Summaryplement-mediated functions in neonates (9,11,25
MATERIALS AND METHODS
h after ip infection at which time mean bacterial concentration~~~~~~i~ and animal E. coli ~1 (strain ~l~k~) , isolated (log,, C F U /~~) ranged from 4.4-4.8 in the blood and from 1.8-from the CSF of a newborn with meningitis, was stored at -70°C 2.3 in the cerebral spinal fluid (CSF). Pre-treatment frequency in BHI broth with 20% glycerol (Difco). For each experiment, of bacteremia (100%) and meningitis (17-23%) was similar for an aliquot was thawed, plated on BHI agar, grown overnight at all experimental groups. Antibiotic concentrations in blood and 3 7 0~ and passed once in mice by IP injection. ~h~ mouse heart CSF 2 h after a dose exceeded the E. coli minimum inhibitory blood isolate was grown to late logarithmic phase in BHI broth concentration with the exception of CSF cephalothin, which was and diluted 1: 100 in sterile non-bacteriostatic 0.9% =line (sciundetectable. Moxalactam, ampicillin, and chloramphenicol sig-entific products). A lmml inoculum containing approximately nificantly reduced the incidence of bacteremia and meningitis 107 E. coli ( L D~~ = 2 106 CW) was injected IP into 7-or 14-relative to cephalothin or Saline controls (P < 0.02). Mortality &old New Zealand white rabbits (Rich-Glo, El Campo, Texas).rates among the former three groups were high (64432%) k t The dynamics of bacterial infection were initially determined in significantly less than in saline or cephalothin-treated rabblts nine 7-d-old rabbits. ~l~~d and CSF for quantitative culture were (100%). 1n this neonatal model of f~lminant sepsis with early obtained hourly from groups of three rabbits until all animals meningitis, moxalactam provided no therapeutic advantage over were dead. ampicillin or chloramphenicol.Blood and CSF cultures. Ketamine hydrochloride (Bristol Laboratories, 44 mg/kg IM) was used for sedation of animals Abbreviations during procedures. Cardiac puncture was done to obtain 0.1 ml BHI, brain heart infusion blood. This was added to 0.9 ml Columbia blood culture broth CFU, colony forming units (Difco) and kept on ice until quantitative cultures could be done CSF, cerebral spinal fluid (within 2 h). Serial 10-fold dilutions of each blood broth mixture IM, intramuscular were made in sterile saline. Duplicate 50-pl samples of each IP, intraperitoneal dilution were cultured on EMG-agar (Difco) plates and incubated MBC, minimum bacteriocidal concentration at 37°C overnight. The initial blood culture tubes were also kept MIC, minimum inhibitory concentration at 37°C and checked for growth if plate cultures were negative. The minimum number of organisms detectable by this method was 10 CFU/ml, although accurate quantitation was only possible for blood samples with 200 CFU/ml or more. The outcome of human neonatal gram-negative meningitis CSF was obtained by cisternal puncture using a neonatal scalp remains grave. Mortality ranges from 15-30% and sequelae vein infusion set with a 25 gauge needle (Argyle, Sherwood occur in 30-50% of survivor...