Predictors of first recurrence of Clostridium difficile infection: implications for initial management

David W Eyre, A Sarah Walker, David Wyllie, Kate E Dingle, David Griffiths, John Finney, Lily O'Connor, Alison Vaughan, Derrick W Crook, Mark H Wilcox, Timothy E A Peto, Infections in Oxfordshire Research Database, P Bejon, T Berendt, C Bunch, D W Crook, J Finney, J Gearing, H Jones, L O'Connor, T E A Peto, J Robinson, B Shine, A S Walker, D Waller, D Wyllie, David W Eyre, A Sarah Walker, David Wyllie, Kate E Dingle, David Griffiths, John Finney, Lily O'Connor, Alison Vaughan, Derrick W Crook, Mark H Wilcox, Timothy E A Peto, Infections in Oxfordshire Research Database, P Bejon, T Berendt, C Bunch, D W Crook, J Finney, J Gearing, H Jones, L O'Connor, T E A Peto, J Robinson, B Shine, A S Walker, D Waller, D Wyllie

Abstract

Symptomatic recurrence of Clostridium difficile infection (CDI) occurs in approximately 20% of patients and is challenging to treat. Identifying those at high risk could allow targeted initial management and improve outcomes. Adult toxin enzyme immunoassay-positive CDI cases in a population of approximately 600,000 persons from September 2006 through December 2010 were combined with epidemiological/clinical data. The cumulative incidence of recurrence ≥ 14 days after the diagnosis and/or onset of first-ever CDI was estimated, treating death without recurrence as a competing risk, and predictors were identified from cause-specific proportional hazards regression models. A total of 1678 adults alive 14 days after their first CDI were included; median age was 77 years, and 1191 (78%) were inpatients. Of these, 363 (22%) experienced a recurrence ≥ 14 days after their first CDI, and 594 (35%) died without recurrence through March 2011. Recurrence risk was independently and significantly higher among patients admitted as emergencies, with previous gastrointestinal ward admission(s), last discharged 4-12 weeks before first diagnosis, and with CDI diagnosed at admission. Recurrence risk also increased with increasing age, previous total hours admitted, and C-reactive protein level at first CDI (all P < .05). The 4-month recurrence risk increased by approximately 5% (absolute) for every 1-point increase in a risk score based on these factors. Risk factors, including increasing age, initial disease severity, and hospital exposure, predict CDI recurrence and identify patients likely to benefit from enhanced initial CDI treatment.

Figures

Figure 1.
Figure 1.
Time to recurrence. A, Months to new enzyme immunoassay (EIA)–positive sample or death ≥14 days after first-ever EIA-positive sample. B, Daily risk of post–14-day new EIA-positive sample. Abbreviations: AIC, Akaike information criterion; EIA, enzyme immunoassay.
Figure 2.
Figure 2.
Time to recurrence ≥14 days after first Clostridium difficile infection according to shared or not shared sequence types. A, Months to new enzyme immunoassay (EIA)–positive sample ≥14 days after first-ever EIA-positive sample. B, Daily risk of new post–14-day EIA-positive sample. Abbreviations: CID, Clostridium difficile infection; EIA, enzyme immunoassay; ST, sequence type.
Figure 3.
Figure 3.
Time to recurrence ≥14 days after first Clostridium difficile infection according to risk score. Abbreviation: EIA, enzyme immunoassay.

