Evaluation of Guideline Recommendations for Dual Antipseudomonal Therapy in Hospitalized Adults with Pneumonia Using Combination Antibiograms

Pharmacotherapy. 2020 Nov;40(11):1089-1098. doi: 10.1002/phar.2466. Epub 2020 Nov 3.


Background: 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 Pseudomonas aeruginosa (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 P. 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 nonsusceptibility to beta-lactams.

Results: Eight hundred 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 nonsusceptibility to beta-lactams: intravenous antibiotics in the 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.

Conclusions: 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.

Keywords: Pseudomonas infections; beta-lactam resistance; healthcare-associated pneumonia.

Publication types

  • Practice Guideline

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Hospitalization*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Pneumonia, Bacterial / drug therapy*
  • Practice Guidelines as Topic*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa*


  • Anti-Bacterial Agents