fidaxomicin and Renal-Insufficiency--Chronic

Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Antimicrobial Stewardship; Broadly Neutralizing Antibodies; Clostridium Infections; Enterocolitis, Pseudomembranous; Fecal Microbiota Transplantation; Fidaxomicin; Hand Hygiene; Health Care Costs; Humans; Infection Control; Kidney Failure, Chronic; Length of Stay; Metronidazole; Patient Isolation; Renal Insufficiency, Chronic; Secondary Prevention; Vancomycin

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.. 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.. At baseline, 27, 21, and 9% of the patients had stage 2 (60-89 ml/min/1.73 m(2)), 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.. Progressive CKD is associated with increased TTROD, lower cure rates, and higher recurrence rates with treatment of CDI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Clostridioides difficile; Enterocolitis, Pseudomembranous; Female; Fidaxomicin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Outcome; Vancomycin; Young Adult