Summary
onobactams and carbapenems are 2 classes of β-lactam antibiotics that were introduced in the 1980s. This review considers the monobactam aztreonam and the carbapenems imipenem and meropenem. Imipenem is administered together with cilastatin, which inhibits the enzymatic breakdown of imipenem in the kidney.
The antibacterial activities of these drugs are quite different from older β-lactams. Aztreonam is directed towards aerobic Gram-negative bacteria, especially Pseudomonas aeruginosa, while imipenem and meropenem are active against both aerobic and anaerobic Gram-positive and Gram-negative bacteria. Thus, these drugs should be reserved for patients who have a special need for them. They are also structurally different from older β-lactams and possess different adverse drug reaction profiles. It was initially suggested that aztreonam would be less immunogenic than previous β-lactams because reactive breakdown products acting as haptens are less likely to be formed. Clinical reports now support this assumption, and, in particular, cross hypersensitivity between aztreonam and other β-lactams seems to be rare which makes the drug a useful therapeutic alternative. However, hypersensitivity to aztreonam does occur.
The predominant concern in terms of adverse reactions to imipenem/cilastatin is the increased tendency to cause seizures compared with other β-lactams. The risk of producing a seizure is highly associated with inadequate dose adjustment in relation to kidney function. If appropriate care is taken, seizures occur in less than 1% of patients treated. However, it is possible that concomitant administration of other drugs with neurotoxic profiles (e.g. theophylline and cyclosporin) given in overdose, may increase the risk of seizures. Meropenem has a similar adverse effect profile to imipenem/cilastatin; more clinical experience is required to assess its relative tolerability.
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References
Brogden RN, Heel RC. Aztreonam: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1986; 31: 96–130
Adkinson Jr NF, Swabb EA, Sugerman AA. Immunology of the monobactam aztreonam. Antimicrob Agents Chemother 1984; 25: 93–7
Adkinson Jr NF. Immunogenicity and cross-allergenicity of aztreonam. Am J Med 1990; 88 Suppl. 3C: 12S–5S
Moss RB. Sensitization to aztreonam and cross-reactivity with other beta-lactam antibiotics in high-risk patients with cystic fibrosis. J Allergy Clin Immunol 1991; 87: 78–88
Koch C, Hjelt K, Stenvang Pedersen S, et al. Retrospective clinical study of hypersensitivity reactions to aztreonam and six other β-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses. Rev Infect Dis 1991; 13 Suppl. 7: S608–11
Jensen T, Stenvang Pedersen S, Høiby N, et al. Safety of aztreonam in patients with cystic fibrosis and allergy to β-lactam antibiotics. Rev Infect Dis 1991; 13 Suppl. 7: S594–7
Vega JM, Bianca M, García JJ, et al. Tolerance to aztreonam in patients allergic to betalactam antibiotics. Allergy 1991; 46: 196–202
Danziger LH, Fish DN, Wesley LC. Aztreonam hypersensitivity in a β-lactam-allergic patient. Infect Dis Clin Pract 1993; 2: 389–93
de la Fuente Prieto R, Armentia Medina A, Sanchez Palla P, et al. Urticaria caused by sensitization to aztreonam. Allergy 1993; 48: 634–6
McDonald BJ, Singer JW, Bianco JA. Toxic epidermal necrolysis possibly linked to aztreonam in bone marrow transplant patients. Ann Pharmacother 1992; 26: 34–5
Hegelmaier C, Hütig HB, Kalbheim HJ. Antibiotikaassoziierte pseudomenbranöse Kolitis — eine literaturgestützte Fallanalyse. Klin Wochenschr 1991; 69 Suppl. XXVI: 57–60
