Carbapenem antibiotics in clinical use today are beta-lactam antibiotics derived from thienamycin, which was isolated from Streptomyces cattleya. They were developed in an era of increasing antibiotic resistance to cephalosporins and penicillins. The name 'carbapenem' may loosely be translated as 'carbon penicillin'. Indeed, the core structure of carbapenems resembles penicillins at first glance. Carbapenems have, however, a modified thiazolidine ring with an additional carbon atom and a double bond between two carbon atoms. This makes them very stable against cleavage by beta-lactamases.
All beta-lactam antibiotics work similarly. They bind to penicillin-binding proteins disrupting cell wall integrity by inhibiting proteoglycan synthesis and activation of autolytic enzymes. Carbapenems are bactericidal antibiotics. Imipenem, the first carbapenem on the market, is metabolised and inactivated by an enzyme in the kidneys called dehydropeptidase. This enzyme is inhibited by the drug cilastin, which is given in combination with imipenem. Carbapenems developed subsequently (doripenem, meropenem, ertapenem) are not metabolised by dehydopeptidase. Bacterial strains producing beta-lactamases that inactivate carbapenem antibiotics ('carbapenemases') have emerged and are on the rise in many countries.
Carbapenems provide very broad coverage including many anaerobes. Their activity against gram-negative organisms is slightly better compared to gram-positives. Ertapenem is the only carbapenem on the market without sufficient activity against Pseudomonas aeruginosae. Carbapenems are not active against MRSA.
Carbapenems have good tissue penetration, cross the blood-brain barrier and are thus useful in CNS infections. Ertapenem can be given once daily, but Meropenem, Doripenem and Imipenem must be administered 6-8 hourly. They are not metabolised by the liver and excreted unchanged by the kidneys
Common adverse effects are similar to other beta-lactam antibiotics including nausea, diarrhoea and skin rashes. Patients with a known history of severe penicillin drug allergy are often considered at increased risk of allergic reactions to carbapenems. However, there is a lack of evidence to support this. Due to their broad spectrum of activity, carbapenems will kill most of the patient's intestinal flora, which increases the risk of opportunistic bacterial and fungal superinfections.