Recurrent Clostridium difficile Infection

Recurrent Clostridium difficile Infection: Enter Fidaxomicin.

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 Fidaxomicin significantly reduced the recurrence rate in patients infected with non-NAP1/BI/027 strains.

Recurrence of Clostridium difficile infection (CDI) is common, whether metronidazole or vancomycin is used as initial therapy. Fidaxomicin, a new macrocyclic antibiotic that has no cross-resistance with other antibiotics, is more active in vitro than vancomycin against clinical C. difficile isolates; in a phase II trial, it was associated with good clinical response and a low CDI recurrence rate. Now, in a manufacturer-sponsored, multicenter, double-blind, phase III trial, researchers have compared this agent with oral vancomycin in 629 adults with CDI.

Participants were randomized to receive fidaxomicin (200 mg twice daily) or vancomycin (125 mg 4 times daily) orally for 10 days. The primary endpoint was clinical cure (resolution of diarrhea; no need for additional CDI therapy as of posttreatment day 2). Secondary endpoints included CDI recurrence during the 4-week period after the end of therapy.

The clinical cure rates with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat (MITT) population (88.2% and 85.8%, respectively) and the per-protocol (PP) population (92.1% and 89.8%). Among patients infected with the NAP1/BI/027 strain, the recurrence rates were similar between treatment arms in the two populations. However, among those infected with non-NAP1/BI/027 strains, the recurrence rates differed dramatically between vancomycin and fidaxomicin in both the MITT population (28.1% vs. 10.3%; P<0.001) and the PP population (25.5% vs. 7.8%; P<0.001). The rates of adverse events and serious adverse events were similar between treatment arms.

Comment: On the basis of the findings from this investigation, an editorialist wrote that fidaxomicin appeared to be “an important advance.” I hope that this is the case — new, more-effective treatments for CDI are badly needed.

Source: Journal Watch Infectious Diseases.

 

Does Recurrent Clostridium difficile Infection Mean Reinfection or Relapse?

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Even after months, most recurrences appear to be relapses.

Both nosocomial and community-acquired Clostridium difficile infections are becoming common enough that when patients have repeated infections, distinguishing between relapse and reinfection often is difficult. Making this distinction can be important both for tracking and for management.

Researchers used a polymerase chain reaction assay to type organisms from 134 paired stool isolates obtained from 102 patients with recurrent C. difficile infections who were seen during 30 months at a single New York City hospital; 24 patients had three or more episodes. Among stool isolates obtained 2 to 8 weeks apart, 88% yielded identical strains, which suggested relapse rather than reinfection; among isolates obtained 8 weeks to 11 months apart, 65% yielded identical strains. Similar patterns were seen among the patients with more than one recurrence: Among the 17 patients with four or more episodes, 11 had the same strain isolated for all episodes.

Comment: These data suggest that recurrent C. difficile infection often represents relapse rather than reinfection, no matter how long between episodes. However, as the authors point out, even patients who are treated and completely asymptomatic can continue to shed organisms into the environment and thus can transmit infection horizontally to themselves, confounding the usual semantics of infection.

Source:Journal Watch General Medicine