Carbenicillin pharmacokinetics in an anephric patient.
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Biomedical subjects
Publications and source records attributed to J D Nelson.
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For infections of the newborn, carbenicillin has theoretical advantages over ampicillin, when given with an aminoglycoside, because of its activity against Pseudomonas and many indole-positive Proteus strains. Agar and broth dilution susceptibility studies demonstrated comparable activities of carbenicillin and ampicillin against coliform organisms but greater resistance of enterococci and Listeria to carbenicillin. However, the significance of the higher inhibitory concentrations is questionable because many serum specimens containing concentrations of carbenicillin lower than the minimal bactericidal values for Listeria and enterococcus strains had demonstrable in vitro bactericidal activity. Carbenicillin and gentamicin combinations had greater antibacterial activities than either drug alone against all enterococci tested and against 50% of Listeria strains. The questions of efficacy raised by contradictory in vitro data may be answered by clinical studies of carbenicillin and gentamicin in infections of the newborn.
Selected cultures of mercury-resistant bacteria degrade the fungicide-slimicide phenylmercuric acetate. By means of a closed system incorporating a flameless atomic absorption spectrophotometer and a vapor phase chromatograph, it was demonstrated that elemental mercury vapor and benzene were products of phenylmercuric acetate degradation.
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A single intramuscular dose of 100 mg carbenicillin/kg produced measured peak concentrations of approximately 150 to 175 mug/ml in newborn infants. The carbenicillin serum half-life of 1.0 hr in normal adults was prolonged to 2.7 hr in infants of normal birth weight and to 4.0 hr in babies of low birth weight in the first week of life. One-third of a dose administered to babies of low birth weight and two-thirds of that given to babies weighing over 2,500 g was excreted by the kidney in 12 hr. Postadministration 6-hr urinary carbenicillin concentrations averaged 1,399 mug/ml after an intramuscular dose of 50 mg/kg and 2,689 mug/ml after a 100 mg/kg injection. Although carbenicillin is excreted by both glomerular and tubular mechanisms in adults, serum half-life and urinary carbenicillin excretion correlated well with creatinine clearance. Recommendations for dosage of carbenicillin and intervals of administration in the neonatal period are made based upon mathematical predictions from pharmacokinetic data.
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