Pseudomonas aeruginosa is the most common infection in patients with cystic fibrosis (CF). Over time these bacteria become resistant to multiple classes of antibiotics. There is concern that multiple antibiotic resistant Pseudomonas aeruginosa (MARPA) may be associated with worse clinical outcomes in CF. However, very little is known about the incidence and risk factors for MARPA. The purpose of this study is to estimate the incidence of MARPA and understand the risk factors that may be associated with developing resistance.
Cohort study of patients followed in the US CF Foundation Patient Registry from 1998 through 2002. Individuals were included if they were 6 years of age or older and if they were culture negative for Pseudomonas during the first 90 days of enrollment. MARPA was defined as any strain of Pseudomonas resistant to at least two of the following antibiotics: tobramycin, ciprofloxacin, and/or meropenem.
4,458 patients developed infection with Pseudomonas and were included in the study. Mean age for the cohort was 15.7 years (range: 6-61.8) with a mean follow-up time of 1545.2 days (range: 7-1821). A total of 638 patients developed MARPA during the study period. The overall incidence of MARPA among CF individuals infected with Pseudomonas was 393.8 cases/1000 patients per year. In multivariable analyses using Cox proportional hazards models after adjusting for important physiologic and clinical confounders, higher baseline FEV1 was associated with a decreased risk of developing MARPA (HR: 0.68; 95%CI: 0.58-0.80). Diabetes (HR: 1.54; 95%CI: 1.21-1.97), inhaled tobramycin usage (HR: 1.41; 95%CI: 1.17-1.71), greater than 5 acute exacerbations/year (HR: 4.69; 95%CI: 3.20-6.87), and being cared for by a CF center in the top quartile for MARPA prevalence (HR: 3.79; 95%CI: 2.76-5.21) independently increased the risk of developing MARPA.
Resistant Pseudomonas is common among patients with CF. Diabetes, inhaled tobramycin usage, and frequent acute exacerbations increase risk of developing resistance.
Identification of potentially modifiable risk factors for MARPA may help to decrease the incidence of resistant Pseudomonas among patients with CF.
Christian Merlo, None.