Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens.
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.
Poulakou
Garyphallia
G
University General Hospital ATTIKON, National and Kapodistrian University, Athens Medical School, 124 62 Athens, Greece. gpoul@med.uoa.gr
Giamarellou
Helen
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D015780:Carbapenems / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D000077726:Doripenem; D004341:Drug Evaluation; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem