Treatment of gonorrhoea has historically been delivered by a single dose of a highly effective antimicrobial agent, to which resistance is not documented, to aid compliance and break transmission. Resistance in Neisseria gonorrhoeae compromises this approach and occurs both by acquisition of plasmids or chromosomal DNA from other bacteria or Neisseria spp or by selection of mutants resulting from misuse or overuse of antimicrobial agents, such as long term use of a single agent.
Resistance to ciprofloxacin, a fluoroquinolone, illustrates the effect of both misuse of earlier generations of quinolones and of suboptimal doses, as well as overuse. Quinolones target the DNA gyrase and topoisomerase enzymes that are responsible for DNA supercoiling and any interference with this process is bactericidal. Ciprofloxacin was widely used, often at low doses because of its high efficacy, but resistance emerged quickly resulting from selection of mutants, altering the target site and giving increasing drifts to resistance. Azithromycin, a macrolide which binds to 23S rRNA component of the 50S ribosome and interferes with protein synthesis, is effective against multiple STIs and therefore the selective pressure for resistance has been considerable. Although low-level resistance emerged quickly, high-level resistance in N. gonorrhoeae, resulting from a single point mutation in the peptidyltransferase loop of domain V of the 23S rRNA gene, was only reported in recent years and threatens to compromise its use. Sporadic use of spectinomycin selected for high-level resistance in a single step, which appears clonal and has not spread widely. Limited use of the aminoglycoside, gentamicin, for which the efficacy data is weak, appears to remain clinically active.
In this era of multi-drug resistant gonorrhoea it is imperative that the selective pressure exerted by continual use of a single agent is understood and clinical practise modified, where necessary, to prevent gonorrhoea becoming untreatable.
- Antimicrobial Resistance
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