PHARMACOKINETICS IN THE CEREBROSPINAL FLUID AFTER SIMULTANEOUS ADMINISTRATION OF LATAMOXEF AND AMPICILLIN TO RABBITS WITH STAPHYLOCOCCAL MENINGITIS

Abstract

The transfer of intravenously-administered latamoxef (moxalactam; LMOX) into the cerebrospinal fluid (CSF) is excellent and the usefulness of LMOX in the treatment of meningitis caused by Gramnegative bacilli has already been well established1-13). Because LMOX has weak activity against Gram-positive bacteria, however, some other complementary antibiotic must be employed concomitantly when LMOX is used before the causative bacterium has been identified. Accordingly, in a clinical study conducted by MCCRACKEN et al.13) in which they compared a group administered LMOX with a group concomitantly administered amikacin and ampicillin (ABPC) with respect to the clinical efficacy in the treatment of neonatal meningitis caused by Gram-negative bacilli, ABPC was also used concomitantly with LMOX until the causative bacteria were identified.
However, there are reports that the transfer of an antibiotic into the CSF is altered when other non-antibiotic drugs are administered concomitantly with the antibiotic14, 15). Therefore, it is thought to be necessary to investigate the effect of concomitant use of antibiotics on the transfer of individual antibiotics into the CSF in meningitis since it is difficult to obtain an effective concentration of an antibiotic in the CSF due to the limitation of its ability to cross the blood-CSF barrier, making it difficult to cure this disease.
On this basis, we administered LMOX and ABPC singly or as a mixture to rabbits with experimental meningitis caused byStaphylococcus aureus and we compared their concentrations in the serum and the CSF in the case of single and mixed administrations.