Gonorrhea is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. It is spread through unprotected oral, anal, or vaginal sex with an infected partner. Gonorrhea can infect the genitals, rectum, and throat. In recent years, gonorrhea has become much harder to treat due to increasing antibiotic resistance. Some strains are now completely resistant to many antibiotics that were once highly effective. This makes gonorrhea more difficult to cure and increases the risk of severe complications.
What is gonorrhea?
Gonorrhea is a common bacterial STI caused by Neisseria gonorrhoeae. The Centers for Disease Control and Prevention (CDC) estimates that in 2018, over 580,000 cases of gonorrhea were reported in the United States. However, the actual number of infections is likely much higher, as gonorrhea often has no symptoms and goes undiagnosed.
The Neisseria gonorrhoeae bacteria can infect mucous membranes including the:
– Urethra
– Cervix
– Rectum
– Pharynx
– Eyes
Gonorrhea spreads through unprotected oral, vaginal, or anal sex with an infected partner. It can also spread from an untreated mother to her baby during childbirth.
Symptoms
Many people with gonorrhea, especially women, do not have any symptoms. When present, symptoms of gonorrhea infection include:
– Thick, cloudy, or bloody discharge from the penis or vagina
– Pain or burning sensation when urinating
– Swelling of the testicles
– Painful or swollen abdomen
– Anal itching, bleeding, discharge, or painful bowel movements
– Sore throat (pharyngeal infection)
Complications
If left untreated, gonorrhea can lead to severe complications in both men and women:
– Pelvic inflammatory disease (PID) – infection of the uterus and fallopian tubes in women, which can cause scarring and infertility
– Epididymitis – inflammation of the coiled tube (epididymis) at the back of the testicles, causing pain and possibly infertility in men
– Disseminated gonococcal infection (DGI) – the spread of bacteria into the bloodstream, causing fever, rash, and arthritis
– Increased risk of HIV transmission
– Infant eye infections (ophthalmia neonatorum) that can lead to blindness if untreated
Why is gonorrhea becoming harder to treat?
Over the past few decades, gonorrhea has become much more resistant to antibiotics once commonly used to reliably cure infections. Some strains are now completely untreatable with certain antibiotics. There are a few key reasons why gonorrhea is becoming harder to treat:
Antibiotic overuse and misuse
The overuse and misuse of antibiotics has accelerated bacteria’s ability to develop resistance. When antibiotics are overprescribed or misused, bacteria like N. gonorrhoeae are exposed to the drugs but not necessarily killed off completely. The bacteria then mutate and change to survive in the presence of antibiotics. These resistant strains then spread. The CDC estimates that each year in the U.S., antibiotic-resistant infections directly cause at least 2.8 million illnesses and 35,000 deaths.
Quick mutation ability
N. gonorrhoeae has a special ability to quickly alter its DNA and adapt to new antibiotics. Its circular DNA structure and natural competence allow it to readily acquire new genetic mutations that can make it antibiotic resistant. Most other bacteria do not mutate and share genes as easily or quickly.
Lack of new antibiotics
No new classes of antibiotics have been developed to treat gonorrhea in over 30 years. Pharmaceutical companies have little financial incentive to develop new antibiotics, as they are often taken for a short time (unlike medicines for chronic conditions) and resistance would eventually develop anyway. With no new antibiotics in the pipeline, treatment options are severely limited when resistance emerges.
| Antibiotic | Resistance Status |
|---|---|
| Penicillin | Most strains resistant |
| Tetracycline | Most strains resistant |
| Fluoroquinolones | High rates of resistance |
| Cephalosporins | Some resistance emerging |
| Azithromycin | Some resistance emerging |
| Spectinomycin | Rare resistance currently |
| Ceftriaxone | Rare resistance currently |
Lack of condom use
Condoms provide effective protection against gonorrhea. However, lack of condom use means more unprotected sex, leading to more transmission of antibiotic resistant strains. The CDC reports condom use is declining, especially among teens and young adults. This contributes to rising rates of STIs.
