A point-prevalence study on community and inpatient Clostridioides difficile infections (CDI): results from Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI), July to November 2018

Background There is a paucity of data on community-based Clostridioides difficile infection (CDI) and how these compare with inpatient CDI. Aim To compare data on the populations with CDI in hospitals vs the community across 12 European countries. Methods For this point-prevalence study (July–November 2018), testing sites sent residual diagnostic material on sampling days to a coordinating laboratory for CDI testing and PCR ribotyping (n = 3,163). Information on whether CDI testing was requested at the original site was used to identify undiagnosed CDI. We used medical records to identify differences between healthcare settings in patient demographics and risk factors for detection of C. difficile with or without free toxin. Results The CDI positivity rate was 4.4% (country range: 0–16.2) in hospital samples, and 1.3% (country range: 0–2.2%) in community samples. The highest prevalence of toxinotype IIIb (027, 181 and 176) was seen in eastern European countries (56%; 43/77), the region with the lowest testing rate (58%; 164/281). Different predisposing risk factors were observed (use of broad-spectrum penicillins in the community (OR: 8.09 (1.9–35.6), p = 0.01); fluoroquinolones/cephalosporins in hospitals (OR: 2.2 (1.2–4.3), p = 0.01; OR: 2.0 (1.1–3.7), p = 0.02)). Half of community CDI cases were undetected because of absence of clinical suspicion, accounting for three times more undiagnosed adults in the community compared with hospitals (ca 111,000 vs 37,000 cases/year in Europe). Conclusion These findings support recommendations for improving diagnosis in patients presenting with diarrhoea in the community, to guide good practice to limit the spread of CDI.


Supplementary
. Organisms detected by the BioFire FilmArray GI Panel assay .
Samples were positive or negative for C. difficile toxin (Cell-cytotoxin neutralisation assay; CCNA). No n/a n/a n/a n/a n/a No No #5 18-49 n/a n/a n/a n/a n/a n/a n/

Supplementary Table S4. Categorical variables (previous exposure) of cases and CD participants groups.
Cases were participants group CCNA positive (presence of C. difficile toxin using reference test). CD term was chosen to describe participants group CTC positive/CCNA negative/SIMOA negative (presence of C. difficile without toxin).
Data are number of patients (%) in hospital or community setting with previous exposure prior to the sample being taken, and calculated odds ratio, 95% CI, Chi-squared p values or Fischers exact test p values (when the cell count was less than 5) of cases versus controls and CD versus controls. Antibiotic use and class of antibiotics refers to antibiotics prescribed for treatment or prophylaxis of an infection other than CDI in the preceding 12 weeks. Significant variables are highlighted in bold (p values <0.05 and 95% CI that do not include 1.0).
CCNA: cell-cytotoxin neutralisation assay; CDI: Clostridioides difficile infection; CI: confidence intervals; CTC: cell cytotoxigenic culture; n= number of participants exposed to indicated variable. ; N= total number of participants in analysis (with data); na=not able to compute odds ratio due to a value of 0 in one of the groups; p: p values; SIMOA: ultra-sensitive toxin single molecule array.

Supplementary Table S5. Categorical variables (number and type of co-morbidities) of cases and CD participants groups.
Cases were participants group CCNA positive (presence of C. difficile toxin using reference test). CD term was chosen to describe participants group CTC positive/CCNA negative/SIMOA negative (presence of C. difficile without toxin).
Data are number of patients (%) in hospital or community setting with reported co-morbidities, and calculated odds ratio, 95% CI, Chi-squared p values or Fischers exact test p values (when the cell count was less than 5) of cases versus controls and CD versus controls. Significant variables are highlighted in bold (p values <0.05 and 95% CI that do not include 1.0).
CCNA: cell-cytotoxin neutralisation assay; CDI: Clostridioides difficile infection; CI: confidence intervals; CTC: cell cytotoxigenic culture; n= number of participants exposed to indicated variable. ; N= total number of participants in analysis (with data); na=not able to compute odds ratio due to a value of 0 in one of the groups; p: p values; SIMOA: ultra-sensitive toxin single molecule array. Categorical variables of patients negative for C. difficile infection at the European Coordinating Laboratory but positive for novel SIMOA technology at bioMérieux. SIMOApos term was chosen to describe participants group SIMOA positive/CCNA negative (presence of C. difficile toxin using novel test).

Cases
Data are number of patients (%) in hospital or community setting with previous exposure prior to the sample being taken, and calculated odds ratio, 95% CI, Chi-squared p values or Fischers exact test p values (when the cell count was less than 5) of SIMOApos versus controls. Antibiotic use and class of antibiotics refers to antibiotics prescribed for treatment or prophylaxis of an infection other than CDI in the preceding 12 weeks. Significant variables are highlighted in bold (p values <0.05 and 95% CI that do not include 1.0).
CCNA: cell-cytotoxin neutralisation assay; CDI: Clostridioides difficile infection; CI: confidence intervals; n= number of participants exposed to indicated variable. ; N= total number of participants in analysis (with data); na=not able to compute odds ratio due to a value of 0 in one of the groups; p: p values; SIMOA: ultra-sensitive toxin single molecule array.