Introduction
Antimicrobial resistance (AMR) in sexually transmitted infections (STIs) now poses a significant and escalating global threat. Two bacteria—Neisseria gonorrhoeae (causative agent of gonorrhea) and Mycoplasma genitalium (MG)—illustrate parallel trajectories of growing resistance, undermining treatment efficacy. This article summarizes current resistance trends, their clinical implications, and the critical role of diagnostics in improving outcomes.
Neisseria gonorrhoeae: A Shape-Shifter in AMR
- Global Burden
In 2020, an estimated 82.4 million new gonorrhea infections occurred among adults aged 15–49 globally1.
- Resistance Trends
Gonococcal resistance has evolved across multiple antibiotic classes—quinolones, cephalosporins, macrolides, and others. As of 2021, over half of isolates exhibited resistance to at least one antibiotic2.
- Treatment Challenges
Emerging resistance has already rendered cefixime no longer recommended as first-line therapy. Some strains now display elevated minimum inhibitory concentrations (MICs) to ceftriaxone and azithromycin, raising fears of untreatable gonorrhea3.
- Therapeutic Innovation
Assessing antibiotic susceptibility prior to treatment presents an innovative approach to treatment of N. gonorrhoeae. Given ciprofloxacin resistance rates as low as ∼30% in some populations, a significant number of patients could benefit from this treatment if susceptibility is known4. As well as reducing the use of ceftriaxone, ciprofloxacin could be taken orally instead of via intramuscular injection.
Mycoplasma genitalium: More than an Emerging Threat
- Prevalence
MG is acknowledged as emerging or even surpassing gonorrhea in prevalence in some regions, with general-population estimates of ~1–3%, and notably higher (10–20% or more) in high-risk groups across multiple countries.5,6
- Antibiotic Resistance
The prevalence of antibiotic resistance in MG is alarmingly high: overall resistance to macrolides, fluoroquinolones, and combination therapy has been reported at 33.3%, 13.3%, and 6.5%, respectively6, and has been reported as high as 50% in some cohorts5. Macrolide resistance is conferred by macrolide-resistance mutations (MRMs).
- Diagnostic Challenges
MG is fastidious and cannot be cultured efficiently; NAATs remain the only reliable detection method, and pairing MG detection with detection of MRMs is essential to guide appropriate therapy7.
Diagnostics: The Cornerstone of Resistance Management
Empiric therapy—once standard—no longer suffices amid rising rates of resistance. Molecular diagnostics enable targeted, evidence-based treatment to maximize cure rates and minimize resistance selection.
- Gonorrhea Diagnostics
Rapid NAAT and antimicrobial susceptibility testing facilitate appropriate antimicrobial selection. Surveillance programs like WHO’s GASP inform local and global trends3. New molecular diagnostics promise quicker resistance profiles, aligning treatment with susceptibility.
- MG Diagnostics
NAAT detection combined with concurrent resistance genotyping empowers resistance-guided therapy (RGT): doxycycline lead-in, followed by azithromycin if MRM-negative, or Moxifloxacin (or alternative fluoroquinolone treatment) if MRM positive. This approach has been shown to achieve cure rates of at least 92% in RGT cohorts and limits macrolide misuse8,9.
Treatment Considerations
An RGT strategy gives healthcare providers options when considering optimal treatment and the increasing importance of antimicrobial stewardship. Current treatment recommendations7 for gonorrhea and MG are summarized in the table below:
Conclusion
Resistance in MG and N. gonorrhoeae represents a looming public health crisis. For MG, macrolide resistance is already widespread; for gonorrhea, creeping multi-drug resistance threatens the utility of current last-line agents. Diagnostics—especially NAATs with genotypic resistance detection—are vital tools. Their deployment supports individualized treatment, preserves drug efficacy, and enhances AMR stewardship. Without widespread adoption of rapid, resistance-informed diagnostics and surveillance, STI treatment may face a future of diminishing options and increasing failure.
Interested in researching AMR markers in MG or N. gonorrhoeae? Contact SpeeDx for more information.
References
1. Global Sexually Transmitted Infections Programme, World Health Organization.
2. Hooshiar, Mohammad Hosseini et. al “Global trends of antimicrobial resistance rates in Neisseria gonorrhoeae: a systematic review and meta-analysis.” Frontiers in pharmacology vol. 15 1284665. 3 Jul. 2024, doi:10.3389/fphar.2024.1284665
3. Riou, Julien et. al “Projecting the development of antimicrobial resistance in Neisseria gonorrhoeae from antimicrobial surveillance data: a mathematical modelling study.” BMC infectious diseases vol. 23,1 252. 20 Apr. 2023, doi:10.1186/s12879-023-08200-4
4. Cotton, S et. al “Evaluation of the molecular detection of ciprofloxacin resistance in Neisseria gonorrhoeae by the ResistancePlus GC assay (SpeeDx).”
Diagnostic Microbiology and Infectious Diseases 2020 Nov 12;99(4):115262
5. Getman D, Jiang A, O’Donnell M, Cohen S. Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States. J Clin Microbiol. 2016;54(9):2278–83.
6. Chua, Teck-Phui et. al. “Evolving patterns of macrolide and fluoroquinolone resistance in Mycoplasma genitalium: an updated systematic review and meta-analysis.” The Lancet. Microbe vol. 6,7 (2025): 101047. doi:10.1016/j.lanmic.2024.101047
7. Sexually Transmitted Infection Treatment Guidelines, 2021. Centers for Disease Control.
8. Read, Tim R H et. al. “Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation.” Clinical infectious diseases: an official publication of the Infectious Diseases Society of America vol. 68,4 (2019): 554-560. doi:10.1093/cid/ciy477
9. Durukan et. al “Resistance-Guided Antimicrobial Therapy Using Doxycycline–Moxifloxacin and Doxycycline–2.5 g Azithromycin for the Treatment of Mycoplasma genitalium Infection: Efficacy and Tolerability. Clin Infect Dis. 2020; 71(6):1461–1468
