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  I2 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 β-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.

Funding: German Center for Infection Research.