Gonorrhoea - the drugs don't work

By Peter Greenhouse
Consultant in sexual health. Bristol

image captionAny new drug 'must work in a single dose'

The prospect of untreatable gonorrhoea has provoked alarm around the world, and there are no new classes of antibiotics in development.

In this week's Scrubbing Up column, Peter Greenhouse of the British Association for Sexual Health & HIV (BASHH) argues financial incentives will be needed to seek a new cure.

We're all familiar with stories about hospital-acquired superbugs - MRSA and the like - becoming more difficult to treat, and are fearful whenever an elderly relative needs in-patient care.

But now, with a report from Japan of multidrug-resistant gonorrhoea, and the festive season in full swing, the spectre of an untreatable sexually transmitted infection looms over us - and our teenagers - for the first time in a generation.

Since penicillin was first used to treat gonorrhoea in 1943, the organism has gradually developed novel means of evading control by each new antibiotic.

For treatment to be effective and practical, it must be simple to administer by mouth as a single dose, achieving a high enough concentration of the drug in the body to treat over 95% of infections.

If the efficacy drops below this figure, the treatment has to change.

But over-the-counter medication, widely available in Africa and Asia means people self-medicate often taking the wrong dose at the wrong time, perhaps with alcohol which further reduces the concentration of the drug.

Strains of gonorrhoea which need a higher concentration of a drug to kill them become the dominant ones. This keeps happening until the drug no longer works.

If gonorrhoea becomes untreatable in these countries, the effect on increasing HIV rates could be disastrous - because any sexually transmitted infection which causes inflammation and discharge increases the transmission efficiency of HIV.

On average, transmission is five times more likely to occur if gonorrhoea or chlamydia are present

'Early-warning system'

In the UK, the situation is monitored annually by the Health Protection Agency, providing an essential early warning of drugs which are about to fail, allowing a switch of treatment regimes before they become ineffective.

Ciprofloxacin - a drug introduced in the mid-1980s after the failure of penicillin - lasted in the UK until 2002: This may have survived longer because of the world-wide drop in gonorrhoea rates following the arrival of HIV, when fear of the new virus meant people practised safe-sex and changed partners less.

But it had already failed in the Far East, some four years previously.

Resistance develops faster in homosexual men, not just because of high rates of partner change.

Most people don't realise that oral sex is an important route of transmission for gonorrhoea, which doesn't usually cause a sore throat.

Gonorrhoea mixes with organisms which live naturally in the rectum and throat, picking up new types of antibiotic resistance from these bugs.

The next drug, cefixime, was introduced around 2003, but lasted only six years in the UK before resistance rose suddenly, hitting 25% among homosexual men.

Now, their only treatment option is an injection (Ceftriaxone) which has recently failed in Japan.

Reward needed?

But why isn't there a new drug in development?

Since the mid-1980s and the arrival of HIV, almost all drug company research has focused on antiviral medicines, with no new classes of antibiotics being produced since the 1970s, and none on the horizon.

There's a desperate world-wide demand for new antibiotics, yet the drug companies aren't interested, so how could we motivate them?

Financial reality dictates research policy: Why bother to develop a drug which works in one day or one week, when you could make one - such as an antidepressant, statin or antiviral - which must be taken for months, for years, or for life?

So either the new drug(s) would have to be seriously expensive, precluding their use where they would be most needed, or there would have to be a substantial reward offered, perhaps of a magnitude only affordable by a fund such as the Gates Foundation.

Yet even if novel drugs could be produced, the biology and transmission dynamics of gonorrhoea mean that each new regime would probably fail within five-to-ten years of its introduction, unless we use multi-dose, multi-drug regimes, which will be less practical and more expensive to administer.

Faced with this, what can we do to stay sexually healthy? Stay at home, or take your partner to the New Year party: If that's not possible, use condoms - meticulously, and visit your local clinic - frequently.

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