netilmicin and Meningitis

A four - month old boy with Salmonella Typhimurium meningitis is presented. This patient was admitted to the hospital with a diagnosis of staphylococcal pneumonia, pyo-pneumothorax, cardiac failure and anemia. He has been treated for 18 days and he was discharged in good condition. Two days after discharge patient was readmitted with a fever, vomiting and feeding problem. In physical examination, stiff neck and bulging of the fontanel were remarkable. Examination of cerebrospinal fluid (CSF) has revealed meningitis and cultures of blood and CSF specimens were positive for S. typhimurium. It was sensitive only to trimethoprim sulphamethoxazole and netilmicin. Trimethoprim sulphamethoxazole (IM) and netilmicin (IV) were given. At the fifth day of this treatment patient expired. Postmortem examination has revealed the same agent in both meninges tissue and CSF cultures.

Topics: Autopsy; Blood; Cerebrospinal Fluid; Humans; Infant; Male; Meninges; Meningitis; Netilmicin; Salmonella Infections; Salmonella typhimurium; Sulfamethoxazole; Trimethoprim

After administration of 150 mg netilmicin samples of CSF and blood were obtained. In one group of nine patients with no or only slight impairment of the blood-CSF-barrier 29 samples of CSF were assayed for netilmicin concentrations. All samples, obtained after the first dose, failed to reveal detectable drug levels. Drug levels up to 0.18 mg/l were detected in samples of CSF of three patients after 3 to 22 doses. Only the lumbar CSF of one patient contained netilmicin concentrations higher than 1.0 mg/l. In comparison 19 samples of CSF, obtained from patients with meningitis after more than one dose of netilmicin, had levels of 0.27-5.0 mg/l. Three CSF samples from patients out of this group, collected after the first dose of netilmicin failed to show any drug activity.

Topics: Adult; Aged; Blood-Brain Barrier; Gentamicins; Humans; Meningitis; Middle Aged; Netilmicin

Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The cerebrospinal fluid concentrations of LY127935 produced median bactericidal titers of 1:64 to 1:128 against five coliform organisms (two Escherichia coli K1 strains, Klebsiella pneumoniae, Salmonella saint-paul, and Citrobacter diversus) used in these experiments compared with median titers of 1:2 to 1:8 for netilmicin and 1:2 to 1:4 for ampicillin. LY127935 was statistically significantly more effective than netilmicin or ampicillin in reducing cerebrospinal fluid bacterial colony counts and in sterilizing cerebrospinal fluid of experimentally infected rabbits. These results suggest that LY127935 has theoretical advantages over netilmicin and ampicillin for therapy of gram-negative bacillary meningitis.

Topics: Ampicillin; Animals; Bacteria; Bacterial Infections; Cephalosporins; Cephamycins; Disease Models, Animal; Gentamicins; Male; Meningitis; Moxalactam; Netilmicin; Rabbits; Species Specificity