Impact of an electronic sepsis initiative on antibiotic use and health care facility–onset Clostridium difficile infection rates


      • Electronic sepsis screening and treatment protocols may have unintended effects.
      • Unintended effects include increased antibiotic use and health care facility–onset Clostridium difficile infection (CDI).
      • We assessed these effects on 4 medicine wards in a large, tertiary, urban hospital.
      • Sepsis screening implementation coincided with increased antibiotic use and CDI.
      • Further study of unintended effects of sepsis screening is warranted.


      Although integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility–onset (HCFO) Clostridium difficile infection (CDI) rates.


      We used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative.


      Antibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P < .05). Remarkably, the main drivers of overall antibiotic use were not those included in the sepsis order set.


      The implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted.

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        • Kaukonen K.M.
        • Bailey M.
        • Suzuki S.
        • Pilcher D.
        • Bellomo R.
        Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.
        JAMA. 2014; 311: 1308-1316
        • Gaieski D.F.
        • Edwards J.M.
        • Kallan M.J.
        • Carr B.G.
        Benchmarking the incidence and mortality of severe sepsis in the United States.
        Crit Care Med. 2013; 41: 1167-1174
        • Stevenson E.K.
        • Rubenstein A.R.
        • Radin G.T.
        • Wiener R.S.
        • Walkey A.J.
        Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis.
        Crit Care Med. 2014; 42: 625-631
        • Dellinger R.P.
        • Levy M.M.
        • Rhodes A.
        • Annane D.
        • Gerlach H.
        • Opal S.M.
        • et al.
        Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.
        Crit Care Med. 2013; 41: 580-637
        • Kumar A.
        • Roberts D.
        • Wood K.E.
        • Light B.
        • Parrillo J.E.
        • Sharma S.
        • et al.
        Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.
        Crit Care Med. 2006; 34: 1589-1596
        • Levy M.M.
        • Dellinger R.P.
        • Townsend S.R.
        • Linde-Zwirble W.T.
        • Marshall J.C.
        • Bion J.
        • et al.
        The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.
        Intensive Care Med. 2010; 36: 222-231
        • Levy M.M.
        • Rhodes A.
        • Phillips G.S.
        • Townsend S.R.
        • Schorr C.A.
        • Beale R.
        • et al.
        Surviving sepsis campaign: association between performance metrics and outcomes in a 7.5-year study.
        Crit Care Med. 2015; 43: 3-12
        • Miller 3rd, R.R.
        • Dong L.
        • Nelson N.C.
        • Brown S.M.
        • Kuttler K.G.
        • Probst D.R.
        • et al.
        Multicenter implementation of a severe sepsis and septic shock treatment bundle.
        Am J Respir Crit Care Med. 2013; 188: 77-82
        • Damiani E.
        • Donati A.
        • Serafini G.
        • Rinaldi L.
        • Adrario E.
        • Pelaia P.
        • et al.
        Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies.
        PLoS ONE. 2015; 10 (e0125827)
        • Rhee C.
        • Gohil S.
        • Klompas M.
        Regulatory mandates for sepsis care–reasons for caution.
        N Engl J Med. 2014; 370: 1673-1676
        • Zilberberg M.D.
        • Shorr A.F.
        • Kollef M.H.
        Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005.
        Emerg Infect Dis. 2008; 14: 929-931
        • Magill S.S.
        • Edwards J.R.
        • Bamberg W.
        • Beldavs Z.G.
        • Dumyati G.
        • Kainer M.A.
        • et al.
        Multistate point-prevalence survey of health care-associated infections.
