1080 EVALUATION OF MOXALACTAM FOR THE TREATMENT OF MENINGITIS DUE TO S. PNEUMONIAE WITH DIFFERING SUSCEPTIBILITIES TO PENICILLIN

Abstract

Thirty-four strains of S. pneumoniae(Sp), 2 penicillin(pen) resistant(r), 12 pen relatively resistant(rr) and 20 pen susceptible(s) were tested against moxalactam(mox) by disk diffusion, agar and micro-broth dilution and killing curve methods. The 2 pen-r strains required >32ug/ml mox for inhibition. MICs of mox for the 12 pen-rr strains ranged from 1-16ug/ml with modal MICs of 8ug/ml. Fifty percent of the pen-s strains were inhibited by 1 ug/ml and 95% by 2ug/ml of mox. Cross-resistance to mox was noted for pen-r and most of the pen-rr strains.

Mox was compared to pen therapy in rabbits with bacterial meningitis induced by intracisternal inoculation of 10⁷-10⁸ CFU/ml. Two different strains were used: strain one mox MIC=lug/ml, pen MIC=0.03ug/ml. strain two mox MIC=8ug/ml, pen MIC=0.5ug/ml. Antibiotics were given every 4hr for 16hr in 50mg/kg/dose(mox) and 100,000U/kg/dose(pen). The mean % penetration into the CSF (CSF/serum × 100) were mox:17%, pen:3%, resulting in peak concentration ≥ fourfold MIC of the pen sensitive strain.

There was no significant reduction of CSF bacterial titers with mox vs untreated controls for both strains, whereas pen reduced titers of sensitive strains (p <.001). Mox is less active than pen against Sp in vitro and in experimental meningitis. It should not be used alone in the initial treatment of infants with meningitis.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD