In vitro activity of a new fluoroquinolone, CP-99,219, against strains of Neisseria gonorrhoeae.

The susceptibilities of 216 strains ofNeisseria gonorrhoeaeto a newfluoroquinolone, CP-99,219 were determined. For strains for which the MICs of ciprofloxacin were #0.06 mg/ml, the MICs at which 90% of the isolates are inhibited (MIC90s) of CP-99,219, ciprofloxacin, and ofloxacin were 0.008, 0.015, and 0.03 mg/ml, respectively. For strains for which the MICs of ciprofloxacin were 0.125 to 0.5 mg/ml, the MIC90s of CP-99,219, ciprofloxacin, and ofloxacin were 0.06, 0.25, and 0.5 mg/ml, respectively. For strains for which the MICs of ciprofloxacin and ofloxacin were 2.0 mg/ml, the MIC of CP-99,219 was 0.25 mg/ml. Although the number of reported cases of gonorrhea in the United States has decreased since the mid-1980s, the proportion caused by antimicrobial agent-resistant strains ofNeisseria gonorrhoeae has increased (2, 4). Because of penicillin and tetracycline resistance inN. gonorrhoeae, the Centers for Disease Control and Prevention recommended in 1993 that broad-spectrum cephalosporins andfluoroquinolones be used to treat uncomplicated gonorrhea (1). Strains exhibiting decreased susceptibilities to ciprofloxacin and ofloxacin have been reported from Asia, the United Kingdom, the United States, and Canada (3‐8). A strain that failed to respond to treatment with ciprofloxacin (500 mg) for which the MIC of ciprofloxacin was 1.0 mg/ml has been isolated in Australia (12). The emergence of resistant strains may limit the future usefulness of fluoroquinolones; more-active agents will be requiredtokillallgonococcalstrains.Wedeterminedtheinvitro activity of a new fluoroquinolone, CP-99,219, against N. gonorrhoeae strains, including strains with decreased susceptibilities to ciprofloxacin. A total of 216 strains of N. gonorrhoeae were tested. These strains representedfive distinct resistance phenotypes according to their susceptibilities to penicillin and tetracycline, b-lactamase production (penicillinase-producing N. gonorrhoeae [PPNG]), and the presence of the TetM determinant (strains with plasmid-mediated resistance to tetracycline [TRNG]) as defined previously (10, 11) (Table 1) and included 183 strains forwhichtheMICofciprofloxacinwas #0.06 mg/ml,30strains for which the MICs of ciprofloxacin were 0.125 to 0.5 mg/ml, and3strainsforwhichtheMICofciprofloxacinwas2.0 mg/ml. PPNGstrainsincluded35of69(50.7%),17of69(24.6%),and 16 of 69 (23.2%) strains possessing 3.2-, 4.4-, or 3.05-MDa plasmids, respectively. All PPNG strains with plasmid-mediated resistance to tetracycline due to the TetM determinant (PP/TR strains) possessed a 3.2-MDa plasmid. The strains were isolated in the following 23 localities in the United States: Honolulu, Hawaii (44 strains); Cleveland, Ohio (25 strains); Baltimore, Md. (20 strains); West Palm Beach, Fla. (14 strains); New Orleans, La. (13 strains); Atlanta, Ga. (12 strains); Birmingham, Ala. (12 strains); Cincinnati, Ohio (12 strains); Orange County and San Diego, Calif. (11 strains each); Long Beach County, Calif. (7 strains); Boston, Mass. (5 strains); San Antonio, Tex. (5 strains); Denver, Colo. (4 strains); Muskegon, Mich. (3 strains); Nassau County, N.Y. (3 strains);Philadelphia,Pa.(3strains);Phoenix,Ariz.(3strains); Portland, Oreg. (3 strains); San Francisco, Calif. (3 strains); Seattle, Wash. (1 strain); St. Louis, Mo. (1 strain); and Tacoma, Wash. (1 strain). The strains belonged to a total of 45