Risk factors for development of Clostridium difficile infection
Keywords:
CLOSTRIDIUM DIFFICILE, RISK FACTORS
Abstract
Clostridium difficile (CD) is the agent responsible for most nosocomial diarrhea episodes. The study aims to identify risk factors for the development of CD infection (CDI) in patients with nosocomial diarrhea at the “Dr. Manuel Quintela” University Hospital. To that end, and observational, analytical study of cases and non-paired controls was conducted. All patients older than 18 years old who developed diarrhea after 72 hours in hospital and who were requested a CD search from April to December, 2013 were included in the study.
Twenty seven patients (18.6%) complied with the case definition and 105 (72.4%) complied with the control definition and 13 (9.0%) were excluded, as they only evidenced a glutamate dehydrogenase (GLDH) positive test. As to the clinical presentation, the significant association of CDI with fever is pointed out.
The single variable analysis revealed that having received antibiotics for over 30 days and the previous use of clindamycin were significantly associated to CDI. In the multivariable analysis, the mere use of clindamycin (p=0.004 OR 5.881 IC95% 1.743-19.841) persisted as an independent risk factor. The latter proves that, upon an endemic situation, the implementation of a policy for the rational use of clindamycin is one of the measure needed to reduce the frequency of CDI.
References
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(2) Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15(4):573-81.
(3) Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults?: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31(5):431-55.
(4) Uruguay. Ministerio de Salud Pública. Infecciones por Clostridium difficile en hospitales centinela. Uruguay 2012. Disponible en: http://www.msp.gub.uy/sites/default/files/Informe_ICD_2012.pdf
Consulta: 20 noviembre 2015.
(5) Kyne L, Hamel MB, Polavaran R, Kelly CP. Health care costs and mortality associated with nosocomial diarrea due to Clostridium difficile. Clin Infec Dis 2002; 34(3):346-53.
(6) Forster AJ, 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(1):37-42.
(7) Polk RE, Fox C, Mahoney A, Letcavage J, MacDougall C. Measurement of adult antibacterial drug use in 130 US hospitals: comparison of defined daily dose and days of therapy. Clin Infect Dis 2007; 44(5):664-70.
(8) Garey KW, Graham G, Gerard L, Dao T, Jiang ZD, Price M, et al. Prevalence of diarrhea at a university hospital and association with modifiable risk factors. Ann Pharmacother 2006; 40(6):1030-4.
(9) Garey KW, Asha NJ, Tompkins D, Wilcox MH. Comparative analysis of prevalence, risk factors, and molecular epidemiology of antibiotic-associated diarrhea due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus. J Clin Microbiol 2006; 44(8):2785-91.
(10) Heimesaat MM, Granzow K, Leidinger H, Liesenfeld O. Prevalence of Clostridium difficile toxins A and B and Clostridium perfringens enterotoxin A in stool samples of patients with antibiotic-associated diarrhea. Infection 2005; 33(5-6): 340-4.
(11) Beaulieu C, Dionne LL, Julien AS, Longtin Y. Clinical characteristics and outcome of patients with Clostridium difficile infection diagnosed by PCR versus a three-step algorithm. Clin Microbiol Infect 2014; 20(10):1067-73.
(12) Siti Asma H, Norlela O, Fauziahs MI, Zaidah AR, Nurahan M, Rosliza AR, Chan GT, et al. Prevalence of Clostridium difficile toxin in diarhoeal stool samples of patients from a tertiary hospital in North Eastern Penisular Malaysia. Med J Malasya 2012; 67(4):402-5.
(13) Lai CC, Lin SH, Tan CK, Liao CH, Huang YT, Hsueh PR. Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan. J Microbiol Immunol Infect 2014; 47(6):491-6.
(14) Zumbado Salas R, Gamboa Coronado M, Rodríguez Cavallini E, Chaves Olarte E. Clostridium difficile in adult patients with nosocomial diarrhea in a Costa Rican hospital. Am J Trop Med Hyg 2008; 79(2):164-5.
(15) Balsamo A, Paciel D, Palacio R, Hernández N, Moreira M, Datti J, et al. Brote de Clostridium difficile en Hospital de Clínicas: descripción, manejo y control. En: XVII Congreso Panamericano de Infectología: API 2015. Quito, Ecuador 15-19 de mayo de 2015.
