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Antimicrobial Agents and Chemotherapy, September 1998, p. 2193-2196, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Sparfloxacin Resistance in Clinical Isolates of Streptococcus pneumoniae: Involvement of Multiple Mutations in gyrA and parC Genes

Hideki Taba* and Nobuchika Kusano

First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan

Received 22 August 1997/Returned for modification 16 April 1998/Accepted 16 June 1998

Antimicrobial susceptibility testing revealed among 150 clinical isolates of Streptococcus pneumoniae 4 pneumococcal isolates with resistance to fluoroquinolones (MIC of ciprofloxacin, >= 32 µg/ml; MIC of sparfloxacin, >= 16 µg/ml). Gene amplification and sequencing analysis of gyrA and parC revealed nucleotide changes leading to amino acid substitutions in both GyrA and ParC of all four fluoroquinolone-resistant isolates. In the case of strains 182 and 674 for which sparfloxacin MICs were 16 and 64 µg/ml, respectively, nucleotide changes were detected at codon 81 in gyrA and codon 79 in parC; these changes led to an Serright-arrowPhe substitution in GyrA and an Serright-arrowPhe substitution in ParC. Strains 354 and 252, for which sparfloxacin MICs were 128 µg/ml, revealed multiple mutations in both gyrA and parC. These strains exhibited nucleotide changes at codon 85 leading to a Gluright-arrowLys substitution in GyrA, in addition to Ser-79right-arrowTyr and Lys-137right-arrowAsn substitutions in ParC. Moreover, strain 252 showed additional nucleotide changes at codon 93, which led to a Trpright-arrowArg substitution in GyrA. These results suggest that sparfloxacin resistance could be due to the multiple mutations in GyrA and ParC. However, it is possible that other yet unidentified mutations may also be involved in the high-level resistance to fluoroquinolones in S. pneumoniae.

* Corresponding author. Mailing address: First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. Phone: 81-98-895-3331, ext. 2438. Fax: 81-98-895-3086. E-mail: h-taba{at}fa2.so-net.or.jp.

Antimicrobial Agents and Chemotherapy, September 1998, p. 2193-2196, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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