[Clinical experience of latamoxef in the field of neurosurgery on the penetration into the cerebrospinal fluid in the patients with postoperative meningitis].

Latamoxef (LMOX) at a dose of 2 g was intravenously administered to 12 cases with postoperative meningitis and the concentrations in serum and cerebrospinal fluid (CSF) were examined up to 2 hours and the results obtained were as follows; The average serum and CSF concentrations of LMOX were 125.0 micrograms/ml, 4.33 micrograms/ml at 0.5 hour, 80.7 micrograms/ml, 4.64 micrograms/ml at 1 hour and 45.8 micrograms/ml, 3.82 micrograms/ml at 2 hours, respectively. The clinical responses of LMOX against postoperative meningitis were revealed excellent in 4 cases and good in 8 cases. No side effects were observed. LMOX was thought to be effective agent in the treatment of the postoperative meningitis.

Cerebrospinal fluid penetration of moxalactam in ventriculostomy patients.

The cerebrospinal fluid penetration of moxalactam was simultaneously investigated in three patients with presumed bacterial meningitis. When ratios of simultaneously drawn ventriculostomy to serum moxalactam levels of 1, 2, 3, and 4 h were examined, the penetration ratios were 7.8 +/- 2.4, 11.2 +/- 1.3, 14.2 +/- 2.5, and 15.0 +/- 4.9%, respectively. These ratios were not statistically different from the penetration of moxalactam calculated by the area under the concentration-time curve technique (8.97 +/- 1.89%).

Pharmacokinetics and CSF penetration of moxalactam in antibiotic prophylaxis in neurosurgery.

Moxalactam, a new oxa-beta-lactam antibiotic, suggests a possible role in prophylaxis in neurosurgery. Therefore, CSF penetration of Moxalactam was determined in 12 patients with absence of clinical or laboratory evidence of meningitis. In the dose employed (25 mg/kg 3 times/day) CSF samples showed a penetration of Moxalactam through the blood-cerebrospinal barrier with concentrations higher than 0.1 microgram/ml which persisted for more than seven hours. The drug was well tolerated and adverse effects were not observed.

High performance liquid chromatographic determination of moxalactam in human plasma and cerebrospinal fluid.

A sensitive and reproducible method for the measurement of moxalactam in plasma and cerebrospinal fluid is described. Plasma proteins were removed by precipitation with ice-cold methanol at pH 5.6 and centrifugation. The supernatant was analysed by HPLC on a mu-Bondapack/phenyl column, with a mobile phase of acetonitrile/water/PIC Reagent A (20/80/1), and detection at 280 nm. The calibration curve was linear for plasma concentrations from 10 micrograms/ml to 60 micrograms/ml. Reproducibility was 4.7% (coefficient of variation) for within-day analysis and 13.8% for day-to-day analysis. Plasma concentrations in 9 moxalactam-treated patients with severe infections ranged from 0.9 micrograms/ml to 409 micrograms/ml. Individual pharmacokinetic parameters were calculated using a personal computer. In selected cases moxalactam concentrations were also determined in cerebrospinal fluid and tracheal aspirates.

Prospective evaluation of moxalactam therapy for gram-negative bacillary meningitis.

In a prospective evaluation twenty patients with gram-negative bacillary meningitis were treated with moxalactam, either alone or in conjunction with other antibiotics. Of thirteen patients who received only moxalactam, eight recovered, one failed to respond, and five died of causes other than meningitis. Cultures of CSF were negative before death in each instance. Thirteen (65%) of 20 treated patients recovered. Reversible hypoprothrombinemia and bleeding occurred secondary to moxalactam therapy in one patient. The mortality from gram-negative bacillary meningitis remains high owing to the incidence of associated underlying disease. Moxalactam brings about bacteriologic control in a large proportion of patients who are infected with highly sensitive gram-negative enteric bacilli.

Moxalactam for the treatment of bacterial meningitis in children.

Increasing resistance to antibiotics in meningeal pathogens has stimulated a search for new antimicrobial agents for the treatment of bacterial meningitis. Moxalactam penetrates well into infected cerebrospinal fluid (CSF) and is highly active against most gram-negative bacteria. The clinical efficacy and safety of moxalactam in the treatment of childhood meningitis caused by Haemophilus influenzae (25 patients) or Neisseria meningitidis (five patients) was evaluated in a random, uncontrolled study. The penetration of the antibiotic into CSF was also evaluated in these patients and in another five children with bacterial meningitis. The clinical results were excellent, with 29 of 30 cases cured. The single adverse clinical reaction noted was the development of a wound hematoma in a postoperative patient; this problem may have been related to moxalactam therapy. The levels of moxalactam achieved in CSF greatly exceeded the minimal bactericidal concentrations for the infecting organisms. Moxalactam appears to be safe and effective as primary therapy for meningitis caused by H influenzae or N meningitidis.