Asymptomatic nature
Because gonorrhea is often asymptomatic, many infected people go untreated. This allows resistant strains to spread quietly and undetected through populations. It also gives the bacteria extended time in the body to continue developing resistance. The CDC estimates over 800,000 new gonorrhea infections occur each year in the U.S. but most cases are not diagnosed or reported.
Which antibiotics still work against gonorrhea?
While many former first-line antibiotics like penicillin and tetracycline are now ineffective against most gonorrhea strains, a limited number of antibiotics remain effective treatment options:
Ceftriaxone
Ceftriaxone is part of the cephalosporin class of antibiotics. It can be given as a shot combined with oral azithromycin. Nearly all N. gonorrhoeae strains still show susceptibility to ceftriaxone, making it the foundation of current recommended treatment. However, isolated cases of ceftriaxone-resistant gonorrhea have emerged around the world, signaling the potential for resistance to spread.
Cefixime
Cefixime is another injectable cephalosporin antibiotic. It was previously the recommended first-line oral medication for gonorrhea treatment. But decreasing susceptibility and treatment failures led the CDC to no longer recommend oral cefixime alone. It must now be given with injectable ceftriaxone to effectively treat most gonorrhea infections.
Azithromycin
Azithromycin is a macrolide antibiotic taken orally. It is given alongside ceftriaxone injections to treat gonorrhea. Azithromycin adds another mechanism of action that may help slow the emergence of ceftriaxone resistance. However, rising azithromycin resistance means this combination therapy may also eventually become ineffective.
Gentamicin
Gentamicin is an aminoglycoside antibiotic given by injection that retains activity against many gonorrhea strains resistant to other antibiotics. In 2019, the CDC began recommending gentamicin combined with azithromycin as alternative treatment in the rare cases where ceftriaxone-resistant gonorrhea is encountered.
Spectinomycin
Spectinomycin is an injectable antibiotic that remains effective against most gonorrhea strains. It is not widely available or used in many countries currently. But spectinomycin, along with gentamicin, offers backup treatment options if gonorrhea becomes resistant to cephalosporins and azithromycin.
Gonorrhea treatment guidelines
Due to increasing antibiotic resistance, gonorrhea treatment guidelines have changed in recent years:
Dual therapy required
Since 2010, the CDC has recommended dual therapy using two antibiotics to treat gonorrhea. This combines mechanisms of action to prevent resistance.
Oral cefixime dropped
In 2012, oral cefixime was removed as a first-line treatment option due to declining effectiveness. It can now only be given as part of dual therapy with an injectable antibiotic.
Higher ceftriaxone dose
In 2010, the recommended ceftriaxone dose was increased from 125mg to 250mg to improve efficacy as susceptibility declined.
Alternative antibiotics
Gentamicin and spectinomycin are now recommended backup treatments if ceftriaxone resistance is encountered.
| Year | Treatment Guidelines |
|---|---|
| Before 2010 | Oral cefixime as monotherapy |
| 2010 | Dual therapy with oral cefixime + injectable ceftriaxone |
| 2012 | Oral cefixime removed, injectable ceftriaxone + oral azithromycin |
| 2019 | Backup antibiotics gentamicin & spectinomycin added |
Test of cure
Due to concerns about emerging resistance, the CDC recommends a test of cure, meaning a repeat test for gonorrhea 7 days after finishing treatment. This ensures the infection was successfully cleared.
Where are resistant gonorrhea strains emerging?
Around the world, pockets of antibiotic resistant gonorrhea have begun emerging:
Asia
Many regions of Asia have high rates of gonorrhea resistance. A 2019 study in China found 97% of gonorrhea samples were resistant to ciprofloxacin and 81% were resistant to tetracycline. Resistance to azithromycin and decreased susceptibility to ceftriaxone have also been reported.
United Kingdom
The United Kingdom reported its first two cases of ceftriaxone-resistant N. gonorrhoeae strains in 2018. Both cases were acquired from Southeast Asia.
Australia
Between 2013-2017, 7% of gonorrhea cases acquired in Australia were found to have reduced susceptibility to ceftriaxone. The first two ceftriaxone treatment failures were reported in 2018.
