Clostridium diffi cile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratifi ed depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mildto-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classifi cation of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI. Am J Gastroenterol 2013; 108:478-498; doi: 10.1038/ajg.2013 12. In patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman's pouch, ileostomy, or colon diversion, vancomycin therapy delivered via enema should be added to treatments above until the patient improves. (Conditional recommendation, low-quality evidence)13. The use of anti-peristaltic agents to control diarrhea from confi rmed or suspected CDI should be limited or avoided, as they may obscure symptoms and precipitate complicated disease. Use of anti-peristaltic agents in the setting of CDI must always be accompanied by medical therapy for CDI. (Strong recommendation, low-quality evidence) Management of severe and complicated CDI14. Supportive care should be delivered to all patients and includes intravenous fl uid resuscitation, electrolyte replacement, and pharmacological venous thromboembolism prophylaxis. Furthermore, in the absence of ileus or signifi cant abdominal distention, oral or enteral feeding should be continued. 17. Vancomycin delivered orally (500 mg four times per day) and per rectum (500 mg in a volume of 500 ml four times a day) plus intravenous metronidazole (500 mg three times a day) is the treatment of choice for patients with complicated CDI with ileus or toxic colon and / or signifi cant abdominal distention. (Strong recommendation, low-quality evidence)18. Surgical consult should be obtained in all patients with complicated CDI. Surgical therapy should be considered in patients with any one of the following attributed to CDI: hypotension requiring vasopressor therapy; clinical signs of sepsis and organ dysfunction (renal and pulmonary); mental status changes; white blood cell count ≥ 50,000 cells / μ l, lactate ≥ 5 mmol / l; or failure to improve on medical therapy after 5 days. (Strong recommendation, moderate-quality evidence) Management of recurrent CDI (RCDI)19. The fi rst recurrence of CDI can be treated ...

In our hospital with an established infection control program designed to contain transmission from symptomatic CDI patients, asymptomatic carriers appear to have played an important role in transmission. Identification and isolation of carriers may be necessary to further reduce transmission of C. difficile in such settings.

Severe Clostridium difficile associated disease is associated with outbreaks of the recently described BI/NAP1 epidemic clone. This clone is characterized by an 18-bp deletion in the tcdC gene and increased production of toxins A and B in vitro. TcdC is a putative negative regulator of toxin A&B production. We characterized tcdC genotypes from a collection of C. difficile isolates from a hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone. Sequence analysis of tcdC was performed on DNA samples isolated from 199 toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences obtained from 36 (18.6%) isolates predicted wild-type TcdC (232 amino acid residues), whereas 12 (6.1%) isolates had tcdC genotypes with previously described 18-or 39-bp deletions. The remaining isolates comprised 15 unique genotypes. Of these, 5 genotypes contain 18-or 36-bp deletions. Of these five genotypes, one is characterized by a single nucleotide deletion at position 117 resulting in a frameshift that introduces a stop codon at position 196, truncating the predicted TcdC to 65 amino acid residues. All 62 of the isolates in this collection comprising the epidemic clone are characterized by this genotype. This result suggests that severe truncation of TcdC is responsible for the increased toxin production observed in strains belonging to the BI/NAP1 clone and that the 18-bp deletion is probably irrelevant to TcdC function. Further investigations are required to determine the effect of this and other tcdC genotypes on toxin production and clinical disease.

bRecurrent Clostridium difficile infection (CDI) occurs in up to 35% of patients. Recurrences can be due to either relapse with the same strain or reinfection with another strain. In this study, multilocus variable-number tandem-repeat analysis (MLVA) was performed on C. difficile isolates from patients with recurrent CDI to distinguish relapse from reinfection. In addition, univariate and multivariate analyses were performed to identify risk factors associated with relapse. Among patients with a single recurrence, relapse due to the original infecting strain was more prevalent than reinfection and the interval between episodes was shorter than among patients who had reinfections. Among patients with >1 recurrence, equal distributions of relapse and reinfection or a combination of the two episode types were observed. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. This finding may have important implications for patient therapy. Classification of recurrent CDI episodes by MLVA can be utilized to make informed patient care decisions and to accurately define new CDI cases for infection control and reimbursement purposes. One of the most problematic aspects of Clostridium difficile infections (CDI) is the propensity of recurrence in 15% to 35% of patients who initially respond to antimicrobial therapy. In addition, recurrent CDI is difficult to treat and contributes to significant morbidity and mortality and increased health care expenditures (10,11,27).The molecular epidemiology of CDI has changed since 2000 with the global spread of an epidemic clone, designated BI/NAP1/ 027 by restriction endonuclease analysis (REA), pulsed-field gel electrophoresis, and PCR ribotyping. However, recent studies have raised doubts regarding the role of BI/NAP1/027 in increased CDI incidence, severity, and recurrence rates (4, 21).Recurrent CDI can caused by either relapse due to the original infecting strain or reinfection with a new strain. Previous studies have demonstrated that continued non-CDI antibiotic treatment and a failed immune response to C. difficile toxins A and B are risk factors for recurrent CDI (15,20,25). Most recently, lower cure rates and higher rates of recurrence due to BI/NAP1/027 infection were reported in phase 3 clinical trials of fidaxomicin (26). Recent estimates suggest that 65% to 88% of recurrent CDI is attributable to relapse with the original infecting strain (2, 3, 12). However, some of the molecular typing methods used in these studies such as PCR-ribotyping and random amplification of polymorphic DNAs (RAPD) lack sufficient discriminatory power and may have misclassified reinfections as relapses. In a study using restriction endonuclease analysis (REA), 83.3% of recurrences were due to relapse (8). In this study, multilocus variable-number tandemrepeat analysis (MLVA), a highly discriminatory C. difficile genotyping method, was used to define relapse in patients with recurrent CDI and to identify risk factors associated with relapse. ...

Background Rifampin is used as adjunctive therapy for Clostridium difficile–associated disease, and the drug’s derivative, rifaximin, has emerged as an attractive antimicrobial for treatment of C. difficile–associated disease. Rifampin resistance in C. difficile strains has been reported to be uncommon. Methods We examined the prevalence of rifampin resistance among 470 C. difficile isolates (51.1% during 2001–2002 and 48.9% during 2005) from a large teaching hospital. Rifampin sensitivity was performed using E-test. The epidemic BI/NAP1 C. difficile clone was identified by tcdC genotyping and multilocus variable number of tandem repeats analysis. A 200–base pair fragment of the rpoB gene was sequenced for 102 isolates. Data on rifamycin exposures were obtained for all patients. Results Rifampin resistance was observed in 173 (36.8%) of 470 recovered isolates and 167 (81.5%) of 205 of epidemic clone isolates (P < .001). Six rpoB genotypes were associated with rifampin resistance. Of 8 patients exposed to rifamycins, 7 had rifampin-resistant C. difficile, compared with 166 of 462 unexposed patients (relative risk, 2.4; 95% confidence interval, 1.8–3.3). Conclusions Rifampin resistance is common among epidemic clone C. difficile isolates at our institution. Exposure to rifamycins before the development of C. difficile–associated disease was a risk factor for rifampin-resistant C. difficile infection. The use of rifaximin may be limited for treatment of C. difficile–associated disease at our institution.