Are carbapenems (beta-lactam antibiotics) less likely to cause drug fevers and myelosuppression compared to other beta-lactam antibiotics?

From the Guidelines

Carbapenems are generally less likely to cause drug fevers and myelosuppression compared to other beta-lactam antibiotics. Among the beta-lactam class, penicillins and cephalosporins more commonly trigger these adverse effects, while carbapenems like meropenem, imipenem-cilastatin, ertapenem, and doripenem have a lower incidence of these specific reactions 1. Drug fevers, characterized by temperature elevation without other obvious causes, occur less frequently with carbapenems, and when they do appear, they typically resolve quickly upon discontinuation. Similarly, myelosuppression (particularly neutropenia) is less common with carbapenems than with other beta-lactams, especially compared to piperacillin-tazobactam or certain cephalosporins used for prolonged courses. This reduced risk is likely related to differences in chemical structure and how these drugs interact with immune system components. However, it's essential to note that carbapenems still carry risks of other adverse effects, including seizures (particularly imipenem), gastrointestinal disturbances, and allergic reactions. Regular monitoring of complete blood counts remains prudent during extended carbapenem therapy, especially in patients with other risk factors for bone marrow suppression.

Some key points to consider:

• The incidence of drug fevers and myelosuppression varies among different beta-lactam antibiotics, with carbapenems generally having a lower risk compared to other classes 1.
• The choice of antibiotic should be guided by the suspected or confirmed pathogen, local resistance patterns, and the patient's individual risk factors for adverse effects 1.
• Carbapenems, such as meropenem and ertapenem, are effective against a broad range of gram-positive and gram-negative pathogens, including ESBL-producing Enterobacteriaceae, but their use should be limited to preserve their activity against multidrug-resistant infections 1.
• Other antibiotic options, such as beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, and fluoroquinolones, may be considered for the treatment of intra-abdominal infections, but their use should be guided by local resistance patterns and the patient's individual risk factors for adverse effects 1.

In terms of morbidity, mortality, and quality of life, the use of carbapenems as first-line therapy for intra-abdominal infections may be associated with improved outcomes compared to other beta-lactam antibiotics, particularly in patients with severe infections or those at risk for multidrug-resistant pathogens 1. However, the benefits of carbapenem therapy must be weighed against the potential risks of adverse effects and the development of resistance. Ultimately, the choice of antibiotic should be individualized based on the patient's specific needs and circumstances.

From the Research

Comparison of Carbapenems with Other Beta-Lactams

• Carbapenems are a class of beta-lactam antibiotics with a broad spectrum of activity, including against aerobic and anaerobic bacteria 2, 3.
• They are generally considered to have a lower risk of causing certain adverse effects, such as drug fevers, compared to other beta-lactam antibiotics, although specific data on this topic is limited.
• Myelosuppression is not commonly associated with carbapenems, but the evidence does not provide a direct comparison with other beta-lactam antibiotics in this regard.

Adverse Effects of Carbapenems

• The main toxic effects of imipenem, a carbapenem, include infusion-related nausea and vomiting, as well as seizures, which occur at a similar frequency to those of other beta-lactam antibiotics 2.
• Meropenem, another carbapenem, has a similar safety profile to imipenem, with a lower risk of neurotoxicity due to its increased stability and higher dosage range 3, 4.
• The risk of seizures with carbapenems is increased with excessive dosages or impaired renal function, but is minimal when dosage recommendations are followed 4, 5.

Mechanism of Action and Resistance

• Carbapenems act by inhibiting bacterial cell wall synthesis, similar to other beta-lactam antibiotics, and are stable to most beta-lactamases 3, 6.
• Resistance to carbapenems can develop through various mechanisms, including changes in penicillin-binding proteins, acquisition of metallo-beta-lactamases, or alterations in membrane permeability 3, 6.