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      In Vitro Susceptibility of Global Surveillance Isolates of Pseudomonas aeruginosa to Ceftazidime-Avibactam (INFORM 2012 to 2014)

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          Abstract

          Broth microdilution antimicrobial susceptibility testing was performed for ceftazidime-avibactam and comparator agents against 7,062 clinical isolates of Pseudomonas aeruginosa collected from 2012 to 2014 in four geographic regions (Europe, Asia/South Pacific, Latin America, Middle East/Africa) as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. The majority of isolates were susceptible to ceftazidime-avibactam, with the proportions susceptible differing marginally across the four regions (MIC 90, 8 to 16 μg/ml; 88.7 to 93.2% susceptible), in contrast to lower susceptibilities to the following comparator β-lactam agents: ceftazidime (MIC 90, 32 to 64 μg/ml; 71.5 to 80.8% susceptible), meropenem (MIC 90, >8 μg/ml; 64.9 to 77.4% susceptible), and piperacillin-tazobactam (MIC 90, >128 μg/ml; 62.3 to 71.3% susceptible). Compared to the overall population, susceptibility to ceftazidime-avibactam of isolates that were nonsusceptible to ceftazidime ( n = 1,627) was reduced to between 56.8% (Middle East/Africa; MIC 90, 64 μg/ml) and 68.9% (Asia/South Pacific; MIC 90, 128 μg/ml), but these percentages were higher than susceptibilities to other β-lactam agents (0 to 44% susceptible, depending on region and agent; meropenem MIC 90, >8 μg/ml; 26.5 to 43.9% susceptible). For this subset of isolates, susceptibilities to amikacin (MIC 90, >32 μg/ml; 53.2 to 80.0% susceptible) and colistin (MIC 90, 1 μg/ml; 98.5 to 99.5% susceptible) were comparable to or higher than that of ceftazidime-avibactam. A similar observation was made with isolates that were nonsusceptible to meropenem ( n = 1,926), with susceptibility to ceftazidime-avibactam between 67.8% (Middle East/Africa; MIC 90, 64 μg/ml) and 74.2% (Europe; MIC 90, 32 μg/ml) but again with reduced susceptibility to comparators except for amikacin (MIC 90, >32 μg/ml; 56.8 to 78.7% susceptible) and colistin (MIC 90, 1 μg/ml; 98.9 to 99.3% susceptible). Of the 8% of isolates not susceptible to ceftazidime-avibactam, the nonsusceptibility of half could be explained by their possession of genes encoding metallo-β-lactamases. The data reported here are consistent with results from other country-specific and regional surveillance studies and show that ceftazidime-avibactam demonstrates in vitro activity against globally collected clinical isolates of P. aeruginosa, including isolates that are resistant to ceftazidime and meropenem.

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          Author and article information

          Journal
          Antimicrob Agents Chemother
          Antimicrob. Agents Chemother
          aac
          aac
          AAC
          Antimicrobial Agents and Chemotherapy
          American Society for Microbiology (1752 N St., N.W., Washington, DC )
          0066-4804
          1098-6596
          23 May 2016
          22 July 2016
          August 2016
          : 60
          : 8
          : 4743-4749
          Affiliations
          [a ]AstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA
          [b ]International Health Management Associates, Inc., Schaumburg, Illinois, USA
          Author notes
          Address correspondence to Krystyna M. Kazmierczak, kkazmierczak@ 123456ihmainc.com .
          [*]

          Present address: Wright W. Nichols, Cambridge, Massachusetts, USA.

          Citation Nichols WW, de Jonge BLM, Kazmierczak KM, Karlowsky JA, Sahm DF. 2016. In vitro susceptibility of global surveillance isolates of Pseudomonas aeruginosa to ceftazidime-avibactam (INFORM 2012 to 2014). Antimicrob Agents Chemother 60:4743–4749. doi: 10.1128/AAC.00220-16.

          Article
          PMC4958170 PMC4958170 4958170 00220-16
          10.1128/AAC.00220-16
          4958170
          27216074
          Copyright © 2016, American Society for Microbiology. All Rights Reserved.
          Page count
          Figures: 0, Tables: 5, Equations: 0, References: 41, Pages: 7, Words: 5919
          Funding
          This investigation was funded by AstraZeneca Pharmaceuticals as part of the INFORM Global Surveillance Program. The sponsor approved the overall study design. All investigative sites were recruited and study supplies were provided by IHMA, Inc. Analysis of the final MIC and molecular data were performed by IHMA, Inc.
          Categories
          Epidemiology and Surveillance

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