Growth Patterns of Clostridium difficile - Correlations with Strains, Binary Toxin and Disease Severity: A Prospective Cohort Study.
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.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Sarah
S
Tschudin-Sutter
Laboratory of Biomechanics and Biocalorimetry, University of Basel, Basel, Switzerland.
Olivier
O
Braissant
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Stefan
S
Erb
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Anne
A
Stranden
Department of Urology, University Hospital Basel, Basel, Switzerland.
Gernot
G
Bonkat
Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
Reno
R
Frei
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Andreas F
AF
Widmer
D000328:Adult; D000368:Aged; D001426:Bacterial Proteins / Q000235:genetics*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics*; D016360:Clostridioides difficile / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D003015:Clostridium Infections / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013557:Switzerland
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D012097:Repressor Proteins; C105615:TcdC protein, Clostridium difficile