Contemporary analysis of ETEST for antibiotic susceptibility and minimum inhibitory concentration agreement against Pseudomonas aeruginosa from patients with cystic fibrosis

Abstract

Objectives: Cystic fibrosis (CF) acute pulmonary exacerbations are often caused by Pseudomonas aeruginosa, including multi-drug resistant strains. Optimal antibiotic therapy is required to return lung function and should be guided by in vitro susceptibility results. There are sparse data describing ETEST performance for CF isolates using contemporary isolates, methods and interpretation, as well as novel antibiotics, such as ceftazidime–avibactam and ceftolozane–tazobactam. Methods: Pseudomonas aeruginosa (n = 105) isolated during pulmonary exacerbation from patients with CF were acquired from 3 US hospitals. Minimum inhibitory concentrations (MICs) were assessed by reference broth microdilution (BMD) and ETEST for aztreonam, cefepime, ceftazidime, ceftazidime–avibactam, ceftolozane–tazobactam, ciprofloxacin, levofloxacin, meropenem, piperacillin–tazobactam, and tobramycin. Broth microdilution was conducted in concordance with the Clinical and Laboratory Standards Institute M100. ETEST methodology reflected package insert recommendations. Performance of ETEST strips was evaluated using the Food and Drug Administration (FDA) and Susceptibility Testing Manufacturers Association (STMA) guidance. Results: Of the 105 P. aeruginosa included, 46% had a mucoid phenotype. ETEST MICs typically read 0–1 dilution higher than BMD for all drugs. Categorical agreement and essential agreement ranged from 64 to 93% and 63 to 86%, respectively. The majority of observed errors were minor. A single very major error occurred with ceftazidime (4.2%). For ceftazidime–vibactam, 2 very major errors were observed and both were within essential agreement. Major errors occurred for aztreonam (3.3%), cefepime (9.4%), ceftazidime–avibactam (5.3%, adjusted 2.1%), ceftolozane–tazobactam (1%), meropenem (3.3%), piperacillin–tazobactam (2.9%), and tobramycin (1.5%). Conclusions: ETEST methods performed conservatively for most antibiotics against this challenging collection of P. aeruginosa from patients with CF.