Aim To synthesize evidence about the influence of individual antimicrobial stewardship programs (ASP) related to the prevention of Clostridium difficile (C. difficile) infection on primary and secondary outcomes. Methods Relevant databases such as Medline, PUBMED, COCHRANE library and EBSCO were searched from 1 April to 27 April 2017. Additional studies were reached by the manual search for original articles in relevant journals. We included all randomized controlled, quasi-experimental and observational studies, published in the English language from 2007 onward, that evaluated effectiveness of ASP in preventing and controlling C. difficile associated disease (CDAD) among adult inpatients. Results Implementation of ASP interventions was associated with CDAD incidence reduction in 62.5% studies, but no significant differences were reported for the duration of hospitalization, readmission and mortality rate. Improvements in prescribing patterns (decreased antimicrobial use or increased rational use) and microbial outcomes (decreased rates of selected antimicrobial-resistant bacteria) were reported. Evidence on the effects of ASP is mainly limited to the results of studies low in methodological quality with great heterogeneity of outcomes, interventions, and units in which CDAD incidence data were reported. Conclusion Despite the low strength of evidence of reviewed studies, consistency of findings suggest the positive impact of antimicrobial stewardship programs on the prevention and control of nosocomial CDAD. The significance of this problem imposes randomized control trial use as the best instrument to provide highquality evidence. Further studies need to systematically analyse changes in all antibiotic use and its outcomes.
Suljagic V, Djordjevic D, Lazic S, Mijovic B. Epidemiological characteristics of nosocomial diarrhea caused by Clostridium difficile in a tertiary level hospital in Serbia. Srp Arh Celok Lek. 2013. p. 482–9.
2.
Mcdonald L, Killgore G, Thompson A, Owens R, Kazakova S, Sambol S. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005. p. 2433–41.
3.
O’brien J, Lahue B, Caro J, Davidson D. The emerging infectious challenge of clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infect Control Hosp Epidemiol. 2007. p. 1219–27.
4.
Bojanjić J, Marković-Denić L, Mijović B. Epidemiological characteristics of hospital-acquired Clostridium difficile-associated diarrhea. Medicinski časopis. 2013. p. 85–90.
5.
Van Dorp S, Kinross P, Gastmeier P, Behnke M, Kola A, Delmee M. Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study. Euro Surv. 2013.
6.
Lessa F, Mu Y, Bamberg W, Beldavs Z, Dumyati G, Dunn J. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015. p. 825–34.
7.
Roncarati G, Dallolio L, Leoni E, Panico M, Zanni A, Farruggia P. Surveillance of Clostridium difficile infections: results from a six-year retrospective study in nine hospitals of a North Italian Local Health Authority. Int J Environ Res Public Health. 2017.
8.
Feazel L, Malhotra A, Perencevich E, Kaboli P, Diekema D, Schweizer M. Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis. J Antimicrob Chemother. 2014. p. 1748–54.
9.
Nowak M, Nelson R, Breidenbach J, Thompson P, Carson P. Clinical and economic outcomes of a prospective antimicrobial stewardship program. Am J Health Syst Pharm. 2012. p. 1500–8.
10.
Davey P, Brown E, Charani E, Fenelon L, Gould I, Holmes A. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database System Rev. 2013.
11.
Wagner B, Filice G, Drekonja D, Greer N, Macdonald R, Rutks I. Antimicrobial stewardship programs in inpatient hospital settings: a systematic review. Infect Control Hosp Epidemiol. 2014. p. 1209–28.
12.
Moher D, Liberati A, Tetzlaff J, Altman D. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010. p. 336–41.
13.
Macdougall C, Polk R. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev. 2005. p. 638–56.
14.
Hammick M, Dornan T, Steinert Y. Conducting a best evidence systematic review. Part 1: from idea to data coding. BEME Guide No. 13. Med Teach. 2010. p. 3–15.
15.
Mays N, Pope C, Popay J. Systematically reviewing qualitative and quantitative evidence to inform management and policy-making in the health field. J Health Serv Res Policy. 2005. p. 6–20.
16.
Davey P, Marwick C, Scott C, Charani E, Mc-Neil K, Brown E. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database System Rev. 2017.
17.
Yu K, Rho J, Morcos M, Nomura J, Kaplan D, Sakamoto K. Evaluation of dedicated infectious diseases pharmacists on antimicrobial stewardship teams. Am J Health Syst Pharm. 2014.
18.
Yam P, Fales D, Jemison J, Gillum M, Bernstein M. Implementation of an antimicrobial stewardship program in a rural hospital. Am J Health Syst Pharm. 2012. p. 1142.
19.
Storey D, Pate P, Nguyen A, Chang F. Implementation of an antimicrobial stewardship program on the medical-surgical service of a 100-bed community hospital. Antimicrob Resist Infect Control. 2012. p. 32.
20.
Ostrowsky B, Ruiz R, Brown S, Chung P, Koppelman E, Van Deusen Lukas C. Lessons learned from implementing Clostridium difficile-focused antibiotic stewardship interventions. Infect Control Hosp Epidemiol. 2014. p. 86–95.
21.
Nuila F, Cadle R, Logan N, Musher D. Antibiotic stewardship and Clostridium difficile-associated disease. Infect Control HospEpidemiol. 2008. p. 1096–7.
22.
Jenkins T, Knepper B, Shihadeh K, Haas M, Sabel A, Steele A. Long-term outcomes of an antimicrobial stewardship program implemented in a hospital with low baseline antibiotic use. Infect Control Hosp Epidemiol. 2015. p. 664–72.
