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STD Prevention Conference: Drug-resistant Gonorrhea Rates Plummet in U.S.

Preliminary results announced at the U.S. 2014 STD Prevention Conference last week in Atlanta have shown that the proportion of cases of gonorrhea that are drug-resistant has fallen since 2011, with a sharp decline between 2012 and 2013. The fall is particularly marked among gay and other men who have sex with men (MSM), who had had the highest rates of drug-resistant gonorrhea.

[Produced in collaboration with Aidsmap]

The Centers for Disease Control and Prevention (CDC), which organized the conference, attributes the fall in gonorrhea resistance to 2 revisions of treatment guidelines in 2010 and 2012 that recommended more aggressive therapy and excluded an antibiotic the gonorrhea bacterium was rapidly becoming resistant to.

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

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

Gonorrhea is one of the most common sexually transmitted infections (STIs), and in higher-income countries it will affect about 1 in every 500-1000 men and women per year, though rates are much higher among men who have sex with men.

The infection 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 throughout the body that may cause a kind of arthritis, heart valve disease, pelvic inflammatory disease and infertility in women, epididymitis and infertility in men, and other complications.

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

Current treatment involved 1 of the "last resort" cephalosporin class of antibiotics plus 1 from another class. But between 2006 and 2010 in the U.S., the proportion of gonorrhea cases resistant to the then-standard cephalosporin drug cefixime (Suprax) increased from less than 0.1% to 1.4%.

At this time, the recommended treatment for gonorrhea was either a 400 mg oral dose of cefixime or an intramuscular dose of the related drug ceftriaxone. Because of concerns about resistance, the CDC changed its recommended gonorrhea 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 gonorrhea.

In the U.S., 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 gonorrhea first appeared in San Francisco, and in the Pacific region resistance declined from 3.0% in 2011 to 0.8% in 2013. In U.S. 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. With regard to the second drug, the proportion of gonorrhea resistant to azithromycin was 0.6% in 2013.

Alongside changes to the guidelines, clinics have improved their adherence to them. A poster from San Francisco at the STD conference showed that before the 2010 treatment revision, only 35% of clinics were treating gonorrhea as recommended, while 53% were "over-treating" -- 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 over-treating.

Meanwhile in the U.K., theBMJ blog noted that U.K.-defined cefixime resistance declined from 3.0% in 2011 to 1.6% in 2012, and from 17.0% to 7.0% in gay men. (NB: the U.K. definition of decreased susceptibility to cefixime is stricter than the U.S. definition: in the U.S. isolates are defined as resistant if they are present at cefixime plasma concentrations of 0.25 mg/L; in the U.K. isolates are defined as resistant at a minimum inhibitory concentration of 0.125 mg/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."

6/19/14

References

RD Kirkcaldy et al. Cephalosporin antimicrobial susceptibility of Neisseria gonorrhoeae in the United States, 2009-2013. U.S. STD Prevention Conference. Atlanta, June 9-12, 2014. Abstract 6A2.

J Newton et al. Adherence to gonorrhea treatment guidelines in San Francisco. US STD Prevention Conference. U.S. STD Prevention Conference. Atlanta, June 9-12, 2014. Abstract TP17.

L Goode. Gonorrhoea antimicrobial resistance: is UK antibiotic stewarding policy showing "some success"? BMJ Sexually Transmitted Infections blog. May 14, 2014.