Abstract
A broad spectrum of symptoms has been associated with C. difficile infection (CDI). Several studies indicate that toxin-production correlates with growth rates of C. difficile. This study aimed to correlate growth rates of C. difficile with disease severity and strain characteristics. From 01/2003 to 10/2011, strains from a prospective cohort of all inpatients with CDI at the University Hospital Basel, Switzerland were analyzed regarding binary toxin, presence of the tcdC deletion and ribotype. Isothermal microcalorimetry was performed to determine growth rates, quantified by the Gompertz function. Ordered logistic regression models were used to correlate disease severity with strain features and clinical characteristics. Among 199 patients, 31 (16%) were infected with binary toxin-producing strains, of which the tcdC gene-deletion nt117 was detected in 9 (4%). Disease severity was classified as mild in 130 patients (65.3%), as severe in 59 patients (29.7%) and as severe/complicated in 10 patients (5.0%). Growth rates were inversely associated with disease severity in univariable (OR 0.514, 95%CI 0.29–0.91, p = 0.023) and multivariable analyses (OR 0.51, 95%CI 0.26–0.97, p = 0.040). While none of the strain characteristics such as presence of the tcdC gene deletion or binary toxin predicted CDI severity, growth rates were inversely correlated with disease severity. Further investigations are needed to analyze growth-regulators and respective correlations with the level of toxin production in C. difficile, which may be important determinants of disease severity.
Highlights
Clostridium difficile is the most frequent cause of healthcare associated diarrhea, and a significant cause of morbidity and mortality among hospitalized patients [1]
Seven cases had to be excluded due to non-detectable growth of their respective strains as determined by microcalorimetry. These seven patients did not differ regarding baseline characteristics, prior exposures, strain characteristics or distribution of disease severity from the patients included in the analyses
Growth rates were inversely correlated with disease severity, while no other strain characteristics as presence of the tcdC gene deletion, binary toxin or ribotype predicted severe C. difficile infection (CDI) in this cohort
Summary
Clostridium difficile is the most frequent cause of healthcare associated diarrhea, and a significant cause of morbidity and mortality among hospitalized patients [1]. In a recently published multistate prevalence survey of health care–associated infections in the United States, C. difficile was the most commonly reported pathogen causing 12.1% of health care–associated.
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