Imipenem/cilastatin: an update of its antibacterial activity, pharmacokinetics and therapeutic efficacy in the treatment of serious infections

Abstract

The prototype carbapenem antibacterial agent imipenem has a very broad spectrum of antibacterial activity, encompassing most Gram-negative and Gram-positive aerobes and anaerobes, including most beta-lactamase-producing species. It is coadministered with a renal dehydropeptidase inhibitor, cilastatin, in order to prevent its renal metabolism in clinical use. Extensive clinical experience gained with imipenem/cilastatin has shown it to provide effective monotherapy for septicaemia, neutropenic fever, and intra-abdominal, lower respiratory tract, genitourinary, gynaecological, skin and soft tissues, and bone and joint infections. In these indications, imipenem/cilastatin generally exhibits similar efficacy to broad-spectrum cephalosporins and other carbapenems and is at least equivalent to standard aminoglycoside-based and other combination regimens. Imipenem/cilastatin is generally well tolerated by adults and children, with local injection site events, gastrointestinal disturbances and dermatological reactions being the most common adverse events. Seizures have also been reported, occurring mostly in patients with impaired renal function or CNS pathology, or with excessive dosage. Although it is no longer a unique compound, as newer carbapenems such as meropenem are becoming available, imipenem/cilastatin nevertheless remains an important agent with established efficacy as monotherapy for moderate to severe bacterial infections. Its particular niche is in treating infections known or suspected to be caused by multiresistant pathogens.