Background: Currently reported risk factors for and outcomes of C. difficile infection (CDI) may be clouded by the use of different diagnostic methods in studies.
Materials/methods: Sites were recruited from 12 countries across Europe (1 site/3 million population). On two days, all diarrhoeal samples (regardless of tests requested, n=3613) were sent to the European coordinating laboratory for C. difficile toxin detection; cell-cytotoxin neutralisation testing (CCNA) ultrasensitive immunoassay (SIMOA) and cytotoxigenic culture (CTC). Cases were defined as C1 (CCNA positive n=94), C2 (CCNA-negative/SIMOA-positive n=43), C3 (toxin-negative/CTC-positive n=34); C4 controls (negative by all assays n=444). Data were collected on patient outcomes and risk factors and comparisons made according to diagnostic categories C1-4.
Results: C1 cases were significantly older vs C3 (median age 71 vs 47 years, p=0.013), and vs controls (C4) (71 vs 55 years p<0.0001). C2 cases were significantly older than controls (C4) (p=0.006), but not C3 (p=0.132); C3 were not significantly older than controls (p=0.859).
Mean white cell count of cases in C1 and C1+C2 (toxin positive) was significantly higher than controls (14.8×109/L vs 10.3×109/L, p=0.008 and14.4 vs 10.3×109/L, p=0.002). Median length of stay (LOS) was significantly longer for C1 (12 versus 10days p=0.157), C2 (30 vs 10days, p=0.011), and C1+C2 (14 vs 10days p=0.011) than controls. There was no significant difference in LOS between C3 and controls. 30-day mortality rate was significantly higher for C1 cases (15.9% vs 6.0%, p=0.002) and C1+C2 (13.3% vs 6.0%, P=0.007) versus controls.
The significant risk factors according to diagnostic categories are shown in Figure 1. There were no significant risk factors identified for C3 patients.
Conclusions: There are significant differences in outcome between patients diagnosed as toxin positive versus only CTC positive cases, when compared with controls, such as higher mortality rates and length of stay in toxin positive individuals. Risk factors for the development of toxin positive CDI were observed, but there were no risk factors identified for the presence of the organism alone, e.g. increasing age, use of antibiotics and increased co-morbidities appear to be a risk factors for toxin positive CDI, but not acquisition of the organism itself.