Pharmacotherapy. 2020 Oct 10. doi: 10.1002/phar.2466. Online ahead of print.
INTRODUCTION: Guidelines for pneumonia recommend empiric dual antipseudomonal therapy in patients with specific risk factors. However, there is lack of consensus on when to use dual antipseudomonal therapy as the recommendations are rated as weak, based on low-quality evidence.
OBJECTIVES: The objectives of this study were to develop combination antibiograms to assess the susceptibility of P. aeruginosa in respiratory cultures to combinations of empiric antibiotics and to use combination antibiograms to delineate the impact of specific risk factors for which guidelines recommend dual antipseudomonal therapy.
METHODS: A retrospective cohort study was conducted of adults hospitalized with pneumonia with positive respiratory cultures for Pseudomonas aeruginosa between September 2014 and September 2018. Data collected included demographics, antimicrobial susceptibility results, and risk factors for which guidelines recommend dual antipseudomonal therapy. Combination antibiograms were developed and logistic regression was performed to identify risk factors for non-susceptibility to beta-lactams.
RESULTS: Eight hundred and nineteen patients were included and 72% received antibiotics. Beta-lactam susceptibility ranged from 58% to 69% and addition of a fluoroquinolone or aminoglycoside resulted in statistically significant increases in susceptibility. However, only addition of tobramycin or amikacin provided susceptibility rates approaching or exceeding 90% stratified by pneumonia type and risk factors. Presence of guideline-based risk factors generally resulted in reduced susceptibility rates. Logistic regression identified three risk factors associated with non-susceptibility to beta-lactams: intravenous antibiotics in previous 90 days, nursing home residence, and mechanical ventilation at onset. The cumulative presence of each additional risk factor affected beta-lactam susceptibility rates, which were 93% in the absence of any risk factors and 39% when all three risk factors co-existed.
CONCLUSION: Risk factors necessitating dual antipseudomonal therapy for pneumonia should be locally validated. When dual antipseudomonal therapy is indicated, tobramycin or amikacin have the best likelihood of providing adequate in vitro activity.