Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis
A. G. Arguedas, H. R. Stutman, M. Zaleska, C. A. Knupp, M. I. Marks and E. Nussbaum
Pediatric Infectious Disease, Division, Memorial Miller Children's Hospital, Long Beach, Calif. 90801-1428.
OBJECTIVE. To measure first-dose and steady-state plasma, urine, and sputum
concentrations of cefepime and make preliminary assessments of the clinical
efficacy of cefepime in patients with cystic fibrosis. DESIGN. Open
noncomparative clinical trial. SETTING. Memorial Miller Children's Hospital
of Long Beach, Calif. PARTICIPANTS. Twelve patients, aged 4 to 41 years,
with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary
infections. INTERVENTIONS. Patients received cefepime at 50 mg/kg per dose
(maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical
evaluations, pulmonary function tests, quantitative sputum cultures, and
sensitivity testing were performed before, at the end of, and 2 weeks after
therapy. MEASUREMENTS AND MAIN RESULTS. Mean (+/- SD) peak plasma
concentrations after the first dose were 148.2 (36.6) mg/L; the following
other values were included: half-life, 1.59 (0.46) hours; area under the
curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01
(1.46) mL/min per kilogram; volume of distribution at steady state, 0.32
(0.10) L/kg; and percent of dose recovered in urine, 52% (27%).
Steady-state and first-dose values were similar. Trough levels varied from
6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied
from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10
patients' conditions were improved as indicated by clinical scores (greater
than 10 points), forced vital capacity (greater than 10%), and a greater
than or equal to 1 log decrease in sputum bacterial concentration. Cefepime
was well tolerated in 10 patients, but rash and light-headedness developed
in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90
increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was
unchanged 2 weeks later. CONCLUSION. Based on these data and the potential
advantage of a single agent for the treatment of mixed infections
(Staphylococcus aureus and P aeruginosa), comparative clinical trials of
cefepime and standard therapy for bronchopulmonary exacerbations in
patients with cystic fibrosis appear to be warranted.
