Species-level assessment of the molecular basis of fluoroquinolone resistance among viridans group streptococci causing bacteraemia in cancer patients.
Viridans group streptococci (VGS) are a major cause of bacteraemia in neutropenic cancer patients, particularly those receiving fluoroquinolone prophylaxis. In this study, we sought to understand the molecular basis for fluoroquinolone resistance in VGS causing bacteraemia in cancer patients by assigning 115 VGS bloodstream isolates to specific species using multilocus sequence analysis (MLSA), by sequencing the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE, and by testing strain susceptibility to various fluoroquinolones. Non-susceptibility to one or more fluoroquinolones was observed for 78% of isolates, however only 68.7% of patients were receiving fluoroquinolone prophylaxis. All but one of the determinative QRDR polymorphisms occurred in GyrA or ParC, yet the pattern of determinative QRDR polymorphisms was significantly associated with the fluoroquinolone prophylaxis received. By combining MLSA and QRDR data, multiple patients infected with genetically indistinguishable fluoroquinolone-resistant Streptococcus mitis or Streptococcus oralis strains were discovered. Together these data delineate the molecular mechanisms of fluoroquinolone resistance in VGS isolates causing bacteraemia and suggest possible transmission of fluoroquinolone-resistant S. mitis and S. oralis isolates among cancer patients.
Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.
Pranoti
P
Sahasrabhojane
Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.
Jessica
J
Galloway-Peña
Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.
Luis
L
Velazquez
Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.
Miguel
M
Saldaña
Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.
Nicola
N
Horstmann
Department of Laboratory Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
Jeffrey
J
Tarrand
Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: sshelburne@mdanderson.org.
Samuel A
SA
Shelburne
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005798:Genes, Bacterial; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D009369:Neoplasms / Q000150:complications*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000382:microbiology*; D013291:Streptococcus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
Bacteraemia; Fluoroquinolone; Molecular epidemiology; Neutropenia; Streptococcus spp.