title: Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy.
abstract: Pseudomonas aeruginosa and Acinetobacter baumannii are major nosocomial pathogens worldwide. Both are intrinsically resistant to many drugs and are able to become resistant to virtually any antimicrobial agent. An increasing prevalence of infections caused by multidrug-resistant (MDR) isolates has been reported in many countries. The resistance mechanisms of P. aeruginosa and A. baumannii include the production of beta-lactamases, efflux pumps, and target-site or outer membrane modifications. Resistance to multiple drugs is usually the result of the combination of different mechanisms in a single isolate or the action of a single potent resistance mechanism. There are many challenges in the treatment of MDR P. aeruginosa and A. baumannii, especially considering the absence of new antimicrobials in the drug-development pipeline. In this review, we present the major resistance mechanisms of P. aeruginosa and A. baumannii, and discuss how they can affect antimicrobial therapy, considering recent clinical, microbiological, pharmacokinetic and pharmacodynamic findings of the main drugs used to treat MDR isolates.
authors.affiliation: Infectious Diseases Unit, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, 90035-903, Porto Alegre, Brazil. azavascki@hcpa.ufrgs.br
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Zavascki
authors.forename: Cecília G
authors.initials: CG
authors.lastname: Carvalhaes
authors.forename: Renata C
authors.initials: RC
authors.lastname: Picão
authors.forename: Ana C
authors.initials: AC
authors.lastname: Gales
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins