Medline ® Abstracts for References 13-17
of 'Clostridium difficile infection in adults: Clinical manifestations and diagnosis'
Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection.
Hu MY, Katchar K, Kyne L, Maroo S, Tummala S, Dreisbach V, Xu H, Leffler DA, Kelly CP
Gastroenterology. 2009;136(4):1206. Epub 2008 Dec 13.
BACKGROUND&AIMS: Prevention of recurrent Clostridium difficile infection (CDI) is a substantial therapeutic challenge. A previous prospective study of 63 patients with CDI identified risk factors associated with recurrence. This study aimed to develop a prediction rule for recurrent CDI using the above derivation cohort and prospectively evaluate the performance of this rule in an independent validation cohort.
METHODS: The clinical prediction rule was developed by multivariate logistic regression analysis and included the following variables: age>65 years, severe or fulminant illness (by the Horn index), and additional antibiotic use after CDI therapy. A second rule combined data on serum concentrations of immunoglobulin G (IgG) against toxin A with the clinical predictors. Both rules were then evaluated prospectively in an independent cohort of 89 patients with CDI.
RESULTS: The clinical prediction rule discriminated between patients with and without recurrent CDI, with an area under the curve of the receiver-operating-characteristic curve of 0.83 (95% confidence interval [CI]: 0.70-0.95) in the derivation cohort and 0.80 (95% CI: 0.67-0.92) in the validation cohort. The rule correctly classified 77.3% (95% CI: 62.2%-88.5%) and 71.9% (95% CI: 59.2%-82.4%) of patients in the derivation and validation cohorts, respectively. The combined rule performed well in the derivation cohort but not in the validation cohort (area under the curve of the receiver-operating-characteristic curve, 0.89 vs 0.62; diagnostic accuracy, 93.8% vs 69.2%, respectively).
CONCLUSIONS: We prospectively derived and validated a clinical prediction rule for recurrent CDI that is simple, reliable, and accurate and can be used to identify high-risk patients most likely to benefit from measures to prevent recurrence.
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis.
Tedesco FJ, Gordon D, Fortson WC
Am J Gastroenterol. 1985;80(11):867.
Twenty-two patients with multiple relapses of antibiotic-associated pseudomembranous colitis underwent a tapering dose of oral vancomycin for 21 days and a pulse dose of vancomycin for 21 days. In follow-up ranging from 2-12 months with a mean of 6 months, all patients have been without recurrence of the antibiotic-associated pseudomembranous colitis.
Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea.
Kyne L, Warny M, Qamar A, Kelly CP
BACKGROUND: We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A, during an episode of C. difficile diarrhoea, influences risk of recurrence.
METHODS: We prospectively studied 63 patients with nosocomial C. difficile diarrhoea. Serial serum IgA, IgG, and IgM concentrations against C. difficile toxin A, toxin B, or non-toxin antigens were measured by ELISA. Individuals were followed for 60 days.
FINDINGS: 19 patients died (30%). Of the 44 who survived, 22 had recurrent C. difficile diarrhoea. Patients with a single episode of C. difficile diarrhoea (n=22) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea (n=22, p=0.004). On day 12, serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea (n=7) than in those who subsequently had recurrent diarrhoea (n=9, p=0.009). The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A, measured 12 days after onset of C. difficile diarrhoea, was 48.0 (95% CI 3.5-663).
INTERPRETATION: A serum antibody response to toxin A, during an initial episode of C. difficile diarrhoea, is associated with protection against recurrence.
Gerontology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. email@example.com
Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada.
Pépin J, Routhier S, Gagnon S, Brazeau I
Clin Infect Dis. 2006;42(6):758.
BACKGROUND: During an epidemic of Clostridium difficile-associated disease (CDAD) caused by a strain that is a hyper-producer of toxins A and B, the frequency of a first recurrence after metronidazole treatment of the initial episode doubled in 2003-2004, compared with 1991-2002.
METHODS: To examine whether administration of metronidazole as treatment for a first recurrence of CDAD remained appropriate, we reviewed data for patients with CDAD diagnosed in a hospital in Quebec, Canada, during 1991-2005, who experienced a first recurrence. The frequency of a second recurrence within 60 days after the first one was measured using Kaplan-Meier analysis. Cox regression was used for multivariate analysis.
RESULTS: A total of 463 patients had a first recurrence of CDAD, of whom 154 (33.3%) experienced a second recurrence. Independent predictors of a second recurrence were age and duration of hospitalization after the first recurrence; this latter finding suggested that many such episodes were reinfections rather than relapses. Neither choice of treatment drug (metronidazole or vancomycin) nor use of the same drug for treatment of first recurrence, as had been used during the initial episode, was associated with increased risk of a second recurrence. However, 51 patients (11.0%) developed at least 1 complication (i.e., shock, need for colectomy, megacolon, perforation, or death within 30 days) during the first recurrence. Older age, a high leukocyte count, and renal failure at first recurrence were strongly associated with a complicated CDAD.
CONCLUSIONS: Metronidazole is not inferior to vancomycin for treatment of patients with a first recurrence of CDAD, but the risk of complications with any treatment of CDAD may be higher than has previously been documented.
Department of Microbiology and Infectious Diseases, University of Sherbrooke, Quebec, Canada. firstname.lastname@example.org
Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence.
Gupta SB, Mehta V, Dubberke ER, Zhao X, Dorr MB, Guris D, Molrine D, Leney M, Miller M, Dupin M, Mast TC
Clin Infect Dis. 2016 Sep;63(6):730-4. Epub 2016 Jun 30.
BACKGROUND: Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels.
METHODS: Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays.
RESULTS: A predictor of recurrence was age≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI.
CONCLUSIONS: Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI.
CLINICAL TRIALS REGISTRATION: NCT00350298.
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