Pharmacokinetics of Linezolid in Children With Cystic Fibrosis

Patients with cystic fibrosis who have pulmonary exacerbations associated with the isolation
of MRSA in their sputum will be identified by their primary physicians and by laboratory
record review. If they meet the inclusion criteria, they will be invited to participate in
the study. The primary outcome variables include pharmacokinetic and pharmacodynamic
indices. The study end points include completion of the sputum and blood sampling for
pharmacokinetic studies of both intravenous and oral formulations of linezolid and
collection of microbiologic specimen (sputum and anterior nares cultures) one month after
discharge. Additionally, pharmacokinetic data will be analyzed for effects of age and CFTR
mutation on clearance of linezolid and for relationship between levels of linezolid achieved
in sputum and blood and clinical outcome

Inclusion Criteria:

- Subjects < 18 years of age inclusive, with a confirmed diagnosis of cystic fibrosis
being admitted to the hospital for acute pulmonary exacerbation with MRSA isolated
from sputum culture.

- Female subject of childbearing potential must have a negative pregnancy test prior to
the first dose of study drug, and if sexually active agrees to use an acceptable
method of birth control per investigator judgment for the duration of the study.

- Subjects who are receiving medications with serotonergic (such as certain types of
antidepressants) and adrenergic activity that can not be discontinued based on
clinical judgment of the primary physician may be enrolled. These subjects will be
monitored closely for serotonin- and sympathomimetic-associated toxicity.

- Subject (when able) and subject's parent /legal guardian agree to comply with the
study requirements.

- Subject has sufficient venous access to permit administration of the study
medication, collection of pharmacokinetic samples and monitoring of safety variables.

- Duration of linezolid therapy is expected to exceed 7 days.

- English and Spanish-speaking subjects.

Exclusion Criteria:

- Subjects with clinical or laboratory evidence of severe hepatic (Child-Pugh class C)
disease

- Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min)

- Subjects with a history of allergy to linezolid.

- Pregnant and breastfeeding subjects.