A report in today’s MMWR, the weekly public health journal published by the Centers for Disease Control and Prevention (CDC), shows why gonorrhea prevention and control is increasingly becoming like the Black Knight’s fight with King Arthur in the movie Monty Python and the Holy Grail.
What was comedy on the silver screen, however, plays as tragedy for public health.
In a scene early in the Holy Grail, the Black Knight and King Arthur engage in a pitched swordfight. The king then lands a blow that severs the knight’s left arm.
“Now stand aside, worthy adversary!” Arthur commands.
“’Tis but a scratch!” the knight retorts, resuming his attack.
Arthur then chops off the knight’s other arm. “Victory is mine!” the king declares.
“Just a flesh wound!” the now-armless knight counters, kicking the king.
Next to go is the knight’s left leg, leaving the knight hopping about, insulting and head-butting the king.
Arthur then lops off the knight’s other leg and walks off, leaving the knight – now just a torso – on the ground, continuing to taunt the king.
The comedy of the scene derives from the knight’s smugness and perseverance, even as he loses limb after limb.
The tragedy in our public health fight against gonorrhea is that we are increasingly becoming like the Black Knight, with barely a leg to stand on in treating a disease that’s the second most commonly reported infection in the United States, with just over 300,000 cases in 2009. Gonorrhea is associated with pelvic inflammatory disease in women, which can lead to infertility, ectopic pregnancy and chronic pelvic pain, and with epididymitis in men, which can lead to infertility. Gonorrhea has also been linked to higher risks of HIV acquisition and transmission.
In the latest evidence of our Black Knight-hood in the fight against gonorrhea, today’s MMWR report, which I co-authored, describes five cases of gonorrhea in San Diego County, California that occurred during a three-month period in 2009.
Those cases are important because laboratory tests, conducted by a CDC surveillance program, showed that the cases had markedly reduced susceptibilities to an antibiotic called azithromycin. That means that azithromycin would likely be less effective – and perhaps ineffective – in treating those cases.
Those five cases – all of which occurred in HIV-negative men who have sex with men (MSM) – represent the most cases with markedly reduced azithromycin susceptibilities ever identified from a single CDC surveillance site in such a short period. Since then, four additional cases have been identified. Similar cases have been reported previously in other countries.
Importantly, none of the men were treated with azithromycin, which is not a CDC-recommended treatment for gonorrhea, precisely because of concerns about resistance. But azithromycin is sometimes used to treat gonorrhea in people who have severe allergies to third-generation cephalosporins, the class of antibiotics that is the sole remaining cornerstone of gonorrhea treatment. All of the men were treated – appropriately, based on CDC guidelines – with ceftriaxone, which is a third-generation cephalosporin.
Treatment options for gonorrhea are so limited because, in the past sixty years, the gonococcus (the bacterium that causes gonorrhea) has proved exceptionally adept at acquiring resistance to antibiotics. Indeed, it’s done to antibiotics what Arthur did to the knight’s limbs: lopped them off the list of effective treatments for gonorrhea, one by one.
It started with sulfonamides, introduced in the 1930s and useless by the 1940s. Next was penicillin, 48,000 units of which constituted effective treatment in the 1940s. By the 1970s, the required dose had skyrocketed to 4.8 million units. By 1989 penicillin was no longer effective at all in most cases.
Tetracyclines were also effective treatment for gonorrhea – until resistance emerged in the 1970s and 1980s. Now, because up to 26 percent of cases in U.S. cities are resistant to tetracyclines, tetracyclines are no longer on CDC’s list of recommended treatments for gonorrhea.
Fluoroquinolones, like ciprofloxacin, were next. CDC began recommending ciprofloxacin as a gonorrhea treatment in 1989. By the early 2000s, however, resistance had developed among cases in California and Hawaii and among MSM, prompting CDC to stop recommending ciprofloxacin in those populations. In 2007, CDC stopped recommending it throughout the United States.
And now we’re left with that sole remaining class, the third-generation cephalosporins.
What needs to be done?
First, we should expand efforts to track antibiotic resistance in gonorrhea, including development and use of advanced molecular techniques.
Second, we should develop rapid tests that can determine which antibiotics could be used to treat a case of gonorrhea. That could increase the number of antibiotic options potentially available to treat gonorrhea and decrease the likelihood of resistance developing to any one particular antibiotic.
Third, to forestall the emergence of resistance, we should use antibiotics more judiciously.
Fourth, we should encourage the development of new drugs for gonorrhea and other infections. One clinical trial of new drugs for gonorrhea is underway. More are needed. The Infectious Disease Society of America’s “10 by ‘20” program, which advocates for the development of ten new antibiotics by 2020, is on the right track.
It’s time to start taking gonorrhea prevention and control more seriously, before we end up – like the Black Knight – without a leg to stand on.
 There are limited data regarding the correlation between laboratory evidence of reduced susceptibility to azithromycin in gonorrhea cases and clinical response to treatment with azithromycin.
 New guidelines from CDC, released in December 2010, now recommend dual treatment for every case of gonorrhea. Details of recommended treatment regimens, which include a third-generation cephalosporin and either azithromycin or doxycyline, are available here.