Impact of vaccination on antibiotic usage: a systematic review and meta-analysis

Abstract Background Vaccines may reduce antibiotic use and the development of resistance. Objectives To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use. Data sources Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry. Study eligibility criteria Randomised-controlled trials (RCTs) and observational studies published January 1998 to March 2018. Participants Any population. Interventions Vaccines versus placebo, no vaccine or another vaccine. Methods Titles, abstracts, and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE. Results 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (1 RCT; n = 4253; rate reduction 28·1% [95% CI 16·0, 38·4]); moderate certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (3 RCTs; n = 610; ratio of means 0·62 [95% CI 0·54, 0·70) and probably reduces community antibiotic use in children aged 3-15 years (1 RCT; n = 10,985 person-seasons; risk ratio 0·69 [95% CI 0·58, 0·83]); moderate certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (2 RCTs; n = 47,945; rate ratio 0·93 [95% CI 0·87, 0·99]) and reduces illness episodes requiring antibiotics in children aged 12-35 months (1 RCT; n = 264; rate ratio 0·85 [95% CI 0·75, 0·97]). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. Conclusions The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. PROSPERO registration CRD42018103881.