Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis.
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.


METHODS
Open noncomparative clinical trial.


METHODS
Memorial Miller Children's Hospital of Long Beach, Calif.


METHODS
Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections.


METHODS
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.


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.


CONCLUSIONS
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.
Arguedas
A G
AG
Pediatric Infectious Disease, Division, Memorial Miller Children's Hospital, Long Beach, Calif. 90801-1428.
Stutman
H R
HR
Zaleska
M
M
Knupp
C A
CA
Marks
M I
MI
Nussbaum
E
E
D000293:Adolescent; D000328:Adult; D002140:California; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D012720:Severity of Illness Index; D013183:Sputum / Q000382:microbiology; D014018:Tissue Distribution; D014797:Vital Capacity
D002511:Cephalosporins; D000077723:Cefepime