105 Antibiotic dosing strategies of colistin on biofilm growing Pseudomonas aeruginosa: pharmacokinetic and pharmacodynamic issues

Abstract

Intensive treatment of lung infection is standard CF care. We explored whether antibiotic (AB) use in Pseudomonas aeruginosa (Pa) colonized patients drives infection with multiresistant Pa (MRPa). In 241 patients born after 1980 bacteriologic data plus AB use between 1995 and 2010 were analysed retrospectively. Chronic Pa infection was defined according to the Leeds criteria. Pa isolates resistant to all the AB of at least 2 classes were considered MR. Days on AB per year were counted in patients with chronic Pa infection who did and did not become infected with MRPa. 163 patients never acquired chronic Pa infection. 11 had chronic MRPa infection from onset, 35 had chronic Pa throughout, 32 had MRPa after chronic Pa. Yearly AB use during chronic Pa infection was analyzed in 25 subjects with chronic Pa and in 24 before onset of MRPa. Median days on IV AB per year was higher pre MRPa (43.2 days, IQR 30.0–62.4) than in patients never becoming MRPa (29.8 days, IQR 10.1–45.4), (p = 0.05). No difference was noted in use of oral AB (median 45.6 days IQR 24.4–68.7 vs 30.5 days IQR 20.5–124.9, p = 0.54) and inhaled AB (median 248.3 days IQR 168.5–365.0 vs 320.7 days IQR 208.5–353.7, p = 0.45). The proportion of patients who ever used azithromycin was not different (11/24 vs 7/25, p = 0.15). More patients with MRPa had siblings with CF (14/24 vs 3/25, p = 0.02). Median number of years of AB use, age and FEV1 at last year of analysis were not significantly different. A quarter of patients have MRPa from onset of chronic Pa infection. In the other MRPa subjects the yearly burden of AB use and having a sibling with CF were related to the development of MRPa infection.