The optimal dose, frequency, and duration of intraventricular therapy for gram-negative meningitis (GNM) have never been determined. A prospective evaluation of the pharmacokinetics of intraventricular amikacin was undertaken in neonates with GNM. After the initial intraventricular instillation of 5 mg of amikacin via a Rickham reservoir, a 10-fold variation in the cerebrospinal fluid (CSF) concentration and a fivefold variation in half-life of the drug were noted. These variations were related to differences in the CSF volume secondary to hydrocephalus, myelomeningocele, and/or brain abscess. Successful therapy required maintaining the concentration of amikacin in CSF well above the minimal inhibitory concentration for the infecting organism at all times. A retrospective review of GNM demonstrated that the mortality was lower after intraventricular than after systemic therapy. These data suggest that if careful attention is given to the pharmacokinetics of intraventricular therapy, this route may be a valuable adjunct to therapy for GNM in neonates.

Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in the developing world. This study describes the type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional initiative designed to determine the ideal serotype composition of a protein polysaccharide pneumococcal conjugate vaccine for use in children less than 5 years old in Latin America. In Colombia, during the study period, centres in Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%), 19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and 3.1% showing high level resistance. Among DSP isolates, 23% were also resistant to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the isolates that have DSP. Penicillin resistance was associated with types 23F (53.8%) and 14 (25.6%). These data provides information on capsular types prevalent in Colombia that will not only allow the formulation of an ideal vaccine for the region but also reinforce the need for ongoing regional surveillance.

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The pharmacokinetic properties of amikacin (BBK8) were similar to those of kanamycin in newborn infants. Peak serum concentrations of both drugs were in the range of 15 to 25 ,ug/ml with the exception of kanamycin in babies weighing greater than 2,000 g at birth where peak levels were 12.5 to 15 ,ug/ml. The purpose of the present communication is to review our experience in newborn infants with a new aminoglycoside, amikacin (BBK8). Previously published data from our laboratory showed that amikacin susceptibilities of gramnegative bacilli and Staphylococcus aureus were comparable to those for kanamycin, with the exception that over 90% of Pseudomonas aeruginosa were susceptible to 15 ,ug or less of amikacin per ml (6). Five kanamycin-resistant E. coli strains isolated from cerebrospinal fluid (CSF) of neonates with meningitis were inhibited and killed by 5 ,ug or less of amikacin per ml.Pharmacological studies in 48 babies demonstrated mean serum levels of 17 to 20 ug/ml at 30 min and of 3.3 to 5.3 ug/ml at 12 h after a 7.5-mg/kg amikacin dose (6). Accumulation of drug in serum and acute renal or hematological toxicity were not observed after repeated doses for 5 to 7 days. Urinary amikacin concentrations were 50 to 650 ,.tg/ml, and the average 12-h urinary excretion of drug was 30 to 50% of the administered dose. Serum half-life values were inversely correlated with postnatal age and ranged from 3 to 9 h.In this paper we present the comparative pharmacokinetic properties of amikacin and kanamycin in neonates and the clinical efficacy of amikacin in 45 infants with bacterial infections. The pharmacological data are based in part on our previously published studies of amikacin (6) and kanamycin (7).

The results of this study indicate that itraconazole is effective for treatment of disseminated childhood histoplasmosis. More studies should be performed to determine the most appropriate dosage and the optimal duration of itraconazole treatment in children.

Twenty-five children with serious Gram-negative infections were treated in a prospective study with amikacin 20 mg/kg administered in a single daily dose as a 30 min iv infusion for 4 to 12 days. In nine cases the amikacin was combined with beta-lactam antibiotics. Escherichia coli were the most frequent bacteria isolated followed by K. pneumoniae, Providencia and Enterobacter spp. and Pseudomonas aeruginosa with MICs ranging from 1 to 16 mg/l. Mean (+/- S.D.) peak and trough concentrations of days 1 and 4 of therapy ranged from 49 +/- 13.5 to 53.6 +/- 13.4 mg/l and 6 + 1.4 to 7.7 +/- 4.1 mg/l respectively. All patients were clinically and bacteriologically cured. No significant adverse reactions were observed. The results suggest that administration of a single daily dose of 20 mg/kg amikacin should be considered practical and safe in children. Further studies are needed.

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Penetration of the aminoglycoside, amikacin, into the cerebrospinal fluid (CSF) of twenty children with acute bacterial meningitis was studied at various times after intramuscular administration and at various stages of therapy. Six of the patients were evaluated during therapy with amikacin at 7.5 mg/kg (intramuscularly) every 12 hours plus ampicillin every 6 hours at 300 mg/kg/day (intravenously); thirteen of the remaining fourteen patients were treated with ampicillin alone, but were given a single intramuscular dose of 7.5 mg/kg of amikacin for evaluation of CSF concentration. Amikacin concentration in CSF with respect to time after administration followed essentially the same pattern as in serum. A minimum concentration of 2 microgram/ml was found in 76% of the CSF samples obtained between 0.5 and 7 hours after administration. A mean amikacin serum/CSF ratio of 3:1 was demonstrated up to 7 hours after dose in all patients who underwent clinical improvement. Patient response was predictable by a correlation of in vitro MIC values with in vivo CSF concentration in three of the six patients who received amikacin therapy.