Canada
Canada has seen increased ceftriaxone MICs as well as isolated cases of high-level resistance. In 2017, the first Canadian treatment failure with dual therapy was reported.
United States
The U.S. still reports mostly susceptible isolates. However, a ceftriaxone resistant strain was discovered in Hawaii in 2016 and another with high-level resistance to azithromycin and decreased ceftriaxone susceptibility was found in 2017.
| Region | Resistance Status |
|---|---|
| Asia | Widespread fluoroquinolone, tetracycline, azithromycin, and some ceftriaxone resistance |
| U.K. | 2 cases of ceftriaxone-resistant gonorrhea reported in 2018 |
| Australia | 7% decreased ceftriaxone susceptibility from 2013-2017, 2 treatment failures in 2018 |
| Canada | Increased ceftriaxone MICs, 1 case of treatment failure in 2017 |
| U.S. | Cases of resistance to azithromycin and ceftriaxone reported in Hawaii and national surveillance |
What is being done to address rising resistance?
To combat antibiotic resistant gonorrhea, public health organizations recommend:
Improved detection and surveillance
Expanded testing, contact tracing, and tracking resistance allows for earlier alert to emerging resistant strains and faster public health response. The CDC’s Gonococcal Isolate Surveillance Project (GISP) monitors N. gonorrhoeae samples from U.S. patients to quickly detect resistance.
Research into new antibiotics and treatments
Only a limited pipeline of new antibiotics exists. More research is urgently needed to develop new drugs or alter existing antibiotics to overcome resistance mechanisms in N. gonorrhoeae. New non-antibiotic treatment options are also being explored.
Stricter antibiotic stewardship
More judicious use of antibiotics in healthcare can help slow resistance. The use of antibiotics as growth promoters in livestock has been banned in many countries to preserve antibiotic efficacy.
Focus on prevention through safe sex practices
Condoms, safe sex education, regular STI testing, and partner treatment help reduce preventable gonorrhea transmission. Breaking cycles of infection limits how much the bacteria are exposed to antibiotics.
Dual therapy with different antibiotic mechanisms
Using two antibiotics with different mechanisms (e.g. ceftriaxone plus azithromycin) suppresses resistance more effectively than a single antibiotic. However, resistance may still eventually develop to both drugs.
What does the future hold?
Gonorrhea treatment is becoming exceedingly difficult as options dwindle. Without active intervention, untreatable gonorrhea may become widespread in the not-too-distant future:
More treatment failures expected
As resistance spreads, public health officials anticipate more reports of ceftriaxone plus azithromycin treatment failures. These multidrug-resistant infections will be challenging to manage.
Reliance on backup antibiotics like gentamicin and spectinomycin
If ceftriaxone and azithromycin double therapy fails, alternative antibiotics like gentamicin and spectinomycin will be crucial last-resort options. But they are imperfect solutions if resistance appears.
Need to develop new antibiotics and treatments
Urgent investment into new antibiotic research and development may provide next-generation treatment options before the crisis of untreatable gonorrhea arrives. Non-antibiotic approaches are also being explored.
Focus on prevention and reducing transmission
If highly resistant strains spread widely, principles of public health and prevention will become even more vital. Promoting safer sex practices, screening, partner notification and reducing high-risk sexual networks can help slow onset of untreatable gonorrhea.
Conclusion
Gonorrhea treatment is in danger as rising antibiotic resistance limits effective options for this common STI. Years of antibiotic misuse and overprescribing, coupled with N. gonorrhoeae’s ability to rapidly develop resistance, have rendered many formerly reliable antibiotics ineffective. Dual therapy with injectable ceftriaxone plus oral azithromycin remains the recommended first-line treatment. But even this regimen is threatened by emerging resistance, evidenced by sporadic treatment failures globally. To avert an era of untreatable gonorrhea, increased research, prevention and antibiotic stewardship are urgently required. Without swift action, multidrug-resistant gonorrhea may soon become widespread, causing serious complications and adverse sequelae of the infection to surge once more.