Mortality and clinical cure rates for pneumonia: a systematic review, meta-analysis, and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments.

BACKGROUND

Bactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia.

OBJECTIVES

We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates.

DATA SOURCES: PubMed, Cochrane Library, Embase, and MedRxiv STUDY ELIGIBILITY CRITERIA: Randomized control trials.

PARTICIAPANTS: Adult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital.

INTERVENTIONS: Bacteriostatic versus bactericidal antibiotics.

ASSESSMENT OF RISK OF BIAS: The Cochrane Collaboration assessing risk of bias 2 tool.

METHODS OF DATA SYNTHESIS: Data on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel-Haenszel method was used for integrating RRs for generalizability of findings. The I2 method was used to assess the magnitude of variation secondary to heterogeneity.

RESULTS

Forty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99-1.05; I2: 37%; TSA-adjusted CI, 0.99-1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81-1.42; I2: 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97-1.03; I2: 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83-1.11; I2: 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50-2.63; I2: 0%) were similar between bactericidal and bacteriostatic antibiotic treatments.

CONCLUSIONS

Bactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia.