Clostridium difficile infection in hospitalized patients with COPD in Spain (2001–2015)


      • Incidence of CDI is increasing overtime (2001–15) in patients with and without COPD.
      • Incidence of CDI was twice higher in COPD patients than in matched non-COPD controls.
      • IHM decreased significantly over time in patients without COPD.
      • For COPD patients IHM remained stable over time.
      • IHM is higher among COPD patients with a secondary diagnosis of CDI.



      The objectives of this study were to examine incidence and in-hospital outcomes of Clostridium difficile infection (CDI) among patients with COPD, to compare clinical variables among COPD patients with matched non-COPD patients hospitalized with CDI, and to identify factors associated with in-hospital mortality (IHM) among COPD patients.


      We performed a retrospective study using the Spanish National Hospital Discharge Database from 2001 to 2015. We included patients aged 40 years or over with a primary or secondary diagnosis of CDI. For each COPD patient, we selected a sex, age, readmission status and year-matched non-COPD patient.


      We identified 44,695 patients with CDI (19.36% with COPD). Incidence of CDI has increased significantly from 2001 to 2015 besides COPD status. Incidence was higher in COPD patients than in patients without this disease (IRR 2.24; 95%CI 2.18–2.29). IHM decreased significantly over time in patients without COPD (from 13.98% in 2001–03 to 10.99% in 2013–15), but there were no changes in those with COPD (from 12.93% in 2001–03 to 13.37% in 2013–15). In COPD patients, higher mortality rates were associated with older age, comorbidities, severe CDI, longer length of hospital stay and readmission. Primary diagnosis of CDI was associated with lower IHM in this group of patients (OR 0.66; 95%CI 0.56–0.77) in comparison with secondary diagnosis.


      Incidence of CDI was twice higher in COPD patients than in matched non-COPD controls and is increasing overtime in both groups. Our results suggest that the management of CDI has improved in Spain during the study period.



      CCI (Charlson comorbidity index), CDI (Clostridium difficile Infection), ICD-9-CM (International Classification Disease-9-Clinical Modification), GRD (Diagnosis-Related Groups), IHM (in-hospital mortality), IRR (Incidence Rate Ratio), LOHS (length of hospital stay), OR (Odds Ratio), SNHDD (Spanish National Hospital Discharge Database)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Campbell K.A.
        • Phillips M.S.
        • Stachel A.
        • Bosco 3rd, J.A.
        • Mehta S.A.
        Incidence and risk factors for hospital-acquired Clostridium difficile infection among inpatients in an orthopaedic tertiary care hospital.
        J Hosp Infect. 2013; 83: 146-149
        • Barbut F.
        • Petit J.C.
        Epidemiology of Clostridium difficile-associated infections.
        Clin Microbiol Infect. 2001; 7: 405-410
        • Pechal A.
        • Lin K.
        • Allen S.
        • Reveles K.
        National age group trends in Clostridium difficile infection incidence and health outcomes in United States community hospitals.
        BMC Infect Dis. 2016; 16: 682
        • Lessa F.C.
        • Mu Y.
        • Bamberg W.M.
        • Beldavs Z.G.
        • Dumyati G.K.
        • Dunn J.R.
        • et al.
        Burden of Clostridium difficile infection in the United States.
        N Engl J Med. 2015; 372: 825-834
        • Forster A.J.
        • Taljaard M.
        • Oake N.
        • Wilson K.
        • Roth V.
        • van Walraven C.
        The effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital.
        CMAJ. 2012; 184: 37-42
        • Nanwa N.
        • Kendzerska T.
        • Krahn M.
        • Kwong J.C.
        • Daneman N.
        • Witteman W.
        The economic impact of Clostridium difficile infection: a systematic review.
        Am J Gastroenterol. 2015; 110: 511-519
        • Chatterjee K.
        • Goyal A.
        • Chada A.
        • Kakkera K.S.
        • Corwin H.L.
        National Trends (2007–2013) of Clostridium difficile infection in patients with septic shock: impact on outcome.
        J Hosp Med. 2017; 12: 717-722
        • Magee G.
        • Strauss M.E.
        • Thomas S.M.
        • Brown H.
        • Baumer D.
        • Broderick K.C.
        Impact of Clostridium difficile-associated diarrhea on acute care length of stay, hospital costs, and readmission: a multicenter retrospective study of inpatients, 2009-2011.
        Am J Infect Control. 2015; 43: 1148-1153
        • Jawa R.S.
        • Mercer D.W.
        Clostridium difficile-associated infection: a disease of varying severity.
        Am J Surg. 2012; 204: 836-842
        • Monot M.
        • Eckert C.
        • Lemire A.
        • Hamiot A.
        • Dubois T.
        • Tessier C.
        • et al.
        Clostridium difficile: new insights into the evolution of the pathogenicity locus.
        Sci Rep. 2015; 5: 15023
        • Hensgens M.P.
        • Goorhuis A.
        • Dekkers O.M.
        • van Benthem B.H.
        • Kuijper E.J.
        All-cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a multicenter cohort study.
        Clin Infect Dis. 2013; 56: 1108-1116
        • Kyne L.
        • Hamel M.B.
        • Polavaram R.
        • Kelly C.P.
        Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile.
        Clin Infect Dis. 2002; 34: 346-353
        • Predrag S.
        Analysis of risk factors and clinical manifestations associated with Clostridium difficile disease in Serbian hospitalized patients.
        Braz J Microbiol. 2016; 47: 902-910
        • Leibovitz A.
        • Yarovoy A.
        • Sharshar N.
        • Buckman Z.
        • Mizrahi E.H.
        • Lubart E.
        Clostridium difficile-associated disease: a primary clinical evaluation of elderly patients in a geriatric hospital.
        Am J Infect Control. 2016; 44: 1158-1160
        • Ziakas P.D.
        • Joyce N.
        • Zacharioudakis I.M.
        • Zervou F.N.
        • Besdine R.W.
        • Mor V.
        • et al.
        Prevalence and impact of Clostridium difficile infection in elderly residents of long-term care facilities, 2011: A nationwide study.
        Medicine (Baltimore). 2016; 95: e4187
        • Furuya-Kanamori L.
        • Clements A.C.A.
        • Foster N.F.
        • Huber C.A.
        • Hong S.
        • Harris-Brown T.
        • et al.
        Asymptomatic Clostridium difficile colonization in two Australian tertiary hospitals, 2012–2014: prospective, repeated cross-sectional study.
        Clin Microbiol Infect. 2017; 23: 48.e1-48.e7
        • Miravitlles M.
        • García-Polo C.
        • Domenech A.
        • Villegas G.
        • Conget F.
        • de la Roza C.
        Clinical outcomes and cost analysis of exacerbations in chronic obstructive pulmonary disease.
        Lung. 2013; 191: 523-530
        • Eckmann C.
        • Wasserman M.
        • Latif F.
        • Roberts G.
        • Beriot-Mathiot A.
        Increased hospital length of stay attributable to Clostridium difficile infection in patients with four co-morbidities: an analysis of hospital episode statistics in four European countries.
        Eur J Health Econ. 2013; 14: 835-846
        • Instituto Nacional de Gestión Sanitaria, Ministerio de Sanidad
        Servicios Sociales e Igualdad. Conjunto Mínimo Básico de Datos, Hospitales del INSALUD.
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Quan H.
        • Sundararajan V.
        • Halfon P.
        • et al.
        Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.
        Med Care. 2005; 43: 1130-1139
        • Gomez-Simmonds A.
        • Kubin C.J.
        • Furuya E.Y.
        Comparison of 3 severity criteria for Clostridium difficile infection.
        Infect Control Hosp Epidemiol. 2014; 35: 196-199
        • Instituto Nacional de la Salud
        CMBD Insalud. Análisis de los GRDs. Año 2000.
        • Ministerio de Sanidad
        Servicios Sociales e Igualdad. [Encuesta Nacional de Salud de España].
        • Miravitlles M.
        • Soriano J.B.
        • García-Río F.
        • Muñoz L.
        • Duran-Tauleria E.
        • Sanchez G.
        • et al.
        Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities.
        Thorax. 2009; 64: 863-868
        • Instituto Nacional de Estadística
        Population estimates 2010.
        Date accessed: December 1, 2015
        • Goyal A.
        • Chatterjee K.
        • Punjabi C.
        • Rangaswami J.
        Thirty-day readmissions after hospitalization for Clostridium difficile enteritis measures and predictors: a Nationwide analysis.
        Infect Control Hosp Epidemiol. 2017; 38: 876-878
        • Shrestha M.P.
        • Bime C.
        • Taleban S.
        Decreasing Clostridium difficile-associated fatality rates among hospitalized patients in the United States: 2004-2014.
        Am J Med. 2018; 131: 90-96
        • Deshpande A.
        • Pant C.
        • Olyaee M.
        • Donskey C.J.
        Hospital readmissions related to Clostridium difficile infection in the United States.
        Am J Infect Control. 2018; 46: 346-347
        • Choi H.Y.
        • Park S.Y.
        • Kim Y.A.
        • Yoon T.Y.
        • Choi J.M.
        • Choe B.K.
        • et al.
        The epidemiology and economic burden of Clostridium difficile infection in Korea.
        Biomed Res Int. 2015; 2015: 510386
        • Radcliff T.A.
        • Lorden A.L.
        • Zhao H.
        Clostridium difficile infection in Texas hospitals, 2007-2011.
        Infect Control Hosp Epidemiol. 2016; 37: 357-359
        • Reveles K.R.
        • Lee G.C.
        • Boyd N.K.
        • Frei C.R.
        The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010.
        Am J Infect Control. 2014; 42: 1028-1032
        • Chmielewska M.
        • Zycinska K.
        • Lenartowicz B.
        • Hadzik-Błaszczyk M.
        • Cieplak M.
        • Kur Z.
        • et al.
        Clostridium difficile infection due to pneumonia treatment: mortality risk models.
        Adv Exp Med Biol. 2017; 955: 59-63
        • Pépin J.
        • Saheb N.
        • Coulombe M.A.
        • Alary M.E.
        • Corriveau M.P.
        • Authier S.
        • et al.
        Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.
        Clin Infect Dis. 2005; 41: 1254-1260
        • Polgreen P.M.
        • Chen Y.Y.
        • Cavanaugh J.E.
        • Ward M.
        • Coffman S.
        • Hornick D.B.
        • et al.
        An outbreak of severe Clostridium difficile-associated disease possibly related to inappropriate antimicrobial therapy for community-acquired pneumonia.
        Infect Control Hosp Epidemiol. 2007; 28: 212-214
        • Becerra M.B.
        • Becerra B.J.
        • Banta J.E.
        • Safdar N.
        Impact of Clostridium difficile infection among pneumonia and urinary tract infection hospitalizations: an analysis of the Nationwide inpatient sample.
        BMC Infect Dis. 2015; 15: 254
        • Soler P.
        • Nogareda F.
        • Cano R.
        Rates of Clostridium difficile infection in patients discharged from Spanish hospitals, 1997-2005.
        Infect Control Hosp Epidemiol. 2008; 29: 887-889
        • Reveles K.R.
        • Lawson K.A.
        • Mortensen E.M.
        • Pugh M.J.V.
        • Koeller J.M.
        • Argamany J.R.
        • et al.
        National epidemiology of initial and recurrent Clostridium difficile infection in the Veterans Health Administration from 2003 to 2014.
        PLoS One. 2017; 12: e0189227