        N Engl J Med. 2014; 370: 1198-1208
        • McDonald L.C.
        • Coignard B.
        • Dubberke E.
        • Song X.
        • Horan T.
        • Kutty P.K.
        • et al.
        Recommendations for surveillance of Clostridium difficile-associated disease.
        Infect Control Hosp Epidemiol. 2007; 28: 140-145
        • Wagner A.K.
        • Soumerai S.B.
        • Zhang F.
        • Ross-Degnan D.
        Segmented regression analysis of interrupted time series studies in medication use research.
        J Clin Pharm Ther. 2002; 27: 299-309
        • Umscheid C.A.
        • Betesh J.
        • VanZandbergen C.
        • Hanish A.
        • Tait G.
        • Mikkelsen M.E.
        • et al.
        Development, implementation, and impact of an automated early warning and response system for sepsis.
        J Hosp Med. 2015; 10: 26-31
        • Rhodes A.
        • Phillips G.
        • Beale R.
        • Cecconi M.
        • Chiche J.D.
        • De Backer D.
        • et al.
        The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study).
        Intensive Care Med. 2015; 41: 1620-1628
        • Marik P.E.
        Iatrogenic salt water drowning and the hazards of a high central venous pressure.
        Ann Intensive Care. 2014; 4: 21
        • Wiedemann H.P.
        • Wheeler A.P.
        • Bernard G.R.
        • Thompson B.T.
        • Hayden D.
        • deBoisblanc B.
        • et al.
        Comparison of two fluid-management strategies in acute lung injury.
        N Engl J Med. 2006; 354: 2564-2575
        • Maitland K.
        • Kiguli S.
        • Opoka R.O.
        • Engoru C.
        • Olupot-Olupot P.
        • Akech S.O.
        • et al.
        Mortality after fluid bolus in African children with severe infection.
        N Engl J Med. 2011; 364: 2483-2495
        • Murphy C.V.
        • Schramm G.E.
        • Doherty J.A.
        • Reichley R.M.
        • Gajic O.
        • Afessa B.
        • et al.
        The importance of fluid management in acute lung injury secondary to septic shock.
        Chest. 2009; 136: 102-109
        • Micek S.T.
        • McEvoy C.
        • McKenzie M.
        • Hampton N.
        • Doherty J.A.
        • Kollef M.H.
        Fluid balance and cardiac function in septic shock as predictors of hospital mortality.
        Crit Care. 2013; 17: R246
        • Andrews B.
        • Muchemwa L.
        • Kelly P.
        • Lakhi S.
        • Heimburger D.C.
        • Bernard G.R.
        Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia.
        Crit Care Med. 2014; 42: 2315-2324
        • Semler M.W.
        • Weavind L.
        • Hooper M.H.
        • Rice T.W.
        • Gowda S.S.
        • Nadas A.
        • et al.
        An electronic tool for the evaluation and treatment of sepsis in the ICU: a randomized controlled trial.
        Crit Care Med. 2015; 43: 1595-1602
        • Durieux P.
        Electronic medical alerts–so simple, so complex.
        N Engl J Med. 2005; 352: 1034-1036
        • Handler J.A.
        • Feied C.F.
        • Coonan K.
        • Vozenilek J.
        • Gillam M.
        • Peacock Jr., P.R.
        • et al.
        Computerized physician order entry and online decision support.
        Acad Emerg Med. 2004; 11: 1135-1141
        • Kanwar M.
        • Brar N.
        • Khatib R.
        • Fakih M.G.
        Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics - side effects of the 4-h antibiotic administration rule.
        Chest. 2007; 131: 1865-1869
        • Quattromani E.
        • Powell E.S.
        • Khare R.K.
        • Cheema N.
        • Sauser K.
        • Periyanayagam U.
        • et al.
        Hospital-reported data on the pneumonia quality measure “Time to First Antibiotic Dose” are not associated with inpatient mortality: results of a nationwide cross-sectional analysis.
        Acad Emerg Med. 2011; 18: 496-503
        • Makam A.N.
        • Nguyen O.K.
        • Auerbach A.D.
