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

Author:

Solli Camilla N12ORCID,Bock Magnus3,Kaur Kamal P12,Kristensen Jonas H24,Greibe Eva56,Hansen Henrik P7,Boesby Lene8,Borg Rikke28,Chaudry Mavish9,Hoffmann-Lücke Elke56,Moser Claus310ORCID,Falkentoft Alexander C12,Fosbøl Emil11ORCID,Østergaard Lauge11ORCID,Torp-Pedersen Christian29,Bundgaard Henning211ORCID,Iversen Kasper24ORCID,Bruun Niels E126

Affiliation:

1. Department of Cardiology, Zealand University Hospital , Sygehusvej 10, Roskilde 4000 , Denmark

2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark

3. Department of Clinical Microbiology, Copenhagen University Hospital—Rigshospitalet , Copenhagen , Denmark

4. Department of Emergency Medicine, Copenhagen University Hospital—Herlev and Gentofte , Copenhagen , Denmark

5. Department of Clinical Biochemistry, Aarhus University Hospital , Aarhus , Denmark

6. Institute of Clinical Medicine, Health, Aarhus University Hospital , Aarhus , Denmark

7. Department of Nephrology, Copenhagen University Hospital—Herlev-Gentofte , Herlev , Denmark

8. Department of Medicine, Zealand University Hospital , Roskilde , Denmark

9. Department of Cardiology, Copenhagen University Hospital—North Zealand , Hilleroed , Denmark

10. Department for Immunology and Microbiology, University of Copenhagen , Copenhagen , Denmark

11. Department of Cardiology, Copenhagen University Hospital—Rigshospitalet , Copenhagen , Denmark

Abstract

AbstractObjectivesIn 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.MethodsAdult 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.ResultsIn 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.DiscussionIn 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.

Funder

Novo Nordisk Foundation

Augustinus Foundation

Health Insurance Denmark

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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