Adverse Effects of Monobactams and Carbapenems

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Abstract
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.