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Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 107 CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h.Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNFa antibodies given IC with 20 ng Hib LOS or 2 X 106 CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response.

The clinical pharmacology of gentamicin was studied in 42 newborn infants. Gentamicin was found to be effective in vitro against most gram negative organisms encountered in neonatal infections; 1.5 mg/kg/dose every 8 to 12 hours in neonates produced mean peak serum levels of 2.5 to 5.0\g=m\g/ml. Serum antibacterial activity persisted for 8 to 12 hours. The serum gentamicin half-life was longer in premature than full-term infants during the first week of life only; beyond this time, the half-lives were similar and approached that reported in adults. No evidence of accumulation was observed after multiple doses. A limited trial of gentamicin in the treatment of severe neonatal infections demonstrated the drug to be effective. Acute toxicity was not observed. Specific recommendations and precautions are outlined for treating selected neonates with gentamicin.

Study objective. To develop guidelines for the care of infants and children from birth to 36 months of age with fever without source. Participants and setting. An expert panel of senior academic faculty with expertise in pediatrics and infectious diseases or emergency medicine. Design and intervention. A comprehensive literature search was used to identify all publications pertinent to the management of the febrile child. When appropriate, meta-analysis was used to combine the results of multiple studies. One or more specific management strategies was proposed for each of decision nodes in draft management algorithms. The draft algorithms, selected publications, and the meta-analyses were provided to the panel, which determined the final guidelines using the modified Delphi technique. Results. All toxic-appearing infants and children and all febrile infants less than 28 days of age should be hospitalized for parenteral antibiotic therapy. Febrile infants 28 to 90 days of age defined at low risk by specific clinical and laboratory criteria may be managed as outpatients if close follow-up is assured. Older children with fever less than 39.0°C without source need no laboratory tests or antibiotics. Children 3 to 36 months of age with fever of 39.0°C or more and whose white blood cell count is 15 000/mm3 or more should have a blood culture and be treated with antibiotics pending culture results. Urine cultures should be obtained from all boys 6 months of age or less and all girls 2 years of age or less who are treated with antibiotics. Conclusion. These guidelines do not eliminate all risk or strictly confine antibiotic treatment to children likely to have occult bacteremia. Physicians may individualize therapy based on clinical circumstances or adopt a variation of these guidelines based on a different interpretation of the evidence.

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The pharmacokinetics and bacteriological efficacy of N-formimidoyl thienamycin were determined in rabbits infected with Escherichia coli Ki. After a single intravenous dose of 25 mg/kg, a peak N-formimidoyl thienamycin concentration in cerebrospinal fluid (CSF) of 2.5 1/ml was ataned at 45 min. The penetration into CSF was calculated to be 31%. In animals that received continuous intravenous infusions of the drug for 9 h, the mean CSF concentration was 8.3 gg/ ml, and the CSF bactericidal titers aginst the E. coli Ki strain were from 1:16 to 1:32. This infusion produced a reduction in the numbers of E. coli in the CSF of 4 logio colony-forming units per ml. N-Formimidoyl thienamycin might prove to be useful for therapy of meningitis caused by E. coli and other susceptible bacteria.N-Formimidoyl thienamycin is a stable derivative ofinamycin, a novel beta-lactam antibiotic with broad antimicrobial activity. The in vitro activity of this compound encomp4sses both aerobic and anaerobic gram-positive and gram-negative microoranisms, including most strains of coliform bacilli, Pseudomonas aeruginosa, Bacteroidesfragilis, Staphylococcus aureus, and S. epidermidis (3,4,6,8). N-Formimidoyl thienamycin is also active in vitro against enterococci and Listeria monocytogenes (2). The in vitro activity against pathogens that frequendy cause nonatal meningitis suggests that N-formimidoyl enamycin might be useful for therapy of this condition. The purpose of this investigation was to determine the penetration of N-formimidoyl thienamycin into cerebrospinal fluid (CSF) and its bacteriological ffiacy in experimental Escherichia coli Ki meningitis of rabbits.

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