Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia

Background: The impact of antibiotic resistance on the outcome of infections due to Gram-negative bacilli, especially Pseudomonas, remains highly controversial. Study objective, design, and patients: We evaluated the impact of piperacillin resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) for patients who had received appropriate empiric antibiotics before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8 vs 15 days of antibiotics. Results: Despite similar characteristics at intensive care unit (ICU) admission, patients infected with piperacillin-resistant Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day mortality rate (37 vs 19%; P=0.04) than those with piperacillin-susceptible Pseudomonas VAP. Factors associated with 28-day mortality retained by multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95% CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61). The VAP recurrence rates, either superinfection or relapse, and durations of mechanical ventilation and ICU stay did not differ as a function of Pseudomonas-resistance status. Conclusions: For patients with Pseudomonas VAP benefiting from appropriate empiric antibiotics, piperacillin resistance was associated with increased disease severity at VAP onset and higher 28-day crude mortality; however, after controlling for confounders, piperacillin-resistance was no longer significantly associated with 28-day mortality. The VAP recurrence rates and durations of ICU stay and mechanical ventilation did not differ for susceptible and resistant strains.