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Incidence and Risk Factors for Multiple Antibiotic-Resistant Pseudomonas aeruginosa in Cystic Fibrosis^*

^* From the Department of Medicine, Division of Pulmonary and Critical Care Medicine (Drs. Merlo, Boyle, Marshall, and Lechtzin), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biostatistics (Dr. Diener-West), The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Medicine, Division of Pulmonary and Critical Care Medicine (Dr. Goss), University of Washington Medical Center, Seattle, WA.

Correspondence to: Christian A. Merlo, MD, MPH, The Johns Hopkins University School of Medicine, 1830 E. Monument St/Fifth Floor, Baltimore, MD 21205; e-mail: cmerlo{at}jhmi.edu

Abstract

Background: Infection with multiple antibiotic-resistant Pseudomonas aeruginosa (MARPA) in individuals with cystic fibrosis (CF) has caused much concern among caregivers, yet little is known about the risks associated with acquiring resistance. The main objective of the study was to estimate the incidence and identify risk factors for the acquisition of MARPA among individuals with CF.

Methods: Five-year cohort study of individuals followed in the Cystic Fibrosis Foundation Registry from 1998 through 2002.

Results: Demographics, anthropometrics, spirometry, respiratory culture results, comorbidities, antibiotic usage, and hospitalizations were collected. Of the 4,293 patients with P aeruginosa infection during the study period, MARPA developed in 341. The overall incidence of MARPA was 1.8%/yr. Independent risk factors for MARPA included CF-related diabetes mellitus (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11 to 2.43), long-term inhaled tobramycin usage (HR, 2.08; 95% CI, 1.56 to 2.77), and care at a CF center with a baseline MARPA prevalence in the top quartile (HR, 2.00; 95% CI, 1.31 to 3.04). Frequent courses of IV antibiotics and repeated hospitalizations were also found to independently increase the risk for MARPA.

Conclusions: Infection with MARPA is common among patients with CF. Diabetes, long-term inhaled tobramycin usage, and frequent acute pulmonary exacerbations requiring hospitalization or IV antibiotics increase the risk for MARPA. Receiving CF care at a center with a high prevalence of resistant Pseudomonas also increases the risk for MARPA in patients with CF. Further study is needed to investigate the mechanisms of acquiring resistant strains and the clinical impact of MARPA on CF outcomes.

Key Words: antibiotic resistance • cystic fibrosis • incidence • Pseudomonas aeruginosa • risk factors