Epileptogenic effect of antibiotic drugs

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  • 1 Institute for Surgical Research and Department of Neurosurgery, Rikshospitalet, National Hospital, University of Oslo, Oslo, Norway
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✓ The epileptogenicity of antibiotic drugs represents a clinical problem, and it is well known that the use of penicillin and certain other preparations can induce seizures. In the present study, the authors investigated the epileptogenic properties of different concentrations of 12 commonly used antibiotic medications belonging to seven separate groups. The drugs were tested in the hippocampus, which has a low threshold for the development of epileptiform activity. The hippocampal slice technique, using rat tissue, was employed since absence of the blood-brain barrier allows administration of the drugs in known concentrations. The preparation was exposed to antibiotics in known concentrations and the amplitude and number of population spikes were recorded. Penicillin G was used as a reference substance. Cloxacillin (≥ 1 gm/liter), cephalothin (≥ 1 gm/liter), gentamicin (≥ 80 mg/liter), chloramphenicol (≥ 1 gm/liter), ciprofloxacin (≥ 50 mg/liter), erythromycin (≥ 1 gm/liter), and ampicillin (≥ 1 gm/liter) showed moderate to marked epileptogenic effects, whereas cefuroxime, clindamycin, cefotaxime, vancomycin, and tobramycin had no epileptogenic effects.

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Contributor Notes

Address reprint requests to: Iver A. Langmoen, M.D., Ph.D., Department of Neurosurgery, Rikshospitalet, N-0027, Oslo, Norway.
  • 1.

    Andersen P, , Bliss TVP, & Skrede KK: Unit analysis of hippocampal population spikes. Exp Brain Res 13:208221, 1971 Andersen P, Bliss TVP, Skrede KK: Unit analysis of hippocampal population spikes. Exp Brain Res 13:208–221, 1971

    • Search Google Scholar
    • Export Citation
  • 2.

    Ayala GF, , Matsumoto H, & Gumnit RJ: Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J Neurophysiol 33:7385, 1970 Ayala GF, Matsumoto H, Gumnit RJ: Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J Neurophysiol 33:73–85, 1970

    • Search Google Scholar
    • Export Citation
  • 3.

    Bakay RAE, , Epstein CM, & Brickley GP: Antibiotic effect on incidence of postcraniotomy seizures. J Neurosurg 74:311, 1991 (Letter) Bakay RAE, Epstein CM, Brickley GP: Antibiotic effect on incidence of postcraniotomy seizures. J Neurosurg 74:311, 1991 (Letter)

    • Search Google Scholar
    • Export Citation
  • 4.

    Barza M, & Weinstein L: Pharmacokinetics of the penicillins in man. Clin Pharmacokinet 1:297308, 1976 Barza M, Weinstein L: Pharmacokinetics of the penicillins in man. Clin Pharmacokinet 1:297–308, 1976

    • Search Google Scholar
    • Export Citation
  • 5.

    Block CS, , Cassel R, & Koornhof HJ, et al: Klebsiella meningitis treated with intrathecal amikacin. Lancet 1:13711372, 1977 (Letter) Block CS, Cassel R, Koornhof HJ, et al: Klebsiella meningitis treated with intrathecal amikacin. Lancet 1:1371–1372, 1977 (Letter)

    • Search Google Scholar
    • Export Citation
  • 6.

    Connors BW, & Gutnick MJ: Cellular mechanisms of neocortical epileptogenesis in an acute experimental model, in Schwartzkroin PA, & Wheal HV (eds): Electrophysiology of Epilepsy. London: Academic Press, 1984, pp 79105 Connors BW, Gutnick MJ: Cellular mechanisms of neocortical epileptogenesis in an acute experimental model, in Schwartzkroin PA, Wheal HV (eds): Electrophysiology of Epilepsy. London: Academic Press, 1984, pp 79–105

    • Search Google Scholar
    • Export Citation
  • 7.

