Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens

Abstract

Background: Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. Objective: This drug evaluation focuses on the position of doripenem, a novel forthcoming carbapenem. Mechanisms of resistance and new drugs with anti-Gram-negative activity are also briefly reviewed. Methods: Literature search was performed for new carbapenems, new antibiotics, doripenem, metallo-β-lactamase inhibitors, multidrug-resistant pathogens, antipseudomonal antibiotics and multidrug-resistant epidemiology. Results: Doripenem possesses a broad spectrum of activity against Gram-negative bacteria, similar to that of meropenem, while retaining the spectrum of imipenem against Gram-positive pathogens. Against P. aeruginosa, doripenem exhibits rapid bactericidal activity with 2 – 4-fold lower MIC values, compared to meropenem. Exploitation of pharmacokinetic/pharmacodynamic applications could offer a treatment opportunity against strains exhibiting borderline resistance to doripenem. Stability against numerous β-lactamases, low adverse event potential and more potent in vitro antibacterial activity against P. aeruginosa and A. baumanni compared to the existing carbapenems, are its principal features.

Keywords::

• Acinetobacter baumannii
• antibiotic policy
• antipseudomonal antibiotic
• colistin
• doripenem
• Klebsiella pneumonia
• multidrug-resistant epidemiology
• multidrug-resistant pathogen
• new antibiotic
• Pseudomonas aeruginosa

Acknowledgements

The authors thank D Plachouras, MD and I Katsarolis, MD for the design of chemical structures.