(16) Grille P, Olano E, Bertullo H, Bagnulo H. Estudio sobre diarrea en una unidad de cuidados intensivos quirúrgica. Rev Méd Urug 2006; 22(2):136-42.
(17) Polage CR, Solnick JV, Cohen SH. Nosocomial diarrea: evaluation and treatment of causes other than Clostridium difficile. Clin Infect Dis 2012; 55(7):982-9.
(18) Becerra MG, Ospina S, Atehortúa SL, Berbesi DY. Factores de riesgo para la infección por Clostridium difficile. Infectio 2011; 15(4):220-26.
(19) Kane SV, Sandborn WJ, Rufo PA, Zholudev A, Boone J, Lyerly D, et al. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol 2003; 98(6):1309-14.
(20) Wren MW, Kinson R, Sivapalan M, Schemko M, Shetty NR. Detection of Clostridium difficile infection: a suggested laboratory diagnostic algorithm. Br J Biomed Sci 2009; 66(4):175-9.
(21) El Feghaly RE, Stauber JL, Deych E, Gonzalez C, Tarr PI, Haslam DB. Markers of intestinal inflammation, not bacterial burden, correlate with clinical outcomes in Clostridium difficile infection. Clin Infect Dis 2013; 56(12):1713-21.
(22) Bartlett JG. Narrative review: The new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006; 145(10):758-64.
(23) Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative Antibiotic Exposures Over Time and the Risk of Clostridium difficile Infection. Clin Infect Dis 2011; 53(1):42-8.
(24) Pepin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Autier 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(9):1254-60.
(25) Owens RC, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile Infection. Clin Infect Dis 2008; 46(Suppl 1):S19-31.
(26) Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 2014; 69(4):881-91.
(27) Vesta KM, Wells PS, Gentry CA, Stipek WJ. Specific risk factors for Clostridium difficile-associated diarrhea: a prospective, multicenter, case control evaluation. Am J Infect Control 2005; 33(8):469-72.
(28) Hensgens MPM, Goorhuis A, Dekkers OM, Kuijper ED. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2012; 67(3):742-8.
(29) Vignoli R, Calvelo E, Cordeiro NF, Lucero R, Ingold E, Quintana A, et al. Association of broad-spectrum antibiotic use with faecal carriage of oxyiminocephalosporin-resistant Enterobacteriaceae in an intensive care unit. J Hosp Infect 2006; 63(3):306–15.
(30) Medina J, Formento C, Pontet J, Curbelo A, Bazet C, Gérez J, et al. Prospective study of risk factors for ventilator-associated pneumonia caused by Acinetobacter species. J Crit Care 2007; 22(1):18-26.
(31) Medina Presentado JC, Paciel López D, Berro Castiglione M, Gérez J. Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas aeruginosa. Rev Panam Salud Pública 2011; 30(6):603-9.
(32) Seija V, Pontet J, Soca A, Gabrielli A, Arregui P, Noveri S, Bentancourt S. Impacto de la restricción de ceftriaxona sobre la ecología bacteriana de una unidad de cuidado intensivo. En: VIII Congreso Panamericano de Medicina Crítica y Terapia Intensiva. Punta del Este, Uruguay 18-21 de noviembre de 2007.
(33) Vardakas KZ, Konstantelias AA, Loizidis Rafailidis PI, Falagas ME. Risk factors for development of Clostridium difficile infection due to BI/NAP1/027 strain: a meta-analysis. Int J Infect Dis 2012; 16(11):e768-73.
(34) Association for Professionals in Infection Control and Epidemiology. Guide to preventing Clostridium difficile infections. Washington, DC: APIC, 2013. Disponible en: http://apic.org/Resource_/EliminationGuideForm/59397fc6-3f90-43d1-9325-e8be75d86888/File/2013 CDiffFinal.pdf. Consulta: 20 noviembre 2015.
(35) Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN. Decrease in nosocomial Clostridium difficile–associated diarrhea by restricting clindamycin use. Ann Intern Med 1994; 120(4):272–7.
(36) Climo MW, Israel DS, Wong ES, Williams D, Coudron P, Markowitz SM. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost. Ann Intern Med. 1998; 128(12 Pt 1):989-95.
