CLINICAL PHARMACOLOGY OF CARBENICILLIN AND GENTAMICIN IN THE NEONATE AND COMPARATIVE EFFICACY WITH AMPICILLIN AND GENTAMICIN

Abstract

Because of its greater activity against Pseudomonas and Proteus and comparable activity against other bacteria, carbenicillin has theoretical advantages over ampicillin or penicillin as initial therapy, along with an aminoglycoside antibiotic, for suspected infections in the neonate. From a previous study of carbenicillin pharmacokinetics, mathematical predictions of dosage and intervals of administration were made and tested in 55 infants from 1 to 45 days of age treated with carbenicillin and gentamicin. Clinical efficacy was compared with a randomly selected group of 55 babies treated with ampicillin and gentamicin. No deaths directly attributable to infection occurred in either group. In bacteriologically documented infections follow-up cultures indicated eradication of the pathogen. All serum specimens tested for bactericidal power against Escherichia coli or Pseudomonas had bacterial titers of 1:2 or greater. Dose response curves and daily serum specimens during subsequent days of treatment were assayed for antibiotic content. Peak serum level and serum half-life were correlated with dosage, interval, age, and weight. The proposed dosage schedule of carbenicillin for neonates is (1) 100 mg/kg initial dose; (2) 75 mg/kg subsequent doses at eight hourly intervals through 7 days of age for infants under 2,000 gm and at six hourly intervals until 4 days of age for babies weighing over 2,000 gm; (3) thereafter, 100 mg/kg every six hours for both weight groups. These dosages should assure therapeutic serum concentrations or carbenicillin when its use is desired or indicated for the neonate. Therapeutic results with carbenicillin and gentamicin were satisfactory in this study, but a larger experience is needed before the relative efficacy of this combination vis-à-vis other antibiotics commonly used for neonatal infections can be assessed.