Fluoroquinolones or macrolides alone versus combined with β-lactams for adults with community-acquired pneumonia: Systematic review and meta-analysis

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. This review compared two of the main treatment alternatives: quinolone or macrolide monotherapy versus their combination with β-lactams. A systematic review and meta-analysis of randomised controlled trials (RCTs) including adult inpatients and outpatients with CAP that compared treatment with any respiratory fluoroquinolone or macrolide administered as single agent with combination therapy of a β-lactam plus either a fluoroquinolone or a macrolide (four separate comparisons) were conducted. The primary outcome was all-cause 30-day mortality. Secondary outcomes included clinical and microbiological failure, treatment discontinuation and adverse events. A comprehensive search was conducted with no date, language or publication status restrictions. Pooled risk ratios (RRs) with 95% confidence intervals are reported. Sixteen RCTs randomising 4809 patients were included. All but one included hospitalised patients. Mortality was low, and no differences between groups were observed in all comparisons. Quinolone monotherapy resulted in significantly less clinical failures [RR = 0.72 (0.57-0.91)], treatment discontinuations [RR = 0.65 (0.54-0.78)] and diarrhoea [RR = 0.13 (0.05-0.34)] compared with β-lactam/macrolide combinations (nine trials). Addition of a β-lactam to quinolones did not improve outcomes (three trials). In all comparisons, treatment discontinuation and diarrhoea were more frequent in patients receiving combination therapy with a β-lactam. Overall, there is no evidence for a benefit of β-lactam/macrolide or β-lactam/quinolone combination therapies over monotherapy with a respiratory fluoroquinolone. The ecological implications of selecting fluoroquinolone or β-lactam monotherapy as the preferred regimen for hospitalised CAP among adults should be further investigated.