Pseudomonas aeruginosa: Résistance et options thérapeutiques à l'aube du deuxième millénaire

Mesaros, N. Nordmann, P. Plésiat, P. Roussel-Delvallez, M. Van Eldere, J. Glupczynski, Gerald [UCL] Van Laethem, Y. Jacobs, F. Lebecque, Patrick [UCL] Malfroot, A. Tulkens, Paul M. [UCL] Van Bambeke, Françoise [UCL] et al.[show all]

Pseudomonas aeruginosa is a major cause of nosocomial infections. Due to its genetic plasticity, it can adapt to a wide variety of environments, causing infections in almost all body sites (with however a predilection for the respiratory tract, especially in cystic fibrosis patients). It also shows a remarkable capacity to resist to antibiotics, either intrinsically (through constitutive expression of β-lactamases and efflux pumps, or low permeability of the outer membrane), or upon exposure to antibiotics through acquisition of resistance genes (coding fo antibiotic-degrading enzymes inactivating or target modifications), overexpression of efflux pumps, decreased expression of porins, or target mutations. Worryingly also, these mechanisms are often present simultaneously, conferring multiresistant phenotypes. Susceptibility testing is therefore crucial in clinical practice. Empiric treatment is usually initiated using a bitherapy, selected based on local epidemiology (β-lactam plus aminoglycoside or fluoroquinolone). However, it should be streamlined as soon as possible, based on susceptibility data and patient's evolution. Alternative drugs (colistin, e.g.) have proven useful for multiresistant strains. Innovative therapeutic options for the future remain scarce, while attempts to develop vaccines have been so far unsuccessful. Among broad-spectrum antibiotics in development, ceftobiprole, sitafloxacin and doripenem show interesting in vitro activity. The two first molecules, however, are evaluated in the clinics towards Gram-positive only. Pump inhibitors are under study but proved much more difficult to develop than originally anticipated. Therefore, selecting appropriate antibiotics and optimizing their use based on pharmacodynamic concepts remains the only way to cope with pseudomonal infections.