ANTIBACTERIAL ACTIVITY AND PASSAGE INTO CEREBROSPINAL FLUID (CSF) OF AC-1370, A NEW CEPHEM ANTIBIOTIC

Abstract

The antibacterial activities of AC-1370 against 16 strains of P. aeruginosa, 44 strains of E. coli, 23 strains of K. pneumoniae, 7 strains of Serratia and 17 strains of S. aureus were compared with those of cefazolin, cefmetazole, latamoxef and cefotaxime.
The activity of AC-1370 against P. aeruginosa was superior to the effects: of 4 kinds of antibiotics mentioned above. The activities against E. coli and K. pneumoniae were the same as cefazolin and its effect against Serratia was equivalent to that of cefmetazole. However its activity against S. aureus was inferior to that of those antibiotics.
CSF concentrations of AC-13 70 were determined after single intravenous injection of 100mg/kg in 5 rabbits with experimental staphylococcal meningitis. The average maximum concentrations of 19.5±1.95μg/ml and 19.5±2.18μg/ml were obtained at 75 and 90 min., respectively after administration of AC-1370 with its CSF/serum ratio of 6.0%.
Under the above experimental conditions, a CSF/serum ratio of area under the curve (AUC) showed 6.21% up to 60 min., 10.4% up to 120 min. and 13.8% up to 180 min. and CSF/serum ratio of half-life (T1/2) was 4.18.
Based on these results it was considered that passage of AC-1370 into CSF was fairly good among cephems, so called as a third generation, and also elimination of AC-1370 from CSF was very slow.