Clostridioides difficile: relationship with previous use of antibiotics, risk factors and preventive measures to reduce transmission
DOI:
https://doi.org/10.56294/shp2025220Keywords:
Clostridium difficile, nosocomial diarrhea, antibiotics, risk factors, preventionAbstract
Background: Clostridioides difficile infection has emerged in recent years as one of the main hospital-acquired infections. This enteric pathogen is responsible for causing diarrhea related to prior antibiotic use in many healthcare settings, particularly hospitals, nursing homes, and rehabilitation clinics. This study aims to demonstrate the relationship between previous antibiotic use and Clostridioides difficile infection and determine the main risk factors and antibiotics associated with the infection, as well as the potential benefit of prevention strategies.
Material and methods: A bibliographic search was carried out analyzing the database platforms of PubMed, Medline, Lilacs, Scielo and Cochrane during the period from May to September 2024. Articles were selected with a focus on risk factors, preventive measures and antibiotics related to the appearance of Clostridioides difficile infection.
Results: Although any antibiotic is a potential risk factor for the development of CDI, the medications most commonly associated with the onset of the infection are Clindamycin, 2nd and 3rd generation Cephalosporins, Fluoroquinolones, Penicillins and Carbapenems.
Conclusion: It is extremely important to know the risk factors and the main antibiotics associated with CDI so that when a certain type of antibiotic is indicated for relatively serious processes, extreme preventive measures are initiated, prior to the possibility that this individual that triggers it does not be the origin of an in-hospital outbreak.
References
Menéndez M, Batista N, et al. Predictores de riesgo para desarrollo de infección por Clostridium difficile. Rev Med Urug. 2016;32(3).
Barcán L, Ducatenzeiler L, et al. Recomendaciones intersociedades para diagnóstico, tratamiento y prevención de las infecciones por Clostridioides difficile. Medicina (B Aires). 2020;80(Supl 1).
Becerra MG, Ospina S, et al. Factores de riesgo para la infección por Clostridium difficile. Infectio. 2011;15(4). DOI: https://doi.org/10.1016/S0123-9392(11)70735-4
Al-Zahrani IA. Clostridioides (Clostridium) difficile: a silent nosocomial pathogen. Saudi Med J. 2023;44(9):825–35. DOI: https://doi.org/10.15537/smj.2023.44.9.20230216
Rocha CH, Pidal P, et al. Consenso chileno de prevención, diagnóstico y tratamiento de la diarrea asociada a Clostridium difficile. Rev Chil Infectol. 2016;33(1). DOI: https://doi.org/10.4067/S0716-10182016000100020
Jorge L, Azula N, et al. Incidencia, características clínicas y evolución de la infección por Clostridioides difficile. Medicina (B Aires). 2021;81(6).
Arteaga A, Santa-Olalla P, et al. Riesgo epidémico de la enfermedad asociada a una nueva cepa de Clostridium difficile. Enferm Infecc Microbiol Clin. 2009;27(5):278–84. DOI: https://doi.org/10.1016/j.eimc.2008.01.003
Stevens V, Dumyati G, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42–8.
Owens RC, Donskey CJ, et al. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008;46(Suppl 1):S19–31. DOI: https://doi.org/10.1086/521859
Hernández DAÁ, González AM, et al. Perspectivas históricas y vigentes sobre la infección por Clostridium difficile. Rev Gastroenterol Mex. 2018;83(1):41–50. DOI: https://doi.org/10.1016/j.rgmx.2017.03.004
Rocha CH, Naour S, et al. Infecciones causadas por Clostridium difficile: una visión actualizada. Rev Chil Infectol. 2012;29(4). DOI: https://doi.org/10.4067/S0716-10182012000400011
Capello MC. Análisis de pacientes con infección por Clostridium difficile en un nosocomio de segundo nivel de atención de la ciudad de Rosario [especialización en clínica médica]. Rosario: UNR; 2019 [acceso 7 jul 2024]. Disponible en: https://www.clinica-unr.com.ar/Posgrado/trabajos-graduados/capello-celeste.pdf
Buffie CG, et al. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect Immun. 2012;80(1):62–73. DOI: https://doi.org/10.1128/IAI.05496-11
Surawicz CM, et al. Antibiotic associated diarrhea and pseudomembranous colitis: are they less common with poorly absorbed antimicrobials? Chemotherapy. 2005;51(Suppl 1):81–9. DOI: https://doi.org/10.1159/000081993
Kuijper EJ, Coignard B, et al. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006;12(Suppl 6):2–18. DOI: https://doi.org/10.1111/j.1469-0691.2006.01580.x
Dos Santos SLF, Barros KBNT, et al. Infecção por Clostridium difficile associada a antibioticoterapia: fisiopatologia, diagnóstico e tratamento. Rev Cienc Med Campinas. 2017;26(1):19–26. DOI: https://doi.org/10.24220/2318-0897v26n1a3631
Olvera CGM, Zubiria LL. Clostridioides difficile in Latin America: an epidemiological overview. Curr Microbiol. 2023;80:357. DOI: https://doi.org/10.1007/s00284-023-03475-x
Abad C, Safdar N, et al. A review of Clostridioides difficile infection and antibiotic-associated diarrhea. Gastroenterol Clin North Am. 2021 Jun. DOI: https://doi.org/10.1016/j.gtc.2021.02.010
Ramirez J, Guarner F, et al. Antibiotics as major disruptors of gut microbiota. Front Cell Infect Microbiol. 2020 Nov. DOI: https://doi.org/10.3389/fcimb.2020.572912
Capurso L, Koch M. Side effects of antibiotics: diarrhea and Clostridium difficile infection. Recenti Prog Med. 2021 Jan.