    Currie TT, , Hayward NJ, & Westlake G, et al: Epilepsy in cardiopulmonary bypass patients receiving large intravenous doses of penicillin. J Thorac Cardiovasc Surg 62:16, 1971 Currie TT, Hayward NJ, Westlake G, et al: Epilepsy in cardiopulmonary bypass patients receiving large intravenous doses of penicillin. J Thorac Cardiovasc Surg 62:1–6, 1971

    • Search Google Scholar
    • Export Citation
  • 8.

    Curtis DR, , Game CJA, & Johnston GAR, et al: Convulsive action of penicillin. Brain Res 43:242245, 1972 Curtis DR, Game CJA, Johnston GAR, et al: Convulsive action of penicillin. Brain Res 43:242–245, 1972

    • Search Google Scholar
    • Export Citation
  • 9.

    Dempsey R, , Rapp RP, & Young B, et al: Prophylactic parenteral antibiotics in clean neurosurgical procedures: a review. J Neurosurg 69:5257, 1988 Dempsey R, Rapp RP, Young B, et al: Prophylactic parenteral antibiotics in clean neurosurgical procedures: a review. J Neurosurg 69:52–57, 1988

    • Search Google Scholar
    • Export Citation
  • 10.

    De Sarro A, , De Sarro GB, & Ascioti C, et al: Epileptogenic activity of some β-lactam derivatives: structure-activity relationship. Neuropharmacology 28:359365, 1989 De Sarro A, De Sarro GB, Ascioti C, et al: Epileptogenic activity of some β-lactam derivatives: structure-activity relationship. Neuropharmacology 28:359–365, 1989

    • Search Google Scholar
    • Export Citation
  • 11.

    Dingledine R, & Gjerstad L: Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J Physiol (Lond) 305:297313, 1980 Dingledine R, Gjerstad L: Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J Physiol (Lond) 305:297–313, 1980

    • Search Google Scholar
    • Export Citation
  • 12.

    Dobell ARC, , Wyant JD, & Seamans KB, et al: Penicillin epilepsy. Studies on the blood-brain barrier during cardiopulmonary bypass. J Thorac Cardiovasc Surg 52:469475, 1966 Dobell ARC, Wyant JD, Seamans KB, et al: Penicillin epilepsy. Studies on the blood-brain barrier during cardiopulmonary bypass. J Thorac Cardiovasc Surg 52:469–475, 1966

    • Search Google Scholar
    • Export Citation
  • 13.

    Esplin B, , Thêorêt Y, & Seward E, et al: Epileptogenic action of penicillin derivatives: structure-activity relationship. Neuropharmacology 24:571575, 1985 Esplin B, Thêorêt Y, Seward E, et al: Epileptogenic action of penicillin derivatives: structure-activity relationship. Neuropharmacology 24:571–575, 1985

    • Search Google Scholar
    • Export Citation
  • 14.

    Frame PT, & McLaurin RL: Treatment of CSF shunt infections with intrashunt plus oral antibiotic therapy. J Neurosurg 60:354360, 1984 Frame PT, McLaurin RL: Treatment of CSF shunt infections with intrashunt plus oral antibiotic therapy. J Neurosurg 60:354–360, 1984

    • Search Google Scholar
    • Export Citation
  • 15.

    Garretson HD, , Reid KH, & Shields CB, et al: The effect of topical application of antibiotics on the cerebral cortex. An experimental update. J Neurosurg 50:792797, 1979 Garretson HD, Reid KH, Shields CB, et al: The effect of topical application of antibiotics on the cerebral cortex. An experimental update. J Neurosurg 50:792–797, 1979

    • Search Google Scholar
    • Export Citation
  • 16.

    Geraghty J, & Feely M: Antibiotic prophylaxis in neurosurgery. A randomized controlled trial. J Neurosurg 60:724726, 1984 Geraghty J, Feely M: Antibiotic prophylaxis in neurosurgery. A randomized controlled trial. J Neurosurg 60:724–726, 1984

    • Search Google Scholar
    • Export Citation
  • 17.

