hr-810 and Meningitis--Pneumococcal

An in vitro pharmacodynamic model was used to determine the killing kinetics of cefpirome against 20 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from patients with meningitis. The concentration of cefpirome was adjusted dynamically to simulate the median concentration profile obtained in the cerebrospinal fluid of adults after the infusion of a single dose of 2 g. The cefpirome MIC at which 90% of isolates are inhibited was 0.5 microgram/ml. Bactericidal activity was observed at 6 h, with mean killing of 3.51 +/- 0.34 log10 CFU/ml for all strains for which the cefpirome MIC was < 0.5 microgram/ml. In contrast, for strains for which the cefpirome MIC was > or = 0.5 microgram/ml, killing was significantly less (P < 0.05), with a mean reduction of only 2.86 +/- 0.57 log10 CFU/ml.

Topics: Adult; Cefpirome; Ceftriaxone; Cephalosporins; Humans; Meningitis, Pneumococcal; Penicillin Resistance; Penicillins; Streptococcus pneumoniae

The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 microgram/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cefpirome; Ceftriaxone; Cephalosporins; Disease Models, Animal; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Fluoroquinolones; Male; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Penicillin Resistance; Quinolones; Rabbits; Rifampin; Thienamycins; Vancomycin

We evaluated the diffusion of cefpirome into the cerebrospinal fluid (CSF) of 25 patients with bacterial meningitis or ventriculitis who were receiving conventional antibiotic treatment. A single cefpirome dose of 2 g was infused at day 2-3 after the onset of therapy. Concentrations of cefpirome in serum and CSF obtained at 2, 4, 8 or 12 h after the infusion were determined by high-performance liquid chromatography. The mean (+/- S.E.M.) concentrations of cefpirome in CSF ranged from 2.26 +/- 1.16 to 4.17 +/- 0.83 mg/L. These concentrations were higher than the MBCs for the pathogens usually responsible for bacterial meningitis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cefpirome; Cephalosporins; Diffusion; Female; Humans; Male; Meningitis, Pneumococcal; Middle Aged

Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs.

Topics: Animals; Cefepime; Cefotaxime; Cefpirome; Cephalosporins; Meningitis, Pneumococcal; Rabbits; Streptococcus pneumoniae