(37) Muto CA, Blank MK, Marsh JW, Vergis EN, O’Leary MM, Shutt KA, et al. Control of an outbreak of infection with the hypervirulent Clostridium difficile BI strain in a university hospital using a comprehensive “bundle” approach. Clin Infect Dis 2007; 45(10):1266-73.
(38) Valiquette L, Cossette B, Garant MP, 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(Suppl 2):S112-21.
(2) Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15(4):573-81.
(3) Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults?: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31(5):431-55.
(4) Uruguay. Ministerio de Salud Pública. Infecciones por Clostridium difficile en hospitales centinela. Uruguay 2012. Disponible en: http://www.msp.gub.uy/sites/default/files/Informe_ICD_2012.pdf
Consulta: 20 noviembre 2015.
(5) Kyne L, Hamel MB, Polavaran R, Kelly CP. Health care costs and mortality associated with nosocomial diarrea due to Clostridium difficile. Clin Infec Dis 2002; 34(3):346-53.
(6) Forster AJ, 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(1):37-42.
(7) Polk RE, Fox C, Mahoney A, Letcavage J, MacDougall C. Measurement of adult antibacterial drug use in 130 US hospitals: comparison of defined daily dose and days of therapy. Clin Infect Dis 2007; 44(5):664-70.
(8) Garey KW, Graham G, Gerard L, Dao T, Jiang ZD, Price M, et al. Prevalence of diarrhea at a university hospital and association with modifiable risk factors. Ann Pharmacother 2006; 40(6):1030-4.
(9) Garey KW, Asha NJ, Tompkins D, Wilcox MH. Comparative analysis of prevalence, risk factors, and molecular epidemiology of antibiotic-associated diarrhea due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus. J Clin Microbiol 2006; 44(8):2785-91.
(10) Heimesaat MM, Granzow K, Leidinger H, Liesenfeld O. Prevalence of Clostridium difficile toxins A and B and Clostridium perfringens enterotoxin A in stool samples of patients with antibiotic-associated diarrhea. Infection 2005; 33(5-6): 340-4.
(11) Beaulieu C, Dionne LL, Julien AS, Longtin Y. Clinical characteristics and outcome of patients with Clostridium difficile infection diagnosed by PCR versus a three-step algorithm. Clin Microbiol Infect 2014; 20(10):1067-73.
(12) Siti Asma H, Norlela O, Fauziahs MI, Zaidah AR, Nurahan M, Rosliza AR, Chan GT, et al. Prevalence of Clostridium difficile toxin in diarhoeal stool samples of patients from a tertiary hospital in North Eastern Penisular Malaysia. Med J Malasya 2012; 67(4):402-5.
(13) Lai CC, Lin SH, Tan CK, Liao CH, Huang YT, Hsueh PR. Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan. J Microbiol Immunol Infect 2014; 47(6):491-6.
(14) Zumbado Salas R, Gamboa Coronado M, Rodríguez Cavallini E, Chaves Olarte E. Clostridium difficile in adult patients with nosocomial diarrhea in a Costa Rican hospital. Am J Trop Med Hyg 2008; 79(2):164-5.
(15) Balsamo A, Paciel D, Palacio R, Hernández N, Moreira M, Datti J, et al. Brote de Clostridium difficile en Hospital de Clínicas: descripción, manejo y control. En: XVII Congreso Panamericano de Infectología: API 2015. Quito, Ecuador 15-19 de mayo de 2015.
(16) Grille P, Olano E, Bertullo H, Bagnulo H. Estudio sobre diarrea en una unidad de cuidados intensivos quirúrgica. Rev Méd Urug 2006; 22(2):136-42.
(17) Polage CR, Solnick JV, Cohen SH. Nosocomial diarrea: evaluation and treatment of causes other than Clostridium difficile. Clin Infect Dis 2012; 55(7):982-9.
(18) Becerra MG, Ospina S, Atehortúa SL, Berbesi DY. Factores de riesgo para la infección por Clostridium difficile. Infectio 2011; 15(4):220-26.
(19) Kane SV, Sandborn WJ, Rufo PA, Zholudev A, Boone J, Lyerly D, et al. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol 2003; 98(6):1309-14.
