Carbapenems in serious infections: a risk-benefit assessment
1Department of Infectious Diseases and Medical Microbiology, University of Lund, Lund University Hospital, Sweden. Ragnar.Norrby@infek.lu.se
Abstract:
The tolerability of the 2 most frequently used carbapenems, imipenem/cilastatin and meropenem, is reviewed. Both of these drugs, but especially imipenem, are potentially neurotoxic and may cause seizures if overdosed relative to renal function and/or bodyweight. The therapeutic margin is considerably narrower with imipenem/cilastatin which cannot be given at doses required for treatment of bacterial meningitis. Meropenem on the other hand, is considerably less prone to cause seizures and its tolerability and efficacy are well documented in 3 relatively large, controlled studies in adults and children with meningitis. They showed that meropenem was as effective and well tolerated as cefotaxime or ceftriaxone. Another potential advantage of meropenem over imipenem/cilastatin is that it can be given intravenously at a high rate without increased risk of nausea or vomiting. An obvious reason for using a carbapenem instead of a cephalosporin for empirical treatment of life-threatening infections is that both imipenem/cilastatin and meropenem have a broader spectrum of activity. They are also more resistant to hydrolysis by the most common beta-lactamases, including the class I cephalosporinase frequently produced by Enterobacter spp. and Pseudomonas spp. and the extended spectrum enzymes, now commonly found in Escherichia coli and Klebsiella spp.
Insights
Meropenem is a safer carbapenem than imipenem/cilastatin, causing fewer seizures. Both drugs offer broad-spectrum activity against serious infections, but meropenem shows better tolerability and efficacy in meningitis treatment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Carbapenems are broad-spectrum antibiotics used for severe infections.
- Imipenem/cilastatin and meropenem are the most common carbapenems.
- Neurotoxicity, particularly seizures, is a known side effect of carbapenems.
Purpose of the Study:
- To review and compare the tolerability of imipenem/cilastatin and meropenem.
- To evaluate the risk of neurotoxicity and seizures associated with these carbapenems.
- To assess the efficacy and safety of meropenem in treating bacterial meningitis.
Main Methods:
- Review of existing literature on carbapenem tolerability.
- Analysis of clinical studies comparing meropenem with other antibiotics.
- Assessment of carbapenem properties, including spectrum of activity and resistance to beta-lactamases.
Main Results:
- Imipenem/cilastatin, especially with overdose relative to renal function/bodyweight, carries a higher risk of neurotoxicity and seizures.
- Meropenem demonstrates a lower propensity for causing seizures and has well-documented tolerability and efficacy in meningitis.
- Meropenem showed comparable efficacy and tolerability to cefotaxime or ceftriaxone in meningitis treatment.
- Meropenem can be administered intravenously at a high rate without increased nausea or vomiting.
Conclusions:
- Meropenem offers a better tolerability profile than imipenem/cilastatin, particularly regarding neurotoxicity.
- Both carbapenems provide broad-spectrum activity and resistance to common beta-lactamases, making them valuable for empirical treatment of life-threatening infections.
- Meropenem is a preferred option for treating bacterial meningitis due to its safety and efficacy profile.
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