Plasma concentration of orally administered amoxicillin and clindamycin in patients receiving haemodialysis

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Objectives
In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin is sufficient during HD after oral administration of amoxicillin and clindamycin at three different time intervals prior to the HD procedure.

Methods
Adult patients receiving chronic HD were investigated twice with an interval of at least 7 days starting with either a tablet of 500/125 mg amoxicillin/clavulanic acid or a tablet of 600 mg clindamycin. Patients were randomized to take the antibiotics either 30, 60 or 120 min prior to the HD procedure. Plasma antibiotic concentrations were measured at start, midway and at the end of HD. A lower threshold was set at 2.0 mg/L for amoxicillin and at 1.0 mg/L for clindamycin. In addition, a population pharmacokinetic (PK) analysis was performed, assessing PTA.

Results
In the amoxicillin cohort (n = 37), 84% of patients and 95% of all plasma amoxicillin concentrations were above or at the threshold throughout the dialysis procedure. In the clindamycin cohort (n = 33), all concentrations were above the threshold throughout the dialysis procedure. Further, in all patients, the mean plasma concentration of both amoxicillin and clindamycin across the HD period was well above the threshold. Finally, the PK model predicted a high PTA in the majority of patients.

Discussion
In patients on chronic HD, oral administration of amoxicillin/clavulanic acid (500/125 mg) or clindamycin (600 mg) within 30–120 min prior to HD leads to a sufficient prophylactic plasma concentration across the HD period.
OriginalsprogEngelsk
TidsskriftJournal of Antimicrobial Chemotherapy
Vol/bind78
Udgave nummer3
Sider (fra-til)724-731
Antal sider8
ISSN0305-7453
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We declare that the results presented in this paper have not been published previously in whole or part. The authors declare no conflict of interest directly related to the content of this paper. H.B. reports grants from the Novo Nordisk Foundation and the Danish Heart Foundation, royalties from GADS publishing house, lecture fees from Amgen, Sanofi-Avensis, MSD and BMS, board membership in Danish authority boards, and stocks in Novo Nordisk A/S. C.M. reports grants from the Novo Nordisk foundation, membership of the Committee for writing the Danish Guidelines for treating Infective Endocarditis, and on the board of the ESCMID Study Group for Biofilms. E.F. reports grants from the Novo Nordisk Foundation and the Danish Heart Foundation. N.E.B. reports grants from the Kaj Hansen Foundation, the Novo Nordisk Foundation, the Augustinus Foundation and Health Insurance Denmark. L.B. reports membership of an AstraZeneca advisory board and paid expert testimony for Vifor Pharma. C.T.P. reports grants from Bayer and the Novo Nordisk Foundation.

Funding Information:
This work was supported by the Novo Nordisk Foundation [Grant-nr NNF19OC0056578], the Augustinus Foundation [Grant-nr 21-1439] and Health Insurance Denmark (Sygeforsikringen Danmark) [Grant-nr 2021-0053].

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.

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