(20) Wren MW, Kinson R, Sivapalan M, Schemko M, Shetty NR. Detection of Clostridium difficile infection: a suggested laboratory diagnostic algorithm. Br J Biomed Sci 2009; 66(4):175-9.
(21) El Feghaly RE, Stauber JL, Deych E, Gonzalez C, Tarr PI, Haslam DB. Markers of intestinal inflammation, not bacterial burden, correlate with clinical outcomes in Clostridium difficile infection. Clin Infect Dis 2013; 56(12):1713-21.
(22) Bartlett JG. Narrative review: The new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006; 145(10):758-64.
(23) Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative Antibiotic Exposures Over Time and the Risk of Clostridium difficile Infection. Clin Infect Dis 2011; 53(1):42-8.
(24) Pepin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Autier 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(9):1254-60.
(25) Owens RC, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile Infection. Clin Infect Dis 2008; 46(Suppl 1):S19-31.
(26) Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 2014; 69(4):881-91.
(27) Vesta KM, Wells PS, Gentry CA, Stipek WJ. Specific risk factors for Clostridium difficile-associated diarrhea: a prospective, multicenter, case control evaluation. Am J Infect Control 2005; 33(8):469-72.
(28) Hensgens MPM, Goorhuis A, Dekkers OM, Kuijper ED. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2012; 67(3):742-8.
(29) Vignoli R, Calvelo E, Cordeiro NF, Lucero R, Ingold E, Quintana A, et al. Association of broad-spectrum antibiotic use with faecal carriage of oxyiminocephalosporin-resistant Enterobacteriaceae in an intensive care unit. J Hosp Infect 2006; 63(3):306–15.
(30) Medina J, Formento C, Pontet J, Curbelo A, Bazet C, Gérez J, et al. Prospective study of risk factors for ventilator-associated pneumonia caused by Acinetobacter species. J Crit Care 2007; 22(1):18-26.
(31) Medina Presentado JC, Paciel López D, Berro Castiglione M, Gérez J. Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas aeruginosa. Rev Panam Salud Pública 2011; 30(6):603-9.
(32) Seija V, Pontet J, Soca A, Gabrielli A, Arregui P, Noveri S, Bentancourt S. Impacto de la restricción de ceftriaxona sobre la ecología bacteriana de una unidad de cuidado intensivo. En: VIII Congreso Panamericano de Medicina Crítica y Terapia Intensiva. Punta del Este, Uruguay 18-21 de noviembre de 2007.
(33) Vardakas KZ, Konstantelias AA, Loizidis Rafailidis PI, Falagas ME. Risk factors for development of Clostridium difficile infection due to BI/NAP1/027 strain: a meta-analysis. Int J Infect Dis 2012; 16(11):e768-73.
(34) Association for Professionals in Infection Control and Epidemiology. Guide to preventing Clostridium difficile infections. Washington, DC: APIC, 2013. Disponible en: http://apic.org/Resource_/EliminationGuideForm/59397fc6-3f90-43d1-9325-e8be75d86888/File/2013 CDiffFinal.pdf. Consulta: 20 noviembre 2015.
(35) Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN. Decrease in nosocomial Clostridium difficile–associated diarrhea by restricting clindamycin use. Ann Intern Med 1994; 120(4):272–7.
(36) Climo MW, Israel DS, Wong ES, Williams D, Coudron P, Markowitz SM. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost. Ann Intern Med. 1998; 128(12 Pt 1):989-95.
(37) Muto CA, Blank MK, Marsh JW, Vergis EN, O’Leary MM, Shutt KA, et al. Control of an outbreak of infection with the hypervirulent Clostridium difficile BI strain in a university hospital using a comprehensive “bundle” approach. Clin Infect Dis 2007; 45(10):1266-73.
(38) Valiquette L, Cossette B, Garant MP, 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(Suppl 2):S112-21.
Published
2016-09-30
How to Cite
1.
Menéndez M, Batista N, Bálsamo A, Seija V. Risk factors for development of Clostridium difficile infection. Rev. Méd. Urug. [Internet]. 2016Sep.30 [cited 2024Nov.26];32(3):159-65. Available from: http://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/164
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