title: Ceftazidime-avibactam and comparator agents tested against urinary tract isolates from a global surveillance program (2011).
abstract: Ceftazidime-avibactam, a combination of ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam, is in advanced clinical development. In this study, we report results of in vitro testing of ceftazidime-avibactam and comparator agents against a collection of urinary tract infection (UTI) isolates from the United States (USA), Europe and Mediterranean region (EMR), Latin America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical isolates (1 per patient episode) were collected from patients with a UTI during 2011. A total of 1797 isolates were collected from 159 medical centers. Isolates were processed at the medical centers and forwarded to a central monitoring laboratory for confirmatory identification and reference susceptibility testing. Ceftazidime-avibactam was highly active against Enterobacteriaceae and Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to 0.5μg/mL. The MIC90 in the APAC was slightly elevated at 1μg/mL. A total of 6.1% (8/131) of Escherichia coli in the USA, 23.5% (43/183) in the EMR, 61.2% (30/49) in LATAM, and 75.0% (9/12) in APAC exhibited an extended-spectrum β-lactamase (ESBL) screen-positive phenotype. A total of 1.6% (2/129) of Klebsiella pneumoniae isolates in the USA were meropenem-non-susceptible (MIC ≥2μg/mL), but a rate of 10.3% (10/97) was observed in the EMR. All ESBL screen-positive phenotype and meropenem-non-susceptible E. coli and K. pneumoniae isolates exhibited a ceftazidime-avibactam MIC ≤4μg/mL. All isolates of P. aeruginosa in the USA and 80.9% (38/47) in the EMR were inhibited at a ceftazidime-avibactam MIC of ≤8μg/mL compared to 88.2% (15/17) and 61.7% (29/47) for ceftazidime alone. Ceftazidime-avibactam demonstrated wide in vitro activity against Gram-negative bacteria from patients with UTI including high potencies against multidrug-resistant organisms.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317 USA. Electronic address: robert-flamm@jmilabs.com.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, IA 52317 USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, IA 52317 USA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, North Liberty, IA 52317 USA; Tufts University School of Medicine, Boston, MA 02111 USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004338:Drug Combinations; D062665:Epidemiological Monitoring; D014943:Global Health; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime
keywords: Ceftazidime-avibactam; Surveillance; UTI