        Diagnostic accuracy and effectiveness of automated electronic sepsis alert systems: a systematic review.
        J Hosp Med. 2015; 10: 396-402
        • van Zanten A.R.
        The golden hour of antibiotic administration in severe sepsis: avoid a false start striving for gold.
        Crit Care Med. 2014; 42: 1931-1932
        • Yealy D.M.
        • Kellum J.A.
        • Huang D.T.
        • Barnato A.E.
        • Weissfeld L.A.
        • et al.
        • ProCESS Investigators
        A randomized trial of protocol-based care for early septic shock.
        N Engl J Med. 2014; 370: 1683-1693
        • van Paridon B.M.
        • Sheppard C.
        • Garcia Guerra G.
        • Joffe A.R.
        • Alberta Sepsis Network
        Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care.
        Crit Care. 2015; 19: 293
        • Sterling S.A.
        • Miller W.R.
        • Pryor J.
        • Puskarich M.A.
        • Jones A.E.
        The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis.
        Crit Care Med. 2015;
        • Rhee C.
        • Murphy M.V.
        • Li L.
        • Platt R.
        • Klompas M.
        • Centers for Disease Control and Prevention Epicenters Program
        Comparison of trends in sepsis incidence and coding using administrative claims versus objective clinical data.
        Clin Infect Dis. 2015; 60: 88-95
        • Gohil S.K.
        • Cao C.
        • Phelan M.
        • Tjoa T.
        • Rhee C.
        • Platt R.
        • et al.
        Impact of policies on the rise in sepsis incidence, 2000-2010.
        Clin Infect Dis. 2016; 62: 695-703
        • McRee L.
        • Thanavaro J.L.
        • Moore K.
        • Goldsmith M.
        • Pasvogel A.
        The impact of an electronic medical record surveillance program on outcomes for patients with sepsis.
        Heart Lung. 2014; 43: 546-549
        • Westphal G.A.
        • Lino A.S.
        Systematic screening is essential for early diagnosis of severe sepsis and septic shock.
        Rev Bras Ter Intensiva. 2015; 27: 96-101
        • Aldeyab M.A.
        • Kearney M.P.
        • Scott M.G.
        • Aldiab M.A.
        • Alahmadi Y.M.
        • Darwish Elhajji F.W.
        • 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; 67: 2988-2996
        • Valiquette L.
        • Cossette B.
        • Garant M.P.
        • Diab H.
        • Pépin 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; 45: S112-21
        • Carling P.
        • Fung T.
        • Killion A.
        • Terrin N.
        • Barza M.
        Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years.
        Infect Control Hosp Epidemiol. 2003; 24: 699-706
        • Leffler D.A.
        • Lamont J.T.
        Clostridium difficile infection.
        N Engl J Med. 2015; 372: 1539-1548
        • Brown K.
        • Valenta K.
        • Fisman D.
        • Simor A.
        • Daneman N.
        Hospital ward antibiotic prescribing and the risks of Clostridium difficile infection.
        JAMA Intern Med. 2015; 175: 626-633
        • Slimings C.
        • Riley T.V.
        Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis.
        J Antimicrob Chemother. 2014; 69: 881-891
        • Schondelmeyer A.C.
        • Brady P.W.
        • Landrigan C.P.
        Alarm fatigue: clearing the air.
        J Hosp Med. 2016; 11: 153-154
        • Vogel L.
        EMR alert cuts sepsis deaths.
        CMAJ. 2014; 186: E80
        • Mathews K.
        • Budde J.
        • Glasser A.
        • Lorin S.
        • Powell S.
        Impact of an in-patient electronic clinical decision support tool on sepsis-related mortality.
        Crit Care Med. 2014; 42
        • van Zanten A.R.
        • Brinkman S.
        • Arbous M.S.
        • Abu-Hanna A.
        • Levy M.M.
        • de Keizer N.F.
        • et al.
        Guideline bundles adherence and mortality in severe sepsis and septic shock.
        Crit Care Med. 2014; 42: 1890-1898