Moore RD, Lerner SA, Levine DP Nephrotoxicity and ototoxicity of aztreonam versus aminoglycoside therapy in seriously ill nonneutropenic patients. J Infect Dis 1992; 165: 683–8
Rietbroek RC, Hoitsma AJ, Koene RAP. Aztreonam can safely be used in combination with cyclosporin without aggravating nephrotoxicity. Transplant Int 1989; 2: 232–4
Buckley MM, Brogden RN, Barradell RB, et al. Imipenem/cilastatin: a reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1992; 44: 408–44
Snavely SR, Hodges GR. The neurotoxicity of antibacterial agents. Ann Intern Med 1984; 101: 92–104
Eng RHK, Munsif AN, Yangco BG, et al. Seizure propensity with imipenem. Arch Intern Med 1989; 149: 1881–3
Brown RB, Sands M, Morris AB. Seizure propensity with imipenem [letter]. Arch Intern Med 1990; 150: 1551
Choucino C, Chopra A, Khardori N. Incidence of seizures in patients treated with imipenem/cilastatin in a teaching hospital [abstract]. Clin Res 1992; 40: 753A
Pestotnik SL, Classen DC, Evans RS, et al. Prospective surveillance of imipenem/cilastatin use and associated seizures using a hospital information system. Ann Pharmacother 1993; 27: 497–501
Semel JD, Allen N. Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole. South Med J 1991; 84: 465–8
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
Asensi F, Otero MC, Pérez-Tamarit D, et al. Risk/benefit in the treatment of children with imipenem-cilastatin for meningitis caused by penicillin-resistant pneumococcus. J Chemother 1993; 5: 133–4
Asensi F, Pérez-Tamarit D, Otero MC, et al. Imipenem/ cilastatin therapy in a child with meningitis caused by a multiply resistant pneumococcus. Pediatr Infect Dis J 1989; 8: 895
Wong UK, Wright HT, Ross LA, et al. Imipenem-cilastatin treatment of bacterial meningitis in children. Pediatr Infect Dis J 1991; 10: 122–5
Lucena M, Andrade R, Cabello M, et al. Imipenem/cilastatin-associated hiccups [letter]. Ann Pharmacother 1992; 26: 1459
O’Riordan J, Javed M, Doherty C, et al. Worsening of myasthenia gravis on treatment with imipenem/cilastatin [letter]. J Neurol Neurosurg Psychiatry 1994; 57: 383
Escallier F, Dalac S, Foucher JL, et al. Pustulose exanthé-matique aigüe généralisée imputabilité a l’imipénème (Tienam®). Ann Dermatol Venereol 1989; 116: 407–9
Spencer JM, Silvers DN, Grossman ME. Pustular eruption after drug exposure: is it pustular psoriasis or a pustular drug eruption? Br J Dermatol 1994; 130: 514–9
Fariñas MC, de Vega T, Garmendia J, et al. Severe neutropenia in a patient treated with imipenem/cilastatin. Eur J Clin Microbiol Infect Dis 1993; 12: 303–4
Arnaud M, Rochet N, Bonnet C, et al. Jaundice secondary to treatment with imipenem [abstract]. Therapie 1990; 45: 70
Arning M, Gehrt A, Wolf M, et al. Letaler Verlauf einer pseudo-membranösen Enterokolitis unter parenteraler Gabe von Vancomycin und Imipenem. Dtsch Med Wochenschr 1992; 117: 91–5
Pryka RD, Haig GM. Meropenem: a new carbapenem antimicrobial. Ann Pharmacother 1994; 28: 1045–54
Del Favero A. Clinically important aspects of carbapenem safety. Curr Opin Infect Dis 1994; 7 Suppl. 1: S38–42
Brismar B, Malmborg AS, Tunevall G, et al. Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections. J Antimicrob Chemother 1995; 35: 139–48
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Alván, G., Nord, C.E. Adverse Effects of Monobactams and Carbapenems. Drug-Safety 12, 305–313 (1995). https://doi.org/10.2165/00002018-199512050-00003
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DOI: https://doi.org/10.2165/00002018-199512050-00003