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

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.

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.

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.

Time to recurrence ≥14 days after first Clostridium difficile infection according to risk score. Abbreviation: EIA, enzyme immunoassay.