title: Clinical isolates of Streptococcus pneumoniae resistant to levofloxacin contain mutations in both gyrA and parC genes.
abstract: Thirty Streptococcus pneumoniae clinical isolates resistant to levofloxacin were analyzed for the quinolone resistance-determining DNA sequences to identify point mutations and were tested for in vitro susceptibility to multiple drug classes. Of these isolates, 29 had mutations in both gyrA and parC genes of DNA gyrase and topoisomerase IV, respectively. In GyrA, an amino acid change from Ser-81-->Phe was detected in 27 isolates and a Glu-85-->Lys change was found in the remaining three. Of the 29 isolates for which ParC data were available, Ser-79-->Tyr or Phe were the predominant mutations observed. MICs for levofloxacin were 4-16 mg/l, whereas those for moxifloxacin were 1-2 mg/l. Twenty-four (80%) isolates were susceptible to erythromycin, 25 (83%) to azithromycin, 26 (87%) to clarithromycin, 27 (90%) to clindamycin, 20 (67%) to penicillin, 21 (70%) to ceftriaxone and 30 (100%) to amoxycillin/clavulanate. These results confirm the presence of double mutations among clinical isolates of S. pneumoniae from diverse geographical regions of North America and also suggest that quinolone resistance may develop independently of resistance to other drug classes.
authors.affiliation: Diagnostic Laboratory Services, The Queen's Health Systems, 650 Iwilei Rd., Suite 300, Honolulu, HI 96817, USA. xzheng@dls.queens.org
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Yanagihara
authors.forename: S
authors.initials: S
authors.lastname: Hollingshead
authors.forename: M
authors.initials: M
authors.lastname: Crain
authors.forename: W
authors.initials: W
authors.lastname: Benjamin
authors.forename: K B
authors.initials: KB
authors.lastname: Waites
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D017354:Point Mutation / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II