Respiratory Fluoroquinolone Monotherapy Vs. Β-Lactam Plus Macrolide Combination Therapy for Hospitalized Adults with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with mild to moderate community-acquired pneumonia (CAP). Efficacy of these regimens has not been adequately evaluated. METHODS We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing respiratory fluoroquinolone monotherapy and β-lactam plus macrolide combination therapy in hospitalised adults with CAP. A meta-analysis was performed using a random effects model. The primary outcome was clinical cure rate. Quality of evidence (QoE) was evaluated using GRADE methodology. RESULTS A total of 4,140 participants in 18 RCTs were included. Levofloxacin (11 trials) or moxifloxacin (six trials) were the predominant respiratory fluoroquinolones trialled, while the β-lactam plus macrolide group used ceftriaxone plus a macrolide (ten trials), cefuroxime plus azithromycin (five trials), and amoxicillin/clavulanate plus a macrolide (two trials). Patients receiving respiratory fluoroquinolone monotherapy had a significantly higher clinical cure rate (86.5% vs. 81.5%; odds ratio [OR] 1.47 [95% CI: 1.17-1.83]; P = 0.0008; I2 = 0%; 17 RCTs; moderate QoE) and microbiological eradication rate (86.0% vs. 81.0%; OR 1.51 [95% CI: 1.00-2.26]; P = 0.05; I2 = 0%; 15 RCTs; moderate QoE). All-cause mortality (7.2% vs. 7.7%; OR 0.88 [95% CI: 0.67-1.17]; I2 = 0%; low QoE) and adverse events (24.8% vs. 28.1%; OR 0.87 [95% CI: 0.69-1.09]; I2 = 0%; low QoE] were similar between groups. CONCLUSION Respiratory fluoroquinolone monotherapy demonstrated an advantage in clinical cure and microbiologic eradication; however, it did not impact mortality.