Key Differences in Diagnosis and Patient Populations between Community and In-Patient Clostridioides Difficile Infections (CDI): Results from Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI)

Background: There is a paucity of data on community-based Clostridioidies difficile infection (CDI) and how these compare with in-patient CDI. Methods: Sites testing both in-patient and community diarrhoeal samples across 12 European countries sent all residual diagnostic material on selected sampling days to a European coordinating-laboratory for CDI testing using reference tests and PCR ribotyping. We used the submitting site test result, or lack thereof, to identify undiagnosed CDI in both settings. We used medical records to identify differences in patient demographics and risk factors for the presence of C. difficile with or without free toxin using reference tests, and for the presence of C. difficile with toxin using a novel ultra-sensitive toxin assay, between each setting. Findings: The burden of CDI was lower in the community than the hospital setting (1·3% vs. 4·4%). The lowest testing rate and highest prevalence of toxinotype IIIb (027, 181 and 176) was seen in Eastern Europe. Different predisposing risk factors for CDI were observed (broad-spectrum penicillins in the community; fluoroquinolones/cephalosporins in the hospital). The proportion of undiagnosed adult CDI was markedly higher in the community (47·3%) than in the hospital (3·7%). Interpretation: Absence of clinical suspicion in the community accounts for three times more undiagnosed adults with CDI compared to hospital settings (1644 vs. 548; yearly across 118 sites). Low testing rates and lack of suspicion may lead to outbreaks of infection and increased burden on healthcare systems. Funding: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement n° 777362. Declaration of Interest: Dr Rupnik reports personal fees from Ferring, personal fees from GSK, outside the submitted work. Dr. Banz, Dr Allantaz and Dr Cleuziat are employees of bioMerieux. Dr. Wilcox reports grants and personal fees from Actelion, Alere, Astellas, Cubist, Da Volterra, Enterobiotix, European Tissue Symposium, Merck, Sanofi-Pasteur, Seres and Summit, personal fees from Astra-Zeneca, Basilea, Bayer, Durata, Idorsia, J&J, Menarini, Nabriva, Novacta, Novartis, Optimer, Pfizer and Roche, grants from Abbott, bioMerieux, Cerexa, The Medicines Company, and Qiagen, outside the submitted work. Dr. Davies reports grants from Astellas Pharma Europe Ltd, grants from Alere, grants from bioMerieux, grants from Cepheid, grants from Pfizer, grants from Sanofi-Pasteur, personal fees from Astellas Pharma Europe Ltd, personal fees from Summit, outside the submitted work. The other authors have nothing to disclose. Ethical Approval: Ethical approval for the study was received from every country taking part, and informed consent was not required for the use of anonymised residual diagnostic material and data.