Objectives: This study was conducted to identify and compare the microbiological and clinical outcomes among hospitalized adults with pneumonia caused by fluoroquinolone-susceptible or -resistant strains of Pseudomonas aeruginosa. Antibiotic regimens used prior to, as well as those used to treat, the infections were characterized. Patients and methods: This non-randomized multicentre study included 100 consecutively identified patients with pneumonia caused by fluoroquinolone-susceptible (n=50) or fluoroquinolone-resistant (n=50) strains of P. aeruginosa. Medical records were examined for demographic, clinical and treatment variables including antibiotics received in the 30 days before the index respiratory or blood culture; AUICs were calculated for each patient using reported or derived MICs. Multivariate logistic and linear regressions were used to identify factors associated with successful clinical and microbiological outcomes. Results: The study population was primarily elderly, frequently in a critical care unit, with low serum albumin and with a high probability of failure and mortality. Patients with pneumonia caused by fluoroquinolone-resistant P. aeruginosa were more likely to have received antibiotics within 7 days before the infection (P=0.027); the antibiotic regimen was more likely to be of a weak potency (mean AUIC of 58 versus 169, P=0.001) and to include levofloxacin (P<0.0001) than what was administered to patients who became infected with a fluoroquinolone-susceptible strain. Regardless of susceptibility, a mean of between 2 and 3 weeks of directed antibiotic therapy was administered to each patient. Conclusions: Pneumonia caused by fluoroquinolone-resistant P. aeruginosa is frequently associated with prior exposure to levofloxacin. Treatment of P. aeruginosa pneumonia is difficult and usually consists of combination regimens with multiple modifications.