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Adverse effects of monobactams and carbapenems
1Department of Clinical Pharmacology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
Abstract:
Monobactams and carbapenems are 2 classes of beta-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 beta-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 beta-lactams and possess different adverse drug reaction profiles. It was initially suggested that aztreonam would be less immunogenic than previous beta-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 beta-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 beta-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Monobactams like aztreonam and carbapenems such as imipenem/cilastatin offer distinct antibacterial spectra and safety profiles compared to older beta-lactams. Aztreonam is effective against aerobic Gram-negative bacteria, while imipenem/cilastatin targets a broader range of bacteria.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Monobactams and carbapenems represent distinct classes of beta-lactam antibiotics introduced in the 1980s.
- This review focuses on aztreonam (monobactam) and imipenem/cilastatin and meropenem (carbapenems).
Purpose of the Study:
- To review the distinct antibacterial activities and adverse drug reaction profiles of aztreonam, imipenem, and meropenem.
- To assess the clinical utility and safety of these newer beta-lactam antibiotics.
Main Methods:
- Comparative review of existing literature on monobactams and carbapenems.
- Analysis of antibacterial spectra, structural differences, and adverse event profiles.
Main Results:
- Aztreonam exhibits activity against aerobic Gram-negative bacteria, including Pseudomonas aeruginosa.
- Imipenem/cilastatin and meropenem are effective against both aerobic and anaerobic Gram-positive and Gram-negative bacteria.
- Aztreonam demonstrates a low incidence of cross-hypersensitivity with other beta-lactams, though hypersensitivity can occur.
- Imipenem/cilastatin use is associated with an increased risk of seizures, particularly with inadequate dose adjustment in renal impairment.
Conclusions:
- Aztreonam serves as a valuable therapeutic alternative due to its specific spectrum and low cross-reactivity.
- Carbapenems like imipenem/cilastatin are potent broad-spectrum agents but require careful dosing to mitigate seizure risk.
- These antibiotics should be reserved for specific clinical indications due to their unique properties and potential adverse effects.