Some studies conducted in vitro and in experimental models found that virulence of P. aeruginosa might be reduced in mutant resistant strains of P. aeruginosa suggesting that antibiotic selleckchem resistance imposes a fitness cost on the bacteria [18,19]. Recent data on in vitro mutants have suggested that virulence of P. aeruginosa might be reduced when mex efflux systems are overexpressed [20]. Indeed, it seems that mutant strains may recover their fitness or virulence by compensatory mutations. Hoquet et al. conducted a study on 120 strains of P. aeruginosa from episodes of septicaemia: 75% of strains displayed a significant resistance to one or more of the tested antimicrobials. P. aeruginosa may accumulate intrinsic (chromosomal) and exogenous resistance mechanisms without losing its ability to generate severe bloodstream infections [21].

Jeannot et al. focused on clinical isolates of P. aeruginosa mexCD-oprJ overproducing efflux mutants: mexCD-oprJ up regulation (which correlated with increase resistance to ciprofloxacin and cefepime, increased susceptibility to ticarcillin, aztreonam, imipenem and aminoglycosides), associated with impaired bacterial fitness although it was isolated from confirmed cases of clinical infections [22].In our study, 153 of 223 patients received adequate antibiotic therapy within 24 hours after pneumonia suspicion (51.4% in the PRPA group and 76.5% in the PSPA group). Garnacho-Montero et al. [23] evaluated the impact on the outcome of a monotherapy or a combined therapy in patients with PA-VAP.

They showed that the initial use of a combination therapy significantly reduced the likelihood of inappropriate therapy, which was associated with a higher risk of death. However, the administration of only one effective antimicrobial or combination therapy provided similar outcomes. For Kang et al. adequate initial antibiotic therapy appeared to be one of the most important factors in the treatment of severe P. aeruginosa infections, as they observed a trend towards higher mortality rates as the interval prior to appropriate treatment increased. However, their results were not statistically significant [24].In our study, antibiotic resistant strains were associated with an increased risk of inadequate antimicrobial therapy, but we did not find that PRPA influenced recurrence, relapse or mortality.

We previously showed that the highest impact of inappropriate therapy on prognosis obtained when patients’ severity score is intermediate [25,26]. The absence of impact of inappropriate antimicrobial Drug_discovery therapy on the prognosis might be due to the high severity of patients at VAP onset (SOFA at 6 in median in the present study).As any delay in the initiation of an adequate antimicrobial therapy is known to be a major prognostic risk factor in nosocomial infection due to P.