FLUOROQUINOLONE TREATMENT FAILURE IN GONORRHEA - EMERGENCE OF A NEISSERIA-GONORRHOEAE STRAIN WITH ENHANCED RESISTANCE TO FLUOROQUINOLONES

Background and Objectives: Although emergence of clinical isolates of Neisseria gonorrhoeae with decreased susceptibilities to fluoroquinolo nes and treatment failures in gonorrhea have been reported, there have been no clinical reports that fluoroquinolone treatments actually sel ect quinolone-resistant strains, nor have isolates that exhibited clin ically significant resistance been analyzed for resistance mechanisms, Goals: To report a case of fluoroquinolone treatment failure in gonor rhea and emergence of a posttreatment isolate with enhanced resistance to fluoroquinolones; and to study mechanisms of quinolone resistance in the isolates from this patient, Study Design: A patient with gonoco ccal urethritis treated with ofloxacin, 200 mg, three times daily for 5 days is described, Pretreatment and posttreatment isolates were test ed for minimum inhibitory concentrations (MICs) of antimicrobial agent s and analyzed for alterations in DNA gyrase and topoisomerase IV, The y were also examined for ofloxacin uptake, Results: Treatment failure with multiple doses of ofloxacin was observed in this case of gonorrhe a, The pretreatment isolate showed decreased susceptibilities to fluor oquinolones (IMC of ofloxacin, 1.0 mg/l; MIC of ciprofloxacin, 0.25 mg /l), and had amino acid changes of Ser-91 --> Phe in GyrA and Ser-87 - -> Ile in ParC. The posttreatment isolate exhibited an increase in res istance to fluoroquinolones (MIC of ofloxacin, 8.0 mg/l; MIC of ciprof loxacin, 1.0 mg/l), This isolate had identical alterations in GyrA and ParC, but exhibited significantly reduced uptake of ofloxacin. This i solate also showed a small decrease in susceptibilities to cephalospor ins. Conclusions: Alterations in DNA gyrase and topoisomerase IV confe r clinically significant resistance to fluoroquinolones in N. gonorrho eae strains, Treatment with multiple doses of fluoroquinolones is like ly to bring about selection of more fluoroquinolone-resistant strains of N, gonorrhoeae and to influence susceptibilities to cephalosporins.