Cefotaxime diffusion into cerebrospinal fluid of children with meningitis.

Cefotaxime diffused consistently and in therapeutic levels into the cerebrospinal fluid (CSF) of 13 children successfully treated for bacterial meningitis. CSF cefotaxime levels early (6.0 micrograms/ml) and late (1.2 micrograms/ml) in treatment were severalfold the MBCs for the infecting organisms. After a single 40-mg/kg dose to each of five infants with ventriculostomies, mean CSF levels of cefotaxime were 6.4, 5.7, and 4.5 micrograms/ml at 2, 4, and 6 h, respectively.

Efficacy and safety of ceforanide in the treatment of childhood infections.

Fifty-seven children, ages 1 month to 17 years, were treated with parenteral ceforanide. Most patients received 20 mg/kg of the drug intramuscularly every 12 hours. The mean duration of ceforanide therapy was 6.3 days (range, 3 to 14 days). Because ceforanide has a relatively long half-life of 1.94 +/- 0.43 hours (range, 1.1 to 3.3 hours), suprainhibitory plasma concentrations against most pathogens recovered from the study patients were maintained for 8 to 12 hours after a dose. Ceforanide diffused well into abscess cavities and joint fluid. Initial clinical response was satisfactory in all patients; however, one patient with Haemophilus influenzae type b bacteremia had relapse of bacteremia one week after ceforanide therapy. Ceforanide was well-tolerated with minimal pain at the site of intramuscular injections. Other side effects were minor and transient.

Susceptibility of Haemophilus influenzae to chloramphenicol and eight beta-lactam antibiotics.

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates of Haemophilus influenzae, 25 of which produced beta-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for beta-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for beta-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicol, ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10(4) or 10(6) colony-forming units per ml). The inoculum size had no appreciable effect on the rate of killing of beta-lactamase-negative strains. The rates at which beta-lactamase-producing strains were killed by chloramphenicol, cefotaxime, and moxalactam was not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 10(6) colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the beta-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of beta-lactamase-producing H. influenzae.

Pharmacokinetic and clinical evaluation of moxalactam in infants and children.

37 patients ranging in age from 9 months to 14 years, with various infections, were treated with moxalactam. The pharmacokinetics of the drug were studied in 18 patients. The mean plasma concentration 1 h after a 25 mg/kg intravenous dose was 41.4 micrograms/ml +/- 15.6 SD, the half-life was 1.5 h +/- 0.4 SD and the mean Vd was 550 ml/kg +/- 239 SD. The total body clearance of moxalactam was 4.1 ml/min/kg +/- 1.5 SD and the mean renal clearance 4.5 ml/min/kg +/- 2.8 SD. Between 52 and 107% of the administered dose was recovered in the urine within 8 h after administration. The pharmacokinetics after the first and multiple doses of moxalactam were similar, indicating no accumulation of the drug with repeated administration. The clinical response was adequate in 35 of 37 patients. Moxalactam was well tolerated and only minor and transient hematological abnormalities were observed.