β-Lactam plus aminoglycoside or fluoroquinolone combination versus β-lactam monotherapy for Pseudomonas aeruginosa infections: A meta-analysis

The objective of this review was to compare the effectiveness and safety of β-lactam combined with aminoglycoside or fluoroquinolone with that of β-lactam monotherapy for the treatment of Pseudomonas aeruginosa infections. We searched Scopus and PubMed databases and synthesised the outcomes of the individual studies in a meta-analysis. Both non-randomised studies and randomised controlled trials (RCTs) that evaluated outcomes of patients with P. aeruginosa infections receiving treatment with β-lactams alone or in combination with an aminoglycoside or a fluoroquinolone were included. Studies including patients with cystic fibrosis were excluded. Nineteen articles (eight RCTs) were included (1721 patients with P. aeruginosa infections). Patients receiving combination therapy had no difference in mortality compared with patients receiving β-lactam monotherapy either as definitive (risk ratio = 0.97, 95% confidence interval 0.77–1.22) or as empirical treatment (1.02, 0.78–1.34). In the definitive treatment group, no difference in mortality was found between combination therapy and monotherapy for patients with bacteraemia (0.95, 0.67–1.34) or severe infections (0.96, 0.75–1.24). Patients receiving definitive combination therapy had non-significantly higher clinical cure compared with patients receiving β-lactam monotherapy (1.36, 0.99–1.86). A higher clinical cure rate was observed for patients receiving empirical treatment with combination therapy (1.23, 1.05–1.43). There was no difference in clinical cure either for RCTs (1.29, 0.91–1.83) or for non-randomised studies (1.18, 0.97–1.45). In conclusion, no benefit in mortality was observed in patients receiving combination therapy for P. aeruginosa infections. A well-designed multicentre RCT is warranted to address this important issue.