An #Assessment of the In Vitro #Activity of #Ceftazidime-Avibactam Against MDR #Klebsiella spp. Collected in the #INFORM Global #Surveillance Study (2012-2014) (Antimicrob Agents Chemother., abstract)

Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

An Assessment of the In Vitro Activity of Ceftazidime-Avibactam Against Multi-Drug Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study (2012-2014)

M. Hackel1, K. Kazmierczak1#, D. Hoban1, D. Biedenbach1, S. Bouchillon1, B.L.M. DeJonge2 and G. Stone2

Author Affiliations: 1International Health Management Associates, Schaumburg, IL, USA – 2AstraZeneca Pharmaceuticals, Waltham, MA, USA

 

ABSTRACT

Increasing resistance in Gram-negative bacilli, including Klebsiella spp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-β-lactam β-lactamase inhibitor, protects β-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) and serine carbapenemases including Ambler class A and/or class C, and some class D enzymes. In this analysis, we report the in vitro activity of ceftazidime-avibactam and comparators against multi-drug resistant (MDR) Klebsiella spp. from the 2012–2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%) Klebsiella spp. isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an extended-spectrum β-lactamase (ESBL) screen positive phenotype and 27.4% were not susceptible to meropenem as an example carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC50/90 values of 0.5/2 μg/mL and 96.6% of all and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value ≤8 μg/mL). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-β-lactamases) either alone or in combination with other enzymes. These in vitro results support the continued investigation of ceftazidime-avibactam for the treatment of MDR Klebsiella spp.

 

FOOTNOTES

#Corresponding author: Krystyna M. Kazmierczak, International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL 60173, Phone: 1-847-303-5003, Fax: 1-847-303-5601, Email: kkazmierczak@ihmainc.com

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Carbapenem; Klebsiella Penumoniae; Avibactam; Ceftazidime.

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