Moderately penicillin-resistant Neisseria meningitidis was responsible for an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada in 1993. We tested fully susceptible and moderately resistant strains of N. meningitidis against ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, penicillin, and rifampin. Eighteen percent of the isolates were moderately resistant to penicillin (MIC, >0.06 g/ml) whereas susceptibility was 100% for the other agents tested.Neisseria meningitidis with decreased susceptibility to penicillin (moderate resistance) was recognized in Spain in 1985 (9, 10) and subsequently in other countries (10) including Canada (8) and the United States (3, 4). In 1993, an outbreak of meningococcal disease occurred in Saskatoon, Saskatchewan, Canada, and the majority of the isolates (serogroup C, enzyme electrophoretic type 15) were found to have decreased susceptibility to penicillin (2). Pulsed-field gel electrophoresis showed that all isolates with decreased susceptibility had the same genomic fingerprints following digestion with any of three separate restriction enzymes and that the genomic fingerprints of isolates not showing decreased susceptibility were different.Ciprofloxacin is a 4-fluoroquinolone antimicrobial agent that has broad-spectrum activity against gram-positive and gram-negative bacteria. For N. meningitidis, MICs were reported to range from Ͻ0.002 to 0.012 g/ml (3). Previously, Pugsley et al. (6) and Renkonen et al. (7) evaluated ciprofloxacin for the treatment of nasopharyngeal carriage of N. meningitidis in studies that showed ciprofloxacin to be highly efficacious for this purpose. With the discovery of the Saskatoon isolates showing decreased susceptibility to penicillin, we were interested in determining if this change had any effects on the in vitro activity of ciprofloxacin. We undertook a study to investigate the in vitro activity of ciprofloxacin against N. meningitidis isolates that were either fully susceptible or showing reduced susceptibility to penicillin and compared the results with those for penicillin, cefotaxime, ceftriaxone, chloramphenicol, and rifampin.A total of 78 N. meningitidis isolates from three different geographical regions of Canada were tested: 30 from British Columbia, provided by J. A. Smith; 32 from Nova Scotia, provided by K. Forward and D. Haldane; and 16 from Saskatchewan. Ten of the isolates from Saskatchewan were identical by pulsed-field gel electrophoresis, and the MICs for these isolates ranged 0.12 to 0.25 g/ml. One of these ten isolates was included in testing to determine the susceptibility rates.The MICs of ciprofloxacin for N. meningitidis were determined by three separate methods: Microscan MIC Plus (Baxter Diagnostics, Inc., Deerfield, Ill.) type 2 panels, agar dilution, and E test (AB Biodisk, Solna, Sweden). The MICs of cefotaxime, ceftriaxone, chloramphenicol, penicillin, and rifampin were determined by using only the E test. The Microscan MIC panels were used according to the manufacturer's instructions, and i...