番茄社区

SAN DIEGO -- Patients with Clostridium difficile infection and underlying impaired renal function who were treated with fidaxomicin fared better than those given vancomycin, a researcher said here.

Patients with toxin-positive C. difficile infection and creatinine clearance below normal (90 mL/min/1.73 m²) were half as likely to experience a recurrence of diarrhea if treated with fidaxomicin (OR 0.46, 95% CI 0.32 to 0.66, P<0.001), reported Kate Mullane, MD, of the University of Chicago.

In addition, patients with moderate to severe renal impairment who received fidaxomicin (Dificid) had almost twice the likelihood of experiencing a 4-week sustained response compared with those given vancomycin (OR 1.89, 95% CI 1.41 to 2.53, P<0.001), Mullane reported at the annual meeting of the Society of Hospital Medicine.

Fidaxomicin and vancomycin are similar drugs, in that they are non-absorbable antibiotics, and they usually have similar initial response rates, she explained.

"However, patients with renal impairment are more immunocompromised and often are unable to fully clear infections and maintain a sustained response," Mullane told 番茄社区 in a poster session.

To determine the effects of the drug in this population of patients, she and her colleagues analyzed data from two randomized trials comparing 400 mg per day of fidaxomicin with 500 mg per day of vancomycin for 10 days.

Of 1,031 patients in the two studies, 27% had mild impaired renal function, 21% had moderate impairment, and in 9% the impairment was severe.

Overall cure rates were 91% for patients with normal renal function and 92% for those with mild impairment, but decreased to 80% for those with moderate impairment and 74% for those with severe impairment.

Mortality in both treatment groups also was greater with increasing degree of renal dysfunction, rising from 2.9% with normal creatinine clearance to 17.4% for severe impairment (P <0.001 for trend).

Following initial cure, the overall recurrence rates increased from 16% with normal renal function to 25% with severe dysfunction.

However, the absolute difference in recurrence rates differed between the treatment groups at 21% with vancomycin and 11% with fidaxomicin among those with normal renal function, and 35% versus 15% for severe dysfunction in the vancomycin and fidaxomicin groups, respectively.

On multivariate analyses, having moderate to severe renal impairment was associated with recurrence (OR 1.80, 95% CI 1.80 to 2.98, P=0.024) and inversely associated with sustained response (OR 0.51, 95% CI 0.34 to 0.77, P=0.001).

An important factor contributing to the superiority of fidaxomicin in this patient group is its greater selectivity for C. difficile, according to Mullane.

"This treatment allows the gut microbiota to repopulate, which contributes to the sustained response," she said.

In addition, spore counts are reduced and there is less toxin production, she noted.

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