1523. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Complicated Urinary Tract Infections: Results from the International Network for Optimal Resistance Monitoring (INFORM) Program
Session: Poster Abstract Session: Urinary Tract Infection
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • IDWeek-2018-CAZ-AVI-cUTI-Final.pdf (1.4 MB)
  • Background: Urinary tract infections (UTIs) are among the most frequent healthcare-associated infections and represent a major source of gram-negative (GN) bacteremia. We evaluated the antimicrobial susceptibility (S) of GN bacteria isolated from patients with complicated UTIs (cUTIs) in United States (US) medical centers.

    Methods: Unique patient isolates were consecutively collected from patients with cUTIs in 83 medical centers in 2015-2017, and the GN organisms (n=9,403) were S tested against CAZ-AVI and comparators by reference broth microdilution methods. Ceftolozane-tazobactam (C-T) was tested in 2017 only. Enterobacteriaceae (ENT) with an extended-spectrum β-lactamase (ESBL) phenotype were evaluated by whole genome sequencing for the presence of genes encoding β-lactamases.

    Results: The most common organisms were E. coli (EC; 53.2%), K. pneumoniae (KPN; 12.5%), E. faecalis (6.0%), P. mirabilis (PM; 5.3%), and P. aeruginosa (PSA; 4.9%). An ESBL phenotype was observed among 13.2%, 13.4% and 7.0% of EC, KPN, and PM, respectively. CAZ-AVI inhibited >99.9% of all ENT, including all EC, PM and E. cloacae (ECL) isolates, at the S breakpoint of ≤8 µg/mL (Table). CAZ-AVI was also highly active against KPN, including ESBL-phenotype (MIC50/90, 0.25/1 µg/mL; 99.5%S) and meropenem (MEM)-non-S isolates (MIC50/90, 1/2 µg/mL; 98.0%S). In contrast, only 72.9% and 73.1% of ESBL-phenotype KPN isolates were S to C-T and MEM, respectively. Only 1 ENT isolate was CAZ-AVI-resistant, a KPN with a CAZ-AVI MIC of 16 μg/mL that produced a KPC-2 and a SHV-12 and exhibited decreased expression of OmpK36. Among ECL (27.2% CAZ-non-S), S to CAZ-AVI, C-T, and MEM were 100.0%, 80.0%, and 98.8%, respectively. CAZ-AVI was also highly active against PSA (MIC50/90, 2/4 µg/mL; 99.1%S), including isolates expressing a multidrug-resistant (MDR) phenotype (MIC50/90, 4/8 µg/mL; 93.8%S). Further 86.2% (25/29) of PSA isolates non-S to MEM, CAZ, and piperacillin-tazobactam were CAZ-AVI-S.

    Conclusion: CAZ-AVI demonstrated potent activity against a large collection of contemporary (2015-2017) GN bacteria isolated from patients with cUTIs in US hospitals, including MDR isolates, and provided greater coverage than the agents currently available in the US for treatment of cUTIs.

    A screenshot of a cell phone
Description generated with very high confidence
     

    Helio S. Sader, MD, PhD1, Mariana Castanheira, PhD2, Rodrigo E. Mendes, Ph.D.2 and Robert K. Flamm, PhD3, (1)JMI Laboratories, North Liberty, IA, (2)JMI Laboratories, Inc., North Liberty, IA, (3)United States Committee on Antimicrobial Susceptibility Testing, Silverton, OR

    Disclosures:

    H. S. Sader, Allergan: Research Contractor , Research support .

    M. Castanheira, Allergan: Research Contractor , Research support .

    R. E. Mendes, Allergan: Research Contractor , Research support .

    R. K. Flamm, Allergan: Research Contractor , Research support .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.