JAC Advance Access originally published online on October 29, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 944-952
© 2003 The British Society for Antimicrobial Chemotherapy
Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme
1 Hospital Ramon y Cajal, Madrid, Spain; 2 University of Bath, Bath; 3 GR Micro Ltd, 7–9 William Road, London NW1 3ER, UK
Received 30 June 2003; returned 29 July 2003; revised 8 August 2003; accepted 28 August 2003
Objectives: To analyse the mutations and epidemiology associated with fluoroquinolone-resistant pneumococci collected as part of the PROTEKT global surveillance programme during 1999–2000.
Methods: Sixty-nine centres in 25 countries submitted a total of 3362 Streptococcus pneumoniae isolates, for which the MICs of antimicrobial agents were determined using NCCLS methodology.
Results: Levofloxacin resistance was low overall (1% worldwide), with higher rates in: Hong Kong (14.3%), South Korea (2.9%), USA (1.8%), Mexico (1.5%), Canada (1.4%) and Japan (1.3%). Levofloxacin resistance was very low or absent in European countries, and absent in Australia. Worldwide, there was a total of 35 levofloxacin-resistant isolates, of which 22 (63%) were resistant and 10 (29%) were intermediate to moxifloxacin. All levofloxacin-resistant isolates were susceptible to telithromycin (
0.5 mg/L), linezolid (2 mg/L) and quinupristin/dalfopristin (1 mg/L). One or more mutations in the topoisomerase genes were identified in all levofloxacin-resistant isolates; most of these isolates (33/35) had a mutation in one of the DNA gyrase encoding genes (gyrA, gyrB) and one of the topoisomerase IV encoding genes (parC, parE). Eighteen (51%) isolates carried the same combination of amino acid substitutions: Ser-81
Phe in GyrA and Ser-79Phe in ParC. Isolates displaying a levofloxacin MIC of 2–4 mg/L generally had no mutation or one mutation in either a DNA gyrase or a topoisomerase IV gene, although most mutations were in parC.
Conclusions: Most levofloxacin-resistant isolates possess two mutations (one in DNA gyrase and one in topoisomerase IV). Although multilocus sequence typing demonstrated that most of these isolates were unrelated, 12 (34%) were the Spain23F-1 clone: 10 from Hong Kong and one each from Saskatchewan, Canada and Sao Paulo, Brazil.
Keywords: multilocus sequence typing, Spain23F-1, topoisomerase mutations, fluoroquinolone resistance
* Corresponding author. Tel: +44-20-7388-7320; Fax: +44-20-7388-7324; E-mail: i.morrissey{at}grmicro.co.uk
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