Efficacy of Doxycycline for Mild-to-Moderate Community-Acquired Pneumonia in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively. RESULTS: We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381/437] vs 82.6% [328/397]; OR 1.29 [95% confidence interval {CI}: .73-2.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196/225] vs 77.8% [165/212]; OR 1.92 [95% CI: 1.15-3.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups. CONCLUSIONS: The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials.

Respiratory fluoroquinolone monotherapy vs. ß-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 ß-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: A systematic review of randomized controlled trials (RCTs) comparing respiratory fluoroquinolone monotherapy and ß-lactam plus macrolide combination therapy in hospitalised adults with CAP was performed. 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 4140 participants in 18 RCTs were included. Levofloxacin (11 trials) or moxifloxacin (6 trials) were the predominant respiratory fluoroquinolones evaluated, and the ß-lactam plus macrolide group used ceftriaxone plus a macrolide (10 trials), cefuroxime plus azithromycin (5 trials), and amoxicillin/clavulanate plus a macrolide (2 trials). Patients receiving respiratory fluoroquinolone monotherapy had a significantly higher clinical cure rate (86.5% vs. 81.5%; odds ratio [OR] 1.47; 95% confidence interval [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) than patients receiving ß-lactam plus macrolide combination therapy. 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 in the two groups. CONCLUSION: Respiratory fluoroquinolone monotherapy demonstrated an advantage in clinical cure and microbiological eradication; however, it did not impact mortality.