    Gjerstad L: The transverse hippocampal slice in vitro as a model of epilepsy. Institute of Neurophysiology, University of Oslo, 1983 (Ph.D. thesis) Gjerstad L: The transverse hippocampal slice in vitro as a model of epilepsy. Institute of Neurophysiology, University of Oslo, 1983 (Ph.D. thesis)

    • Search Google Scholar
    • Export Citation
  • 18.

    Gjerstad L. Andersen P, & Langmoen IA, et al: Synaptic triggering of epileptiform discharges in CA1 pyramidal cells in vitro. Acta Physiol Scand 113:245252, 1981 Gjerstad L. Andersen P, Langmoen IA, et al: Synaptic triggering of epileptiform discharges in CA1 pyramidal cells in vitro. Acta Physiol Scand 113:245–252, 1981

    • Search Google Scholar
    • Export Citation
  • 19.

    Gjerstad L, , Langmoen IA, & Andersen P: Monosynaptic transmission during epileptiform activity induced by penicillin in hippocampal slices in vitro. Acta Physiol Scand 113:355362, 1981 Gjerstad L, Langmoen IA, Andersen P: Monosynaptic transmission during epileptiform activity induced by penicillin in hippocampal slices in vitro. Acta Physiol Scand 113:355–362, 1981

    • Search Google Scholar
    • Export Citation
  • 20.

    Goodman SJ, & Stern WE: Cranial and intracranial bacterial infections, in Youmans JR (ed): Neurological Surgery, ed 2. Philadelphia: WB Saunders, 1982, pp 33233357 Goodman SJ, Stern WE: Cranial and intracranial bacterial infections, in Youmans JR (ed): Neurological Surgery, ed 2. Philadelphia: WB Saunders, 1982, pp 3323–3357

    • Search Google Scholar
    • Export Citation
  • 21.

    Graybill JR, , Mann J, & Charache P: Intrathecal gentamicin in treatment of bacterial meningitis. Johns Hopkins Med J 133:5156, 1973 Graybill JR, Mann J, Charache P: Intrathecal gentamicin in treatment of bacterial meningitis. Johns Hopkins Med J 133:51–56, 1973

    • Search Google Scholar
    • Export Citation
  • 22.

    Gutnick MJ, & Prince DA: Penicillinase and the convulsant action of penicillin. Neurology 21:759764, 1971 Gutnick MJ, Prince DA: Penicillinase and the convulsant action of penicillin. Neurology 21:759–764, 1971

    • Search Google Scholar
    • Export Citation
  • 23.

    Gutnick MJ, , Van Duijn H, & Citri N: Relative convulsant potencies of structural analogues of penicillin. Brain Res 114:139143, 1976 Gutnick MJ, Van Duijn H, Citri N: Relative convulsant potencies of structural analogues of penicillin. Brain Res 114:139–143, 1976

    • Search Google Scholar
    • Export Citation
  • 24.

    Haas HL, , Schaerer B, & Vosmansky M: A simple perfusion chamber for the study of nervous tissue slices in vitro. J Neurosci Methods 1:323325, 1979 Haas HL, Schaerer B, Vosmansky M: A simple perfusion chamber for the study of nervous tissue slices in vitro. J Neurosci Methods 1:323–325, 1979

    • Search Google Scholar
    • Export Citation
  • 25.

    Hablitz JJ: Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. J Neurophysiol 51:10111027, 1984 Hablitz JJ: Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. J Neurophysiol 51:1011–1027, 1984

    • Search Google Scholar
    • Export Citation
  • 26.

    Haines SJ, & Goodman ML: Antibiotic prophylaxis of postoperative neurosurgical wound infection. J Neurosurg 56:103105, 1982 Haines SJ, Goodman ML: Antibiotic prophylaxis of postoperative neurosurgical wound infection. J Neurosurg 56:103–105, 1982

    • Search Google Scholar
    • Export Citation
  • 27.

