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
| Autor: | Guttiga Halue, Saraporn Matayart, Kearkiat Praditpornsilpa, Thidarat Kitrungphaiboon, Krittaya Tiskajornsiri, Pongpratch Puapatanakul, Talerngsak Kanjanabuch, Monchai Siribamrungwong, Wanida Somboonsilp, Ussanee Poonvivatchaikarn, David W. Johnson, Pisut Katavetin, Somchai Eiam-Ong, Chanchana Boonyakrai, Kamonrat Chongthanakorn, Piyatida Chuengsaman |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Combination therapy Cefepime medicine.medical_treatment 030232 urology & nephrology Cefazolin Peritonitis Ceftazidime law.invention Peritoneal dialysis 03 medical and health sciences 0302 clinical medicine Peritoneal Dialysis Continuous Ambulatory Randomized controlled trial law Internal medicine Clinical endpoint Humans Medicine Prospective Studies 030212 general & internal medicine Dose-Response Relationship Drug business.industry Continuous ambulatory peritoneal dialysis Middle Aged medicine.disease Anti-Bacterial Agents Treatment Outcome Nephrology Drug Therapy Combination Female business Injections Intraperitoneal Follow-Up Studies medicine.drug |
| Zdroj: | American Journal of Kidney Diseases. 74:601-609 |
| ISSN: | 0272-6386 |
| DOI: | 10.1053/j.ajkd.2019.05.011 |
| Popis: | 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, 1g/d, or IP combination of cefazolin and ceftazidime, 1g/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=0.9and 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. |
| Databáze: | OpenAIRE |
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