title: In vitro activity of ceftazidime-avibactam against 338 molecularly characterized gentamicin-nonsusceptible Gram-negative clinical isolates obtained from patients in Canadian hospitals.
abstract: The mechanism of aminoglycoside resistance among 338 gentamicin-nonsusceptible Gram-negative bacteria (207 Enterobacteriaceae and 131 Pseudomonas aeruginosa) was assessed, and the in vitro activity of ceftazidime-avibactam against these isolates was determined. Aminoglycoside-modifying enzymes were detected in 91.8% of Enterobacteriaceae and 13.7% of P. aeruginosa isolates. A single strain of Klebsiella pneumoniae harbored a 16S rRNA methylase (ArmA). The ceftazidime-avibactam MIC90 values were 0.5 μg/ml (MIC, ≤8 μg/ml for 100% of isolates) and 16 μg/ml (MIC, ≤8 μg/ml for 87.8% of isolates) against gentamicin-nonsusceptible Enterobacteriaceae and P. aeruginosa isolates, respectively.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Denisuik
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Tyler
authors.initials: T
authors.lastname: Denisuik
authors.affiliation: AstraZeneca, Infection Innovative Medicines, Waltham, Massachusetts, USA.
authors.forename: Wright W
authors.initials: WW
authors.lastname: Nichols
authors.affiliation: AstraZeneca, Infection Innovative Medicines, Waltham, Massachusetts, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Keating
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Adam
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Baxter
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walkty
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada ggzhanel@pcs.mb.ca.
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002170:Canada; D002442:Ceftazidime / Q000494:pharmacology*; D004338:Drug Combinations; D005839:Gentamicins / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006761:Hospitals; D006801:Humans; D008826:Microbial Sensitivity Tests; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; D005839:Gentamicins; D012336:RNA, Ribosomal, 16S; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime
references.citation: J Antimicrob Chemother. 2013 May;68 Suppl 1:i7-22
references.pmid: 23587781
references.citation: Drugs. 2013 Feb;73(2):159-77
references.pmid: 23371303
references.citation: Expert Opin Pharmacother. 2013 Aug;14(12):1585-97
references.pmid: 23746121
references.citation: Antimicrob Agents Chemother. 2014;58(3):1684-92
references.pmid: 24379201
references.citation: Clin Microbiol Rev. 2003 Jul;16(3):430-50
references.pmid: 12857776
references.citation: Clin Infect Dis. 2002 Mar 1;34(5):634-40
references.pmid: 11823954
references.citation: J Chemother. 2014 Dec;26(6):333-8
references.pmid: 24125508
references.citation: Microbiol Rev. 1993 Mar;57(1):138-63
references.pmid: 8385262
references.citation: Clin Infect Dis. 1997 Jan;24 Suppl 1:S46-62
references.pmid: 8994779
references.citation: Antimicrob Agents Chemother. 2008 May;52(5):1843-5
references.pmid: 18347105
references.citation: Antimicrob Agents Chemother. 2010 Nov;54(11):4636-42
references.pmid: 20805391
references.citation: Drug Resist Updat. 2010 Dec;13(6):151-71
references.pmid: 20833577
references.citation: J Antimicrob Chemother. 2011 Jan;66(1):48-53
references.pmid: 21078604
references.citation: Antimicrob Agents Chemother. 2012 Mar;56(3):1606-8
references.pmid: 22214778
references.citation: Drug Resist Updat. 2012 Jun;15(3):133-48
references.pmid: 22673098
references.citation: J Antimicrob Chemother. 2013 Jul;68(7):1543-50
references.pmid: 23580560