Abstract
Pseudomonas aeruginosa 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-P.aeruginosa drug regimens. We conducted a retrospective cross-sectional analysis of the antimicrobial susceptibility of all nonduplicate P.aeruginosa 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 in vitro rates of susceptibility to potential anti-P.aeruginosa 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 P.aeruginosa isolates ranged from 72.7% for fluoroquinolones to 85.0% for piperacillin-tazobactam. Susceptibility rates were higher for blood isolates than for respiratory isolates (P < 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 P.aeruginosa 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.
Highlights
Pseudomonas aeruginosa is an important pathogen associated with significant morbidity and mortality
To provide further insights on the potential utility of combination antibiograms in evaluating antipseudomonal coverage, we used data from a large nationwide clinical database to assess in vitro antimicrobial susceptibility rates for nonduplicate P. aeruginosa respiratory or blood isolates in intensive care unit (ICU) and non-Intensive care unit (ICU) settings in U.S hospitals
Of the 11,701 nonduplicate P. aeruginosa blood or respiratory isolates, most (89.4%) were obtained from respiratory samples and about 44% were obtained from an ICU (Table 1)
Summary
Pseudomonas aeruginosa is an important pathogen associated with significant morbidity and mortality. Because of the high mortality from HAP/VAP caused by P. aeruginosa, current U.S and European guidelines recommend empirical combination therapy with two antipseudomonal antibiotics from different classes to cover Gram-negative bacteria in high-risk patients [10, 11]. Dual antipseudomonal therapy is recommended for VAP patients with risk factors for antimicrobial resistance, including recent hospitalization or intravenous antibiotic use, or in units where Ͼ10% of Gramnegative bacterial isolates are resistant to an agent being considered for monotherapy [10]. To provide further insights on the potential utility of combination antibiograms in evaluating antipseudomonal coverage, we used data from a large nationwide clinical database to assess in vitro antimicrobial susceptibility rates for nonduplicate P. aeruginosa respiratory or blood isolates in intensive care unit (ICU) and non-ICU settings in U.S hospitals
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