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Neurotoxicity of Carbapenem Antibacterials

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Summary

Similar to other β-lactam antibacterials, carbapenems have a neurotoxic potential that seems to be higher than that of the penicillins and cephalosporins. Seizures have been reported in several large studies of patients treated with imipenem/cilastatin. However, it seems clear that the main factor increasing the risk of neurotoxicity with imipenem/cilastatin is administration of excessive dosages relative to bodyweight and/or renal function. If the manufacturer’s dosage recommendations are followed, the risk of seizures in patients receiving this combination is minimal. With meropenem, a newly registered carbapenem, the safety margin with respect to neurotoxic reactions has been increased compared with imipenem and meropenem can be used at higher doses than imipenem/cilastatin.

Since the neurotoxicity of β-lactam antibacterials seems to be caused by an interaction with γ-aminobutyric acid (GABA) receptors, other drugs with a similar mechanism of action, such as fluoroquinolone antibacterials, should be used with caution when combined with carbapenems.

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References

  1. Schliamser SE, Cars O, Norrby SR. Neurotoxicity of beta-lactam antibiotics. J Antimicrob Chemother 1991; 27: 405–26

    Article  PubMed  CAS  Google Scholar 

  2. Schliamser S, 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 1988; 21: 365–72

    Article  PubMed  CAS  Google Scholar 

  3. Schliamser S, Bolander H, Kourtopoulos H, et al. Neurotoxicity of benzylpenicillin in rabbits with meningitis. J Antimicrob Chemother 1988; 21: 365–72

    Article  PubMed  CAS  Google Scholar 

  4. Schliamser SE, Bolander H, Broholm KA, et al. Neurotoxicity of benzylpenicillin in experimental renal failure and Enterobacter cloacae meningitis. J Antimicrob Chemother 1989; 24: 215–25

    Article  PubMed  CAS  Google Scholar 

  5. Schliamser SE, Broholm KA, Norrby SR. Comparative neurotoxicity of benzylpenicillin, imipenem/cilastatin and FCE 22101, a new injectable penem. J Antimicrob Chemother 1988; 22: 687–96

    Article  PubMed  CAS  Google Scholar 

  6. Calandra GB, Wang C, Aziz M, et al. The safety profile of imipenem/cilastatin: worldwide clinical experience based on 3470 patients. J Antimicrob Chemother 1986; 18 Suppl. E: 193–203

    PubMed  Google Scholar 

  7. Calandra G, Lydick E, Carrigan J, et al. Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin. Am J Med 1988; 84: 911–8

    Article  PubMed  CAS  Google Scholar 

  8. Pestotnik SL, Classen DC, Evans CR, et al. Prospective surveillance of imipenem/cilastatin use and associated seizures using a hospital information system. Ann Pharmacother 1993; 27: 497–500

    PubMed  CAS  Google Scholar 

  9. O’Donovan C, White ML, Cheung A, et al. Seizure incidence with imipenem use at a VA hospital. Hosp Formul 1995; 30: 172–5

    Google Scholar 

  10. Townsend KA, Alaniz C, Stumpf JL, et al. Imipenem-cilastatin use: evaluation of dosing and survey of adverse effects. Hosp Pharm 1992; 27: 298–310

    Google Scholar 

  11. Eng RHK, Munsif AN, Yangco BG, et al. Seizure propensity with imipenem. Arch Intern Med 1989; 149: 1881–3

    Article  PubMed  CAS  Google Scholar 

  12. Semel JD, Allen N. Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole. South Med J 1991; 84: 465–8

    Article  PubMed  CAS  Google Scholar 

  13. Job ML, Dretler RH. Seizure activity with imipenem therapy: incidence and risk factors. DICP 1990; 24: 467–9

    PubMed  CAS  Google Scholar 

  14. Leo RJ, Ballow CH. Seizure activity associated with imipenem use: clinical case reports and review of the literature. DICP 1991: 25: 351–4

    PubMed  CAS  Google Scholar 

  15. Bösmüller C, Steurer W, Königsrainer A, et al. Increased risk of central nervous system toxicity in patients treated with ciclosporin and imipenem/cilastatin. Nephron 1991; 58: 362–4

