Fidaxomicin versus Vancomycin for<i>Clostridium difficile</i>Infection

Louie, Thomas; Miller, Mark A.; Mullane, Kathleen M.; Weiss, Karl Heinz; Lentnek, Arnold; Golan, Yoav; Gorbach, Sherwood L.; Sears, P.S.; Shue, Youe‐Kong

doi:10.1056/nejmoa0910812

Cited by 1,374 publications

(1,340 citation statements)

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“…On the basis of two RCTs with oral vancomycin, the FDA granted approval for fi daxomicin in May 2011 ( 53,54 ). In both published phase III trials, fi daxomicin demonstrated non-inferiority to vancomycin in the modifi ed intention-to-treat and the per-protocol analyses for clinical response at the end of therapy and at 25 days post therapy.…”

Section: Management Of Mild Moderate and Severe CDImentioning

confidence: 99%

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

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,457

1,406

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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 ...

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Section: Management Of Mild Moderate and Severe CDImentioning

confidence: 99%

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

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,457

1,406

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“…Multiple recurrences can occur and the recommended treatment is pulsed or tapered vancomycin therapy to allow spore germination between doses to improve efficacy [McFarland et al 2002]. Recently the use of fidaxomycin has been indicated in multiple recurrent CDI [de Lalla et al 1992;Louie et al 2011; There is therefore a strong reliance on antimicrobial therapeutics to treat initial episode, severe and recurrent CDI. The deleterious effect on the protective gut flora may explain why standard antimicrobial treatment can fail to resolve recurrent CDI in up to 23% of cases [Surawicz, 2004].…”

Section: Antimicrobial Therapymentioning

confidence: 99%

The host immune response to Clostridium difficile infection

Solomon

2013

Therapeutic Advances in Infection

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Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host.Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways.Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response.The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future.

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“…Low-risk patients can still safely receive metronidazole therapy, but patients with severe diseases require treatment with either oral vancomycin or fidaxomicin. 23 However, in one study, fidaxomicin compared to oral vancomycin decreased the relapse rate from 24% to 13.3% and decreased the risk of vancomycinresistant Enterococcus colonization from 31% to 7%. 13 …”

Section: Clostridium Difficile Colitismentioning

confidence: 98%