Intraperitoneal cefepime monotherapy versus combination therapy of cefazolin plus ceftazidime for empirical treatment of CAPD-associated peritonitis: A multicenter, open-label, noninferiority, randomized, controlled trial

Rationale & Objective: Compared to combination therapy, intraperitoneal (IP) cefepime monotherapy for continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis may provide potential benefits in lowering staff burden, shortening time-consuming antibiotic preparation, and reducing bag contamination risk. This study sought to evaluate whether cefepime monotherapy is noninferior to combination regimens. Study Design: Multicenter, open-label, noninferiority, randomized, controlled trial. Setting & Participants: Adult incident peritoneal dialysis (PD) patients with CAPD-associated peritonitis in 8 PD centers in Thailand. Interventions: Random assignment to either IP monotherapy of cefepime, 1 g/d, or IP combination of cefazolin and ceftazidime, 1 g/d, both given as continuous dosing. Outcomes: Primary end point: resolution of peritonitis at day 10 (primary treatment response). Secondary outcomes: initial response (day 5), complete cure (relapse/recurrence-free response 28 days after treatment completion), relapsing/recurrent peritonitis, and death from any cause. Noninferiority would be confirmed for the primary outcome if the lower margin of the 1-sided 95% CI was not less than −10% for difference in the primary response rate. A 2-sided 90% CI was used to demonstrate the upper or lower border of the 1-sided 95% CI. Results: There were 144 eligible patients with CAPD-associated peritonitis, of whom 70 and 74 patients were in the monotherapy and combination-therapy groups, respectively. Baseline demographic and clinical characteristics were not different between the groups. The primary response was 82.6% in the monotherapy group and 81.1% in the combination-therapy group (treatment difference, 1.5%; 90% CI, −9.1% to 12.1%; P = 0.04). There was no significant difference in the monotherapy group compared with the combination-therapy group in terms of initial response rate (65.7% vs 60.8%; treatment difference, 4.9%; 95% CI, −10.8% to 20.6%; P = 0.5) and complete cure rate (80.0% vs 80.6%; treatment difference, −0.6%; 95% CI, −13.9% to 12.8%; P = 0.7). Relapsing and recurrent peritonitis occurred in 4.6% and 4.6% of the monotherapy group and 4.2% and 5.6% of the combination-therapy group (P = 0.9 and P = 0.8, respectively). There was nominally higher all-cause mortality in the monotherapy group (7.1% vs 2.7%; treatment difference, 4.4%; 95% CI, −2.6% to 11.5%), but this difference was not statistically significant (P = 0.2). Limitation: Not double blind. Conclusions: IP cefepime monotherapy was noninferior to conventional combination therapy for resolution of CAPD-associated peritonitis at day 10 and may be a reasonable alternative first-line treatment. Funding: This study is supported by The Kidney Foundation of Thailand (R5879), Thailand; Rachadaphiseksompotch Fund (RA56/006) and Rachadaphicseksompotch Endorsement Fund (CU-GRS_61_06_30_01), Chulalongkorn University, Thailand; National Research Council of Thailand (156/2560), Thailand; and Thailand Research Foundation (IRG5780017), Thailand. Trial Registration: Registered at ClinicalTrials.gov with study number NCT02872038