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JAC Advance Access originally published online on May 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 1431-1434
© 2003 The British Society for Antimicrobial Chemotherapy

Intrapulmonary penetration of linezolid

David Honeybourne1,*, Caroline Tobin2, Gail Jevons3, Jenny Andrews3 and Richard Wise3

1 Department of Respiratory Medicine, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS; 2 Department of Microbiology, Southmead Hospital, Bristol; 3 Department of Medical Microbiology, City Hospital, Birmingham, UK

Received 23 October 2002; returned 6 December 2002; revised 3 March 2003; accepted 19 March 2003

Objective: This study was designed to measure the concentrations of linezolid in bronchial mucosa, pulmonary macrophages and epithelial lining fluid and to compare them with simultaneous blood levels.

Methods: Ten adult patients undergoing bronchoscopy for diagnostic purposes were given oral linezolid at a dosage of 600 mg twice a day for a total of six doses. Patients with active lung infection were excluded from the study. Flexible bronchoscopy was carried out between 2 and 8 h after the last dose of linezolid. Bronchial biopsies and bronchoalveolar lavage were carried out and a simultaneous blood sample obtained. Linezolid levels were measured using high-performance liquid chromatography (HPLC).

Results: Mean concentrations of linezolid were 13.4 mg/L in serum, 10.7 mg/kg in mucosa, 8.1 mg/L in alveolar macrophages and 25.1 mg/L in epithelial lining fluid. The mean site/serum concentration ratios were 0.79 for bronchial mucosa, 0.71 for macrophages and 8.35 for epithelial lining fluid.

Conclusions: The MIC90 (<=4 mg/L) of linezolid for Staphylococcus aureus and Streptococcus pneumoniae was exceeded in serum and bronchial mucosa in all subjects, in epithelial lining fluid in nine subjects and in macrophages in six subjects.

Keywords: linezolid, lung penetration

* Corresponding author. Tel: +44-121-424-3731; Fax: +44-121-424-3147; E-mail: david.honeybourne{at}heartsol.wmids.nhs.uk


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