Ertapenem-Associated Seizures in a Peritoneal Dialysis Patient

Abstract

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French

OBJECTIVE:

To report a case of a patient undergoing peritoneal dialysis who developed refractory seizures after 2 doses of ertapenem.

CASE SUMMARY:

A 56-year-old white man with end-stage renal disease requiring continuous ambulatory peritoneal dialysis experienced 5 seizures following 2 doses of ertapenem 500 mg given intravenously. The first generalized tonic—clonic seizure occurred 16 hours after the second ertapenem dose and lasted 3 minutes. Three hours after his first seizure, the patient experienced 2 more seizures 15 minutes apart, lasting 3 minutes each. After suffering a fifth seizure, the patient became apneic and pulseless and was not resuscitated, as he had previously requested a “do not resuscitate” status.

DISCUSSION:

Carbapenem treatment has been associated with simple partial, complex partial, and generalized tonic—clonic seizures, with generalized seizures representing the most frequently occurring type. Safety data from 7 published clinical trials of ertapenem revealed a seizure incidence of 0.18%. To our knowledge, there are no previously published reports of ertapenem neurotoxicity in patients undergoing peritoneal dialysis. Moreover, little information is available regarding the pharmacokinetics of carbapenems in end-stage renal disease. Ertapenem pharmacokinetics were not tested in any patients receiving peritoneal dialysis during published clinical trials.

CONCLUSIONS:

Our patient experienced 5 seizures, possibly induced by ertapenem, as validated by the Naranjo probability scale. Clinicians administering ertapenem to patients undergoing peritoneal dialysis should use caution, as clinical experience with the agent is limited and pharmacokinetic data are lacking.

Keywords

carbapenem end-stage renal disease ertapenem neurotoxicity peritoneal dialysis

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References

1 Prescribing information. Primaxin IV (imipenem and cilastatin sodium). Whitehouse Station, NJ: Merck & Co., August 2003.

2 Prescribing information. Merrem IV (meropenem). Wilmington, DE: AstraZeneca Pharmaceuticals, January 2004.

3 Prescribing information. Invanz (ertapenem). Whitehouse Station, NJ: Merck & Co., April 2004.

De Sarro

Ammendola

Zappala

Grasso

De Sarro

GB.

Relationship between structure and convulsant properties of some β-lactam antibiotics following intracerebroventricular microinjection in rats. Antimicrob Agents Chemother 1995;39: 232–7.

5 Carbapenems. In: Hebel

, ed. Drug facts and comparisons. St. Louis: Facts and Comparisons, 2002:1269–74d.

Curran

Simpson

Perry

CM.

Ertapenem: A review of its use in the management of bacterial infections. Drugs 2003;63: 1855–78.

Koppel

Hauser

Politis

van Duin

Daras

Seizures in the critically ill: The role of imipenem. Epilepsia 2001;42: 1590–3.

Calandra

Lydick

Carrigan

Weiss

Guess

Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: Experience with imipenem/cilastatin. Am J Med 1988;84: 911–8.

Pestotnik

Classen

Evans

Stevens

Burke

JP.

Prospective surveillance of imipenem/cilastatin use and associated seizures using a hospital information system. Ann Pharmacother 1993;27: 497–501.

10.

10 Ortiz-Ruiz

Caballero-Lopez

Friedland

Woods

Carides

, and the Protocol 018 Ertapenem Community-Acquired Pneumonia Study Group. A study evaluating the efficacy, safety, and tolerability of ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults. Clin Infect Dis 2002;34: 1076–83.

11.

Vetter

Cambronero-Hernandez

Rohlf

Simon

Carides

Oliveria

A prospective, randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia. Clin Ther 2002;24: 1770–85.

12.

Solomkin

Yellin

Rotstein

Christou

Dellinger

Tellado

Ertapenem versus piperacillin/tazobactam in the treatment of complicated intra-abdominal infections. Ann Surg 2003;237: 235–45.

13.

Graham

Lucasti

Malafaia

Nichols

Holtom

Perez

Ertapenem once daily versus piperacillin-tazobactam 4 times per day for treatment of complicated skin and skin-structure infections in adults: Results of a prospective, randomized, double-blind multicenter study. Clin Infect Dis 2002;34: 1460–8.

14.

Tomera

Burdmann

Pamo Reyna

Jiang

Wimmer

Woods

Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment of complicated urinary tract infections in adults: Results of a prospective, randomized, double-blind multicenter study. Antimicrob Agents Chemother 2002;46: 2895–900.

15.

Yellin

Hassett

Fernandez

Geib

Adeyi

Woods

Ertapenem monotherapy versus combination therapy with ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections in adults. Int J Antimicrob Agents 2002;20: 165–73.

16.

Jimenez-Cruz

Jasovich

Cajigas

Jiang

Imbeault

Woods

A prospective, multicenter, randomized, double-blind study comparing ertapenem and ceftriaxone followed by appropriate oral therapy for complicated urinary tract infections in adults. Urology 2002;60: 16–22.

17.

Klugman

Dagan

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group. Antimicrob Agents Chemother 1995;39: 1140–6.

18.

Cunha

BA.

Meropenem in elderly and renally impaired patients. Int J Antimicrob Agents 1999;11: 167–77.

19.

Campise

Neurological complications during imipenem/cilastatin therapy in uremic patients. Nephrol Dial Transplant 1998;13: 1895–6.

20.

Rivera

Crespo

Teruel

Marcen

Ortuno

Neurotoxicity due to imipenem/cilastatin in patients on continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 1998;14: 258–9.

21.

Holland

Majumdar

Musson

Pharmacokinetics of ertapenem in renal insufficiency (abstract). Clin Pharmacol Ther 2001;69:P16.

22.

Konishi

Suzuki

Saruta

Hayashi

Deguchi

Tazaki

Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure. Antimicrob Agents Chemother 1991;35: 1616–20.

23.

Christensson

Nilsson-Ehle

Hutchison

Haworth

Oqvist

Norrby

SR.

Pharmacokinetics of meropenem in subjects with various degrees of renal impairment. Antimicrob Agents Chemother 1992;36: 1532–7.

24.

Shah

Isaacs

RD.

Ertapenem, the first of a new group of carbapenems. J Antimicrob Chemother 2003;52: 538–42.

25.

25 Gilbert

Moellering

Eliopoulos

Sande

, eds. The Sanford guide to antimicrobial therapy. 34th ed. Hyde Park, VT: Antimicrobial Therapy, Inc. 2004:130.

26.

Laethem

De Lepeleire

McRea

Zhang

Majumdar

Musson

Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers. Antimicrob Agents Chemother 2003;47: 1439–42.

27.

Kushner

Peckman

Snyder

CR.

Seizures associated with fluoroquinolones. Ann Pharmacother 2001;35: 1194–8. DOI 10.1345/aph.10359.

28.

Korevaar

Burney

Moore

PA.

Convulsions during stellate ganglion block: A case report. Anesth Analg 1979;58: 329–30.

29.

Coates

Sanders

Edmonds-Seal

Convulsions following regional hip blockade with bupivacaine and adrenaline. Anaesthesia 1983;38: 588–9.

30.

30 Prescribing information. Procrit (epoetin alfa). Raritan, NJ: Ortho Biotech Products, June 2004.

31.

Jones

Boykett

Klok

Propofol, apisthotonus, and epilepsy (letter). Anaesthesia 1988;43:905.

32.

Sutherland

Burt

Propofol and seizures. Anaesth Intensive Care 1994;22: 733–7.

33.

Michel

Knodel

LC.

Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm 1986;43: 1709–14.