Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae:: data from the global PROTEKT surveillance programme

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 (less than or equal to0.5 mg/L), linezolid (less than or equal to2 mg/L) and quinupristin/dalfopristin (less than or equal to1 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-79-->Phe 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 Spain(23F)-1 clone: 10 from Hong Kong and one each from Saskatchewan, Canada and Sao Paulo, Brazil.