Potency of parenteral antimicrobials including ceftolozane/tazobactam against nosocomial respiratory tract pathogens: considerations for empiric and directed therapy

Background: Empiric therapy decisions are predicated on knowledge of both the epidemiology and antimicrobial susceptibility of the probable infecting pathogen(s). The objective of this study was to evaluate the microbial distribution and phenotypic profiles of nosocomial respiratory isolates collected from multiple US hospitals and assess the clinical utility of various monotherapy and combination regimens. Methods: Hospitals provided consecutive non-duplicate adult inpatients Gram-negative nosocomial respiratory isolates from cultures received >= 48 h after hospital admission. Minimum inhibitory concentrations (MICs) for 12 antimicrobials were determined using broth microdilution methods. An antibiogram was constructed for monotherapy regimens as well as combinations inclusive of either tobramycin (TOB) or ciprofloxacin (CIP). Results: Six hospitals provided 518 nosocomial respiratory isolates. P. aeruginosa (PSA) comprised 28% of the population followed by Klebsiella pneumoniae (13%), Enterobacter spp. (13%), S. maltophilia (9%), S. marcesens (6%), A. baumannii (6%), and others (18%). When considering monotherapy for the Enterobacteriaceae & PSA ceftolozane/tazobactam (C/T) provided the highest (87%) percent susceptibility (% S) followed by meropenem (MEM), CIP, cefepime (FEP), ceftazidime (CAZ) and piperacillin-tazobactam (TZP) at 71-85 % S. The addition of TOB > CIP improved the probability that the antimicrobial combination would provide >= 1 active agent. Conclusions: PSA was the predominant nosocomial respiratory pathogen; however, the Enterobacteriaceae comprised an additional 53% in this survey. When considering empiric beta-lactam monotherapy therapy for the entire spectrum of pathogens C/T provided the highest (78%) % S followed by MEM, FEP and TZP. The addition of either TOB > CIP to these beta-lactams enhances the likelihood that an active agent would be selected when considering empirical therapy choices for nosocomial respiratory tract infections.