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.
H. S. Sader,
R. E. Mendes, Allergan: Research Contractor , Research support .
R. K. Flamm, Allergan: Research Contractor , Research support .