Drug-resistant gonorrhoea rates plummet in US

Preliminary results announced at the US 2014 STD Prevention Conference in Atlanta have shown that the proportion of cases of gonorrhoea that are drug-resistant has fallen since 2011, with a sharp decline between 2012 and 2013.

The fall is particularly marked in gay and other men who have sex with men (MSM), who had had the highest rates of drug-resistant gonorrhoea.

The Centers for Disease Control and Prevention (CDC), who organise the conference, attribute the fall in gonorrhoea resistance to two revisions of treatment guidelines in 2010 and 2012 that recommended more aggressive therapy and excluded an antibiotic the gonorrhoea bacterium was rapidly becoming resistant to.

In the UK, a blog in the British Medical Journal (BMJ) comments that the prevalence of drug-resistant gonorrhoea is also in decline in the UK, and that new drugs are in the pipeline to treat it.

However, both the CDC and the BMJ remind readers that the gonorrhoea organism has ended up developing resistance to every class of antibiotic used against it. “The potential that gonorrhoea could become untreatable remains real,” the CDC comments, urging both new treatment options and improved prevention efforts.

Gonorrhoea is one of the most common sexually transmitted infections (STIs) and in higher-income countries will affect about one in every 500-1000 men and women a year, though rates are much higher in MSM.

It causes urethral pain and discharge in men and vaginal discharge and pelvic pain in women, though about 50% of women experience no symptoms. It also causes rectal pain and discharge in people who have had receptive anal sex, and is also common in the throat. Initial symptoms are usually self-limiting, but up to 3% of cases left untreated cause inflammatory disease in the rest of the body that may cause a kind of arthritis, heart valve disease, inflammatory pelvic disease and infertility in women, epididymitis and infertility in men, and other complications.

After antibiotics were discovered, gonorrhoea was first treated with penicillin and then the tetracycline and fluoroquinolone classes of antibiotics, but developed resistance to them.

Current treatment involved one of the ‘last resort’ cephalosporin class of antibiotics plus one from another class. But between 2006 and 2010 in the US, the proportion of gonorrhoea resistant to the then-standard cephalosporin drug cefixime increased from less than 0.1% to 1.4%.

At this time the recommended treatment for gonorrhoea was either a 400mg oral dose of cefixime, or an intramuscular dose of the related drug ceftriaxone. Because of concern about resistance, the CDC changed its recommended gonorrhoea regimen in December 2010. It recommended a double dose of intramuscular ceftriaxone or, as an alternative, cefixime, plus another antibiotic, azithromycin or doxycycline.

Resistance remained high in 2011, so the CDC made a second revision in August 2012, recommending the use of ceftriaxone, along with a second antibiotic, as the only first-line recommended treatment.

This, plus improved adherence of STI clinics to the regimens, appears to have resulted in a considerable drop in multidrug-resistant gonorrhoea.

In the US, the proportion of cases that were resistant to cefixime declined from 1.4% in 2011 to 0.9% in 2012 and 0.4% in 2013. Cefixime-resistant gonorrhoea first appeared in San Francisco, and in the Pacific region resistance declined from 3.0% in 2011 to 0.8% in 2013. In US gay men it declined from 4.0% in 2010 to 0.6% in 2013.

There has been an almost complete disappearance of ceftriaxone resistance, which in 2011 stood at 0.38% of cases in general and 0.95% in gay men; in 2013 it was 0.03% generally and 0.07% in gay men.

In respect of the second drug, the proportion of gonorrhoea resistant to azithromycin was 0.6% in 2013.

Alongside changes to the guidelines has been improved adherence to the guidelines by clinics. A poster from San Francisco at the STD conference showed that before the 2010 treatment revision, only 35% of clinics were treating gonorrhoea as recommended while 53% were ‘overtreating’: they were prescribing antibiotics in excess of the CDC recommendations, which is one cause of resistance. After the institution of the second set of guidelines in August 2012, 82% were prescribing in accordance with the guidelines and only 6% were overtreating.

Meanwhile in the UK, the blog in the British Medical Journal notes that UK-defined cefixime resistance declined from 3% in 2011 to 1.6% in 2012 and from 17% to 7% in gay men. (NB: the UK definition of decreased susceptibility to cefixime is stricter than the US definition: in the US isolates are defined as resistant if they are present at cefixime plasma concentrations of 0.25 mg/L; in the UK isolates are defined as resistant at a minimum inhibitory concentration of 0.125mg/L.)

The BMJ blog hails new antibiotics in the pipeline such as solithromycin or AZD0914, but warns that the reprieve given by the more careful use of current antibiotics “could be short lived”.

Kirkcaldy Robert D et al. Cephalosporin antimicrobial susceptibility of Neisseria gonorrhoeae in the United States, 2009-2013. US STD Prevention Conference, abstract 6A2. 2014.

Newton J et al. Adherence to gonorrhea treatment guidelines in San Francisco. US STD Prevention Conference, abstract TP17. 2014.

Goode L Gonorrhoea antimicrobial resistance: is UK antibiotic stewarding policy showing “some success”? Sexually Transmitted Infections blog. See http://blogs.bmj.com/sti/2014/05/14/gonorrhoea-antimicrobial-resistance-is-uk-antibiotic-stewarding-policy-shows-some-success/