Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis

Abstract

Objectives: Azithromycin is used to modulate exuberant inflammatory response in patients with cystic fibrosis (CF). The purpose of this study was to determine the association between long-term use of azithromycin in CF patients and change over time in macrolide susceptibility of Staphylococcus aureus and Haemophilus spp.

Methods: The study was performed at the Erasmus MC-Sophia Children's Hospital. CF patients' sputum cultures were obtained at routine visits and at pulmonary exacerbations. All cultures between January 1999 and March 2004 were included. Antibiotic susceptibility of S. aureus and Haemophilus spp. was tested routinely. Susceptibility was compared with isolates from sputum of non-CF patients. Logistic regression was used to analyse the association between azithromycin use and resistance, adjusting for age, Pseudomonas carriage and time-trends.

Results: In March 2004 one-third of CF patients were on azithromycin maintenance treatment. S. aureus (715 isolates) and/or Haemophilus (537 isolates) were cultured in 141 of the 155 patients on one or more occasions. The study period was divided into octiles. Erythromycin resistance in S. aureus increased from 6.9 to 53.8% and clarithromycin resistance in Haemophilus spp. from 3.7 to 37.5%. Resistance but also isolation rates were strongly related to azithromycin use. Resistance of 3217 S. aureus control isolates remained stable and resistance of 3257 Haemophilus controls increased, although at a slower rate than CF isolates.

Conclusions: Over a 4 year period, azithromycin maintenance therapy in our CF population was associated with an increase in macrolide resistance in S. aureus and Haemophilus spp.