BHIVA: 60% increase in drug-resistant gonorrhoea amongst UK gay men last year, HIV-positive men disproportionately affected

Gay men fuelled a major rise in the prevalence of ciprofloxacin-resistant gonorrhoea in the United Kingdom last year, according to a new report from the Health Protection Agency (HPA), parts of which were presented to the British HIV Association (BHIVA) conference in London last week. Gonorrhoea isolates resistant to penicillin also increased significantly last year. The HPA report also reveals that one third of all gonorrhoea diagnosed in gay men in 2005 was seen in men who were already or newly diagnosed with HIV infection.

According to data presented by the HPA in July, the total number of new cases of gonorrhoea in the UK fell by 13% last year, from 22,350 in 2004 to 19,495 in 2005, which was the first time fewer than 20,000 new cases had been diagnosed since 1999.

Although this was characterised as “real progress” at the time by Professor Peter Borriello, the Director of the HPA's Centre for Infections, new data from the HPA's Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) suggest that this decrease was not seen across all UK subpopulations. Of particular concern is that HIV-positive and HIV-negative gay men are bucking the downwards trend.

GRASP, which began six years ago, is a Department of Health-funded collaboration between 24 laboratories and 26 sexual health clinics in England and Wales. As well as determining the annual antimicrobial susceptibility patterns of Neisseria gonorrhoeae - the bacterial cause of gonorrhoea - the programme is also able to characterise the demographic and behavioural characteristics of individuals with infections caused by antibiotic-resistant gonococci, which can then inform national treatment guidelines, as well as help target individual approaches to the treatment - and prevention - of the second most prevalent bacterial sexually transmitted infection (STI) in the UK.

During a three month period in 2005, a total of 1948 N. gonorrhoeae isolates were collected by the 24 GRASP collaborating laboratories and sent to the HPA's Sexually Transmitted Bacteria Reference Laboratory in Colindale, north London, for antimicrobial susceptibility testing. After excluding duplicates, 1823 isolates remained, of which 1030 (56.5%) were recovered successfully and confirmed as N. gonorrhoeae. To allow for the relatively low retrieval rate for some participating laboratories in 2005, the results were weighted. For comparison, previous years' results were also weighted and, thus, may be different to those reported previously.

Gonorrhoea prevalence rise in gay men

Although the majority of gonococcal infections were diagnosed in young women aged between 16-19 (43% of all females diagnosed with gonorrhoea) and in heterosexual men aged between 20-24 (42% of all males diagnosed with gonorrhoea), gay men were disproportionally affected by gonorrhoea, as were ethnic minorities, the latter accounting for 41% of the total gonorrhoea diagnoses in 2005 - a reduction from 42.3% in 2004.

In contrast, however, 2005 saw an increase in the proportion of gay men diagnosed with gonorrhoea, rising to 33% from 30.7% in 2004. In addition, gonorrhoea predominantly affected gay men aged between 25-34 (42% of all gay men diagnosed with gonorrhoea).

HIV-positive gay men were also disproportionately affected - one third of all gonorrhoea diagnosed in gay men in 2005 was seen in men who were already or newly diagnosed with HIV infection.

How is drug-resistant gonorrhoea being acquired?

Ciprofloxacin and other drugs from the fluoroquinolone class (oflxacin and levoflaxacin) have not been recommended as a first-line treatment for gonorrhoea in the UK since 2003. Although prescriptions have fallen from 69% in 2002 to 18.6% in 2005, almost one-in-five of all prescriptions to treat gonorrhoea in the UK in 2005 were for drugs from the fluoroquinolone class.

“A continued increase in the prevalence of ciprofloxacin resistance despite decreased usage of fluoroquinolones in England and Wales suggests that the use of ciprofloxacin in the treatment of gonorrhoea is not the only factor driving resistance,” note the authors of the report, who provide data showing that ciprofloxacin-resistant gonorrhoea is more likely to be acquired in people who have recently had sex abroad.

In fact, individuals of any gender or sexuality who had had sex abroad in the three months prior to being diagnosed were more than twice as likely to have acquired ciprofloxacin-resistant gonorrhoea (39% versus 18%) than those who only had sexual partners in the UK.

Notably, the prevalence of ciprofloxacin-resistant gonorrhoea in heterosexual men who had sex abroad was 50%, compared with a prevalence of 6% in those who did not. “With several countries in Asia having a prevalence of ciprofloxacin resistance greater than 90% and parts of Europe reaching greater than 50% the importation of new resistant strains into these sexual networks is inevitable,” says the report's authors.

Ciprofloxacin-resistant gonorrhoea

Overall, 21.7% of GRASP isolates were found to be resistant to ciprofloxacin in 2005, a significant increase from the 14% observed in 2004 (p<0.0005). In fact, the prevalence of ciprofloxacin-resistant gonorrhoea reached greater than 10% in almost every region of England and Wales for the first time.

Driving this increased prevalence were gay men, with a greater than 60% increase – from 26% in 2004 to 42% in 2005 (p<0.0005). In contrast, the prevalence of ciprofloxacin-resistant gonorrhoea remained stable in heterosexual men and women between 2004 and 2005.

Resistance to other gonorrhoea treatments

The most commonly administered treatments for gonorrhoea in 2005 are cefixime and ceftriaxone, together accounting for more than 70% of all prescriptions in individuals who are diagnosed with gonorrhoea as their only STI. Fortunately, no resistance to either was seen in 2005, despite the first cases of multidrug-resistant gonorrhoea being reported in the United States in 2003.

However, there was an increase seen in the prevalence of penicillin-resistant gonorrhoea, up from 11.4% in 2004 to 17.9% in 2005 (p=0.004). However, penicillin - usually ampicilin - was only prescribed in London and Wales in 2005.

Gonorrhoea and chlamydia

Overall, more than one-in-four (27%) individuals with gonorrhoea also were diagnosed with Chlamydia.

Tetracycline, in the form of doxycycline, is often prescribed to individuals with both gonorrhoea and chlamydia. In 2005, 43% of patients with both STIs were prescribed tetracycline. However, almost half of all gonorrhoea isolates demonstrated resistance to tetracycline, up slightly from 2004.

Azithromycin is also prescribed to individuals with both STIs. In 2005, 28% of individuals with both gonorrhoea and chlamydia were prescribed azithromycin. Although the national prevalence of azithromycin resistance is low, at 2%, it is significantly higher in the south east (7%), where 55% of all prescriptions for individuals with both gonorrhoea and chlamydia were for azithromycin.

Conclusions

The reports' authors conclude that “in 2005, we observed a further increase in the prevalence of ciprofloxacin resistance to 21.7% in England and Wales, which is comparable to the prevalence in Scotland (25%) and several countries in Europe.”

They note that “the prevalence of ciprofloxacin resistance in isolates from [gay men] (42%) rose significantly to over four times that of heterosexual males (12%) in 2005, and the prevalence amongst certain ethnic groups continues to rise.”

They also note some discrepancies in prescribing practice, and in particular the fact that 17% of gay and bisexual men were prescribed a fluoroquinolone in 2005, which they describe as “particularly worrying given their high prevalence of ciprofloxacin resistance.”

They conclude by saying that “the findings discussed in this report continue to highlight the changes in prevalence of antimicrobial resistance observed in England and Wales, alongside the continued constancy in the epidemiology of gonococcal infection in 2005.”

The striking differences seen in the prevalence of antimicrobial resistance seen across the regions and in different subpopulations “highlights the continued need for local and national monitoring of antimicrobial resistance so treatment strategies can remain responsive to its changing epidemiology.”