Clostridioides difficile infection undertreated in Singapore

Severe and severe complicated Clostridioides difficile infection (CDI) is prevalent in Singapore, according to a recent study. Meanwhile, treatment with oral metronidazole remains suboptimal.

“This is the first study in Singapore, to our best knowledge, to report on the severity of CDI and describe the treatment and outcomes of hospitalized patients,” said researchers.

A total of 272 patients (median age, 77 years; 42.6 percent male) positive for CDI were included in the retrospective cohort analysis, of whom 40 percent (n=109; median age, 75 years; 47.7 percent male) had severe and/or severe complicated infections. Further disaggregation showed that 56 had severe CDI, while 53 had severe complicated disease. [Sci Rep 2019;9:13340]

Multivariable logistic regression analysis found that a high APACHE II score (adjusted odds ratio [OR], 1.112, 95 percent CI, 1.014–1.219; p=0.024) and elevated C-reactive protein (CRP; adjusted OR, 1.01, 1.004–1.019; p=0.004) were both significantly associated with the risk of severe and/or severe complicated CDI.

The same was true for carbapenem use in the last 90 days (adjusted OR, 3.259, 1.105–9.609; p=0.032), which had the strongest magnitude of effect.

Subgroup analysis then revealed that risk factors for severe CDI included a higher APACHE II score, concurrent antibiotic use for other infections and the onset of CDI in the intensive care unit, among other variables. However, after adjustments for covariates only elevated CRP remained independently predictive of severe infection (adjusted OR, 1.015, 1.008–1.022; p<0.001).

In comparison, more independent risk factors of severe complicated CDI were identified. These included a high APACHE II score (adjusted OR, 1.132, 1.029–1.246; p=0.011), the male gender (adjusted OR, 3.526, 1.343–9.258; p=0.010) and concurrent use of histamine-2 receptor antagonists (adjusted OR, 3.603, 1.170–11.096; p=0.026).

Despite the prevalence of severe and severe complicated CDI, concordance with treatment guidelines remained low at 55.9 percent. This was highest among patients with mild-to-moderate disease. Majority (83.9 percent) were given oral metronidazole alone, while none received the recommended treatment of oral vancomycin.

Similarly, 77.3 percent of the 53 severe complicated CDI episodes were treated with oral metronidazole alone. Only one received oral vancomycin with intravenous metronidazole, the recommended intervention.

“An important finding of this study was the low usage of oral vancomycin to treat severe and severe complicated CDI. This may be due to the under-recognition of severe CDI as this is the first report in Singapore on the prevalence of severe CDI,” the researchers explained.

Overall 30-day mortality was 12.5 percent. Deaths were more common in the severe (16.1 percent; p=0.056) and severe complicated (24.5 percent; p=0.001) CDI groups relative to those with mild-to-moderate disease.

“Our study documented significant burden of severe and severe complicated CDI in Singapore, the suboptimal treatment with oral metronidazole with persistent diarrhoea, major complications and mortality that correlated with severity of CDI,” said the researchers.

“This emphasizes the importance of better surveillance for … and increasing awareness among doctors of severe CDI and optimal treatment with oral vancomycin,” they added.