[Clinical studies of cefoperazone in neurosurgery]

A multicenter trial consisting of 164 institutions through out Japan, has been conducted to study the transfer of cefoperazone (CPZ) into the cerebrospinal fluid (CSF), and the clinical effectiveness of CPZ as a therapeutic or prophylactic agent in neurosurgery. The levels of CPZ in serum and CSF were determined in 96 patients. After initial dose of 2 g CPZ (intravenous drip infusion for 30 minutes), the serum level of CPZ after 1 hour was 124.5 +/- 6.6 micrograms/ml (Mean +/- S.E.), and even after 6 hours, it maintained as high as 47.8 +/- 16.6 micrograms/ml. The peak CPZ levels in CSF in patients with normal or minimal impairment in blood-CSF-barrier (BCB) (group I) and in those of localized impairment in BCB (group II) were 1.0 +/- 0.5 micrograms/ml at 2 hours and 3.0 +/- 1.8 micrograms/ml at 3 hours, respectively. The highest CSF level was seen in patients with meningitis (group III) and showed 5.0 +/- 2.4 micrograms/ml at 6 hours. After multiple dose of 2 g CPZ (intravenous drip infusion for 30 minutes), the serum kinetics of CPZ were not significantly different from those obtained after initial dose. However, the CPZ levels in CSF were higher than those observed after initial dose in all 3 groups and were higher than MIC75 against relevant pathogens for meningitis such as Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. Moreover, in group III peak level of CPZ in CSF exceeded the MIC75 against Pseudomonas aeruginosa which is also frequently isolated from patients with meningitis in neurosurgery. As a therapeutic agent CPZ administered as sole agent was effective in 42 out of 55 cases (76.4%) in meningitis, in 78 out of 116 cases (67.2%) in pneumonia and in 36 out of 47 cases (76.6%) in urinary tract infection (UTI). Its efficacy rate against all infections treated was 72.2% (184/255). Regarding CPZ's prophylactic use, 39 out of 514 cases (7.6%) were judged as having or possibly having infections as follows; meningitis (13/514, 2.5%), pneumonia (15/514, 2.9%), UTI (2/514, 0.4%). In prophylactic use of CPZ, the incidence rates of postoperative meningitis and other central nervous system (CNS) infection following ventricular drainage and supratentorial craniotomy for aneurysm were higher than those observed in other types of operation, 12.0% (3/25) and 6.2% (8/130), respectively. Also, regarding prophylactic use of CPZ, the organisms isolated by culture from 13 cases of postoperative CNS infections included 2 strains of Staphylococcus sp., 1 strain of Serratia sp. and 3 strains of other Gram-negative bacteria (GNB).(ABSTRACT TRUNCATED AT 400 WORDS)