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

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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.Methods: 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 0·68 [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. Funding: Wellcome TrustPROSPERO registration: CRD42018103881