Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa.
Acinetobacter baumannii and Pseudomonas aeruginosa are gram-negative pathogens that target immunocompromised patients. They express a variety of determinants that confer resistance to a broad array of antimicrobial agents. Mechanisms of resistance include impaired entry through the bacterial outer membrane, production of antibiotic-modifying enzymes, active efflux, and target mutations that reduce antimicrobial affinity. It has been a challenge to identify new agents that have activity against the more resistant variants of these species. Doripenem is a carbapenem in phase 3 trials that has excellent activity against P. aeruginosa and A. baumannii. However, it lacks activity against strains that express resistance to the currently available carbapenems. Tigecycline is a newly licensed glycylcycline that lacks activity against P. aeruginosa but has encouraging activity against many A. baumannii isolates. Resistance to tigecycline can emerge during therapy, however, and is due to expression of multidrug efflux pumps.
Rice
Louis B
LB
Louis Stokes Cleveland VA Medical Center and Case Medical School, Cleveland, Ohio 44106, USA. louis.rice@med.va.gov
D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects; D015780:Carbapenems / Q000008:administration & dosage* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects; D008911:Minocycline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D000078304:Tigecycline
D000890:Anti-Infective Agents; D015780:Carbapenems; D000078304:Tigecycline; D000077726:Doripenem; D008911:Minocycline