Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection.

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.

A prospective study of risk factors and historical trends in metronidazole failure for Clostridium difficile infection.

BACKGROUND & AIMS: Recent studies of Clostridium difficile infection (CDI) have indicated a dramatic increase in metronidazole failure. The aims of this study were to compare current and historical rates of metronidazole failure and to identify risk factors for metronidazole failure. METHODS: Eighty-nine patients with CDI in 2004 to 2006 were followed for 60 days and were compared with a historical cohort of 63 CDI patients studied prospectively in 1998. Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin. Stool samples were analyzed for the presence of the North American pulsed-field gel electrophoresis type-1 (NAP-1) strain. RESULTS: Metronidazole failure rates were 35% in both cohorts. There was no difference in the median time to resolution of diarrhea (8 vs 5 d; P = .52) or the proportion with >10 days of diarrhea (35% vs 29%; P = .51). Risk factors for metronidazole failure included recent cephalosporin use (odds ratio [OR], 32; 95% confidence interval [CI], 5-219), CDI on admission (OR, 23; 95% CI, 3-156), and transfer from another hospital (OR, 11; 95% CI, 2-72). The frequency of NAP-1 infection in patients with and without metronidazole failure was similar (26% vs 21%; P = .67). CONCLUSIONS: We found no difference in metronidazole failure rates in 1998 and 2004 to 2006. Patients with recent cephalosporin use, CDI on admission, and transfer from another hospital were more likely to metronidazole failure. Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI.

A faculty development program to train tutors to be discussion leaders rather than facilitators.

PURPOSE: During 2003, 2004, and 2005, the role of 70 tutors was changed from that of facilitator to discussion leader, in a preclinical PBL learning course, Gastrointestinal Pathophysiology, by use of three key business school teaching strategies: questions, summaries, and schematics. The purpose of this study was to learn what difference this new approach made. METHOD: During each of the three study years, 171 (2003), 167 (2004), and 170 (2005) students were given Likert-scale attitudinal questionnaires to rate whether their tutors encouraged student direction of the tutorials and whether the summaries and closure schematics benefited their learning. Students' overall course evaluations and mean USMLE scores were quantitatively analyzed, pre- and postintervention. A variety of statistical tests were used to assess the statistical significance of means at the confidence level of .05. RESULTS: In the third year of the program, student ratings indicated that their tutors were significantly better at encouraging student direction of the tutorials than in the first year (P < .05). The students reported that the tutorial made a more important contribution to their learning (P < .05), and the course objectives were better stated (P = .038) and better met (P = .007). Overall satisfaction with the course also improved significantly (P = .006). Part I gastrointestinal system mean scores of the USMLE showed a statistically significant increase in 2005 compared with 2001 or 2002. CONCLUSIONS: The tutor as a discussion leader who questions, summarizes, and uses schematics to illustrate concepts had a significant and positive impact on learning in tutorials, achieving course objectives, improving overall course satisfaction, and increasing a standardized national exam's mean score.

Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea.

BACKGROUND & AIMS: Recurrent C difficile -associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD. METHODS: Subjects received 4, 50-microg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay. RESULTS: Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence. CONCLUSIONS: A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.