Methods: We used data from 2 large, randomized phase 3 clinical trials in which adults with CDI symptoms and a positive toxin test received oral fidaxomicin or vancomycin for 10 days. ALD was defined as having a diagnosis of liver cirrhosis or its complications (esophageal varices or ascites). CDI outcomes (cure, death, recurrence, and sustained response) were compared to patients without ALD. We also examined the effectiveness of fidaxomicin vs vancomycin in patients with ALD. Subjects with history of hepatitis or alcoholism but no evidence of ALD were excluded.
Results: We compared 94 subjects with ALD and 963 without ALD. Subjects with ALD were more likely to be male (68% vs 38%, p<0.01), treated as inpatient (78% vs 61%, p<0.01), have chronic kidney disease (29% vs 17%, p<0.01), and receive concomitant antibiotics (42% vs 28%, p=0.01). CDI outcomes were similar between subjects with and without ALD and remained comparable after adjustment for confounders. Of subjects with ALD, 50 (53%) and 44 (47%) received fidaxomicin and vancomycin, respectively. In univariate analysis, CDI outcomes for subjects with ALD receiving fidaxomicin vs vancomycin included cure (Fidaxomicin 90% vs vancomycin 80%, p=0.16), death (2% vs 11%, p=0.06), recurrence (11% vs 26%, p=0.09), and sustained response (80% vs 59%, p=0.03). As compared to subjects without ALD, for those with ALD, the level of sustained response was higher for fidaxomicin (ALD 80% vs no-ALD 76%) and lower for vancomycin (59% vs 65%). In multivariate analysis, the improved differential effect of fidaxomicin vs vancomycin in subjects with ALD as compared to subjects without ALD was maintained (ALD: fidaxomicin vs vancomycin OR 3.2, 95% CI 1.1-8.9, non-ALD: OR 1.7, 1.3-2.3).
Conclusion: CDI outcomes in subjects with ALD were comparable to subjects without ALD. Fidaxomicin maintained its superiority over vancomycin in achieving sustained response in subjects with ALD.