Pharmacokinetics of Intraperitoneal Gentamicin in Peritoneal Dialysis Patients with Peritonitis (GIPD Study)

Overview

Journal Clin J Am Soc Nephrol

Specialty Nephrology

Date 2012 Jun 16

PMID 22700884

Citations 9

Authors

Julie M Varghese

Jason A Roberts

Steven C Wallis

Robert J Boots

Helen Healy

Robert G Fassett

Jeffrey Lipman

Dwarakanathan Ranganathan

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Peritonitis is a major infectious complication in peritoneal dialysis patients, and intraperitoneal antibiotic administration is preferred to ensure maximal antibiotic concentrations at the site of infection. This study aimed to describe the plasma and infection site pharmacokinetics of intraperitoneal gentamicin in patients with peritonitis.

Design, Setting, Participants, & Measurements: This prospective pharmacokinetic study of intraperitoneal gentamicin was conducted in peritoneal dialysis patients presenting to hospital with clinically defined signs and symptoms of peritonitis. Twenty-four patients were administered a 0.6-mg/kg dose of intraperitoneal gentamicin, which was allowed to dwell for 6 hours. Serial blood and dialysate samples were collected for 24 hours after the first dose. Gentamicin concentrations in plasma and dialysate were measured using a validated assay.

Results: The median percentage of the dose absorbed into the systemic circulation was 76% (interquartile range=69%-82%) and significantly different between patients with low average, high average, and high peritoneal membrane transporter status (P=0.03). The calculated pharmacokinetic parameters were plasma terminal elimination half-life of 24.7 (20.4-29.9) hours, terminal volume of distribution of 0.30 (0.20-0.36) L/kg, observed peak plasma concentration of 3.1 (2.4-3.4) mg/L, and observed trough plasma concentration of 1.9 (1.4-2.2) mg/L. The peak gentamicin concentration in dialysate was at least eight times the minimum inhibitory concentration of the likely pathogens.

Conclusions: The high systemic absorption of gentamicin in patients with peritonitis and prolonged plasma elimination half-life may lead to drug accumulation in the systemic circulation, increasing the risk of toxicity.

Citing Articles

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review.

Hodiamont C, van den Broek A, de Vroom S, Prins J, Mathot R, Van Hest R Clin Pharmacokinet. 2022; 61(8):1075-1094.

PMID: 35754071 PMC: 9349143. DOI: 10.1007/s40262-022-01143-0.

Population Pharmacokinetics of Intraperitoneal Gentamicin and the Impact of Varying Dwell Times on Pharmacodynamic Target Attainment in Patients with Acute Peritonitis Undergoing Peritoneal Dialysis.

Farkas A, Oikonomou K, Ghanbar M, Villasurda P, Varghese J, Lipman J Antimicrob Agents Chemother. 2021; 66(2):e0167921.

PMID: 34902267 PMC: 8846465. DOI: 10.1128/AAC.01679-21.

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype.

Mcdermott J, Wolf J, Hoshitsuki K, Huddart R, Caudle K, Whirl-Carrillo M Clin Pharmacol Ther. 2021; 111(2):366-372.

PMID: 34032273 PMC: 8613315. DOI: 10.1002/cpt.2309.

Intraperitoneal ampicillin treatment for peritoneal dialysis- related peritonitis with Listeria monocytogenes - a case report.

Boss K, Wiegard-Szramek I, Dziobaka J, Kribben A, Dolff S BMC Nephrol. 2020; 21(1):404.

PMID: 32948148 PMC: 7501657. DOI: 10.1186/s12882-020-02068-1.

ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment.

Kam-Tao Li P, Szeto C, Piraino B, de Arteaga J, Fan S, Figueiredo A Perit Dial Int. 2016; 36(5):481-508.

PMID: 27282851 PMC: 5033625. DOI: 10.3747/pdi.2016.00078.

