Comparison of cefamandole, cephalothin, ampicillin, and chloramphenicol in experimental Escherichia coli meningitis

Abstract

The activities of cefamandole, cephalothin, ampicillin, and chloramphenicol were compared in fulminant and temperate Escherichia coli meningitis in rabbits. Intensive dosing schedules were employed to achieve maximal therapeutic benefits with short-term treatment. In an 8-h schedule chloramphenicol was significantly more effective in sterilizing the cerebrospinal fluid and curing both fulminant and temperate infections than cefamandole or ampicillin. Cephalothin was without effect in fulminant meningitis. Cefamandole and ampicillin were equivalent in activity in this and longer (12-and 24-hr) fly needle, which cannulated a marginal ear vein, to a Harvard infusion/withdrawal pump (model 940; Harvard Apparatus, Millis, Mass.). Untreated controls had unlimited access to food and water; intakes were negligible after inoculation. Treated animals had access to water but no food. Except for the modifications summarized below, methods of procedure were those detailed previously (1).E. coli C13NK1, isolated from a neonate with meningitis, was provided for this study by George McCracken, Jr., University of Texas Health Science Center, Dallas. After overnight growth on Mueller-Hinton (MH) agar (Difco), a suspension of organisms in phosphate-buffered saline was prepared and adjusted with the help of nephelometry (Coleman 6A Spectrophotometer; Coleman Instruments, Maywood, Ill.) to a density of 7.0 x 107 to 8.0 x 107 colony-forming units (CFU)/ml. A cisternal puncture was performed with a 20-gauge needle and a 1.0-ml tuberculin syringe; 0.5 ml of CSF was withdrawn, and 0.5 ml of the bacterial suspension was injected. To produce fuhminant infections, 0.5-ml quantities of undiluted suspension were injected intracisternally; temperate infections were induced by injecting 0.5 ml of a 1:100 dilution. If visible blood contamination resulted, the animal was not included in the study. Gentle reaspiration and injection were performed to insure intracisternal inoculation. The needle was withdrawn, and the animal was returned to its cage for 14 h.Untreated controls were included every other week to insure constancy of virulence (11). Treated animals received an antibiotic in groups of four. Antibiotics were chosen in a nonrandom sequence before therapy. At the completion of therapy, rabbits with fulminant meningitis were sacrificed by an overdose of pentobarbital, at which time serum, CSF, and brain were obtained for assay. Pairs of treated rabbits with temperate meningitis were either sacrificed or anesthetized

Paradox between the responses of Escherichia coli K1 to ampicillin and chloramphenicol in vitro and in vivo

“…However, their results were based on a brief period of observation and continuous infusion with much higher doses of antibiotics in adult rabbits infected by direct instillation of bacteria in CSF. The rabbit model differs in several respects from disease in the infant rat and in humans, including spontaneous resolution of infection in some rabbits (4).…”

Bactericidal activity of cefoperazone with CP-45,899 against large inocula of beta-lactamase-producing Haemophilus influenzae

“…CP-45,899 similarly enhanced the bactericidal activity of cefoperazone against f8-lactamase-producing strains of H. influenzae in our study. (3). Unless, therefore, CP-45,899 penetrates the central nervous system in sufficient quantity to exert a synergistic effect on the bactericidal activity of cefoperazone against large numbers of ,B-lactamase-producing strains of H. influenzae, there probably should be serious reservations about the use of cefoperazone alone in the treatment of bacterial meningitis.…”