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‘Super Gonorrhea’ is Evolving as a Greater Treatment Challenge


The rise of multidrug-resistant gonorrhea strains, especially those with high-level resistance to ceftriaxone and azithromycin, has led to the term “super gonorrhea.”

A recent commentary in JAMA discussed the growing concerns around a Neisseria gonorrhoeae strain.1 Specifically the identification of the penA 60.001 allele in N gonorrhoeae, a genetic variation helps contribute to antibiotic resistance. The penA 60.001 allele alters the bacterial response to cephalosporins.2

As incidence rates continue to increase, the rise of this drug-resistant strain become a greater possibility.

According to the Centers for Disease Control and Prevention (CDC) there were more than 2.5 million cases of chlamydia, gonorrhea, and syphilis reported in the United States in 2022.3 And the World Health Organization (WHO) reports that in 2020, there were an estimated 82.4 million [47.7 million-130.4 million] new gonorrhea cases infected among adolescents and adults aged 15–49 years worldwide, with a global incident rate of 19 (11–29) per 1000 women and 23 (10–43) per 1000 men. Most cases were in the WHO African Region and the Western Pacific Region.4

Although the multidrug-resistant gonorrhea strain has been seen mostly outside the UNited States, last year 2 cases of this pathogen were confirmed in the US and identified by the Massachusetts Department of Public Health.

Massachusetts officials reported that clinicians were able to treat the patients successfully with ceftriaxone. However, this strain of the sexually transmitted infection had reduced susceptibility to 5 antibiotic classes—including cephalosporins, the group of last-resort drugs that includes ceftriaxone.1

The Rise of Multidrug-Resistant Gonorrhea
The commentator points out that among the 18 bacteria and fungi on the CDC 2019 antibiotic resistance threats report, N gonorrhoeae ranked among the highest-tier “urgent threats.” 1 And just last month, the WHO released its drug-resistant pathogens list, and included N gonorrhoeae, third-generation cephalosporin- and/or fluoroquinolone-resistant as a high priority.5

What You Need to Know

The incidence rates of gonorrhea are rising globally, with a significant number of new cases reported annually.

The penA 60.001 allele variation has been identified in the US, with two cases confirmed by the Massachusetts Department of Public Health. Although these cases were successfully treated with ceftriaxone, the strain showed reduced susceptibility to 5 antibiotic classes.

N gonorrhoeae ranked among the highest-tier “urgent threats” in the CDC’s 2019 antibiotic resistance threats report. The WHO also recently included it as a high-priority pathogen resistant to third-generation cephalosporins and/or fluoroquinolones.

In fact, the drug resistance associated with this strain has given rise to an unsettling moniker.

“The rise of multidrug-resistant gonorrhea strains with high-level resistance to ceftriaxone and azithromycin in addition to previously used first-line antibiotics has earned the name ‘super gonorrhea,’” the JAMA commentator wrote.

The Utility of an Old Antibiotic, What’s in the Pipeline
The JAMA commentator wrote that the data shows that about half of gonococcal infections in the US are resistant to an older antibiotic, ciprofloxacin, but that conversely, half of these infections are susceptible to it. And testing can clearly show its utility. “Resistance to ciprofloxacin derives from a single point mutation that can be reliably detected in a polymerase chain reaction (PCR) assay developed 2 decades ago,” the commentator writes.

In terms of antibiotic development, the commentary mentions 2 investigational antimicrobials, gepotidacin and zoliflodacin, and their possible utility in a future armamentarium, if they are FDA approved.

References
1. Landhuis EW. Multidrug-Resistant “Super Gonorrhea” Rallies Multipronged Effort. JAMA. 2024;331(20):1695–1697. doi:10.1001/jama.2023.15355
2. Abene S. A Growing Concern About Gonorrhea’s Resistance to Antibiotics. Contagion. January 26, 2024. Accessed June 4, 2024.
https://www.contagionlive.com/view/a-growing-concern-about-gonorrhea-s-resistance-to-antibiotics
3. Sexually Transmitted Infections Surveillance 2022.CDC. Last reviewed January 30, 2024. Accessed June 4, 2024.
https://www.cdc.gov/std/statistics/2022/default.htm
4. Multi-drug resistant gonorrhoea. WHO July 11, 2023. Accessed June 4, 2024.
https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea
5. Parkinson J. WHO Updates List of Drug-Resistant Pathogens. Contagion. January 26, 2024. Accessed June 4, 2024.
https://www.contagionlive.com/view/who-updates-list-of-drug-resistant-pathogens



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