The last line of therapeutic defense against gonorrhea is losing its strength, according to an editorial published February 9 in the The New England Journal of Medicine. With no new antibiotics effective against the sexually transmitted infection (STI) on the horizon, Gail Bolan, MD, of the U.S. Centers for Disease Control and her fellow authors are worried about an upswing in gonorrhea samples showing to be less susceptible to cephalosporins—the only class of drugs still widely effective against the bacteria.

“It is time to sound the alarm,” the authors state. “During the past 3 years, the wily gonococcus has become less susceptible to our last line of antimicrobial defense, threatening our ability to cure gonorrhea and prevent severe [associated illnesses].”

Gonorrhea, caused by the bacteria Neisseria gonorrhoeae, is the second most commonly reported communicable disease in the United States, with more than 600,000 new cases reported annually. Typically spread through sexual activity, it disproportionately affects vulnerable populations such as minorities who are marginalized because of their race, ethnicity or sexual orientation.

Untreated gonorrhea can cause serious and permanent health problems in both women and men. Gonorrhea is a common cause of pelvic inflammatory disease (PID), affecting roughly 750,000 women every year in the United States. It can be painful and may lead to internal abscesses—pus-filled “pockets” that are hard to cure. PID can also lead to fallopian tube damage and ultimately cause infertility or increase the risk of ectopic pregnancy. 

In men, gonorrhea can cause epididymitis, a painful condition of the ducts attached to the testicles that may lead to infertility if left untreated.

Gonorrhea can also spread to the blood or joints, which can be life threatening. Additionally, gonorrhea can make it easier to either transmit or become infected with HIV.

Over the past 40 years, the rate of resistance to multiple gonorrhea treatments has sharply increased, rendering historically effective antibiotics like sulfonamides, penicillin, tetracycline and fluoroquinolones largely ineffective. In 2009 alone, more than 23 percent of gonorrhea samples tested by the CDC were highly resistant to at least one or some combination of these drugs. 

To effectively treat gonorrhea, all that’s left is a cephalosporin—usually either oral Suprax (cefixime) or injectable Rocephin (ceftriaxone)—combined with either Zithromax (azithromycin) or doxycycline. No other antibiotics, either commercially available or in development, have therapeutic activity against the infection.

What concerns Bolan and her colleagues is the upward trend in tested gonorrhea samples—about 6,000 samples collected annually for 10 years through the CDC’s Gonococcal Isolate Surveillance Project—showing decreased susceptibility to the cephalosporins.

In 2006, 0.1 percent of gonorrhea samples tested for drug resistance were found to be less sensitive to the drugs. By the end of the first half of 2011, according to data reported last year in the CDC’s Morbidity and Mortality Weekly Report (MMWR), 1.7 percent of gonorrhea samples tested were less susceptible to cephalosporins. In other words, the rate of gonorrhea with reduced susceptibility to the last remaining class of antibiotics is now 17 times higher than it was five years ago.

The increases, Bolan and her colleagues note, were most pronounced in the western United States (up to 3.6 percent) and among men who have sex with men (up to 4.7 percent).

“These geographic and demographic patterns are worrisome because they mirror those observed during the emergence of fluoroquinolone-resistant [gonorrhea],” the authors note, referring to a class of drugs that was written off as being useful for drug-resistant gonorrhea in 2007.

Though no gonorrhea samples tested in the United States have been found to be completely resistant to cephalosporin therapy—this has been documented only once, in 2009, involving a man with gonorrhea in Kyoto, Japan—Bolan and her colleagues remain concerned about the dulled efficacy of the drugs in a growing number of American residents.  While it is possible that higher doses of available cephaloporins might work against gonorrhea strains with reduced susceptibility to the drugs, the authors note that it is not yet known whether upping Suprax or Rocephin concentrations will prove successful.

“Although [these] cephalosporins are still highly effective against most U.S. gonorrhea strains, investing in rebuilding our defenses against gonococcal infections now, with involvement of the health care, public health, and research communities, is paramount if we are to control the spread and reduce the consequences of cephalosporin-resistant strains,” the authors write.

“For the long term, a gonococcal vaccine remains key to prevention and control, but that is a distant goal,” the authors say. “The immediate priority is replenishing the drug pipeline to treat gonococcal infections.”

“There is much to do, and the threat of untreatable gonorrhea is emerging rapidly.”