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PARKE-DAVIS CI-934 GRAM POSITIVE ACTIVITY IN VITRO

Executive Summary

PARKE-DAVIS CI-934 GRAM POSITIVE ACTIVITY IN VITRO may be superior to other drugs in the new crop of quionolone antimicrobials, company researchers suggested in presentations to the Oct. 8-10 Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, D.C. At the meeting, the firm's M. A. Cohen, et al., reported the results of comparative in vitro minimum inhibitory concentration (MIC) tests "against 229 bacterial isolates representing over 63 common pathogenic species." The comparative tests included another quinolone, ofloxacin, "because it represented the best gram positive quinolone we knew of before CI-934," Cohen said. Against 19 strains of methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus, CI-934's overall "activity was superior to that of ofloxacin, erythromycin, oxacillin and vancomycin," Cohen reported. Tested against 25 strains of Streptococci, erythromycin had the leading inhibitory rate, he said. However, CI-934 "was superior to penicillin G and cefazolin." In studies of 66 Enterobacteriaceae strains, CI-934 and ofloxacin were "comparable" and both "outperformed ampicillin and the combination of sulfamethoxazole and trimethoprim," he explained. The broad spectrum anti-bacterial is headed for human testing in the near future. At a recent meeting with security analysts, Warner-Lambert Pharmaceutical Div. President Jerry Weisbach, MD, said CI-934 will enter clinical trials "shortly." Weisbach added that the firm intends to position the drug for outpatient use. Preclinical data indicate the drug is active orally and parenterally. CI-934 will be Parke-Davis' second quinolone to enter clinical trials. Another compound, enoxacin, which is licensed from Dainippon, is currently undergoing Phase III testing. Overall, Cohen reported, "based in MIC values, CI-934 is highly potent v. a variety of common gram positive pathogens including staphlococci, beta-hemolytic [streptococci] (Mansfield Groups A, B, and C), pneumococcus, Group D [Streptococci] (enterococcal as well as non-enterococcal strains), Viridans streptococci, Listeria monocytogenes. The drug is also highly potent against gonococcus and Haemophilus influenzae, against Enterobacteriaceae and against anaerobes, for the most part excluding the Bacteroides fragilis group." In addition, he said, bactericidal studies indicate activity "against both gram positive and gram negative bacteria."

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