Serum and sputum concentrations following the oral administration of linezolid in adult patients with cystic fibrosis.
OBJECTIVE
Linezolid is a new oxazolidinone antibiotic with efficacy against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the serum and sputum linezolid concentrations in adults with cystic fibrosis (CF) following oral drug administration.


METHODS
Eleven adult patients with CF were recruited. Subjects received 600 mg of linezolid orally every 12 h for a total of six doses. Serum and sputum levels were measured just before and at 2 h after the final dose of linezolid. A further serum level was measured at 4 h.


RESULTS
Ten adult patients completed the study. Mean (s.d.) serum linezolid concentrations were 2.3 mg/L (1.5) at 12 h following the fifth dose. At 2 and 4 h following the sixth dose, concentrations were 13.5 (4.3) and 8.1 (3.3). Mean (s.d.) linezolid sputum concentrations were 3.6 (2.1) and 17.4 (7.2) mg/L at 0 and 2 h following drug administration.


CONCLUSIONS
The oral administration of linezolid results in good sputum penetration in patients with CF. Mean levels exceed the required MIC for the treatment of MRSA for >80% of the dosing period for serum and the majority of the dosing period for sputum.
Saralaya
Dinesh
D
Regional Adult Cystic Fibrosis Unit, Seacroft Hospital, York Road, Leeds LS14 6UH, UK.
Peckham
Daniel G
DG
Hulme
Bill
B
Tobin
Caroline M
CM
Denton
Miles
M
Conway
Steve
S
Etherington
Christine
C
D000081:Acetamides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010182:Pancreatic Diseases / Q000378:metabolism; D011446:Prospective Studies; D013183:Sputum / Q000378:metabolism*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid