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Antimicrobial Agents and Chemotherapy, February 2000, p. 304-310, Vol. 44, No. 2
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antipneumococcal Activities of Gemifloxacin Compared to Those of Nine Other Agents

Todd A. Davies,1 Linda M. Kelly,1 Glenn A. Pankuch,1 Kim L. Credito,1 Michael R. Jacobs,2 and Peter C. Appelbaum1,*

Department of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033,1 and Department of Pathology (Clinical Microbiology), Case Western Reserve University, Cleveland, Ohio 441062

Received 21 June 1999/Returned for modification 22 September 1999/Accepted 29 October 1999

The activities of gemifloxacin compared to those of nine other agents was tested against a range of penicillin-susceptible and -resistant pneumococci by agar dilution, microdilution, time-kill, and post-antibiotic effect (PAE) methods. Against 64 penicillin-susceptible, 68 penicillin-intermediate, and 75 penicillin-resistant pneumococci (all quinolone susceptible), agar dilution MIC50s (MICs at which 50% of isolates are inhibited)/MIC90s (in micrograms per milliliter) were as follows: gemifloxacin, 0.03/0.06; ciprofloxacin, 1.0/4.0; levofloxacin, 1.0/2.0; sparfloxacin, 0.5/1.0; grepafloxacin, 0.125/0.5; trovafloxacin, 0.125/0.25; amoxicillin, 0.016/0.06 (penicillin-susceptible isolates), 0.125/1.0 (penicillin-intermediate isolates), and 2.0/4.0 (penicillin-resistant isolates); cefuroxime, 0.03/0.25 (penicillin-susceptible isolates), 0.5/2.0 (penicillin-intermediate isolates), and 8.0/16.0 (penicillin-resistant isolates); azithromycin, 0.125/0.5 (penicillin-susceptible isolates), 0.125/>128.0 (penicillin-intermediate isolates), and 4.0/>128.0 (penicillin-resistant isolates); and clarithromycin, 0.03/0.06 (penicillin-susceptible isolates), 0.03/32.0 (penicillin-intermediate isolates), and 2.0/>128.0 (penicillin-resistant isolates). Against 28 strains with ciprofloxacin MICs of >= 8 µg/ml, gemifloxacin had the lowest MICs (0.03 to 1.0 µg/ml; MIC90, 0.5 µg/ml), compared with MICs ranging between 0.25 and >32.0 µg/ml (MIC90s of 4.0 to >32.0 µg/ml) for other quinolones. Resistance in these 28 strains was associated with mutations in parC, gyrA, parE, and/or gyrB or efflux, with some strains having multiple resistance mechanisms. For 12 penicillin-susceptible and -resistant pneumococcal strains (2 quinolone resistant), time-kill results showed that levofloxacin at the MIC, gemifloxacin and sparfloxacin at two times the MIC, and ciprofloxacin, grepafloxacin, and trovafloxacin at four times the MIC were bactericidal for all strains after 24 h. Gemifloxacin was uniformly bactericidal after 24 h at <= 0.5 µg/ml. Various degrees of 90 and 99% killing by all quinolones were detected after 3 h. Gemifloxacin and trovafloxacin were both bactericidal at two times the MIC for the two quinolone-resistant pneumococci. Amoxicillin at two times the MIC and cefuroxime at four times the MIC were uniformly bactericidal after 24 h, with some degree of killing at earlier time points. Macrolides gave slower killing against the seven susceptible strains tested, with 99.9% killing of all strains at two to four times the MIC after 24 h. PAEs for five quinolone-susceptible strains were similar (0.3 to 3.0 h) for all quinolones, and significant quinolone PAEs were found for the quinolone-resistant strain.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psghs.edu.

Antimicrobial Agents and Chemotherapy, February 2000, p. 304-310, Vol. 44, No. 2
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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