Renal Impairment and Clinical Outcomes of <i>Clostridium difficile</i> Infection in Two Randomized Trials

Abstract

Background/Aims: Patients with chronic kidney disease (CKD) have increased risk for Clostridium difficile infection (CDI) and for subsequent mortality. We determined the effect of CKD on response to treatment for CDI. Methods: This is a post hoc analysis of two randomized controlled phase 3 trials that enrolled patients with CDI. Patients received either fidaxomicin 200 mg b.i.d. or vancomycin 125 mg q.i.d. for 10 days. Univariate and multivariate analyses compared end points by treatment received and CKD stage. Results: At baseline, 27, 21, and 9% of the patients had stage 2 (60-89 ml/min/1.73 m²), stage 3 (30-59), and stage 4 or higher (<30) CKD. Cure rates were similar for normal (91%) and stage 2 CKD (92%), but declined to 80% for stage 3 and to 75% for stage 4 CKD (p < 0.001 for trend). Time to resolution of diarrhea (TTROD) increased with stage 3 and stage 4 CKD. CDI recurrence rates 4 weeks after treatment were 16, 20, 27, and 24% for normal, stage 2, stage 3, and stage 4 or higher CKD, respectively. Mortality increased with CKD stage. In multivariate analyses, stage 3 or higher CKD correlated with lower odds of cure, greater chance of recurrence, and lower odds of sustained response 28 days after treatment. Initial cure rates were similar in the vancomycin or fidaxomicin groups; however, the rate of recurrence was higher following vancomycin treatment independent of renal function. The presence of immunosuppression did not alter this effect. Conclusion: Progressive CKD is associated with increased TTROD, lower cure rates, and higher recurrence rates with treatment of CDI.

Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain

“…All the characteristics of the Markov model have been extensively described in the assessment reports by the Welsh and Scottish authorities in the United Kingdom [18,19], as well as in several publications [17,20,21]. Patients in the model were treated orally with fidaxomicin [200 mg twice daily (BID) for 10 days] or vancomycin [125 mg four times daily (QID) for 10 days] [3][4][5]18]. All patients initially had CDI and, following treatment, were either clinically cured or not clinically cured (i.e.…”

“…Data on the effectiveness of the antibiotics in the treatment of CDI and the main probabilities of transition between health states used in the model were obtained from the clinical trial publications that reported the results in the specific populations studied [3][4][5] and from other published sources [1,2,[31][32][33][34][35] (Table 3). Quality-adjusted life-years (QALYs) for the CDI patients were calculated from utilities obtained from Slobogean et al…”

“…& Two randomised controlled trials reported the efficacy of fidaxomicin compared to vancomycin in three CDI patient subgroups: those with cancer, treated with concomitant antibiotic therapy and with renal impairment [3][4][5]. & Previous studies have reported that CDI in these subgroups is associated with greater mortality [6], with higher recurrence rates and longer hospital stays than other CDI patients [7].…”

“…Of the patients included in the clinical trials, additional subgroup analyses were performed in patient subgroups with a higher risk of recurrence than the overall CDI population. These subgroups were patients with cancer [odds ratio (OR)=0.37; p=0.018] [3], patients treated with concomitant antibiotic treatment (OR= 0.492; p=0.0499) [4] and patients with renal impairment (OR=0.487; p<0.001) [5]. Moreover, in these patients, CDI had a greater impact on morbidity and mortality and increased hospital costs [7] compared to the overall CDI patient group.…”

The Risks of Incident and Recurrent Clostridium difficile-Associated Diarrhea in Chronic Kidney Disease and End-Stage Kidney Disease Patients: A Systematic Review and Meta-Analysis

“…The findings of previous studies assessing the risk of CDAD in patients with CKD and end-stage renal disease (ESRD), however, are conflicting. Several studies have shown that a history of CKD or ESRD is significantly associated with incident and recurrent CDAD [7,[9][10][11][12][13][14][15][16][17]. Conversely, a number of studies have shown no significant increased risk of incident and recurrent CDAD in patients with CKD or ESRD [18][19][20][21][22][23][24][25][26].…”