Role of previous systemic antibiotic therapy on the probability of recurrence after an initial episode of Clostridioides difficile infection treated with vancomycin

Nicolás Merchante, Rocío Herrero, María Dolores Valverde-Fredet, Miguel Rodríguez-Fernández, Héctor Pinagorte, Francisco J Martínez-Marcos, Concepción Gil-Anguita, María García-López, María Tasias Pitarch, Vicente Abril López De Medrano, Miguel Nicolás Navarrete Lorite, Cristina Gómez-Ayerbe, Eva León, Pilar González-De La Aleja, Ana Ruiz Castillo, Ana I Aller, Juan Carlos Rodríguez, Julia Ternero Fonseca, Juan E Corzo, Alberto Naranjo Pérez, Marta Trigo-Rodríguez, Esperanza Merino, Nicolás Merchante, Rocío Herrero, María Dolores Valverde-Fredet, Miguel Rodríguez-Fernández, Héctor Pinagorte, Francisco J Martínez-Marcos, Concepción Gil-Anguita, María García-López, María Tasias Pitarch, Vicente Abril López De Medrano, Miguel Nicolás Navarrete Lorite, Cristina Gómez-Ayerbe, Eva León, Pilar González-De La Aleja, Ana Ruiz Castillo, Ana I Aller, Juan Carlos Rodríguez, Julia Ternero Fonseca, Juan E Corzo, Alberto Naranjo Pérez, Marta Trigo-Rodríguez, Esperanza Merino

Abstract

Objectives: To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin.

Methods: Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed.

Results: Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving 5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06-0.29; P < 0.0001] whereas exposure for 5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4-27.1; P < 0.0001).

Conclusions: Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.

© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.

Figures

Figure 1.
Figure 1.
Risk of CDI recurrence according to previous exposure to systemic non-CDI antibiotics (ATB) (n = 244). TZP, piperacillin/tazobactam. (a) TZP. (b) Cephalosporins.

