Garyphallia Poulakou1, Helen Giamarellou. 1. University General Hospital ATTIKON, National and Kapodistrian University, Athens Medical School, 124 62 Athens, Greece. gpoul@med.uoa.gr
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-beta-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 beta-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.
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-beta-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 beta-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.
Authors: Tze Shien Lo; Stephanie M Borchardt; Justin M Welch; Melissa A Rohrich; Augusto M Alonto; Anne V Alonto Journal: Infect Drug Resist Date: 2009-06-30 Impact factor: 4.003