Molecular Characterization of Increasing Fluoroquinolone Resistance in Streptococcus pneumoniae Isolates in Canada, 1997 to 2005

Abstract

Molecular characterization of fluoroquinolone-resistant Streptococcus pneumoniae in Canada was conducted from 1997 to 2005. Over the course of the study, 205 ciprofloxacin-resistant isolates were evaluated for ParC and GyrA quinolone resistance-determining region (QRDR) substitutions, substitutions in the full genes of ParC, ParE, and GyrA, reserpine sensitivity, and serotype and by pulsed-field gel electrophoresis. Rates of ciprofloxacin resistance of S. pneumoniae increased significantly, from less than 1% in 1997 to 4.2% in 2005. Ciprofloxacin resistance was greatest in people >64 years of age and least in those <16 years of age. Significant increases were also noted in rates of resistance to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, to the current rates of 1.6%, 1.0%, 1.1%, and 1.0%, respectively. The most common genotype observed consisted of QRDR substitutions in GyrA (Ser81Phe) and ParC (Ser79Phe). Substitutions outside the QRDR of GyrA, ParC, and ParE were not associated with fluoroquinolone resistance in this study. Overall, 21% of isolates were reserpine-sensitive and were thus assumed to be efflux positive. The ciprofloxacin-resistant isolates belonged to 35 different serotypes, but 10 (19F, 11A, 23F, 6B, 22F, 12F, 6A, 14, 9V, and 19A) accounted for 72% of all isolates. The majority of the isolates were found to be genetically unrelated by pulsed-field gel electrophoresis. Within the observed clusters, there was considerable genetic heterogeneity with regard to fluoroquinolone resistance mechanisms and serotypes. Continued surveillance and molecular analysis of fluoroquinoloneresistant S. pneumoniae in Canada are essential for appropriate empirical treatment of infections and early detection of novel resistance mechanisms.

Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials

“…49,50 However, resistance to fluoroquinolones may increase in the future, and this may have an impact on treatment outcomes. 55 Administration of fluoroquinolones was associated with better treatment success among patients with severe pneumonia. The diversity in the definition of severe pneumonia among the individual trials and the use of the Pneumonia Severity Index score as a measure for severe pneumonia may limit this finding.…”

Fatal Levofloxacin Failure in Treatment of a Bacteremic Patient Infected with Streptococcus pneumoniae with a Preexisting parC Mutation

“…By PCR and sequencing (12), the first isolate showed a mutation in the QRDR of parC (Ser79Phe), and the second one had an additional gyrA mutation (Ser81Phe). These mutations are most commonly found in fluoroquinolone-resistant S. pneumoniae strains (1,18). In addition, genetic relatedness was supported by several polymorphisms identified in the QRDRs of the two isolates: Met1Leu in parC and Ile460Val in parE.…”

“…Isolates with a single first-step parC mutation are frequently susceptible to fluoroquinolones because the MICs are at or below the Clinical and Laboratory Standards Institute (CLSI) breakpoints (4). However, a firststep parC mutation increases the likelihood of a subsequent gyrA mutation, high-level resistance, and therapeutic failure (1,18). At the same time, it has also been observed that once a parC mutation has taken place in an S. pneumoniae strain, the mutation prevention concentration (MPC) increases dramatically for all fluoroquinolones (17).…”

Increasing Genetic Relatedness of Ciprofloxacin-Resistant Streptococcus pneumoniae Isolated in Canada from 1997 to 2005

“…We recently reported that ciprofloxacin resistance in Canadian S. pneumoniae isolates increased from 0.6% in 1997/1998 to 1.7% in 2000/2001 (1). In 2003, resistance rates increased significantly to 2.3% (P Ͻ 0.05) and continued to rise annually to 4.2% by 2005 (1).…”

“…In 2003, resistance rates increased significantly to 2.3% (P Ͻ 0.05) and continued to rise annually to 4.2% by 2005 (1). The objectives of this study were to investigate the role of clonal spread in the rapid increase of ciprofloxacin resistance in S. pneumoniae in Canada since 2003 and to determine whether these isolates are genetically related to each other or to known pandemic clones.…”