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Antimicrobial Agents and Chemotherapy, March 2005, p. 1046-1054, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.1046-1054.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Activity of Gemifloxacin against Quinolone-Resistant Streptococcus pneumoniae Strains In Vitro and in a Mouse Pneumonia Model

E. Azoulay-Dupuis,1* J. P. Bédos,1 J. Mohler,1 P. Moine,1 C. Cherbuliez,2 G. Peytavin,1 B. Fantin,1 and T. Köhler2

INSERM EMI-U 9933, Faculté de Médecine Xavier Bichat, Paris, France,1 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland2

Received 2 June 2004/ Returned for modification 26 July 2004/ Accepted 9 November 2004

Gemifloxacin is a novel fluoronaphthyridone quinolone with enhanced in vitro activity against Streptococcus pneumoniae. We investigated the activities of gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro and in vivo, and their efficacies in a mouse model of acute pneumonia. Immunocompetent Swiss mice were infected with 105 CFU of a virulent, encapsulated S. pneumoniae strain, P-4241, or its isogenic parC, gyrA, parC gyrA, and efflux mutant derivatives (serotype 3); and leukopenic mice were infected with 107 CFU of two poorly virulent clinical strains (serotype 11A) carrying either a parE mutation or a parC, gyrA, and parE triple mutation. The drugs were administered six times every 12 h, starting at either 3 or 18 h postinfection. In vitro, gemifloxacin was the most potent agent against strains with and without acquired resistance to fluoroquinolones. While control mice died within 6 days, gemifloxacin at doses of 25 and 50 mg/kg of body weight was highly effective (survival rates, 90 to 100%) against the wild-type strain and against mutants harboring a single mutation, corresponding to area under the time-versus-serum concentration curve at 24 h (AUC24)/MIC ratios of 56.5 to 113, and provided a 40% survival rate against a mutant with a double mutation (parC and gyrA). A total AUC24/MIC ratio of 28.5 was associated with poor efficacy and the emergence of resistant mutants. Trovafloxacin was as effective as gemifloxacin against mutants with single mutations but did not provide any protection against the mutant with double mutations, despite treatment with a high dose of 200 mg/kg. Gemifloxacin preferentially selected for parC mutants both in vitro and in vivo.

* Corresponding author. Mailing address: INSERM EMI-U 9933, Faculté Xavier Bichat, 16, rue Henri Huchard, 75870 Paris Cedex 18, France. Phone: (33) 1 44 85 61 53. Fax: (33) 1 44 85 61 47. E-mail: eazoulay{at}bichat.inserm.fr.

Antimicrobial Agents and Chemotherapy, March 2005, p. 1046-1054, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.1046-1054.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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  • Chiavolini, D., Pozzi, G., Ricci, S. (2008). Animal Models of Streptococcus pneumoniae Disease. Clin. Microbiol. Rev. 21: 666-685 [Abstract] [Full Text]  
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  • Poole, K. (2005). Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56: 20-51 [Abstract] [Full Text]  


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