    Jasper H, , Cone W, & Pudenz R, et al: The electroencephalograms of monkeys following the application of micro-crystalline sulfonamides to the brain. Surg Gynecol Obstet 76:599611, 1943 Jasper H, Cone W, Pudenz R, et al: The electroencephalograms of monkeys following the application of micro-crystalline sulfonamides to the brain. Surg Gynecol Obstet 76:599–611, 1943

    • Search Google Scholar
    • Export Citation
  • 28.

    Johnson HC, & Walker AE: Intraventricular penicillin. A note of warning. JAMA 127:217219 1945 Johnson HC, Walker AE: Intraventricular penicillin. A note of warning. JAMA 127:217–219 1945

    • Search Google Scholar
    • Export Citation
  • 29.

    Kaiser AB, & McGee ZA: Aminoglycoside therapy of Gram-negative bacillary meningitis. N Engl J Med 293:12151220, 1975 Kaiser AB, McGee ZA: Aminoglycoside therapy of Gram-negative bacillary meningitis. N Engl J Med 293:1215–1220, 1975

    • Search Google Scholar
    • Export Citation
  • 30.

    Kramer PW, , Griffith RS, & Campbell RL: Antibiotic penetration of the brain. A comparative study. J Neurosurg 31:295302, 1969 Kramer PW, Griffith RS, Campbell RL: Antibiotic penetration of the brain. A comparative study. J Neurosurg 31:295–302, 1969

    • Search Google Scholar
    • Export Citation
  • 31.

    Langmoen IA, & Andersen P: The hippocampal slice in vitro. A description of the technique and some examples of the opportunities it offers, in Kerkut GA, & Wheal HV (eds): Electrophysiology of Isolated Mammalian CNS Preparations. London: Academic Press, 1981, pp 51105 Langmoen IA, Andersen P: The hippocampal slice in vitro. A description of the technique and some examples of the opportunities it offers, in Kerkut GA, Wheal HV (eds): Electrophysiology of Isolated Mammalian CNS Preparations. London: Academic Press, 1981, pp 51–105

    • Search Google Scholar
    • Export Citation
  • 32.

    Langmoen IA, , Hegstad E, & Berg-Johnsen J: An experimental study of the effect of isoflurane on epileptiform bursts. Epilepsy Res 11:153157, 1992 Langmoen IA, Hegstad E, Berg-Johnsen J: An experimental study of the effect of isoflurane on epileptiform bursts. Epilepsy Res 11:153–157, 1992

    • Search Google Scholar
    • Export Citation
  • 33.

    Lorenzo AV, & Spector R: The distribution of drugs in the central nervous system, in Levi G, , Battistin L, & Lajtha A (eds): Transport Phenomena in the Nervous System. Physiological and Pathological Aspects. New York: Plenum Press, 1976, pp 447461 Lorenzo AV, Spector R: The distribution of drugs in the central nervous system, in Levi G, Battistin L, Lajtha A (eds): Transport Phenomena in the Nervous System. Physiological and Pathological Aspects. New York: Plenum Press, 1976, pp 447–461

    • Search Google Scholar
    • Export Citation
  • 34.

    Manzella JP, , Paul RL, & Butler IL: CNS toxicity associated with intraventricular injection of cefazolin. Report of three cases. J Neurosurg 68:970971, 1988 Manzella JP, Paul RL, Butler IL: CNS toxicity associated with intraventricular injection of cefazolin. Report of three cases. J Neurosurg 68:970–971, 1988

    • Search Google Scholar
    • Export Citation
  • 35.

    Michenfelder JD, , Cucchiara RF, & Sundt TM Jr: Influence of intraoperative antibiotic choice on the incidence of earlv postcraniotomy seizures. J Neurosurg 72:703705, 1990 Michenfelder JD, Cucchiara RF, Sundt TM Jr: Influence of intraoperative antibiotic choice on the incidence of earlv postcraniotomy seizures. J Neurosurg 72:703–705, 1990

    • Search Google Scholar
    • Export Citation
  • 36.

    Moellering RC Jr, & Fischer EG: Relationship of intraventricular gentamicin levels to cure of meningitis. Report of a case of proteus meningitis successfully treated with intraventricular gentamicin. J Pediatr 81:534537, 1972 Moellering RC Jr, Fischer EG: Relationship of intraventricular gentamicin levels to cure of meningitis. Report of a case of proteus meningitis successfully treated with intraventricular gentamicin. J Pediatr 81:534–537, 1972

    • Search Google Scholar
    • Export Citation
  • 37.

    New PS, & Wells CE: Cerebral toxicity associated with massive intravenous penicillin therapy. Neurology 15:10531058, 1965 New PS, Wells CE: Cerebral toxicity associated with massive intravenous penicillin therapy. Neurology 15:1053–1058, 1965

    • Search Google Scholar
    • Export Citation
  • 38.

    Nicholls PJ: Neurotoxicity of penicillin. J Antimicrob Chemother 6:161165, 1980 Nicholls PJ: Neurotoxicity of penicillin. J Antimicrob Chemother 6:161–165, 1980

    • Search Google Scholar
    • Export Citation
  • 39.

    Oldstone MBA, & Nelson E: Central nervous system manifestations of penicillin toxicity in man. Neurology 16:693700, 1966 Oldstone MBA, Nelson E: Central nervous system manifestations of penicillin toxicity in man. Neurology 16:693–700, 1966

    • Search Google Scholar
    • Export Citation
  • 40.

    Porter J, & Jick H: Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms. Lancet 1:587588, 1977 Porter J, Jick H: Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms. Lancet 1:587–588, 1977

    • Search Google Scholar
    • Export Citation
  • 41.

    Salmon JH: Ventriculitis complicating meningitis. Am J Dis Child 124:3540, 1972 Salmon JH: Ventriculitis complicating meningitis. Am J Dis Child 124:35–40, 1972

    • Search Google Scholar
    • Export Citation
  • 42.

    Schliamser SE, , Bolander H, & Kourtopoulos H, et al: Neurotoxicity of benzylpenicillin: correlation to concentrations in serum, cerebrospinal fluid and brain tissue fluid in rabbits. J Antimicrob Chemother 21:365372, 1988 Schliamser SE, Bolander H, Kourtopoulos H, et al: Neurotoxicity of benzylpenicillin: correlation to concentrations in serum, cerebrospinal fluid and brain tissue fluid in rabbits. J Antimicrob Chemother 21:365–372, 1988

    • Search Google Scholar
    • Export Citation
  • 43.

    Schwartzkroin PA, & Prince DA: Cellular and field potential properties of epileptogenic hippocampal slices. Brain Res 147:117130, 1978 Schwartzkroin PA, Prince DA: Cellular and field potential properties of epileptogenic hippocampal slices. Brain Res 147:117–130, 1978

    • Search Google Scholar
    • Export Citation
  • 44.

    Schwartzkroin PA, & Prince DA: Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183:6167, 1980 Schwartzkroin PA, Prince DA: Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183:61–67, 1980

    • Search Google Scholar
    • Export Citation
  • 45.

    Schwartzkroin PA, & Prince DA: Penicillin-induced epileptiform activitv in the hippocampal in vitro preparation. Ann Neurol 1:463469, 1977 Schwartzkroin PA, Prince DA: Penicillin-induced epileptiform activitv in the hippocampal in vitro preparation. Ann Neurol 1:463–469, 1977

    • Search Google Scholar
    • Export Citation
  • 46.

    Seamans KB, , Gloor P, & Dobell ARC, et al: Penicillin-induced seizures during cardiopulmonary bypass. A clinical and electroencephalographic study. N Engl J Med 278:861868, 1968 Seamans KB, Gloor P, Dobell ARC, et al: Penicillin-induced seizures during cardiopulmonary bypass. A clinical and electroencephalographic study. N Engl J Med 278:861–868, 1968

    • Search Google Scholar
    • Export Citation
  • 47.

    Sells CJ, , Shurtleff DB, & Loeser JD: Gram-negative cerebrospinal fluid shunt-associated infections. Pediatrics 59:614618, 1977 Sells CJ, Shurtleff DB, Loeser JD: Gram-negative cerebrospinal fluid shunt-associated infections. Pediatrics 59:614–618, 1977

    • Search Google Scholar
    • Export Citation
  • 48.

    Serdaru M, , Diquet B, & Lhermitte F: Generalised seizures after ampicillin. Lancet 2:617618, 1982 (Letter) Serdaru M, Diquet B, Lhermitte F: Generalised seizures after ampicillin. Lancet 2:617–618, 1982 (Letter)

    • Search Google Scholar
    • Export Citation
  • 49.

    Skrede KK, & Westgaard RH: The transverse hippocampal slice: a well-defined cortical structure maintained in vitro. Brain Res 35:589593, 1971 Skrede KK, Westgaard RH: The transverse hippocampal slice: a well-defined cortical structure maintained in vitro. Brain Res 35:589–593, 1971

    • Search Google Scholar
    • Export Citation
  • 50.

    Smith H, , Lerner PI, & Weinstein L: Neurotoxicity and “massive” intravenous therapy with penicillin. A study of possible predisposing factors. Arch Intern Med 120:4753, 1967 Smith H, Lerner PI, Weinstein L: Neurotoxicity and “massive” intravenous therapy with penicillin. A study of possible predisposing factors. Arch Intern Med 120:47–53, 1967

    • Search Google Scholar
    • Export Citation
  • 51.

    Smithers JL, , Nicholls PJ, & Maddocks JL: Penetration of ampicillin into brain of rats with chronic renal failure. J Antimicrob Chemother 2:385386, 1976 (Letter) Smithers JL, Nicholls PJ, Maddocks JL: Penetration of ampicillin into brain of rats with chronic renal failure. J Antimicrob Chemother 2:385–386, 1976 (Letter)

    • Search Google Scholar
    • Export Citation
  • 52.

    Warwick R, & Williams PL (eds): Gray's Anatomy, ed 35. Edinburgh: Longman, 1973, 1471 pp Warwick R, Williams PL (eds): Gray's Anatomy, ed 35. Edinburgh: Longman, 1973, 1471 pp

    • Search Google Scholar
    • Export Citation
  • 53.

    Weinstein L, , Lerner PI, & Chew WH: Clinical and bacteriologic studies of the effect of “massive” doses of penicillin G on infections caused by Gram-negative bacilli. N Engl J Med 271:525533, 1964 Weinstein L, Lerner PI, Chew WH: Clinical and bacteriologic studies of the effect of “massive” doses of penicillin G on infections caused by Gram-negative bacilli. N Engl J Med 271:525–533, 1964

    • Search Google Scholar
    • Export Citation
  • 54.

    Wong RKS, , Traub RD, & Miles R: Epileptogenic mechanisms as revealed by studies of the hippocampal slice, in Schwartzkroin PA, & Wheal HV (eds): Electrophysiology of Epilepsy. London: Academic Press, 1984, pp 253275 Wong RKS, Traub RD, Miles R: Epileptogenic mechanisms as revealed by studies of the hippocampal slice, in Schwartzkroin PA, Wheal HV (eds): Electrophysiology of Epilepsy. London: Academic Press, 1984, pp 253–275

    • Search Google Scholar
    • Export Citation
  • 55.

    Wong VK, , Wright HT Jr, & Ross LA, et al: Imipenem/cilastatin treatment of bacterial meningitis in children. Pediatr Infect Dis J 10:122125, 1991 Wong VK, Wright HT Jr, Ross LA, et al: Imipenem/cilastatin treatment of bacterial meningitis in children. Pediatr Infect Dis J 10:122–125, 1991

    • Search Google Scholar
    • Export Citation

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