A Combination Antibiogram Evaluation for <i>Pseudomonas aeruginosa</i> in Respiratory and Blood Sources from Intensive Care Unit (ICU) and Non-ICU Settings in U.S. Hospitals

Abstract

<i>Pseudomonas aeruginosa</i> is an important pathogen associated with significant morbidity and mortality. U.S. guidelines for the treatment of hospital-acquired and ventilator-associated pneumonia recommend the use of two antipseudomonal drugs for high-risk patients to ensure that ≥95% of patients receive active empirical therapy. We evaluated the utility of combination antibiograms in identifying optimal anti-<i>P.</i><i>aeruginosa</i> drug regimens. We conducted a retrospective cross-sectional analysis of the antimicrobial susceptibility of all nonduplicate <i>P.</i><i>aeruginosa</i> blood and respiratory isolates collected between 1 October 2016 and 30 September 2017 from 304 U.S. hospitals in the BD Insights Research Database. Combination antibiograms were used to determine <i>in vitro</i> rates of susceptibility to potential anti-<i>P.</i><i>aeruginosa</i> combination regimens consisting of a backbone antibiotic (an extended-spectrum cephalosporin, carbapenem, or piperacillin-tazobactam) plus an aminoglycoside or fluoroquinolone. Single-agent susceptibility rates for the 11,701 nonduplicate <i>P.</i><i>aeruginosa</i> isolates ranged from 72.7% for fluoroquinolones to 85.0% for piperacillin-tazobactam. Susceptibility rates were higher for blood isolates than for respiratory isolates (<i>P</i> < 0.05). Antibiotic combinations resulted in increased susceptibility rates but did not achieve the goal of 95% antibiotic coverage. Adding an aminoglycoside resulted in higher susceptibility rates than adding a fluoroquinolone; piperacillin-tazobactam plus an aminoglycoside resulted in the highest susceptibility rate (93.3%). Intensive care unit (ICU) isolates generally had lower susceptibility rates than non-ICU isolates. Commonly used antipseudomonal drugs, either alone or in combination, did not achieve 95% coverage against U.S. hospital <i>P.</i><i>aeruginosa</i> isolates, suggesting that new drugs are needed to attain this goal. Local institutional use of combination antibiograms has the potential to optimize empirical therapy of infections caused by difficult-to-treat pathogens.