LAUSR

IntroductionMucoid Pseudomonas aeruginosa (MP) strains in cystic fibrosis (CF) patients are thought to initiate the chronic infection stage of CF and are associated with pulmonary function decline.ObjectivesThe purpose of this study was to assess the susceptibility of MP strains to ceftolozane/tazobactam and the efficacy of ceftolozane/tazobactam against MP strains compared with those for standard-of-care antipseudomonal antibiotics.MethodsTen clinical isolates of MP from CF patients were tested for susceptibility with Etest and time–kill analysis with ceftolozane/tazobactam compared with ceftazidime, cefepime, ciprofloxacin, meropenem, tobramycin, and polymyxin B. The physiologic free peak concentrations were used in the time–kill experiments.ResultsCeftolozane/tazobactam minimum inhibitory concentrations ranged from 0.032 to 1.5 mg/L. In the time–kill analysis, the mean starting inoculum for the isolates was 6.29 ± 0.22 log10 colony forming units (CFU) per milliliter. On average, ceftolozane/tazobactam, cefepime, ciprofloxacin, meropenem, tobramycin, and polymyxin B all demonstrated bactericidal activity. With all isolates taken into account, polymyxin B, tobramycin, meropenem, and ceftolozane/tazobactam 3 g were the most potent, with reductions in inoculum of 5.07 ± 0.45, 4.58 ± 2.2, 4.76 ± 0.71, and 4.17 ± 0.94 log10 CFU/mL, respectively. Ceftolozane/tazobactam 1.5 g, cefepime, and ciprofloxacin reduced the starting inoculum by 3.74 ± 0.99, 3.42 ± 1.4, and 3.23 ± 2.0 log10 CFU/mL, respectively. Despite 90% susceptibility, ceftazidime was bactericidal against seven of ten strains, with an average reduction in starting inoculum of 2.91 ± 2.2 log10 CFU/mL.ConclusionCeftolozane/tazobactam activity against MP strains derived from CF patients was comparable to that of standard-of-care agents at both the 1.5-g dose and the 3-g dose. Further in vitro modeling and clinical trials are warranted.