References

Bailie G, Haqqie S, Eisele G, Gorman T, Low C . Effectiveness of once-weekly vancomycin and once-daily gentamicin, intraperitoneally, for CAPD peritonitis. Perit Dial Int. 1995; 15(6):269-71. View

Blunden M, Zeitlin D, Ashman N, Fan S . Single UK centre experience on the treatment of PD peritonitis--antibiotic levels and outcomes. Nephrol Dial Transplant. 2007; 22(6):1714-9. DOI: 10.1093/ndt/gfm079. View

Brown F, Liu W, Kotsanas D, Korman T, Atkins R . A quarter of a century of adult peritoneal dialysis-related peritonitis at an Australian medical center. Perit Dial Int. 2007; 27(5):565-74. View

Craig W . Does the dose matter?. Clin Infect Dis. 2001; 33 Suppl 3:S233-7. DOI: 10.1086/321854. View

Lye W, Wong P, van der Straaten J, Leong S, Lee E . A prospective randomized comparison of single versus multidose gentamicin in the treatment of CAPD peritonitis. Adv Perit Dial. 1995; 11:179-81. View

Vogelman B, Gudmundsson S, Turnidge J, Leggett J, Craig W . In vivo postantibiotic effect in a thigh infection in neutropenic mice. J Infect Dis. 1988; 157(2):287-98. DOI: 10.1093/infdis/157.2.287. View

Ranganathan D, Varghese J, Fassett R, Lipman J, DIntini V, Healy H . Optimising intraperitoneal gentamicin dosing in peritoneal dialysis patients with peritonitis (GIPD) study. BMC Nephrol. 2009; 10:42. PMC: 2800106. DOI: 10.1186/1471-2369-10-42. View

Kent J, Almond M . A survey of CAPD peritonitis management and outcomes in North and South Thames NHS regions (U.K.): support for the ISPD guidelines. International Society for Peritoneal Dialysis. Perit Dial Int. 2000; 20(3):301-5. View

JACKSON G, ARCIERI G . Ototoxicity of gentamicin in man: a survey and controlled analysis of clinical experience in the United States. J Infect Dis. 1971; 124 Suppl:S130-7. DOI: 10.1093/infdis/124.supplement_1.s130. View

10.

Low C, Bailie G, Evans A, Eisele G, Venezia R . Pharmacokinetics of once-daily IP gentamicin in CAPD patients. Perit Dial Int. 1996; 16(4):379-84. View

11.

Rubin J . Tobramycin absorption from the peritoneal cavity. Perit Dial Int. 1990; 10(4):295-7. View

12.

Wilson T, Mahon W, Inaba T, Johnson G, KADAR D . Elimination of tritiated gentamicin in normal human subjects and in patients with severely impaired renal function. Clin Pharmacol Ther. 1973; 14(5):815-22. DOI: 10.1002/cpt1973145815. View

13.

Kam-Tao Li P, Szeto C, Piraino B, Bernardini J, Figueiredo A, Gupta A . Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int. 2010; 30(4):393-423. DOI: 10.3747/pdi.2010.00049. View

14.

Weber J, Staerz E, Mettang T, Machleidt C, Kuhlmann U . Treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) with intraperitoneal cefazolin and gentamicin. Perit Dial Int. 1989; 9(3):191-5. View

15.

Turnidge J . Pharmacodynamics and dosing of aminoglycosides. Infect Dis Clin North Am. 2004; 17(3):503-28, v. DOI: 10.1016/s0891-5520(03)00057-6. View

16.

Blaser J, Stone B, Groner M, Zinner S . Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance. Antimicrob Agents Chemother. 1987; 31(7):1054-60. PMC: 174871. DOI: 10.1128/AAC.31.7.1054. View

17.

Tosukhowong T, Eiam-Ong S, Thamutok K, Wittayalertpanya S, Na Ayudhya D . Pharmacokinetics of intraperitoneal cefazolin and gentamicin in empiric therapy of peritonitis in continuous ambulatory peritoneal dialysis patients. Perit Dial Int. 2002; 21(6):587-94. View

18.

Piraino B, Bailie G, Bernardini J, Boeschoten E, Gupta A, Holmes C . Peritoneal dialysis-related infections recommendations: 2005 update. Perit Dial Int. 2005; 25(2):107-31. View

19.

Dahlgren J, Anderson E, HEWITT W . Gentamicin blood levels: a guide to nephrotoxicity. Antimicrob Agents Chemother. 1975; 8(1):58-62. PMC: 429261. DOI: 10.1128/AAC.8.1.58. View

20.

De Paepe M, Lameire N, Belpaire F, Bogaert M . Peritoneal pharmacokinetics of gentamicin in man. Clin Nephrol. 1983; 19(3):107-9. View