Regional and temporal genotype profiling of Clostridioides difficile in a multi-institutional study in Japan

Abstract

Clostridioides difficile, a cause of healthcare-associated infections, poses a significant global health threat. This multi-institutional retrospective study focuses on epidemic dynamics, emphasizing minor and toxin-negative clinical isolates through high-resolution genotyping. The genotype of the C. difficile clinical isolates during 2005 to 2022 was gathered from 14 hospitals across Japan (N = 982). The total number of unique genotypes was 294. Some genotypes were identified in every hospital (cross-regional genotypes), while others were unique to a specific hospital or those in close geographic proximity (region-specific genotypes). Notably, a hospital located in a sparsely populated prefecture exhibited the highest prevalence of region-specific genotypes. The isolation rate of cross-regional genotypes positively correlated with the human mobility flow. A 6-month interval analysis at a university hospital from 2019 to 2021 revealed a temporal transition of the genotype dominance. The frequent isolation of identical genotypes over a brief timeframe did not always align with the current criteria for defining nosocomial outbreaks. This study highlights the presence of diverse indigenous C. difficile strains in regional environments. The cross-regional strains may have a higher competency to spread in the human community. The longitudinal analysis underscores the need for further investigation into potential nosocomial spread.

Keywords: Clostridioides difficile; Cross-regional genotype; Infection; Molecular epidemiology; Region-specific genotype.

Fig. 1

A map of Japan depicting the locations of the hospitals included in this study and the POT genotype profile. (a) The 14 hospitals are illustrated on the density map of Japan, reflecting the number of passengers using railways. The pie graph displays the profile of POT genotypes for clinical isolates from all 14 hospitals. (b) Comparison of POT genotypes in C. difficile clinical isolates from 3 hospitals in Osaka prefecture to those from 8 hospitals in non-Osaka areas. Cross-regional genotypes are underlined. Region-specific genotypes (beige) are presented within other genotypes (gray) at the top-left. An asterisk denotes statistical significance in the isolation rate of the genotype in Osaka area relative to non-Osaka areas (P = 0.00002 by Fischer’s exact test, two-sided).

Fig. 2

The correlation between the isolation rate of cross-regional genotypes of C. difficile and the number of passengers utilizing the railroad station closest to each hospital. The two parameters exhibit a positive correlation with a correlation coefficient of r = 0.792 (N = 10, P < 0.008, by Student’s t-test, two-sided).

Fig. 3

Temporal profiling of POT genotypes of clinical isolates in the hospital E. The six most frequently isolated genotype strains are presented across six intervals from 2019 to 2021. *, P = 0.0001; **, P = 0.004 by Fischer’s exact test, two-sided.