Antibiotic-Resistant Gonorrhea on the Rise, New Drugs Needed

Data from 77 countries show that antibiotic resistance is making gonorrhea – a common sexually-transmitted infection – much harder, and sometimes impossible, to treat.

"The bacteria that cause gonorrhea are particularly smart. Every time we use a new class of antibiotics to treat the infection, the bacteria evolve to resist them," said Dr. Teodora Wi, medical officer for human reproduction at the World Health Organization (WHO).

WHO reports widespread resistance to older and cheaper antibiotics. Some countries – particularly high-income ones, where surveillance is best – are finding cases of the infection that are untreatable by all known antibiotics.

"These cases may just be the tip of the iceberg, since systems to diagnose and report untreatable infections are lacking in lower-income countries where gonorrhoea is actually more common," adds Wi.

Each year, an estimated 78 million people are infected with gonorrhea.* Gonorrhea can infect the genitals, rectum, and throat. Complications of gonorrhea disproportionally affect women, including pelvic inflammatory disease, ectopic pregnancy and infertility, as well as an increased risk of HIV.

Decreasing condom use, increased urbanization and travel, poor infection detection rates, and inadequate or failed treatment all contribute to this increase.

The WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP), monitors trends in drug-resistant gonorrhea. WHO GASP data from 2009 to 2014 find widespread resistance to ciprofloxacin [97 percent of countries that reported data in that period found drug-resistant strains], increasing resistance to azithromycin [81%], and the emergence of resistance to the current last-resort treatment: the extended-spectrum cephalosporins (ESCs) oral cefixime or injectable ceftriaxone [66%].

Currently, in most countries, ESCs are the only single antibiotic that remain effective for treating gonorrhea. But resistance to cefixime – and more rarely to ceftriaxone – has now been reported in more than 50 countries. As a result, WHO issued updated global treatment recommendations in 2016 advising doctors to give 2 antibiotics: ceftriaxone and azithromycin.

The R&D pipeline for gonorrhea is relatively empty, with only 3 new candidate drugs in various stages of clinical development: solithromycin, for which a phase III trial has recently been completed; zoliflodacin, which has completed a phase II trial; and gepotidacin, which has also completed a phase II trial.

The development of new antibiotics is not very attractive for commercial pharmaceutical companies. Treatments are taken only for short periods of time (unlike medicines for chronic diseases) and they become less effective as resistance develops, meaning that the supply of new drugs constantly needs to be replenished.

The Drugs for Neglected Diseases initiative (DNDi) and WHO have launched the Global Antibiotic Research and Development Partnership (GARDP), a not-for-profit research and development organization, hosted by DNDi, to address this issue. GARDP’s mission is to develop new antibiotic treatments and promote appropriate use, so that they remain effective for as long as possible, while ensuring access for all in need. One of GARDP’s key priorities is the development of new antibiotic treatments for gonorrhea.

"To address the pressing need for new treatments for gonorrhea, we urgently need to seize the opportunities we have with existing drugs and candidates in the pipeline. In the short term, we aim to accelerate the development and introduction of at least one of these pipeline drugs, and will evaluate the possible development of combination treatments for public health use," said Dr. Manica Balasegaram, GARDP director. "Any new treatment developed should be accessible to everyone who needs it, while ensuring it’s used appropriately, so that drug resistance is slowed as much as possible."

Gonorrhea can be prevented through safer sexual behavior, in particular consistent and correct condom use. Information, education, and communication can promote and enable safer sex practices, improve people’s ability to recognize the symptoms of gonorrhea and other sexually transmitted infections, and increase the likelihood they will seek care. Today, lack of public awareness, lack of training of health workers, and stigma around sexually transmitted infections remain barriers to greater and more effective use of these interventions.

There are no affordable, rapid, point-of-care diagnostic tests for gonorrhea. Many people who are infected with gonorrhea do not have any symptoms, so they go undiagnosed and untreated. On the other hand, however, when patients do have symptoms, such as discharge from the urethra or the vagina, doctors often assume it is gonorrhea and prescribe antibiotics – even though people may be suffering from another kind of infection. The overall inappropriate use of antibiotics increases the development of antibiotic resistance in gonorrhea as well as other bacterial diseases.

“To control gonorrhea, we need new tools and systems for better prevention, treatment, earlier diagnosis, and more complete tracking and reporting of new infections, antibiotic use, resistance and treatment failures,” said Dr. Marc Sprenger, director of antimicrobial resistance at WHO. “Specifically, we need new antibiotics, as well as rapid, accurate, point-of-care diagnostic tests – ideally, ones that can predict which antibiotics will work on that particular infection – and longer term, a vaccine to prevent gonorrhea.”

* Each year, an estimated 35.2 million people are infected in the WHO Western Pacific Region, 11.4 million people in the WHO South-East Asian Region, 11.4 million in the WHO African Region, 11.0 million in the WHO Region of the Americas, 4.7 million in the WHO European Region and 4.5 million in the WHO Eastern Mediterranean Region.

Source: WHO