Management of Pseudomonas osteochondritis complicating puncture wounds of the foot.

Pseudomonas osteochondritis following puncture wounds of the foot is described in 13 children. All children had received at least one oral antibiotic and local wound therapy before admission; none had improved on these modalities. Pseudomonas aeruginosa was isolated alone from seven patients and with one or more other organisms from six patients. Initial administration of parenteral antibiotics active against Pseudomonas for one to 14 days did not result in clinical improvement. Eradication of Pseudomonas osteochondritis occurred in each patient only after thorough surgical debridement and curettage of all infected tissue. Following thorough surgical debridement, anti-Pseudomonas antibiotic therapy was continued for five to 14 days (10.8 +/- 2.7 days). The successful treatment of Pseudomonas osteochondritis should include adequate surgical debridement of all infected tissue; following thorough debridement, only one to two weeks of anti-Pseudomonas antibiotic therapy appears to be necessary.

Chloramphenicol succinate kinetics in infants and young children.

We sought to estimate the serum and urine pharmacokinetics of chloramphenicol succinate (CmS) and the effects of variation of these parameters on chloramphenicol (Cm) kinetics in 24 infants and young children ages two weeks to seven years. The mean T(1/2) of CmS was 0.40 hours; the mean body clearance was 0.72 liter/KG/hour; the mean apparent volume of distribution was 0.42 liter/kg. Variation in CmS T(1/2) did not correlate with significant variation in Cm T(1/2) (r2 = 0.002, P = 0.84). Urine collected during the dosing interval in nine patients contained 35% (mean) of the administered dose. Adjusting the infusion duration to 5 minutes or 120 minutes had no effect on the amount of CmS lost in the urine. The quantity of CmS lost in the urine affects the amount bioavailable, and secondarily the calculated volume of distribution and body clearance of Cm. We conclude that variation in urinary prodrug excretion affects the amount of Cm bioavailable to the patient, but variation in CmS T(1/2) has little effect on Cm T(1/2).

Oral chloramphenicol in the treatment of Haemophilus influenzae meningitis.

We conducted a prospective, randomized evaluation of oral chloramphenicol administration for completion of therapy of Haemophilus influenza type b meningitis in 44 children: 21 received drug by this route after the second day of therapy, the remainder continued to receive the drug intravenously. Resolution of clinical manifestations and cerebrospinal fluid indicators of meningitis was equivalent with both routes in 43 patients. One infant failed to achieve efficacious serum concentrations by either route of administration. Paired analysis of the area under the serum concentration versus time curve in 13 patients after oral and intravenous administration indicated equivalent bioavailability. Neutropenia was the only observed drug-related toxicity and correlated with the highest observed serum concentration. We conclude that: (1) chloramphenicol can be used by the oral route to complete treatment of H. influenzae type b meningitis; (2) a dose of 75 mg/kg/day is effective and less likely than higher doses to cause neutropenia; and (3) the measurement of serum chloramphenicol concentrations is important, regardless of route of administration.

Rapid estimation of chloramphenicol clearance in infants and children.

A method is presented by which chloramphenicol clearance (CL) can be estimated from a single serum sample obtained 6 hours after the initial intravenous dose. The method was evaluated prospectively in 20 infants and children who received intravenous chloramphenicol sodium succinate. Agreement between predicted and observed clearance was excellent (r = 0.914, p less than 0.001). The equation of the observed regression line was: observed 0.886x predicted + 0.019. The method appears to provide reasonably accurate estimates of clearance which can be used for rapid clinical adjustment of dose.

Chloramphenicol pharmacokinetics in infants and young children.

We measured serum chloramphenicol concentrations in 17 hospitalized pediatric patients (aged 1 month to 6 years) after intravenous infusion of chloramphenicol succinate. The serum T1/2 ranged from 2.1 to 8.3 hours with a mean of 3.98 (SD 1.75) hours, while the apparent volume of distribution ranged from 0.78 to 2.09 liters/kg with a mean of 1.39 (SD 0.34) liters/kg. The total body clearance ranged 0.122 to 0.429 liters/kg/hour with a mean of 0.281 (SD 0.117) liters/kg/hour. Two patients were restudied, and had increased clearance during their hospitalization. Because of the wide variability in pharmacokinetics, we conclude that serum chloramphenicol concentrations should be monitored in infants and children.

Hypothesis for the individualisation of drug dosage.

Computer simulations based on the pharmacokinetics of chloramphenicol and theophylline in patients, indicate a very strong correlation (r = 0.988 for chloramphenicol and r = 0.971 for theophylline) between log maintenance dose required to achieve a desired average drug concentration in serum at steady-state, and the drug concentration in serum 6 hours after an initial test dose administered by constant rate intravenous infusion over 0.5h. Accordingly, we have developed a nomogram to predict individual daily dosing requirements for these drugs in uncomplicated patients from a single serum assay following an initial dose. Within defined limits, predictions made with the nomogram are essentially equivalent to those made by iraditional pharmacokinetic methods which require substantially more drug concentration-time data following a test dose. Predictions based on the nomogram are relatively unaffected by small but typical errors in magnitude of the test dose, infusion time, sampling time and assay. Protocols for the administration of the test dose other than described, e.g. administration of an oral theophylline solution, may be equally useful for dosage predictions. In principle, this approach should apply to other drugs.

Effect of inoculum size on the susceptibility of Haemophilus influenzae b to beta-lactam antibiotics.

The current prevalence of ampicillin-resistant Haemophilus influenzae b meningitis requires accurate knowledge of susceptibility to alternative antibiotics. One variable affecting susceptibility is inoculum size. We studied the susceptibility of 200 clinical isolates of H. influenzae b to ampicillin, carbenicillin, and cefamandole at inocula of 10(5) and 10(7) CFU by two techniques. Fifty ampicillin-susceptible and fifty ampicillin-resistant strains were tested for susceptibility to ampicillin by broth dilution while 100 of each were tested by agar dilution. An inoculum effect was found, being greatest with the ampicillin-resistant strains. The range of minimal inhibitory concentrations for the resistant strains was 25 to 800 microgram of ampicillin per ml at an inoculum of 10(5) and 2,000 to less than 6,000 microgram of ampicillin at 10(7); 1.0 to 150 microgram of carbenicillin per ml at 10(5) and 6.2 to 2,000 microgram of carbenicillin per ml at 10(7); 0.4 to 2.0 microgram of cefamandole at 10(5) and 1.0 to 125 microgram/ml at 10(7). Because of this inoculum effect, we would not recommend the use of carbenicillin or cefamandole for therapy of ampicillin-resistant H. influenzae meningitis.