Pharmacotherapy of Complicated Urinary Tract and Intra-abdominal Infections with Doripenem

Abstract

Due to the growing rate of multi-drug resistant bacteria in complicated infections, the need for new broad-spectrum antimicrobials is paramount. Doripenem, a new addition to the intravenous carbapenem class, has recently been approved for the treatment of complicated lower urinary tract infections and/or pyelonephritis (cUTI) and complicated intra-abdominal infections (cIAI) in adult patients. Doripenem exhibits potent in vitro and in vivo bactericidal activity against an assortment of Gram-positive and Gram-negative aerobic and anaerobic organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae that produce extended spectrum beta-lactamases (ESBL). Relative to other available carbapenems, doripenem typically displays MICs that are 1-2 dilutions lower than meropenem and 2-4 dilutions lower than imipenem against P. aeruginosa. Since the kidneys primarily excrete doripenem as whole drug, dose adjustments are needed in patients with renal impairment. Doripenem 500 mg q8 h demonstrated non-inferiority to levofloxacin 250 mg q24 h in clinical trials of patients with cUTI; it was non-inferior to meropenem 1000 mg q8 h in patients with cIAI. Doripenem's broad spectrum of activity, in vitro potency against particularly difficult to treat organisms, and desirable safety profile make it an attractive option in the treatment of cUTI and cIAI.