STD Awareness: Gonorrhea’s Ever-Growing Resistance to Antibiotics

Gonococci, the bacteria that cause gonorrhea.

Ever since the advent of effective antibacterial therapies less than a century ago, humans with access to these drugs can easily cure gonorrhea. Most of us in the developed world have forgotten that this disease was once a leading cause of infertility in women and blindness in babies — sulfa drugs and antibiotics not only erased these infections from our bodies, they also erased memories of gonorrhea’s dangers from our collective consciousness.

There are two drugs remaining to treat gonorrhea, and resistance to them is climbing higher as the years march on.

Unfortunately, thanks to their talent for genetic gymnastics, gonococci, the bacteria that cause gonorrhea, have been evolving resistance to every drug we’ve thrown at them — to tetracycline, to penicillin, and more recently to fluoroquinolones. One class of antibiotics remains to treat gonorrhea: cephalosporins. In 2013, Centers for Disease Control and Prevention (CDC) Director Tom Frieden warned that we could find ourselves in a “post-antibiotic era” – unless we take precautions. And, just two weeks ago, the latest study from the CDC’s Gonococcal Isolate Surveillance Project sounded the alarm that the post-antibiotic era is drawing ever closer, especially when it comes to gonorrhea.

Azithromycin and ceftriaxone, the two drugs that are used in combination to deliver a one-two punch to invading gonococci, are the best antibiotics remaining in our arsenal. Azithromycin is taken by mouth, while ceftriaxone is administered by a shot, and when taken together they team up to target different weak points in gonococci’s armor. Azithromycin interferes with the bacteria’s ability to make proteins, shutting the cells down, while ceftriaxone causes the cell wall to fall apart. However, the gonococci can acquire resistance. For example, in the case of azithromycin, a resistant bacterium can spit out the drug before it has a chance to kill it, or it can change the shape of its protein-making apparatus such that the drug can’t attach to it. 

We’ve anticipated for a while now that the azithromycin/ceftriaxone combo would only hold up for so long, and the new data from the CDC give credence to this prediction. In a nutshell, the CDC reports that resistance to cefixime has increased eightfold between 2006 and 2014 — and cefixime hasn’t been recommended for gonorrhea since 2012 due to this rising resistance. Luckily, cefixime’s close cousin, ceftriaxone, didn’t see as dramatic an increase in resistance. Resistance to azithromycin, however, more than quadrupled between 2013 and 2014 — and Arizona was among the sites with the largest number of resistant samples.

The good news is that only 1.4 percent of samples were resistant to azithromycin in 2014, compared to more than 25 percent that were resistant to tetracycline, a type of antibiotic that is no longer recommended for gonorrhea. So, while today’s gonorrhea drugs aren’t expected to remain effective forever, we’re safe for now. However, for reasons explained below, it’s better to focus on the overall upward trajectory of gonococci’s growing resistance to these drugs, rather than the seemingly diminutive percentages of samples that exhibit this resistance.

The Gonococcal Isolate Surveillance Project, or GISP, was established in 1986 to monitor gonorrhea for trends in antimicrobial resistance by taking samples from gonorrhea-infected men in 27 cities across the country, from Honolulu to Boston. The CDC’s recommendations for treatment of gonorrhea are based on GISP data, which also allow us to identify risk groups and understand where resistance is coming from and what direction it might be traveling.

However, GISP does not take samples from a representative cross-section of the population, and the Western region of the United States is overrepresented. This oversampling was a deliberate choice by GISP’s designers, as history has shown that antibiotic resistance tends to emerge in the West and spread eastward. Focusing on the West allows disease detectives to catch drug resistance as it emerges. GISP sites are located in large cities in fewer than half of the states in the country, and many rural states are not currently included.This over- and undersampling could lead to an underestimation of antibiotic-resistance if there are highly resistant strains running amok in cities where no GISP sites are located — or it could overestimate prevalence if its sites collect a disproportionately high number of resistant isolates.

So, rather than focusing on what percentage of GISP samples are resistant to the last remaining drugs used to treat gonorrhea, we should be zooming out to look at the bigger pictures — and that is that resistance is on the rise, hovering ever higher as the years march on. See, for example, the huge increase in azithromycin-resistant samples collected by GISP in 2014.

Percentage of urethral Neisseria gonorrhoeae isolates with reduced azithromycin susceptibility,* by region and year — Gonococcal Isolate Surveillance Project, United States, 2000–2014

Percentage of gonococci samples collected by GISP with reduced susceptibility to azithromycin, by region and year, United States, 2000–2014

Growing drug resistance looms in the constantly shifting genetic material of the wily gonococci as these bacteria stalk the world’s sexual networks. Azithromycin and ceftriaxone are still effective treatments for now, but we can’t take them for granted and we can’t be complacent. Sexually active people should use latex barriers, such as condoms and dental dams, during vaginal, anal, and oral sex. They should also keep up-to-date on their STD status by receiving screening and treatment for gonorrhea. You can drop by to pick up condoms, or make an appointment to be tested (you’ll just need to provide a urine sample), at any Planned Parenthood health center.

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