Decreased Cure and Increased Recurrence Rates for Clostridium difficile Infection Caused by the Epidemic C. difficile BI Strain

Petrella, Laurica A.; Sambol, Susan P.; Cheknis, Adam; Nagaro, Kristin; Kean, Yin; Sears, P.S.; Babakhani, Farah; Johnson, Stuart; Gerding, Dale N.

doi:10.1093/cid/cis430

Cited by 165 publications

(103 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two very recent studies have described increased recurrence rates and a trend toward a higher incidence of relapse among patients infected with BI strains as defined by REA typing (8,26). These data could have major implications for treatment and development of new therapeutics that specifically target infection with BI/NAP1/027 strains.…”

Section: Discussionmentioning

confidence: 93%

“…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).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Association of Relapse of Clostridium difficile Disease with BI/NAP1/027

et al. 2012

View full text Add to dashboard Cite

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. ...

show abstract

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Association of Relapse of Clostridium difficile Disease with BI/NAP1/027

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Thus far, widespread evidence has revealed that various factors predictive of rCDI-similar to those already mentioned for CDI-are suspected of microbiome modulation, including PPIs, antibiotic re-exposure after CDI treatment, fluoroquinolone use, appendectomy, surgery, chemotherapy, low immunoglobulin levels against C. difficile toxin A or B, age, and infection with hypervirulent B1/NAP1/ribotype 027 strains [45][46][47][48][49][50][51]. Other risk factors include the presence of an ileal pouch [52], fecal incontinence, and concomitant antacid use and hypoalbuminemia [47,[53][54][55].…”

Section: Recurrent C Difficile Infection (Rcdi)mentioning

confidence: 91%

Recurrent Clostridium difficile infection and the microbiome

2015

View full text Add to dashboard Cite

The diverse and densely populated gastrointestinal microbiota is essential for the regulation of host physiology and immune function. As our knowledge of the composition and function of the intestinal microbiota continues to expand, there is new interest in using these developments to tailor fecal microbiota transplantation (FMT) and microbial ecosystem therapeutics (MET) for a variety of diseases. The potential role of FMT and MET in the treatment of Clostridium difficile infection (CDI)-currently the leading nosocomial gastrointestinal infection-has proven highly effective for recurrent CDI, and has emerged as a paradigm shift in the treatment of this disease. The current review will serve as a summary of the key aspects of CDI, and will introduce the essential framework and challenges of FMT, as is currently practiced. MET represents the progression of conventional bacteriotherapy that fundamentally capitalizes on the restorative properties of intestinal bacterial communities and may be viewed as the culmination of a rationally designed therapeutic modality. As our understanding of the composition and function of the intestinal microbiota evolves, it will likely drive next-generation microbiota therapies for a range of medical conditions, such as inflammatory bowel disease, obesity, and metabolic syndrome.

show abstract

“…Th e NAP1 / BI / 027 strains have a higher rate of fl uoroquinolone resistance, produce 16 times more toxin A, and 23 times more toxin B in vitro than other C. diffi cile strains ( 215 ); and produce a binary toxin. Patients infected with this strain are reported to have lower clinical cure rates and higher rates of CDI recurrences than patients with other strains ( 216 ). However, several studies have failed to demonstrate an association between NAP1 / BI / 027 strains and severe disease ( 217 -220 ).…”

Section: Appendixmentioning

confidence: 98%

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,457

1,408

View full text Add to dashboard Cite

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 ...

show abstract

Decreased Cure and Increased Recurrence Rates for Clostridium difficile Infection Caused by the Epidemic C. difficile BI Strain

Cited by 165 publications

References 19 publications

Association of Relapse of Clostridium difficile Disease with BI/NAP1/027

Association of Relapse of Clostridium difficile Disease with BI/NAP1/027

Recurrent Clostridium difficile infection and the microbiome

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Contact Info

Product

Resources

About