title: Selection of a gyrA mutation and treatment failure with gatifloxacin in a patient with Streptococcus pneumoniae with a preexisting parC mutation.
abstract: An 81-year-old woman had pneumonia caused by Streptococcus pneumoniae (levofloxacin Etest minimum inhibitory concentration [MIC] 1.5 microg/ml) and was treated with intravenous gatifloxacin 200 mg/day. After 3 days of therapy, repeat sputum cultures were positive for S. pneumoniae, which was resistant to levofloxacin (Etest MIC > 32 microg/ml). The isolate obtained before therapy showed a preexisting parC mutation of aspartic acid-83 to asparagine (Asp83-->Asn), and the isolate obtained during therapy showed an acquired gyrA mutation from serine-81 to phenylalanine (Ser81-->Phe) and a second parC mutation from lysine-137 to Asn (Lys137-->Asn). Both isolates were the same strain, as determined with pulsed-field gel electrophoresis. This case demonstrates the potential for resistance to emerge during 8-methoxy fluoroquinolone therapy for fluoroquinolone-susceptible S. pneumoniae with a preexisting parC mutation. Additional clinical failures with a fluoroquinolone may occur unless these first-step parC mutants can be identified to assist clinicians in selecting appropriate antimicrobial therapy.
authors.affiliation: Department of Pharmacy Practice, Purdue University School of Pharmacy and Pharmaceutical Sciences, Indianapolis, Indiana 43202-2879, USA. mkays@iupui.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: Megan A
authors.initials: MA
authors.lastname: Reimann
authors.forename: Judi
authors.initials: J
authors.lastname: Jacobi
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Denys
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Wack
mesh_terms: D000369:Aged, 80 and over; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D000077734:Gatifloxacin; D006801:Humans; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D017211:Treatment Failure
chemical_list: D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D000077734:Gatifloxacin