    Article  PubMed  Google Scholar 

  16. Jazgornik J, Schein W, Heimberger K, et al. Potentiation of neurotoxic side effects by coadministration of imipenem to cyclosporin therapy in a kidney transplant recipient: synergism of side effects or drug interaction? Clin Nephrol 1986; 26: 265–6

    Google Scholar 

  17. Hammer C, Thies JC, Mraz W, et al. Reduction of cyclosporin (CsA) nephrotoxicity by imipenem/cilastatin after kidney transplantation in rat. Transplant Proc 1989; 4: 1111–5

    Google Scholar 

  18. Markewitz A, Hammer C, Pfeiffer M, et al. Reduction of cyclosporin-induced nephrotoxicity by cilastatin following clinical heart transplantation. Transplantation 1994; 57: 865–70

    Article  PubMed  CAS  Google Scholar 

  19. Wong VK, Wright Jr HT, Ross LA, et al. Imipenem/cilastatin treatment of bacterial meningitis in children. Pediatr Infect Dis J 1991; 10: 122–5

    Article  PubMed  CAS  Google Scholar 

  20. Asensi S, Pérez-Tamarit D, Otero MC, et al. Imipenemcilastatin therapy in a child with meningitis caused by a multiply resistant pneumococcus. Pediatr Infect Dis J 1989; 8: 895

    PubMed  CAS  Google Scholar 

  21. Stuart RL, Turnidge J, Grayson ML. Safety of imipenem in neonates. Pediatr Infect Dis J 1995; 14: 804–5

    Article  PubMed  CAS  Google Scholar 

  22. Nalin DR, Jacobsen CA. Imipenem/cilastatin therapy for serious infections in neonates and infants. Scand J Infect Dis 1987; Suppl. 52: 46–55

    Google Scholar 

  23. Patel JB, Giles RE. Meropenem: evidence of lack of proconvulsive tendency in mice. J Antimicrob Chemother 1989; 24 Suppl. A: 307–9

    PubMed  CAS  Google Scholar 

  24. Sunbagawa M, Matsumura H, Sumita Y, et al. Structural features resulting in convulsive activity of carbapenem compounds: effect of C-2 side chain. J Antibiot 1995; 48: 408–16

    Article  Google Scholar 

  25. Hikida M, Musakawa Y, Nishiki K, et al. Low neurotoxicity of LJC 10,627, a novel lS-methyl carbapenem antibiotic: inhibition of gamma-aminobutyric acid, benzodiazepine, and glycine receptor binding in relation to lack of central nervous system toxicity in rats. Antimicrob Agents Chemother 1995; 37: 199–202

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Lopez E. Meropenem versus cefotaxime or ceftriaxone for bacterial meningitis [abstract]. In: 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy 1993: 236

    Google Scholar 

  28. Norrby SR, Newell PA, Faulkner KL, et al. Safety profile of meropenem: international clinical experience based on the first 3125 patients treated with meropenem. J Antimicrob Chemother 1995; 36 Suppl. A: 207–223

    PubMed  CAS  Google Scholar 

  29. Donnelly JP, Horrevorts AM, Sauerwein RW, et al. High-dose meropenem in meningitis due to Pseudomonas aeruginosa. Lancet 1992; 339: 1117

    Article  PubMed  CAS  Google Scholar 

  30. Chmelik V, Gutvirth J. Meropenem treatment of post-traumatic meningitis due to Pseudomonas aeruginosa. J Antimicrob Chemother 1993; 32: 922–3

    Article  PubMed  CAS  Google Scholar 

  31. Reid Jr R, Bradley JS, Hindler J. Pneumococcal meningitis during therapy of otitis media with clarithromycin. Pediatr Infect Dis J 1995; 14: 1104–5

    Article  PubMed  Google Scholar 

  32. Maies JFGM, Groot-Loonen J, Hoogkamp-Kastanje JAA. A brain abscess due to multiply resistant Enterobacter cloacae successfully treated with meropenem. Clin Infect Dis 1995; 20: 1567

    Article  Google Scholar 

  33. Data on file, Zeneca Pharmaceuticals

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  1. Department of Infectious Diseases, University of Lund, Lund University Hospital, S-22185, Lund, Sweden

    S. Ragnor Norrby

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  1. S. Ragnor Norrby
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Norrby, S.R. Neurotoxicity of Carbapenem Antibacterials. Drug-Safety 15, 87–90 (1996). https://doi.org/10.2165/00002018-199615020-00001

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