It was simple to treat gonorrhea in the first half of the twentieth century. A single dose of penicillin cured most cases of the sexually transmitted infection (STI). Unfortunately, many bacteria have adapted in the decades since antibiotics were introduced, developing resistance to these powerful medications. Now there are signs that gonorrhea, an infection that could increase risk of HIV transmission or acquisition, is becoming even more resilient.
Emerging Resistance to Azithromycin
Resistance to an antibiotic develops when a drug "has lost its ability to effectively control or kill bacterial growth" and bacteria "continue to multiply," notes the Tufts University-based Alliance for the Prudent Use of Antibiotics. Neisseria gonorrhoeae, the bacteria that causes gonorrhea, first developed resistance to penicillin. It eventually became resistant to tetracycline and fluoroquinolones.
Now gonorrhea resistance to azithromycin is slowly emerging, according to findings released in the July 21 issue of Morbidity and Mortality Weekly Report (MMWR). Azithromycin is an antibiotic used to treat various bacterial infections, including pneumonia, strep throat and pink eye. It is one of two drugs (ceftriaxone is the other) that are recommended together as a first-line treatment for gonorrhea by the U.S. Centers for Disease Control and Prevention (CDC).
Gonorrhea is the second more-common STI transmitted during vaginal, oral and anal sex. It can cause infections in the genitals, rectum and throat. An infection can usually be detected from a urine sample or swab samples of the infected area.
The number of new U.S. cases of gonorrhea declined rapidly from 1975 until the late '90s, then reached an all-time low in 2009, according to the CDC . This trend has since reversed and the number of new cases is increasing. About 350,000 new cases were reported in 2014. According to the CDC, this is less than half of the more than 800,000 new infections estimated to occur each year.
Gonorrhea can cause serious health concerns if it remains untreated, especially for women. Those consequences include chronic pelvic pain and potentially infertility. In women it can cause a rare and life-threatening ectopic pregnancy, which is when a fertilized egg attaches itself outside the uterus. There is also a risk of an untreated infection spreading beyond the genitals to the skin, bloodstream, heart, joints or membranes protecting the brain and spinal cord. This condition is known as disseminated gonococcal infection (DGI), and it happens in 0.4%-3% of untreated cases. DGI is also treated with antibiotics.
The CDC recommends that gonorrhea be treated with a combination of two antibiotics: an oral dose of azithromycin and single shot of ceftriaxone. No treatment failures have been reported in the U.S. -- but at least one case of treatment failure has been recorded in the United Kingdom.
Treatment Failure in the UK
In June, the New England Journal of Medicine reported a case of throat gonorrhea that was not remedied by the standard regimen of azithromycin and ceftriaxone. The infection continued for over three months and was finally cured by a second, double dose. "Higher-dose treatments are not suitable for all patients, and resistance to higher doses is likely to develop eventually," Gwenda Hughes, section head of STIs at Public Health England, told Health Day.
MMWR data show that "[t]he percentage of gonorrhea isolates with decreased susceptibility to azithromycin, an indicator of emerging resistance, increased more than 300 percent between 2013 and 2014." The actual numbers are deceptively modest. Around 5000 gonorrhea samples -- known as "isolates" -- were collected in 2014. Only 2.5% demonstrated resistance to azithromycin compared with 0.6% in 2013. Since the CDC began monitoring gonorrhea antibiotic resistance in 1986, it has collected thousands samples for its Gonococcal Isolate Surveillance Project.
"The confluence of emerging drug resistance and very limited alternative options for treatment creates a perfect storm for future gonorrhea treatment failure in the U.S.," said Jonathan Mermin, M.D., director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Disease and Tuberculosis Prevention in a press release on the MMWR findings. "History shows us that bacteria will find a way to outlast the antibiotics we're using to treat it. We are running just one step ahead in order to preserve the remaining treatment option for as long as possible."
Gonorrhea and HIV
A well-documented body of research has demonstrated the association between STIs and HIV. Syphilis, herpes and gonorrhea increase the likelihood of both HIV acquisition and transmission. This risk is even greater among gay, bisexual and other men who have sex with men (MSM), who are disproportionately impacted by STIs. African-American and Latino/x MSM -- especially those with lower incomes or facing economic, housing or health care barriers -- are particularly vulnerable to poor health outcomes.
"Rectal gonorrhea is a definite risk marker in becoming more susceptible for HIV seroconversion," David P. Holland, M.D., M.H.S., chief clinical officer for the Communicable Disease Prevention Branch of the Fulton County Health Services Department and assistant professor at the Emory University School of Medicine told TheBody.com.
"STIs ... can injure the delicate tissue on or inside the anus, genitals, mouth and throat. STIs can also cause inflammation. The sores (sometimes painless) or lesions associated with STIs in these tissues can provide a point of entry for HIV (and other germs) into the body," noted Canadian AIDS Treatment Information Exchange's Sean R. Hosein in October 2013.
Gonorrhea inflammation can also increase the risk of transmitting HIV to a partner. According to the CDC, "HIV-infected persons are more likely to shed HIV when they have urethritis or a genital ulcer."
Drug resistance problems go far beyond antibiotic resistance. Antimicrobial resistance, defined by the World Health Organization (WHO) as "a broader term, encompassing resistance to drugs to treat infections caused by other microbes ... such as parasites (e.g., malaria), viruses (e.g., HIV) and fungi (e.g., Candida)," has become a global crisis.
The problem is so serious that it "threatens the achievements of modern medicine," WHO emphasized in 2014 report "Antimicrobial Resistance: Global Report on Surveillance." "A post-antibiotic era -- in which common infections and minor injuries can kill -- far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century," it added.
Each year at least two million people in the United States become infected with bacteria that are resistant to antibiotics, reports the CDC. The primary cause of resistance is the widespread and improper use of antibiotics. Doctors have been overprescribing them for many years.
"It's important to use antibiotics only when they are needed, when there is a real need for treatment of a bacterial infection," Holland cautioned when speaking with TheBody.com. "Treatment for things that are likely viral -- such as an upper respiratory infection -- is a very bad idea."
Rod McCullom has written and produced for ABC News and NBC, Scientific American, The Atlantic, The Nation, Ebony, Poz and many others. Rod is a Knight Science Journalism Fellow at the Massachusetts Institute of Technology.