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Antimicrobial Agents and Chemotherapy, November 2000, p. 3049-3054, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae: Contributions of Type II Topoisomerase Mutations and Efflux to Levels of Resistance

Darrin J. Bast,1,2 Donald E. Low,1,2 Carla L. Duncan,1 Laurie Kilburn,1 Lionel A. Mandell,3 Ross J. Davidson,4 and Joyce C. S. de Azavedo1,2,*

Department of Microbiology, Mount Sinai Hospital and Toronto Medical Laboratories, University Health Network,1 and Department of Laboratory Medicine and Pathobiology, University of Toronto,2 Toronto, Ontario, Division of Infectious Diseases, McMaster University, Henderson Site, Hamilton Health Sciences Corporation, Hamilton, Ontario,3 and Department of Microbiology, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia,4 Canada

Received 20 April 2000/Returned for modification 27 June 2000/Accepted 12 August 2000

We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >= 4 µg/ml and 28 isolates for which the ciprofloxacin MIC is <= 2 µg/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 µg/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 µg/ml) and high-level (MICs, 64 µg/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.

* Corresponding author. Mailing address: Department of Microbiology, Rm 1483, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, Canada M5G 1X5. Phone: (416) 586-8459. Fax: (416) 586-8746. E-mail: jdeazavedo{at}mtsinai.on.ca.

Antimicrobial Agents and Chemotherapy, November 2000, p. 3049-3054, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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