title: Incidence and epidemiology of levofloxacin resistance in Streptococcus pneumoniae: experience from a tertiary referral hospital in England.
abstract: OBJECTIVE
  To investigate the incidence of levofloxacin resistance in Streptococcus pneumoniae isolates cultured by Lancashire Teaching Hospitals NHS Foundation Trust (LTHTR), and detect cases of in vivo resistance development.
  
  
  METHODS
  During the study period (September 2004-February 2007), isolates of S. pneumoniae cultured by the LTHTR microbiology laboratory were examined by Etest to determine MICs of levofloxacin. Isolates from patients in whom there was a shift towards colonization with S. pneumoniae of reduced levofloxacin susceptibility were further characterized by serotyping, multilocus sequence typing (MLST) and sequencing of parC and gyrA genes.
  
  
  RESULTS
  Eight hundred and sixty-five isolates were collected; however, 772 isolates from 652 patients were recoverable; 412 (53.4%) came from hospitalized patients, 12 (1.6%) were resistant to levofloxacin according to the BSAC breakpoint (>2 mg/L) and 29 (3.8%) had MICs at the breakpoint (MIC = 2 mg/L). Of six patients in whom there was a shift towards isolates with reduced levofloxacin susceptibility, five had acquired new distinct strains. One patient, who had a parC mutation (Ser79Phe) in the original susceptible isolate and an additional second-step mutation in the gyrA gene (Ser81Phe) of the later resistant one, had isolates belonging to the same pneumococcal clone.
  
  
  CONCLUSIONS
  S. pneumoniae resistance to levofloxacin was uncommon and we managed to identify only one case of probable in vivo resistance development in the 2.5 years of the study. Strain replacement accounted for the majority of incidences where there was an apparent shift towards colonization with isolates of reduced levofloxacin susceptibility.
authors.affiliation: Department of Microbiology, Royal Preston Hospital, Sharoe Green Lane, Fulwood, Preston PR2 9HT, UK. David.orr@lthtr.nhs.uk
authors.forename: David
authors.initials: D
authors.lastname: Orr
authors.forename: Paul
authors.initials: P
authors.lastname: Wilkinson
authors.forename: Laura
authors.initials: L
authors.lastname: Moyce
authors.forename: Siobhan
authors.initials: S
authors.lastname: Martin
authors.forename: Robert
authors.initials: R
authors.lastname: George
authors.forename: Bruno
authors.initials: B
authors.lastname: Pichon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D016172:DNA Fingerprinting; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004739:England / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006784:Hospitals, Teaching; D006801:Humans; D015994:Incidence; D007223:Infant; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015242:Ofloxacin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D012703:Serotyping; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D055815:Young Adult; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase