Fluoroquinolone-resistant Pseudomonas aeruginosa:: risk factors for acquisition and impact on outcomes

Objectives: Resistance among Pseudomonas aeruginosa has risen dramatically and parallels the increase in fluoroquinolone (FQ) prescribing in recent years. Risk factors for FQ resistance in P. aeruginosa and its impact on outcomes need to be well characterized. Methods: A case-control study was carried out on hospitalized adult patients from whom FQ-resistant (case) and FQ-susceptible (control) P. aeruginosa were isolated. Results: A total of 177 patients with positive cultures (91 cases and 86 controls) and 119 with documented infections (65 cases, 54 controls) were included in risk factor and outcomes analysis, respectively. Independent risk factors for FQ resistance were: FQ exposure (OR 12.6, CI 4.95-32), nosocomial acquisition (OR 8.6, CI 3.5-20.7), and diabetes mellitus (OR 6.4, CI 2.1-19.3). An FQ agent was prescribed in 59% of patients receiving an 'antipseudomonal' empirical regimen. Compared with controls, FQ-resistant cases had a median delay to receiving effective therapy of 3.5 days versus 1 day and poorer outcomes: (i) lower complete response rate (45% versus 63%, P=0.04); (ii) longer time to achieve clinical stability (8 days versus 3 days, P=0.005); and (iii) higher infection-related mortality (21% versus 7%; OR = 2.9, 0.9-9.4). Empirical FQ use (OR 4.6, CI 1.5-14.3), FQ resistance (OR 3.6, CI 1.0-13.1), and high APACHE II score (OR 1.1, CI 1.0-1.2) were independent risk factors for increased mortality. Conclusions: FQ exposure from widespread prescribing is a modifiable risk factor for FQ resistance in P. aeruginosa. FQ empirical therapy for Pseudomonas infections may be associated with significant delays in administering effective therapy resulting in adverse outcomes.