Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis

Background Antibiotic stewardship programmes have been shown to reduce antibiotic use and hospital costs. We aimed to evaluate evidence of the effect of antibiotic stewardship on the incidence of infections and colonisation with antibiotic-resistant bacteria. Methods For this systematic review and meta-analysis, we searched PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Web of Science for studies published from Jan 1, 1960, to May 31, 2016, that analysed the effect of antibiotic stewardship programmes on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infections in hospital inpatients. Two authors independently assessed the eligibility of trials and extracted data. Studies involving long-term care facilities were excluded. The main outcomes were incidence ratios (IRs) of target infections and colonisation per 1000 patient-days before and after implementation of antibiotic stewardship. Meta-analyses were done with random-effect models and heterogeneity was calculated with the I-2 method. Findings We included 32 studies in the meta-analysis, comprising 9 056 241 patient-days and 159 estimates of IRs. Antibiotic stewardship programmes reduced the incidence of infections and colonisation with multidrug-resistant Gram-negative bacteria (51% reduction; IR 0.49, 95% CI 0.35-0.68; p<0.0001), extended-spectrum beta-lactamase-producing Gram-negative bacteria (48%; 0.52, 0.27-0.98; p=0.0428), and meticillin-resistant Staphylococcus aureus (37%; 0.63, 0.45-0.88; p=0.0065), as well as the incidence of C difficile infections (32%; 0.68, 0.53-0.88; p=0.0029). Antibiotic stewardship programmes were more effective when implemented with infection control measures (IR 0.69, 0.54-0.88; p=0.0030), especially hand-hygiene interventions (0.34, 0.21-0.54; p<0.0001), than when implemented alone. Antibiotic stewardship did not affect the IRs of vancomycin-resistant enterococci and quinolone-resistant and aminoglycoside-resistant Gram-negative bacteria. Significant heterogeneity between studies was detected, which was partly explained by the type of interventions and co-resistance patterns of the target bacteria. Interpretation Antibiotic stewardship programmes significantly reduce the incidence of infections and colonisation with antibiotic-resistant bacteria and C difficile infections in hospital inpatients. These results provide stakeholders and policy makers with evidence for implementation of antibiotic stewardship interventions to reduce the burden of infections from antibiotic-resistant bacteria.