Fluoroquinolone Treatment Failure in Gonorrhea

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Abstract
Although emergence of clinical isolates of Neisseria gonorrhoeae with decreased susceptibilities to fluoroquinolones and treatment failures in gonorrhea have been reported, there have been no clinical reports that fluoroquinolone treatments actually select quinolone-resistant strains, nor have isolates that exhibited clinically significant resistance been analyzed for resistance mechanisms. To report a case of fluoroquinolone treatment failure in gonorrhea and emergence of a posttreatment isolate with enhanced resistance to fluoroquinolones; and to study mechanisms of quinolone resistance in the isolates from this patient. A patient with gonococcal urethritis treated with ofloxacin, 200 mg, three times daily for 5 days is described. Pretreatment and posttreatment isolates were tested for minimum inhibitory concentrations (MICs) of antimicrobial agents and analyzed for alterations in DNA gyrase and topoisomerase IV. They were also examined for ofloxacin uptake. Treatment failure with multiple doses of ofloxacin was observed in this case of gonorrhea. The pretreatment isolate showed decreased susceptibilities to fluoroquinolones (MIC 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 resistance to fluoroquinolones (MIC of ofloxacin, 8.0 mg/l; MIC of ciprofloxacin, 1.0 mg/l). This isolate had identical alterations in GyrA and ParC, but exhibited significantly reduced uptake of ofloxacin. This isolate also showed a small decrease in susceptibilities to cephalosporins. Alterations in DNA gyrase and topoisomerase IV confer clinically significant resistance to fluoroquinolones in N. gonorrhoeae strains. Treatment with multiple doses of fluoroquinolones is likely to bring about selection of more fluoroquinolone-resistant strains of N. gonorrhoeae and to influence susceptibilities to cephalosporins.