This occurs in 10–20% of men treated for acute NGU. Its aetiology is multifactorial, an infectious agent being identified in < 50% cases. Mycoplasma genitaliumhas been identified in 20–40% and Chlamydia trachomatis in up to 20%. Ureaplasma urealyticummay also play a role. Trichomonas vaginalis is identified in up to 10% in populations where it is endemic.

Until recently azithromycin 1grm and doxycycline 100 mgs bd 7days were considered equally effective in treating men with acute NGU. However this is not the case. The microbiological failure rate of azithromycin 1 grm is 13 – 30% for M. genitalium and associated with 23S rRNA gene macrolide antimicrobial resistance mutations, which it can induce. This has also been demonstrated to occur women. A prolonged course of azithromycin for 5 days appears to be effective but not always, possibly because of prior macrolide resistance. Up to 20% of men with Chlamydia will also fail azithromycin 1grm but do not develop antimicrobial resistance mutations. Doxycycline 100 mgs bd 7 days has a failure rate > 50% with M. genitalium but probably < 5% with Chlamydia. It does not induce antimicrobial resistance mutations. Ofloxacin is probably effective against Chlamydia but has a high failure rate (∼50%) against M. genitalium and may result in quinolone antimicrobial resistance mutations. Moxifloxacin is effective against both micro-organisms.

Any treatment of recurrent/persistent NGU should cover M. genitaliumand T. vaginalis.As there is a significant risk of macrolide and quinolone resistance developing in M. genitalium, an infection for which there is no commercial test, the most sensible strategy would be to use doxyccline 100mgs bd 7dys as first line treatment and when using azithromycin to restrict prescribing to a five day course for both index cases and partners. The use of quinolones should be limited to moxifloxacin in those who fail azithromycin 5dys treatment.