hr-810 and Meningitis

Twenty patients (mean age 52 +/- 12 years, mean weight 75 +/- 15 kg) scheduled for elective myelogram or spinal anaesthesia were enrolled to determine the cerebrospinal fluid (CSF) penetration of a new expanded spectrum cephalosporin antibiotic, cefpirome (HR-810). A single 2 g intravenous dose of cefpirome was administered as a bolus between 1 and 8 h before lumbar puncture. Blood samples were collected at 15 pre-determined times and a single CSF sample was obtained at the time of lumbar puncture. Serum and CSF cefpirome concentrations were determined by high performance liquid chromatography. The mean maximal serum concentration of cefpirome was 264 +/- 76 mg/L. A mean steady-state volume of distribution of 20 +/- 4 L, clearance of 7.4 +/- 1.3 L/h, and half-life of 2.5 +/- 0.5 h were determined. Mean CSF concentrations were 0.50 +/- 0.11 mg/L at 1-2 h post dose (n = 4), 0.57 +/- 0.13 mg/L at 2-4 h post dose (n = 4), 0.76 +/- 0.34 mg/L at 4-6 h post dose (n = 7), and 0.83 +/- 0.29 mg/L at 6-8.3 h post dose (n = 5). Blood:brain barrier permeability to cefpirome may not be a limiting factor as CSF concentrations were rapidly attained. Further studies are required to determine the mechanism of cefpirome transport between plasma and CSF.

Topics: Adolescent; Adult; Aged; Anesthesia, Spinal; Cefpirome; Cephalosporins; Female; Humans; Male; Meninges; Meningitis; Middle Aged; Myelography; Spinal Puncture

Cefpirome (HR 810, CPR), a new cephem antibiotic, was investigated for its experimental and clinical studies in pediatrics. The results obtained are summarized as follows. 1. Plasma and urinary levels of CPR were determined in 2 children (age 5 and 7 years) after the one shot intravenous injection of the drug at 20 mg/kg. Average plasma levels of the drug were 44.7 micrograms/ml, 28.5 micrograms/ml, 10.5 micrograms/ml, 4.6 micrograms/ml and 1.5 micrograms/ml at 1/2 hour, 1 hour, 2 hours, 4 hours and 6 hours, respectively, and the average half life was 1.57 hours. Average urinary levels of the drug were 1,785 micrograms/ml, 545 micrograms/ml and 198 micrograms/ml at 0-2 hours, 2-4 hours, 4-6 hours, respectively and the average urinary elimination rate was 52.0%. The results were nearly equivalent to those in adults except for urinary elimination rate which tended to be slightly lower than that in adults. 2. Cerebrospinal fluid levels in 3 cases of purulent meningitis treated with CPR were investigated. Cerebrospinal fluid levels in a case of Neisseria meningitidis were 11.5-23.1 micrograms/ml at 1 hour and 0.94 microgram/ml at 5 hours after intravenous injection of 44.4 mg/kg, 4 times a day. Cerebrospinal fluid levels in a case of Streptococcus pneumoniae were 1.01-4.23 micrograms/ml at 1 hour after intravenous injection of 49.0 mg/kg, 6 times a day, and in the other case with Streptococcus pneumoniae, the levels were 16.8-37.1 micrograms/ml at 1 hour, 11.3 and 3.60 micrograms/ml at 3 and 4 hours after intravenous injection 52.2 mg/kg, 6 times a day. These results are not inferior to those with cefotaxime or ceftriaxone. These levels appear to be higher than MIC90 values against Escherichia coli, Streptococcus agalactiae, S. pneumoniae or Haemophilus influenzae which are the major pathogens of these diseases. 3. CPR was given to 62 patients and clinical efficacy, bacteriological response and adverse reactions were evaluated. Evaluated cases for clinical efficacy included 3 cases of purulent meningitis, 1 case of acute purulent otitis media, 2 cases of acute purulent tonsillitis, 1 case of acute bronchitis, 49 cases of acute pneumoniae, 1 case of scarlet fever, 1 case of acute osteomyelitis, 1 case of acute enterocolitis, and 2 cases of acute UTI, totalling 61 cases. Clinical efficacies were excellent in 38 cases, good in 22 cases and fair in 1 case with an efficacy rete of 98.4% (excellent + good).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acute Disease; Adolescent; Bacterial Infections; Bronchitis; Cefpirome; Cephalosporins; Child; Child, Preschool; Enterocolitis; Female; Humans; Infant; Male; Meningitis; Osteomyelitis; Otitis Media; Pneumonia; Scarlet Fever; Tonsillitis; Urinary Tract Infections

The transferability of cefpirome (HR810, CPR) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 362 +/- 6.63 micrograms/ml at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 60 minutes after administration, and the mean maximum concentration was 14.6 +/- 2.85 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows, Cmax (CSF/serum): 4.04%; AUC (CSF/serum): 5.14% between 15 and 60 minutes, 8.12% between 15 and 120 minutes and 10.4% between 15 and 180 minutes; T 1/2 for CPR in CSF: 154 minutes; T 1/2 (CSF/serum): 3.96. In comparison to those of other beta-lactam antibiotics which were obtained in the same way, the transferability of CPR was intermediate, but the peak CSF level was high, and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for this drug.

Topics: Animals; Cefpirome; Cephalosporins; Disease Models, Animal; Injections, Intravenous; Meningitis; Rabbits; Staphylococcal Infections

Cefpirome is a new aminothiazolyl cephalosporin with a low protein binding, a long half-life of elimination and a wide antibacterial spectrum including pseudomonas and staphylococcus. We studied its diffusion into the cerebrospinal fluid (CSF). Cefpirome, 2 g, was administered intravenously over 3 min. Nineteen patients, aged 12-75 y (mean +/- SD = 40 +/- 20) were studied: 13 had meningitis (septic = 6; chronic = 2; viral = 4). Seric and CSF samples were assayed by the high pressure liquid chromatography (HPLC) procedure. Results at 1, 3, 6, 9 and 12 hours after the infusion were (mean +/- SD) 62.44 +/- 19.8 mg/l, 26.51 +/- 3.7 mg/l, 10.19 +/- 3.3 mg/l, 3.99 +/- 2.3 mg/l, 2 +/- 1.72 mg/l in the serum and 1.1 +/- 1 mg/l, 2.6 +/- 1.8 mg/l, 2.83 +/- 1.7 mg/l, 1.92 +/- 1 mg/l, 1.83 +/- 0.36 mg/l in CSF of bacterial meningitidis respectively. The half-life of elimination were 2.45 h and 9.8 h in the blood and CSF respectively. The area under the curve CSF/serum ratio was 28%. We conclude that cefpirome concentrations in the CSF were above the minimal inhibitory concentrations of almost all the bacteria causing meningitis.

Topics: Adolescent; Adult; Aged; Cefpirome; Cephalosporins; Child; Chromatography, High Pressure Liquid; Female; Humans; Male; Meninges; Meningitis; Middle Aged