Knecht H, Neulinger S, et al. Effects of β-lactam antibiotics and fluoroquinolones on human gut microbiota in relation to Clostridium difficile-associated diarrhea. PLoS One. 2014 Feb. DOI: https://doi.org/10.1371/journal.pone.0089417
Gerding D. Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile-associated diarrhea: this is an antimicrobial resistance problem. Clin Infect Dis. 2004 Mar. DOI: https://doi.org/10.1086/382084
Blondeau JM. What have we learned about antimicrobial use and the risks for Clostridium difficile-associated diarrhoea? J Antimicrob Chemother. 2009 Feb;63:238–42. DOI: https://doi.org/10.1093/jac/dkn477
Dethlefsen L, Huse S, et al. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008 Nov;6(11):e280. DOI: https://doi.org/10.1371/journal.pbio.0060280
Croswell A, Amir E, et al. Prolonged impact of antibiotics on intestinal microbial ecology and susceptibility to enteric Salmonella infection. Infect Immun. 2009 Apr;77(7):2741–53. DOI: https://doi.org/10.1128/IAI.00006-09
Deshpande A, Pasupuleti V, et al. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. J Antimicrob Chemother. 2013 Sep;68(9):1951–61. DOI: https://doi.org/10.1093/jac/dkt129
Rafey A, Jahan S, et al. Antibiotics associated with Clostridium difficile infection. Cureus. 2023 May. DOI: https://doi.org/10.7759/cureus.39029
Mullish BH, Williams HR, et al. Clostridium difficile infection and antibiotic-associated diarrhoea. Clin Med (Lond). 2018 Jun;18(3):237–41. DOI: https://doi.org/10.7861/clinmedicine.18-3-237
Stevens V, Dumyati G, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011 Jul 1;53(1):42–8. DOI: https://doi.org/10.1093/cid/cir301
Hensgens MPM, Goorhuis A, et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012 Mar;67(3):742–8. DOI: https://doi.org/10.1093/jac/dkr508
Brown KA, Khanafer N, et al. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother. 2013 Apr;57(5):2326–32. DOI: https://doi.org/10.1128/AAC.02176-12
Brown KA, Langford B, et al. Antibiotic prescribing choices and their comparative Clostridium difficile infection risks: a longitudinal case-cohort study. Clin Infect Dis. 2021 Mar;72(5):836–44. DOI: https://doi.org/10.1093/cid/ciaa124
Slimings C, Riley TV, et al. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother. 2014 Apr;69(4):881–91. DOI: https://doi.org/10.1093/jac/dkt477
Tariq R, Cho J, et al. Low risk of primary Clostridium difficile infection with tetracyclines: a systematic review and meta-analysis. Clin Infect Dis. 2018 Feb;66(4):514–22. DOI: https://doi.org/10.1093/cid/cix833
Webb BJ, Subramanian A, et al. Antibiotic exposure and risk for hospital-associated Clostridioides difficile infection. Antimicrob Agents Chemother. 2020 Mar;64(4):e02169-19. DOI: https://doi.org/10.1128/AAC.02169-19
Tabak YP, Srinivasan A, et al. Hospital-level high-risk antibiotic use in relation to hospital-associated Clostridioides difficile infections: retrospective analysis of 2016–2017 data from US hospitals. Infect Control Hosp Epidemiol. 2019 Nov;40(11):1229–35. DOI: https://doi.org/10.1017/ice.2019.236
Wilcox MH, Chalmers JD, et al. Role of cephalosporins in the era of Clostridium difficile infection. J Antimicrob Chemother. 2017 Jan;72(1):1–18. DOI: https://doi.org/10.1093/jac/dkw385
Büchler AC, Rampini SK, et al. Antibiotic susceptibility of Clostridium difficile is similar worldwide over two decades despite widespread use of broad-spectrum antibiotics: an analysis done at the University Hospital of Zurich. BMC Infect Dis. 2014 Nov;14:607. DOI: https://doi.org/10.1186/s12879-014-0607-z
Pepin J, Saheb N, 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 Sep;41:1254–60. DOI: https://doi.org/10.1086/496986
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