1: Clin Microbiol Infect. 2007 Jan 31; [Epub ahead of print]

Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the
new millennium.

Mesaros N, Nordmann P, Plesiat P, Roussel-Delvallez M, van Eldere J, Glupczynski
Y, van Laethem Y, Jacobs F, Lebecque P, Malfroot A, Tulkens PM, van Bambeke F.

Unite de Pharmacologie cellulaire and moleculaire, Universite catholique de
Louvain, Bruxelles, Belgium.

Pseudomonas aeruginosa is a major cause of nosocomial infections. This organism
shows a remarkable capacity to resist antibiotics, either intrinsically (because
of constitutive expression of beta-lactamases and efflux pumps, combined with
low permeability of the outer-membrane) or following acquisition of resistance
genes (e.g., genes for beta-lactamases, or enzymes inactivating aminoglycosides
or modifying their target), over-expression of efflux pumps, decreased
expression of porins, or mutations in quinolone targets. Worryingly, these
mechanisms are often present simultaneously, thereby conferring multiresistant
phenotypes. Susceptibility testing is therefore crucial in clinical practice.
Empirical treatment usually involves combination therapy, selected on the basis
of known local epidemiology (usually a beta-lactam plus an aminoglycoside or a
fluoroquinolone). However, therapy should be simplified as soon as possible,
based on susceptibility data and the patient's clinical evolution. Alternative
drugs (e.g., colistin) have proven useful against multiresistant strains, but
innovative therapeutic options for the future remain scarce, while attempts to
develop vaccines have been unsuccessful to date. Among broad-spectrum
antibiotics in development, ceftobiprole, sitafloxacin and doripenem show
interesting in-vitro activity, although the first two molecules have been
evaluated in clinics only against Gram-positive organisms. Doripenem has
received a fast track designation from the US Food and Drug Administration for
the treatment of nosocomial pneumonia. Pump inhibitors are undergoing phase I
trials in cystic fibrosis patients. Therefore, selecting appropriate antibiotics
and optimising their use on the basis of pharmacodynamic concepts currently
remains the best way of coping with pseudomonal infections.

PMID: 17266725 [PubMed - as supplied by publisher]

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