Epidemiology, Treatments, and Vaccine Development for Antimicrobial-Resistant Neisseria gonorrhoeae: Current Strategies and Future Directions

Abstract

Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection in the world after Chlamydia trachomatis . The pathogen has developed resistance to every antibiotic currently approved for treatment, and multidrug-resistant strains have been identified globally. The current treatment recommended by the World Health Organization is ceftriaxone and azithromycin dual therapy. However, resistance to azithromycin and ceftriaxone are increasing and treatment failures have been reported. As a result, there is a critical need to develop novel strategies for mitigating the spread of antimicrobial-resistant N. gonorrhoeae through improved diagnosis and treatment of resistant infections. Strategies that are currently being pursued include developing molecular assays to predict resistance, utilizing higher doses of ceftriaxone, repurposing older antibiotics, and developing newer agents. In addition, efforts to discover a vaccine for N. gonorrhoeae have been reignited in recent years with the cross-protectivity provided by the N. meningitidis vaccine, with several new strategies and targets. Despite the significant progress that has been made, there is still much work ahead to combat antimicrobial-resistant N. gonorrhoeae globally.

Dissemination and genome analysis of high-level ceftriaxone-resistant penA 60.001 Neisseria gonorrhoeae strains from the Guangdong Gonococcal antibiotics susceptibility Programme (GD-GASP), 2016–2019

“…Currently, the World Health Organization (WHO) has included N. gonorrhoeae as a high priority pathogen because of therapy failures and dramatic case number increases [ 2 ]. The pathogen has developed antimicrobial resistance (AMR) to every antibiotic currently approved for treatment [ 3 ], and the effectiveness of the last remaining option for first-line antimicrobial monotherapy, ceftriaxone, has come into question due to the evolving resistance and, especially, spread of the FC428 clone [ 4 ].…”

“…The presence of FC428, which is a globally disseminated ceftriaxone-resistant clone characterized by mosaic penA 60.001, has been widely documented, including in Japan, Denmark, South Korea, Ireland, Canada, Australia, Singapore, France and the UK, since 2015 [ 4 ], raising concerns about the long-term effectiveness of ceftriaxone therapy. In a study analyzing FC428 isolates from 2016 to 2019, the first case was identified in northern China (July 2016, Beijing) [ 5 ] and then FC428 disseminated to the central (2017 June to September, Hunan) [ 6 ], western (2018, Sichuan) [ 7 ] and eastern (May to October 2019, Zhejiang) [ 8 ] region, showing that highly resistant to ceftriaxone FC428 related clones had already appeared in China.…”

Structural and Functional Annotation and Molecular Docking Analysis of a Hypothetical Protein from Neisseria gonorrhoeae: An In-Silico Approach

“…In addition, it is a non-motile [ 9 ] and obligate-human pathogen [ 10 ] that can thrive aerobically or anaerobically in the presence of nitrite [ 11 ]. These diplococci, kidney-shaped bacteria infecting both men and women can cause the sexually transmitted disease (STD) named gonorrhea [ 12 , 13 ]. Every year, 87 million new infections are being reported for this quick-spreading contagious disease.…”

“…Every year, 87 million new infections are being reported for this quick-spreading contagious disease. This STD has already emerged as a major problem in low- and middle-income countries in Africa, Asia, Latin America, and the Caribbean [ 1 , 5 , 12 ]. Gonorrhea can be asymptotic or develop with symptoms.…”

“…However, there is still no effective treatment for gonococci and even no gonococcal vaccination is available yet. To make the situation worse, N. gonorrhoeae has been found resistant to several antimicrobial drugs such as penicillins, tetracyclines, sulphonamides, fluoroquinolones, macrolides, azithromycin, and ceftriaxone [ 12 , 16 , 17 ]. Hence, WHO recommends azithromycin and ceftriaxone as a dual therapy for the time being against this disease [ 12 ].…”