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

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: Randomized controlled trials ( RCTs) and observational studies published from 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: In all, 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 ( one 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 ( three RCTs; n = 610; ratio of means 0.62; 95% CI 0.54-0.70) and probably reduce community antibiotic use in children aged 3-15 years ( one RCT; n = 10 985 person-seasons; risk ratio 0.69, 95% CI 0.58 -0.83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years ( two 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 ( one 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. (c) 2019 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license