How has this impacted on drug resistance in gonorrhoea? The researchers compared what are called Minimum Inhibitory Concentrations (MICs) of azithromycin, cefixime and ceftriaxone in samples sent to the Belgian and UK surveillance laboratories. MIC is the minimum amount of drug needed to stop the growth of the organism in the lab dish. A higher MIC indicates more drug resistance. In HIV drug level and resistance testing, a similar measure called the IC90 is used, which stands for 90% inhibitory concentration – it measures the amount of drug needed to reduce viral replication by 90%.
The researchers looked at gonorrhoea resistance in the UK at two time-points – 2011, before the switch to ceftriaxone/azithromycin – and 2014. They compared these to resistance in Belgium during the year 2013-14. They compared resistance rates in gay men with heterosexual women (heterosexual men were excluded because of the possibility some might be non-disclosing men who have sex with men).
The researchers’ original hypothesis was partly supported by the fact that in 2011 in the UK the MIC for all three drugs in the UK was higher in gay men than in women.
In the UK, the MIC for azithromycin was 0.25 milligrams per litre (mg/L) for gay men, while for women it was 0.06 mg/L. For ceftriaxone it was 0.008 mg/L for gay men and 0.002 mg/L in women (although this drug was not part of the recommended therapy before 2011, it was being used). For cefixime, the median MIC was the same in gay men and women (0.008 mg/L) but there was a minority of gay men (15%) who had more than a 15-fold higher MIC at 0.125 mg/L. This “bimodal distribution”, where a sizeable minority has considerably higher MICs than the rest, suggests that significant resistance may be developing.
In contrast in the data from Belgium, gathered two years later, there was little evidence of more resistance in gay men than in women. The median MIC for all three drugs was the same for both populations.
Interestingly, however, this was not because there was less resistance in Belgian gay men than in UK gay men – it was because there was more resistance in Belgian women. For instance, the MIC of azithromycin was 0.25 mg/L in both gay men and women in Belgium. And in the two cephalosporin drugs, it was in women, not gay men, that there were signs of bimodal distribution: for cefixime, over 20% of women had MICs of 0.125mg/L or more (eight times the median) compared with about 5% of gay men, and for ceftriaxone 39% of women had MICs over 0.03 mg/L (three times the median) compared with 18% of gay men.
Why might this be? One explanation is that the spread of drug resistance is connected to cases acquired in Asia, which is the part of the world with the highest prevalence of drug-resistant gonorrhoea. The initial reports of multidrug-resistant gonorrhoea in Europe suggested that they were more often acquired by heterosexuals abroad, even if they later spread to the gay population. This, combined with less treatment of asymptomatic gonorrhoea in gay men compared with the UK, might well lead to more resistance in women than gay men (though we must be careful here as the Belgian numbers – only 189 cases in women – are relatively small).
Finally, we come to the UK in 2014 after dual gonorrhoea therapy was adopted. Here we see promising signs that resistance might actually be decreasing in gay men. The median MIC of azithromycin in gay men, for instance, was 0.125mg/L – half of what it was three years earlier and only double, rather than four times, what it was in women. The MICs of cefixime were still slightly ‘right shifted’ in gay men versus women (i.e. there were slightly more high ones and slightly fewer low ones). But the MICs for ceftriaxone had completely changed and were now almost identical in gay men and women at 0.004 mg/dL.