References

    1. Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect. 2009;58:403–10.
    1. Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis. 2005;5:549–57.
    1. Garey KW, Sethi S, Yadav Y, DuPont HL. Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect. 2008;70:298–304.
    1. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591–7.
    1. Hu MY, Katchar K, Kyne L, et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology. 2009;136:1206–14.
    1. McFarland LV, Surawicz CM, Rubin M, Fekety R, Elmer GW, Greenberg RN. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Infect Control Hosp Epidemiol. 1999;20:43–50.
    1. McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 1994;271:1913–8.
    1. Olson MM, Shanholtzer CJ, Lee JT, Jr, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982–1991. Infect Control Hosp Epidemiol. 1994;15:371–81.
    1. Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2006;145:758–64.
    1. Johnson S, Adelmann A, Clabots CR, Peterson LR, Gerding DN. Recurrences of Clostridium difficile diarrhea not caused by the original infecting organism. J Infect Dis. 1989;159:340–3.
    1. Barbut F, Richard A, Hamadi K, Chomette V, Burghoffer B, Petit JC. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol. 2000;38:2386–8.
    1. Wilcox MH, Fawley WN, Settle CD, Davidson A. Recurrence of symptoms in Clostridium difficile infection—relapse or reinfection? J Hosp Infect. 1998;38:93–100.
    1. O'Neill GL, Beaman MH, Riley TV. Relapse versus reinfection with Clostridium difficile. Epidemiol Infect. 1991;107:627–35.
    1. van den Berg RJ, Ameen HA, Furusawa T, Claas EC, van der Vorm ER, Kuijper EJ. Coexistence of multiple PCR-ribotype strains of Clostridium difficile in faecal samples limits epidemiological studies. J Med Microbiol. 2005;54(Pt 2):173–9.
    1. Cohen SH, Gerding DN, Johnson S, et al. Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. 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;31:431–55.
    1. Louie TJ, Miller MA, Mullane KM, et al. OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–31.
    1. Griffiths D, Fawley W, Kachrimanidou M, et al. Multilocus sequence typing of Clostridium difficile. J Clin Microbiol. 2010;48:770–8.
    1. Finney JM, Walker AS, Peto TE, Wyllie DH. An efficient record linkage scheme using graphical analysis for identifier error detection. BMC Med Inform Decis Mak. 2011;11:7.
    1. Royston P, Parmar MK. Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects. Stat Med. 2002;21:2175–97.
    1. Burnham KP, Anderson DR. Model selection and multimodel inference. 2nd ed. New York, NY: Springer; 2002.
    1. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
    1. Royston P. Multiple imputation of missing values: update of ice. Stata J. 2005;5:527–36.
    1. van Buuren S, Boshuizen HC, Knook DL. Multiple imputation of missing blood pressure covariates in survival analysis. Stat Med. 1999;18:681–94.
    1. Sterne JA, White IR, Carlin JB, et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009;338:b2393.
    1. Hess KR. Assessing time-by-covariate interactions in proportional hazards regression models using cubic spline functions. Stat Med. 1994;13:1045–62.
    1. Dingle KE, Griffiths D, Didelot X, et al. Clinical Clostridium difficile: clonality and pathogenicity locus diversity. PLoS One. 2011;6:e19993.
    1. Eastwood K, Else P, Charlett A, Wilcox M. Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods. J Clin Microbiol. 2009;47:3211–7.
    1. Planche T, Aghaizu A, Holliman R, et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis. 2008;8:777–84.
    1. Rolfe RD, Helebian S, Finegold SM. Bacterial interference between Clostridium difficile and normal fecal flora. J Infect Dis. 1981;143:470–5.
    1. Claesson MJ, Cusack S, O'Sullivan O, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4586–91.
    1. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357:189–93.
    1. Leav BA, Blair B, Leney M, et al. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI) Vaccine. 2010;28:965–9.
    1. Emerson JE, Reynolds CB, Fagan RP, Shaw HA, Goulding D, Fairweather NF. A novel genetic switch controls phase variable expression of CwpV, a Clostridium difficile cell wall protein. Mol Microbiol. 2009;74:541–56.
    1. Vonberg R-P, Kuijper EJ, Wilcox MH, et al. Infection control measures to limit the spread of Clostridium difficile. Clin Microbiol Infect. 2008;14(Suppl 5):2–20.
    1. Eyre DW, Walker AS, Griffiths D, et al. Clostridiium difficile mixed infection and reinfection. J Clin Microbiol. 2012;50:142–4.
    1. Eastwood K, Wilcox MH. Do enzyme immunoassays (EIAs) for Clostridium difficile toxins yield higher optical densities for faecal samples that are ribotype 027 culture-positive? [abstract D-126]. Presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; 12–15 September 2010; Boston, Massachusetts.
    1. Issa M, Ananthakrishnan AN, Binion DG. Clostridium difficile and inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:1432–42.
    1. Kelsen JR, Kim J, Latta D, et al. Recurrence rate of Clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2011;17:50–5.
    1. Selinger CP, Greer S, Sutton CJ. Is gastrointestinal endoscopy a risk factor for Clostridium difficile associated diarrhea? Am J Infect Control. 2010;38:581–2.
    1. Rodrigues MA, Brady RR, Rodrigues J, Graham C, Gibb AP. Clostridium difficile infection in general surgery patients; identification of high-risk populations. Int J Surg. 2010;8:368–72.
    1. Abou Chakra CN, Pepin J, Valiquette L. Prediction tools for unfavourable outcomes in Clostridium difficile infection: a systematic review. PLoS One. 2012;7:e30258.
    1. Freeman J, Bauer MP, Baines SD, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev. 2010;23:529–49.
    1. Burns DA, Heap JT, Minton NP. The diverse sporulation characteristics of Clostridium difficile clinical isolates are not associated with type. Anaerobe. 2010;16:618–22.
    1. Sirard S, Valiquette L, Fortier LC. Lack of association between clinical outcome of Clostridium difficile infections, strain type, and virulence-associated phenotypes. J Clin Microbiol. 2011;49:4040–6.
    1. Kim JW, Lee KL, Jeong JB, et al. Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea. World J Gastroenterol. 2010;16:3573–7.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren