Pharmacology Review: Newer Antibiotics: Imipenem/cilastatin and Meropenem

Abstract

The carbapenem antibiotics imipenem/cilastatin and meropenem offer therapeutic options for unusual and highly antibiotic-resistant organisms encountered in the neonatal intensive care unit. The agents have a very broad spectrum of antibiotic activity, favorable safety profiles, and good drug penetration into all body sites, making them a reasonable choice for term and preterm infants who have difficult-to-treat infections. Although a moderate amount of pharmacokinetic data support the safe use of carbapenem antibiotics in neonates, the broad-spectrum activity of the agents dictates that their use be limited to the treatment of highly resistant, nosocomially acquired bacteria and mixed aerobic and anaerobic infections. Carbapenems are beta-lactam antibiotics that have broad-spectrum aerobic and anaerobic activity. Like other beta-lactam antibiotics, they exert an antibacterial effect by binding penicillin-binding proteins, thereby disrupting bacterial cell wall synthesis. Because imipenem is rapidly degraded by renal proximal tubule dipeptidases, it is marketed in combination with the dipeptidase inhibitor cilastatin. Meropenem is stable to renal dipeptidases and requires no cilastatin. In adults and older children, imipenem and meropenem have been used extensively for treatment of a wide variety of infections, most notably intra-abdominal, gynecologic, lower respiratory tract, and urinary tract. These clinical uses, particularly in mixed and highly resistant infections, reflect the broad-spectrum activity of carbapenems against important clinical pathogens. Imipenem and meropenem have excellent in vitro activity against streptococci (including S pyogenes , S agalactiae , and viridans group streptococci), enterococci, pneumococci, and methicillin-susceptible (but not methicillin-resistant) staphylococci. These drugs also are active against almost all enteric gram-negative rods (GNRs) (eg, Escherichia coli, Klebsiella, Enterobacter, Serratia, Citrobacter, Proteus sp) and most nonenteric GNRs (eg, Pseudomonas, Acinetobacter sp). A notable exception is Stenotrophomonas maltophilia . Anaerobes, including Bacteroides fragilis and clostridia, are very susceptible to carbapenem antibiotics. Although in vitro susceptibility data suggest that imipenem offers superior gram-positive activity and …