23.
Cook P, Rizzo S, Gooch M, Jordan M, Fang X, Hudson S. Sustained reduction in antimicrobial use and decrease in methicillin-resistant Staphylococcus aureus and Clostridium difficile infections following implementation of an electronic medical record at a tertiary-care teaching hospital. J Antimicrob Chemother. 2011. p. 205–9.
24.
Beaulac K, Corcione S, Epstein L, Davidson L, Doron S. Antimicrobial stewardship in a long-term acute care hospital using offsite electronic medical record audit. Infect Control Hosp Epidemiol. 2016. p. 433–9.
25.
Valiquette L, Cossette B, Garant M, Diab H, Pepin J. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis. 2007. p. 112–21.
26.
Palmay L, Elligsen M, Walker S, Pinto R, Walker S, Einarson T. Hospital-wide rollout of antimicrobial stewardship: A stepped-wedge randomized trial. Clin Infect Dis. 2014. p. 867–74.
27.
Leung V, Gill S, Sauve J, Walker K, Stumpo C, Powis J. Growing a “positive culture” of antimicrobial stewardship in a community hospital. Can Journal Hosp Pharm. 2011. p. 314–20.
28.
Elligsen M, Walker S, Pinto R, Simor A, Mubareka S, Rachlis A, et al. Audit and feedback to reduce broad-spectrum antibiotic use among intensive care unit patients: a controlled interrupted time series analysis. Infect Control Hosp Epidemiol. 2012. p. 354–61.
29.
Aldeyab M, Kearney M, Scott M, Aldiab M, Alahmadi Y, Elhajji D, et al. An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings. J Antimicrob Chemother. 2012. p. 2988–96.
30.
Dancer S, Kirkpatrick P, Corcoran D, Christison F, Farmer D, Robertson C. Approaching zero: temporal effects of a restrictive antibiotic policy on hospitalacquired Clostridium difficile, extended-spectrum beta-lactamase-producing coliforms and meticillinresistant Staphylococcus aureus. Int J Antimicrob Agents. 2013. p. 137–42.
31.
Price J, Cheek E, Lippett S, Cubbon M, Gerding D, Sambol S. Impact of an intervention to control Clostridium difficile infection on hospital-and community-onset disease; an interrupted time series analysis. Clin Microbiol Infect. 2010. p. 1297–302.
32.
Sarma J, Marshall B, Cleeve V, Tate D, Oswald T, Woolfrey S. Effects of fluoroquinolone restriction (from 2007 to 2012) on Clostridium difficile infections: interrupted time-series analysis. J Hosp Infect. 2015. p. 74–80.
33.
Talpaert M, Rao G, Cooper B, Wade P. Impact of guidelines and enhanced antibiotic stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection. J Antimicrob Chemother. 2011. p. 2168–74.
34.
Schon T, Sandelin L, Bonnedahl J, Hedeback F, Wistedt A, Brudin L. A comparative study of three methods to evaluate an intervention to improve empirical antibiotic therapy for acute bacterial infections in hospitalized patients. Scand J Infect Dis. 2011. p. 251–7.
35.
Borde J, Litterst S, Ruhnke M, Feik R, Hubner J, Dewith K. Implementing an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a 200-bed community hospital in Germany. Infection. 2015. p. 45–50.
36.
Wenisch J, Equiluz-Bruck S, Fudel M, Reiter I, Schmid A, Singer E. Decreasing Clostridium difficile infections by an antimicrobial stewardship program that reduces moxifloxacin use. Antimicrob Agents Chemother. 2014. p. 5079–83.
37.
Bouza E, Torres M, Radice C, Cercenado E, De Diego R, Sanchez-Carrillo C, et al. Direct E-test (AB Biodisk) of respiratory samples improves antimicrobial use in ventilator-associated pneumonia. Clin Infect Dis. 2007. p. 382–7.
38.
Hernandez-Garcia CRN, Salinas-Caballero R, Perez-Rodriguez A, Garza-Gonzalez E, Camacho-Ortiz E, A. The effect of pharmacy restriction of clindamycin on Clostridium difficile infection rates in an orthopedics ward. Am J Infect Control. 2014. p. 71–3.
39.
Chan Y, Lin T, Huang C, Deng S, Wu T, Leu H, et al. Implementation and outcomes of a hospital-wide computerised antimicrobial stewardship programme in a large medical centre in Taiwan. Int J Antimicrob Agents. 2011. p. 486–92.
40.
Shardell M, Harris A, El-Kamary S, Furuno J, Miller R, Perencevich E. Statistical analysis and application of quasi experiments to antimicrobial resistance intervention studies. Clin Infect Dis. 2007. p. 901–7.
41.
Kaki R, Elligsen M, Walker S, Simor A, Palmay L, Daneman N. Impact of antimicrobial stewardship in critical care: a systematic review. J Antimicrob Chemother. 2011. p. 1223–30.
42.
Tonkin-Crine S, Yardley L, Little P. Antibiotic prescribing for acute respiratory tract infections in primary care: a systematic review and meta-ethnography. J Antimicrob Chemother. 2011. p. 2215–23.
43.
Filice G, Drekonja D, Greer N, Butler M, Wagner B, Macdonald R, et al. Antimicrobial stewardship programs in inpatient settings: a systematic review. Department of Veterans Affairs (US; 2013.
44.
File T, Srinivasan A, Bartlett J. Antimicrobial stewardship: importance for patient and public health. Clin Infect Dis. 2014. p. 93–6.
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