Format

Send to

Choose Destination
Am J Kidney Dis. 2019 Nov;74(5):601-609. doi: 10.1053/j.ajkd.2019.05.011. Epub 2019 Jul 19.

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.

Author information

1
King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand.
2
Banphaeo Dialysis Group (Bangkok), Banphaeo Hospital, Bangkok, Thailand.
3
Phayao Hospital, Phayao, Thailand.
4
Lerdsin Hospital, Bangkok, Thailand.
5
Buddhasothorn Hospital, Chachoengsao, Thailand.
6
Charoenkrung Pracharak Hospital, Bangkok, Thailand.
7
Nakhonpathom Hospital, Nakhonpathom, Thailand.
8
Division of Nephrology, Department of Internal Medicine, Taksin Hospital, Bangkok Metropolitan Administration, Bangkok.
9
Chaophraya Yommarat Hospital, Suphanburi, Thailand.
10
Department of Nephrology, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia.
11
King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Kidney Metabolic Disorders, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; CAPD Excellent Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Electronic address: golfnephro@hotmail.com.

Abstract

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.

KEYWORDS:

Antibacterial agents; antibiotic regimen; catheter removal; cefazolin; cefepime; ceftazidime; complete cure; continuous ambulatory peritoneal dialysis (CAPD); end-stage renal disease (ESRD); monotherapy; outcomes; peritonitis; primary response; randomized controlled trial (RCT)

PMID:
31331757
DOI:
10.1053/j.ajkd.2019.05.011

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center