The Clap Came Back: Multidrug-Resistant Gonorrhea

Among the many unintended consequences of the 30-year AIDS epidemic has been a profound change in status for other sexually transmitted diseases. It feels slightly bizarre, for anyone who came of age after HIV arrived, to realize that syphilis and gonorrhea and their ilk were once as profoundly dreaded as AIDS is now, so important that they were considered major threats to military campaigns and were the first treatment targets for the earliest antimicrobial drugs.

Judging by data released Friday by the Centers for Disease Control, it might be time to take them seriously once again.

(This is not to say that sexually transmitted diseases, STDs, are not a major public health problem, because they are: The CDC’s most recent national data, from 2009, describes the millions of new cases annually as a “hidden epidemic.” But I think it’s fair to say that when everyday people think of important public health problems, STDs are not high on their mental list.)

So, gonorrhea: The CDC said in its weekly bulletin that a US sentinel surveillance system has recorded rising incidence of gonorrhea that is resistant to the drug class cephalosporins. This would not be too remarkable, except that since the 1970s, gonorrhea has become resistant first to penicillins, then to tetracycline, and then to fluoroquinolones (such as Cipro).

Cephalosporins are the last remaining drugs that combine several key attributes vital for STD control: They are inexpensive and require only a single dose to be effective. That’s especially important when you consider that a lot of STD control in the United States occurs, not in a hospital or even in a primary-care office, but in publicly funded clinics operated by health departments. Having an antibiotic regimen that is cheap to buy, quick to dispense and doesn’t require return visits is vital — and, apparently, beginning to slip out of reach.

Multi-drug resistance in gonorrhea has been building for a while, but with those infections not on the radar of many outside the public health system, few people have noticed. Back in 2007, researchers from two hospitals in Japan warned in a letter to a CDC journal that they had seen four cases of gonorrhea that did not respond to cefixime, the oral cephalosporin that is the most-recommended treatment, but did respond to ceftriaxone, an injectable. In 2010, Norwegian physicians reported they had seen the same in two patients there. In January this year, Japanese researchers said they had identified a strain resistant to cefixime and ceftriaxone in a Japanese sex worker.

Now comes the CDC to say that, in a survey of gonorrhea (Neisseria gonorrhoeae) isolates from across the US between 2000 and 2010, the agency has spotted rising rates of decreasing susceptibility not only to cefixime, but also to ceftriaxone. The increases are small — from 0.2% of about 5,900 isolates per year in 2000 to 1.4%  in 2010 for cefixime, and from 0.1% in 2000 to 0.3% in 2010 for ceftriaxone — but that they are occurring at all should ring an alarm bell.

Breaking down their data, the increases are greater in the West, especially Hawaii and California, and in men who have sex with men rather than men who have sex exclusively with women. (Note, for clarification: MSM, in public-health parlance, doesn’t indicate only men who have sex exclusively with other men; it also includes men who think of themselves as heterosexual but opportunistically have sex with men as well.) This mirrors the pattern by which fluoroquinolone resistance spread in the 1990s.

The CDC, with its usual understatement, underlines in its report why this is important:

The potential emergence of gonococcal cephalosporin resistance is of particular concern because the U.S. gonorrhea control strategy relies upon effective antibiotic therapy. Previously, the emergence and spread of gonococcal antibiotic resistance in the United States was addressed by changing the recommended antibiotics for treatment. No other well-studied and effective antibiotic treatment options or combinations currently are available. The emergence of gonococcal cephalosporin resistance would substantially limit available treatment options.

And, an important footnote: Current gonorrhea treatment guidelines call for a simultaneous dose of azithromycin; that drug also takes care of any lurking chlamydia infection, and can be used to treat gonorrhea in people with cephalosporin allergy as well. But back in May, the CDC reported the first signs of rising azithromycin resistance too.

There’s an important backdrop to this development: At the same time that drugs to treat STDs may be on the verge of becoming more rare and expensive, STD-control funding in the US is becoming scarce as well. As I said, STD clinics are run by state health departments — and as the shutdown of the Team D foodborne effort in Minnesota has demonstrated, states are running out of money.

Here’s an example from San Francisco: The Bay Area Reporter said last fall that syphilis in the area had risen by 22 percent while funding for STD programs was cut by 25 percent. The National Coalition of STD Directors — the people who run STD clinics in states — last year released an analysis of what funding cuts are doing to STD control in the states, and the news was not good:

  • 69 percent of state programs took budget cuts from 2008 to 2009
  • 74 percent of HIV programs had budget cuts
  • 27 percent of state programs had staff layoffs
  • 20 percent of STD public-health worker jobs were eliminated.

For more about this, visit Michael Coston’s Avian Flu Diary, who got to this story days before I did. (Gotta get better about checking that RSS feed.)

Update: By bizarre serendipity, it turns out that there is a major STD meeting in Quebec this week, of the International Society for Sexually Transmitted Diseases Research. An abstract was released this morning about an isolate with significant cefixime and ceftriaxone resistance. It’s actually the Japanese research I linked to above (this paper, from January) but with additional genomic analysis. Here’s a Reuters story about it and here’s Mike Coston’s take. The abstract itself (p.76 of this very long pdf) contains very dramatic language (exclamation points original to them):

The first Neisseria gonorrhoeae strain (H041) worldwide that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, which is the last remaining option for empirical treatment of gonorrhoea, has now been identified! This is a large public health problem and the era of untreatable gonorrhoea may now have been initiated… [A] public health response plan (including sustainable clinical, microbiological and epidemiological components) for a global perspective is essential. Ultimately, new drugs are essential to develop for efficacious gonorrhoea treatment.

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