was consistently active against isolates from all infection sites. K. pneumoniae (83.3% of the collection) susceptibility rates were 99.2% for ceftazidime-avibactam, 98.9% for tigecycline, and 80.1% for colistin. Ceftazidime-avibactam susceptibility did not vary substantially when comparing isolates from intensive care unit (ICU) patients to those from non-ICU patients. Ceftazidime-avibactam was active against this large collection of isolates carrying blaKPC and represents a valuable addition to the armamentarium currently available for the treatment of infections caused by KPC-producing Enterobacteriaceae.

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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28031200

Citation

Castanheira, Mariana, et al. "Low Frequency of Ceftazidime-Avibactam Resistance Among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals From 2012 to 2015." Antimicrobial Agents and Chemotherapy, vol. 61, no. 3, 2017.
Castanheira M, Mendes RE, Sader HS. Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals from 2012 to 2015. Antimicrob Agents Chemother. 2017;61(3).
Castanheira, M., Mendes, R. E., & Sader, H. S. (2017). Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals from 2012 to 2015. Antimicrobial Agents and Chemotherapy, 61(3). https://doi.org/10.1128/AAC.02369-16
Castanheira M, Mendes RE, Sader HS. Low Frequency of Ceftazidime-Avibactam Resistance Among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals From 2012 to 2015. Antimicrob Agents Chemother. 2017;61(3) PubMed PMID: 28031200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying blaKPC Collected in U.S. Hospitals from 2012 to 2015. AU - Castanheira,Mariana, AU - Mendes,Rodrigo E, AU - Sader,Helio S, Y1 - 2017/02/23/ PY - 2016/11/07/received PY - 2016/12/22/accepted PY - 2016/12/30/pubmed PY - 2017/9/13/medline PY - 2016/12/30/entrez KW - KPC KW - ceftazidime-avibactam KW - permeability JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 61 IS - 3 N2 - Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying blaKPC collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC50/90, 0.5/1 μg/ml; 98.9% susceptible at ≤2 μg/ml) were the most active agents. Only 80.5% and 59.0% of isolates were susceptible to colistin and amikacin, respectively. All three isolates (0.7%) displaying resistance to ceftazidime-avibactam (K. pneumoniae; MICs, ≥16 μg/ml) were evaluated using whole-genome sequencing analysis and relative quantification of expression levels of porins and efflux pump. Two isolates carried metallo-β-lactamase genes, blaNDM-1 or blaVIM-4, among other β-lactam resistance mechanisms, and one displayed a premature stop codon in ompK35 and decreased expression of ompK36 Ceftazidime-avibactam was active against 100.0 and 99.3% of isolates carrying blaKPC-3 (n = 221) and blaKPC-2 (n = 145), respectively. Isolates carrying blaKPC were more commonly recovered from pneumonia (n = 155), urinary tract (n = 93), and skin/soft tissue (n = 74) infections. Ceftazidime-avibactam (97.8 to 100.0% susceptible) was consistently active against isolates from all infection sites. K. pneumoniae (83.3% of the collection) susceptibility rates were 99.2% for ceftazidime-avibactam, 98.9% for tigecycline, and 80.1% for colistin. Ceftazidime-avibactam susceptibility did not vary substantially when comparing isolates from intensive care unit (ICU) patients to those from non-ICU patients. Ceftazidime-avibactam was active against this large collection of isolates carrying blaKPC and represents a valuable addition to the armamentarium currently available for the treatment of infections caused by KPC-producing Enterobacteriaceae. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/28031200/Low_Frequency_of_Ceftazidime_Avibactam_Resistance_among_Enterobacteriaceae_Isolates_Carrying_blaKPC_Collected_in_U_S__Hospitals_from_2012_to_2015_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=28031200 DB - PRIME DP - Unbound Medicine ER -