Ertapenem, Imipenem, Meropenem, Doripenem, and Aztreonam

Carbapenems are active against a broad range of gram-positive and gram-negative aerobic and anaerobic bacteria due to their efficient penetration through the bacterial outer membrane, their high affinity for multiple penicillin-binding proteins (PBPs), and their stability against most β-lactamases, including class A extended-spectrum β-lactamases (ESBLs) and class C (AmpC) β-lactamases but not carbapenemases, including Klebsiella pneumoniae carbapenemase (KPC) and class B metallo-β-lactamases. Carbapenems preferentially bind to PBPs 1a, 1b, 2, and 4 and to a lesser extent PBP3. Ertapenem, imipenem, meropenem, and doripenem are the most widely available carbapenems. Among them, ertapenem is unique for its longer half-life, allowing daily administration, and its limited activity against enterococci as well as lactose-nonfermenting species such as Pseudomonas aeruginosa. Increasing incidence of carbapenem-resistant Enterobacteriaceae has raised concern about erosion of the utility for this important class of antibacterial agents. Aztreonam is the only monobactam currently in wide clinical use. Its spectrum of activity is limited to aerobic gram-negative bacteria via high affinity for their PBP3. It is resistant to hydrolysis by class B metallo-β-lactamases and most class A β-lactamases but is hydrolyzed by ESBLs, AmpC, and KPC β-lactamases. Cross-reactivity of aztreonam with penicillins and cephalosporins is extremely rare, even in patients with immunologically proven hypersensitivity to other β-lactams. As β-lactam agents, the most important pharmacodynamic parameter predicting bacteriologic and clinical efficacy of both carbapenems and aztreonam is the time of free plasma drug concentration exceeding the minimum inhibitory concentration (fT > MIC) of the infecting organism.