The effect of combination antibiotic therapy on mortality in patients with sepsis or septic shock due to Pseudomonas aeruginosa bloodstream infections: a systematic review.

Abstract

Introduction: Pseudomonas aeruginosa bloodstream infections (BSIs) complicated by sepsis or septic shock are associated with high mortality. Although combination antibiotic therapy may increase early antimicrobial coverage, its effect on survival remains uncertain. This systematic review evaluated the impact of appropriate empirical and definitive combination therapy compared with monotherapy on mortality in this population.

Methods: Following PRISMA guidelines, we systematically searched eight databases through 31 August 2025, for studies enrolling adults with sepsis or septic shock due to confirmed P. aeruginosa BSIs that compared combination therapy with monotherapy. Data on study characteristics, treatment phase, and mortality outcomes were extracted. Risk of bias was assessed using ROBINS-I, and certainty of evidence was evaluated with GRADE.

Results: Eight observational studies including 1201 patients met the inclusion criteria. No consistent survival benefit was observed with definitive combination therapy. Some studies assessing empirical therapy reported lower mortality in selected high-risk subgroups; however, results were characterized by substantial clinical heterogeneity. Adverse events were infrequently reported, and overall certainty of evidence was very low.

Conclusions: Current evidence does not support routine use of combination therapy over monotherapy. Empirical combination therapy may be considered in carefully selected high-risk patients, with prompt de-escalation once susceptibilities are known.