Incubation period of Clostridioides difficile infection in hospitalized patients and long-term care facility residents: a prospective cohort study

Abstract

Background: The incubation period for Clostridioides difficile infection (CDI) is generally considered to be less than 1 week, but some recent studies suggest that prolonged carriage prior to disease onset may be common.

Objective: To estimate the incubation period for patients developing CDI after initial negative cultures.

Methods: In 3 tertiary care medical centers, we conducted a cohort study to identify hospitalized patients and long-term care facility residents with negative initial cultures for C. difficile followed by a diagnosis of CDI with or without prior detection of carriage. Cases were classified as healthcare facility-onset, community-onset, healthcare facility-associated, or community-associated and were further classified as probable, possible, or unlikely CDI. A parametric accelerated failure time model was used to estimate the distribution of the incubation period.

Results: Of 4,179 patients with negative enrollment cultures and no prior CDI diagnosis within 56 days, 107 (2.6%) were diagnosed as having CDI, including 19 (17.8%) with and 88 (82.2%) without prior detection of carriage. When the data were censored to only include participants with negative cultures collected within 14 days, the estimated median incubation period was 6 days with 25% and 75% of estimated incubation periods occurring within 3 and 12 days, respectively. The observed estimated incubation period did not differ significantly for patients classified as probable, possible, or unlikely CDI.

Conclusion: Our findings are consistent with the previous studies that suggested the incubation period for CDI is typically less than 1 week and is less than 2 weeks in most cases.

Figure 1.

Flow diagram for the study participants. CDI, Clostridioides difficile infection.

Figure 2.

Examples of patients diagnosed as having Clostridioides difficile infection (CDI) with (A, C) and without (B) prior detection of asymptomatic carriage. A, Diagnosis of CDI with a ribotype F027 strain with detection of the carriage 13 days prior; B, Diagnosis of CDI with a ribotype F014-020 strain with no prior detection of carriage (estimated incubation period 2 days); C, Diagnosis of CDI with a ribotype F014-020 strain with detection of the carriage 53 days prior. LTCF, long-term care facility; CFU, colony-forming units; PCR, polymerase chain reaction; Neg, negative.

Figure 3.

Estimated log-normal distributions of incubation periods for Clostridioides difficile infection (CDI) with median values and 95% confidence intervals indicated based on all patients with CDI after an initial negative culture and censored to exclude those with negative cultures collected more than 30 or 14 days prior to CDI diagnosis with no intervening culture collection.