The antimicrobial activities of amphotericin B, itraconazole, and miconazole against 101 filamentous fungi from patients with cystic fibrosis were tested by a reproducible microdilution method. Itraconazole was very active against Aspergillus species and Scedosporium species (MIC at which 90% of the isolates were inhibited [MIC90], 0.06 to 0.5 mg/liter), whereas amphotericin B was less effective (MIC90, 0.5 to 8 mg/liter).

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients <18 months old and 100 mg/kg once daily to patients .18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD] Current management of bacterial meningitis in children more than 2 months old now includes dexamethasone administration (1, 9). The beneficial effects of dexamethasone therapy have been clearly shown in a recent double-blind trial for 101 infants and children with bacterial meningitis (12). Dexamethasone is believed to improve the outcome of meningitis by modulating cytokine production (10, 11) and thus decreasing the patient's inflammatory response to bacterial endotoxins or endotoxin-like substances (13, 16). However, because of its action on meningeal inflammation, dexamethasone might reduce the penetration of antibiotics into cerebrospinal fluid (CSF). Were this the case, dexamethasone administration might result in delayed CSF sterilization (3), which has been shown to correlate with the occurrence of neurological sequelae (7). Indeed, concentrations of most antibiotics in CSF are higher in patients with inflamed meninges than in those with uninflamed meninges and higher in patients with bacterial meningitis than in patients with aseptic meningitis (2). In experimental models of meningitis, the administration of steroid agents has been shown to result in a marked decrease in CSF antibiotic levels (14). In this study, we measured the CSF correlations of an expanded-spectrum cephalosporin, ceftriaxone, for children with bacterial meningitis receiving dexamethasone as adjunctive therapy.Between March 1992 and March 1993, 11 patients (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis were included in the study. The infecting organism was Haemophilus influenzae in four cases, Streptococcus pneumoniae in three cases, Streptococcus agalactiae in one case, Neisseria meningitidis in one case, and unknown in two cases. The bacterial strains were isolated from CSF and, for five patients, from blood. All patients had normal renal function. Ceftriaxone was given intravenously over 15 min at a dose of 50 mg/kg of body weight twice daily (to patients aged less than 18 months) or of 100 mg/kg once daily (to other patients) for the first 48 h and then at a dose of 50 mg/kg once daily (to all * Corresponding author. patients). The total duration of therapy was 7 to 10 days, depending on the nature of the infecting organism and the clinical response. Intravenous amikacin (7.5 mg/kg twice daily) was administered in combination with ceftriaxone for the first 48 h. Dexamethaso...

No abstract

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of <1, 1 to 2, and >2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is <1 mmol/liter on admission.

No abstract