References

    1. Lessa FC, Mu Y, Bamberg WM et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372: 825–34. 10.1056/NEJMoa1408913
    1. Davies KA, Longshaw CM, Davis GL et al. Underdiagnosis of Clostridium difficile across Europe: the European, multicenter, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalized patients with diarrhea (EUCLID). Lancet Infect Dis 2014; 14: 1208–19. 10.1016/S1473-3099(14)70991-0
    1. Longo DL, Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med 2015; 372: 1539–48. 10.1056/NEJMra1403772
    1. Stevens V, Dumyati G, Fine LS et al. Cumulative antibiotic exposure over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011; 53: 42–8. 10.1093/cid/cir301
    1. Kavanagh K, Pan J, Marwick C et al. Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case-control study using administrative data. J Antimicrob Chemother 2017; 72: 1193–201. 10.1093/jac/dkw528
    1. Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 2014; 69: 881–91. 10.1093/jac/dkt477
    1. Brown KA, Langford B, Schwartz KL et al. Antibiotic prescribing choices and their comparative C. difficile infection risks: a longitudinal case-cohort study. Clin Infect Dis 2021; 72: 836–44. 10.1093/cid/ciaa124
    1. Webb BJ, Subramanian A, Lopansri B et al. Antibiotic exposure and risk for hospital-associated Clostridioides difficile infection. Antimicrob Agents Chemother 2020; 64: e01269-19. 10.1128/AAC.02169-19
    1. Freedberg DE, Salmasian H, Cohen B et al. Receipt of antibiotics in hospitalized patients and risk of Clostridium difficile infection in subsequent patients who occupy the same bed. JAMA Intern Med 2016; 176: 1801–8. 10.1001/jamainternmed.2016.6193
    1. Lawes T, Lopez-Lozano JM, Nebot CA et al. Effect of a national 4C antibiotic stewardship intervention on the clinical and molecular epidemiology of Clostridium difficile infections in a region of Scotland: a non-linear time-series analysis. Lancet Infect Dis 2017; 17: 194–206. 10.1016/S1473-3099(16)30397-8
    1. Kazakova SV, Baggs J, McDonald LC et al. Association between antibiotic use and hospital-onset Clostridioides difficile infection in US acute care hospitals, 2006-2012: an ecologic analysis. Clin Infect Dis 2020; 70: 11–8. 10.1093/cid/ciz169
    1. Kazakova SV, Baggs J, Yi SH et al. Associations of facility-level antibiotic use and hospital-onset Clostridioides difficile infection in US acute-care hospitals, 2012–2018. Infect Control Hosp Epidemiol 2021; 7: 1067–9. 10.1017/ice.2021.151
    1. Louie TJ, Miller MA, Mullane KM et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364: 422–31. 10.1056/NEJMoa0910812
    1. Wilcox MH, Gerding DN, Poxton IR et al. Bezlotoxumab for the prevention of recurrent Clostridium difficile infection. N Eng J Med 2017; 376: 305–17. 10.1056/NEJMoa1602615
    1. Guery B, Menichetti F, Anttila VJ et al. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis 2018; 18: 296–307. 10.1056/NEJMoa1602615
    1. Sheitoyan-Pesant C, Abou Chakra CN, Pepin J et al. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. Clin Infect Dis 2016; 62: 574–80. 10.1093/cid/civ958
    1. Cornely OA, Miller MA, Louie TJ et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis 2012; 55 Suppl 2: 154–61. 10.1093/cid/cis462
    1. Asensio A, Bouza E, Grau S et al. Cost of Clostridium difficile associated diarrhea in Spain. Rev Esp Salud Publ 2013; 1: 25–33. 10.4321/S1135-57272013000100004
    1. Chen J, Gong CL, Hitchcock MM et al. Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection. Clin Microb Infect 2021; 27: 1448–54. 10.1016/j.cmi.2021.04.004
    1. Mullane KM, Miller MA, Weiss K et al. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis 2011; 53: 440–7. 10.1093/cid/cir404
    1. Appaneal HJ, Caffrey AR, Beganovic M et al. Predictors of Clostridioides difficile recurrence across a national cohort of veterans in outpatient, acute, and long-term care settings. Am J Health Syst Pharm 2019; 76: 581–90. 10.1093/ajhp/zxz032
    1. Fitzpatrick F, Safdar N, van Prehn J et al. How can patients with Clostridioides difficile infection on concomitant antibiotic treatment be best managed? Lancet Infect Dis 2022; 22: e336–40. 10.1016/S1473-3099(22)00274-2
    1. van Rossen TM, Ooijevaar RE, Vandenbroucke-Grauls CMJE et al. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin Microbiol Infect 2022; 28: 321–31. 10.1016/j.cmi.2021.09.026
    1. van Prehn J, Reigadas E, Vogelzang EH et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect 2021; 27 Suppl 2: S1–S21. 10.1016/j.cmi.2021.09.038
    1. McDonald CL, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66: 987–94. 10.1093/cid/ciy149
    1. ECDC . European surveillance of Clostridioides (Clostridium) difficile infections. Surveillance protocol version 2.4. 2019. .
    1. Crobach MJ, Planche T, Eckert C et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 2016; 22 Suppl 4: 63–81. 10.1016/j.cmi.2016.03.010
    1. Lee JD, Heintz BH, Mosher HJ et al. Risk of acute kidney injury and Clostridioides difficile infection with piperacillin/tazobactam, cefepime and meropenem with or without vancomycin. Clin Infect Dis 2021; 73: e1579–86. 10.1093/cid/ciaa1902
    1. Sholeh M, Krutova M, Forouzesh M et al. Antimicrobial resistance in Clostridioides (Clostridium) difficile derived from humans: a systematic review and meta-analysis. Antimicrob Resist Infect Control 2020; 9: 158. 10.1186/s13756-020-00815-5
    1. Kundrapu S, Sunkesula VCK, Jury LA et al. Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization? BMC Infect Dis 2016; 16: 159. 10.1186/s12879-016-1514-2
    1. Chilton CH, Crowther GS, Ashwin H et al. Association of fidaxomicin with C. difficile spores: effects of persistence on subsequent spore recovery, outgrowth and toxin production. PLoS One 2016; 11: e0161200. 10.1371/journal.pone.0161200
    1. Smith AB, Jenior ML, Keenan O et al. Enterococci enhance Clostridioides difficile pathogenesis. Nature 2022; 611: 780–6. 10.1038/s41586-022-05438-x
    1. Zimmermann P, Curtis N. The effect of antibiotics on the composition of the intestinal microbiota - a systematic review. J Infect 2019; 79: 471–89. 10.1016/j.jinf.2019.10.008
    1. Krutova M, Wilcox M, Kuijper JE. Clostridioides difficile infection: are the three currently used antibiotic treatment options equal from pharmacological and microbiological points of view? Int J Infect Dis 2022; 124: 118–23. 10.1016/j.ijid.2022.09.013
    1. Hensgens MP, Goorhuis A, Dekkers OM et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2012; 67: 742–8. 10.1093/jac/dkr508

Source: PubMed

3
Se inscrever