Abstract
Antipseudomonal carbapenems have played a useful role in our antimicrobial armamentarium for 20 years. However, a review of their use during that period creates concern that their clinical effectiveness is critically dependent on attainment of an appropriate dosing range. Unfortunately, adequate carbapenem dosing is missed for many reasons, including benefit/risk misconceptions, a narrow therapeutic window for imipenem and meropenem (due to an increased rate of seizures at higher doses), increasingly resistant pathogens requiring higher doses than are typically given, and cost containment issues that may limit their use. To improve the use of carbapenems, several initiatives should be considered: increase awareness about appropriate treatment with carbapenems across hospital departments; determine optimal dosing regimens for settings where multidrug resistant organisms are more likely encountered; use of, or combination with, an alternative antimicrobial agent having more favorable pharmacokinetic, pharmacodynamic, or adverse event profile; and administer a newer carbapenem with lower propensity for resistance development (for example, reduced expression of efflux pumps or greater stability against carbapenemases).
Highlights
Antipseudomonal carbapenems have proven to be valuable in the treatment of serious Gram-negative and polymicrobial mixed aerobic and anaerobic infections
It is increasingly clear that the clinical efficacy of carbapenems, imipenem and meropenem, is critically dependent on optimal dosing, especially in intensive care units (ICUs), burn units, and extended care facilities where multiresistant organisms are frequently encountered
Empiric treatment to cover multiresistant pathogens may necessitate using regimens at the higher end of the dosage range; the use of such high doses may be problematic in practice
Summary
Antipseudomonal carbapenems have proven to be valuable in the treatment of serious Gram-negative and polymicrobial mixed aerobic and anaerobic infections. This article explores the clinical impact of the relationship between carbapenem dosing and adverse event risks, pharmacodynamic-based dosing, and costs It focuses on imipenem, meropenem, and doripenem, as they are more commonly used as empiric treatments for seriously ill patients in settings such as the ICU [9]. Antipseudomonal carbapenems - imipenem, meropenem and doripenem - have excellent activity against most strains of many bacterial species and are regarded as safe and generally well-tolerated Because of their broad spectrum, the antipseudomonal carbapenems are often effective against organisms resistant to other antimicrobial agents and are frequently used as empiric therapy in the ICU for polymicrobial infections. Summary of selected reports of seizure adverse events in patients receiving imipenem or meropenem
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