Gonorrhea is the second most commonly diagnosed sexually transmitted infection (STI) in the world [3]. It is usually easy to treat; however, its recent increased resistance to antibiotics makes it a major threat to future human health. Gonorrhea is an infection caused by the bacterium Neisseria gonorrhoeae [3], which can infect the genitals, rectum and throat [2]. Symptoms include painful urination, abnormal discharge in both men and women, painful or swollen testicles in men, and lower abdomen pain and irregular menstruation in women [3]. If left untreated, it can lead to complications including pelvic inflammation, infertility, and increased risk of HIV transmission. However, people can be asymptomatic and still spread the infection [3]. The best way to prevent transmission is through treatment, but practicing safe sex, including condom use, are highly encouraged to prevent spread [2].
An increase in antibiotic-resistant gonorrhea is due to increased transmission of the bacteria through increased urbanization and travel, poor infection detection and inadequate or failed treatment [2]. Barriers to effective interventions include lack of public awareness, inadequate training of health workers and stigma around STIs. Inappropriate use of antibiotics in medical settings has also significantly increased the development of resistance [2].
Currently, there have been three reported cases of all-antibiotic-resistant gonorrhea, recorded between February and April of 2018 [3]. These cases include two Australian men and one British man who, according to the European Center for Disease Control, were infected after having unprotected sex in Southeast Asia. The British man is currently undergoing experimental treatment with a carbapenem antibiotic called ertapenem [3]. Carbapenems are considered “antibiotics of last resort”, reserved for use in situations of multi-drug resistant infection [5].
It is estimated that each year, 78 million people are infected with gonorrhea [2], and 30% of these new infections are resistant to at least one antibiotic [4]. The World Health Organization Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP) monitors drug-resistant gonorrhea. WHO GASP’s data from 2009 to 2014 found widespread resistance to ciprofloxacin (97% of countries reported drug resistant strains), increased resistance to azithromycin (81%) and, for the first time, resistance to extended-spectrum cephalosporins (ESCs) oral cefixime or injectable ceftriaxone (66%) [2]. In most countries, ESCs are the last antibiotic that remain effective for treating gonorrhea, but more than 50 countries have already reported resistance [2]. As of yet, there are no reports by the CDC about treatment failures using cephalosporin in the USA [1]. Changes in resistance in the last few years have led WHO to update global recommendations in 2016 and advise the prescription of a combination of two antibiotics – ceftriaxone and axithromycin [2].
Drug research and development for gonorrhea is not attractive because treatment for the STI is taken only for a short period of time, and, as with all antibiotics, becomes less effective as the bacteria develop resistance to it, meaning new antibiotics would have to be developed frequently [2]. Fortunately, the Drugs Neglected Diseases initiative (DNDi) and WHO have launched the Global Antibiotic Research and Development Partnership (GARDP), a not-for-profit research and development organization addressing the issue of development of new antibiotics treatments, and promotion of their appropriate use to ensure the drugs remain effective for as long as possible. Currently, there are only three new candidate drugs; the drug solithromycin has completed phase III of testing and research, and both xoliflodacin and gepotidacin have completed phase II trials [2].
The gonorrhea bacterium, in particular, can evolve and adapt rapidly to new antibiotics [3]. For this reason, it requires constant monitoring and surveillance for resistant cases. To control resistant gonorrhea, it is necessary to track and report new infections, treatment failures as well as ensure appropriate antibiotic use [2]. High income countries with good surveillance are capable of capturing cases of resistant gonorrhea, but these might only represent a small portion of cases worldwide, considering resource-poor countries may not be able to detect and track cases as easily.
In the USA, surveillance for resistant gonorrhea is conducted through the following projects; Gonococcal Isolate Surveillance Project (GISP), the enhanced Gonococcal Isolate Surveillance Project (eGISP), and Strengthening the United States Response to Resistant Gonorrhea (SURRG) [1]. The GISP project collects gonorrhea specimens each month from men with symptoms of urethritis in 26 STI clinics across the USA [4]. The specimens are sent to the Antimicrobial Regional Laboratory Network (ARLN) for culture and isolation to observe susceptibility and resistance patterns in the Neisseria bacteria. A selection of those isolated bacteria can then be archived in the CDC’s ARLN isolate bank for gonorrhea diagnostic, drug and vaccine development [4]. Clinical surveillance in the USA includes requesting that clinicians report any gonorrhea specimen with decreased cephalosporin susceptibility, and any gonorrhea cephalosporin treatment failure to the CDC through their state or local health departments [1].
A major challenge to surveillance of resistant gonorrhea in the US is the decline in use of gonorrhea culture testing by clinicians and laboratories, necessary for antibiotic susceptibility testing [1]. This is due to an increase in use of newer laboratory technology, such as the diagnostic test Nucleic Acid Amplification Test (NAAT). Culture testing is currently the only effective way to test for antibiotic susceptibility, there is no other well-studied or reliable technology for antibiotic susceptibility testing from nonculture specimens [1].
Gonorrhea, a common STI once easy to treat, has now become a major threat to worldwide health because it may soon become impossible to treat. Research and development of new drugs do not offer a great solution considering the time and costs involved and the difficulty in keeping up with the bacteria’s developing resistance. Surveillance of resistant cases in low-income countries should be improved to help prevent the worldwide spread of antibiotic-resistant gonorrhea. Timely surveillance, appropriate antibiotic use, and treatment adherence remains our best defense against the development of antibiotic resistance, in gonorrhea and all pathogens.
References:
[1] “Antibiotic-Resistant Gonorrhea Basic Information.” Centers for Disease Control and
Prevention, Centers for Disease Control and Prevention, 28 Mar. 2018, www.cdc.gov/std/gonorrhea/arg/basic.htm.
[2] “Antibiotic-Resistant Gonorrhoea on the Rise, New Drugs Needed.” World Health
Organization, World Health Organization, 7 July 2017, www.who.int/en/news-room/detail/07-07-2017-antibiotic-resistant-gonorrhoea-on-the-rise-new-drugs-needed.
[3] Berke, Jeremy. “An Antibiotic-Resistant Strain of 'Super Gonorrhea' Is Spreading around the
Globe.” San Antonio Express-News, Express-News.com, 17 May 2018, www.mysanantonio.com/technology/businessinsider/article/An-antibiotic-resistant-strain-of-super-12920547.php.
[4] “Combating the Threat of Antibiotic-Resistant Gonorrhea.” Centers for Disease Control and
Prevention, Centers for Disease Control and Prevention, 15 Feb. 2018, www.cdc.gov/std/gonorrhea/arg/carb.htm.
[5] Papp-Wallace, Krisztina M., et al. “Carbapenems: Past, Present, and Future.” Antimicrobial
Agents and Chemotherapy, vol. 55, no. 11, Nov. 2011, pp. 4943–4960. American Society for Microbiology, doi:10.1128/AAC.00296-11.
