Mycoplasma Genitalium Resistance — A Growing Public Health Concern

The sexually transmitted infection (STI) Mycoplasma genitalium (M. genitalium) is quickly becoming a public health concern. Although it’s known to cause serious complications such as pelvic inflammatory disease (PID) and infertility, this bacterium often goes undiagnosed. Its elusiveness is mainly due to its nonspecific symptoms that often go unnoticed. 

With STIs, early detection and identification are critical for effective treatment. However, people with M. genitalium may not even know they have it, and could unknowingly infect other people, preventing them from finding treatment. Even though it responds well to antibiotics, the organism is quickly showing signs of antimicrobial resistance (AMR), particularly to macrolides and fluoroquinolones. 

As a result, M. genitalium‘s AMR is leaving clinicians with limited therapeutic options. Clinical laboratories and diagnostic professionals are thus urgently in need of more accessible, accurate, and rapid molecular testing capable of detecting AMR gene mutations. 

There is an urgent need for molecular diagnostic assays capable of detecting M. genitalium and resistance-associated genetic determinants, including single-nucleotide polymorphism (SNPs) in the 23SrRNA, parC, and gyrA loci.

Rising Resistance Trends

M. genitalium is one of the smallest, free-living bacteria that lack a cell wall. This makes penicillin and other ß-lactam (beta-lactam) antibiotics that target cell-wall biosynthesis ineffective. Fortunately, there are two other primary antibiotic classes used as a therapeutic intervention — macrolides and fluoroquinolones. That said, M. genitalium is increasingly showing global resistance trends. 

Macrolide Resistance

Macrolide antibiotics like azithromycin should be used as a first-line treatment for M. genitalium according to the Centers for Disease Control and Prevention (CDC) and European guidelines. However, macrolide-resistant Mycoplasma genitalium strains are quickly spreading and developing across the globe. These strains are reaching countries at varying prevalence, such as Sweden, Germany, the United Kingdom, Japan, and Australia. 

Research suggests that the single-nucleotide mutations in domain V of the 23S rRNA gene could mediate this Mycoplasma genitalium azithromycin resistance. Common positions that are targeted include A2058G and A2059G, and to a lesser extent: 

• A2058C
• A2058T
• A2059C
• A2059T

M. genitalium‘s macrolide resistance almost doubled — from over 17% between 2014 and 2018 to over 32% between 2019 and 2021. This increase was more prevalent in the A2058 and A2059G mutations than in the A2058T mutations. 

Fluoroquinolone Resistance

Due to the rising Mycoplasma genitalium macrolide resistance, fluoroquinolone use has increased in the past decade as a second-line treatment. However, moxifloxacin-resistant Mycoplasma genitalium​ is also on the rise, but at a lower rate than macrolides. It’s thought that the coexistence of macrolide resistance is associated with quinolone resistance. 

The Asia-Pacific region, for example, has already reached a 20% resistance rate, which further increases case failure rates. Specific mutations in the parC and gyrA genes have been consistently linked to these failures in moxifloxacin and sitafloxacin treatments. 

These trends show that M. genitalium is quickly becoming multidrug-resistant (MDR), with rates rising from 2.9% to 8.3%. This further complicates treatment. If unchecked, this will escalate to a global health crisis. The CDC added M. genitalium to its AMR watch list. 

Diagnostic Gaps

Despite M. genitalium‘s recognition as a highly infectious AMR STI, it remains under-reported and underdiagnosed worldwide. There could be several factors that contribute to its diagnostic gap. 

Lack of Awareness

Firstly, M. genitalium may go undetected in clinical settings. It’s not as well-known as other AMR STIs such as Neisseria gonorrhoeae (N. gonorrhoeae) or Chlamydia trachomatis (C. trachomatis). As a result, not all clinicians may suspect it at first. 

Unlike the above-mentioned STIs, M. genitalium is not recommended for routine screening, especially in asymptomatic individuals. This could result in testing being overlooked until symptoms persist or standard treatments fail. Failure to pursue further diagnostics presents missed opportunities for early intervention, thus increasing the risk of spreading the organism. 

Inadequate Test Access

For clinicians who suspect M. genitalium, testing may not be readily available. Not all labs may offer validated nucleic acid amplification tests (NAATs) to test and diagnose patients. Some may rely on send-out testing with delayed turnaround times (TATs). 

Until recently, there was a lack of FDA-cleared commercial assays in many regions. The time it took further contributed to diagnostic gaps in accuracy and availability. 

Absence of Resistance Testing

Another diagnostic gap is the lack of resistance testing in standard panels. Although several FDA-cleared NAATs exist for STI detection, most lack integrated detection of resistance-conferring mutations in M. genitalium.

While there are single and multi-target FDA-cleared polymerase chain reaction (PCR) based kits for STIs, they cannot simultaneously detect nucleic acids of multiple STI pathogen targets and gene mutations associated with AMR.

Mycoplasma genitalium resistance PCR kits are nonnegotiable. Detecting M. genitalium is only part of the equation since its rise in macrolide and fluoroquinolone resistance. Accurate molecular diagnostic tools that can detect M. genitalium and resistance markers are critical to help close the gap. 

Lack of Treatment Guidelines

What further complicates Mycoplasma genitalium resistant treatment​ is the lack of standardized and globally accepted guidelines. That said, there are some regions that have developed protocols, but compared to other regions, they can vary. This could thus result in inconsistent clinical practices. 

For instance, the 2021 European guideline recommends azithromycin for infections not macrolide-resistant and moxifloxacin for macrolide-resistant cases. However, there are no treatment guidelines in China and no AMR mutation detection kits. 

In the absence of a resistance test for Mycoplasma genitalium, clinicians may resort to empirical treatment. This risks therapeutic failure and facilitates clonal spread of resistant M. genitalium strains.

Global organizations must urgently team together to update protocols and incorporate resistance profiling to effectively treat M. genitalium and mitigate its risk of resistance proliferation. 

Why Trust Applied BioCode Inc.

Partner with Applied BioCode Inc. for optimized STI research testing. Our advanced solution, BioCode^® STI + Resistance Panel (RUO), is a sensitive and accurate PCR-based assay. It’s capable of detecting and simultaneously identifying nucleic acids from: 

• M. genitalium

• N. gonorrhoeae
• C. trachomatis
• Trichomonas vaginalis (T. vaginalis)

It can also detect SNP mutations associated with AMR for M. genitalium and N. gonorrhoeae. This is thanks to our Barcoded Magnetic Bead (BMB) technology, which enables labs to test for multiple targets in a single sample, in a single well. 

Additionally, the assay works with the BioCode^® MDx-3000 Instrument, an advanced molecular diagnostic system made for panel testing. It’s capable of providing high-throughput, multiplex testing — processing up to 96 samples in a single run and running up to three different panels at a time. 

Better Understand Mycoplasma Genitalium Resistance With Applied BioCode Inc.

Antibiotic-resistant Mycoplasma genitalium is a growing public health concern. Clinical laboratories and diagnostic professionals can help reduce the STI’s impact through proactive testing, molecular diagnostics, and high-quality, efficient research and Mycoplasma genitalium resistance testing solutions. 

Consider implementing our BioCode^® STI + Resistance Panel (RUO) into your STI testing workflow. Our assay can be a powerful tool to help guide effective STI treatments. Thanks to its high sensitivity, fast results, and scalable throughput, researchers can better understand AMR in STIs. 

Contact us for more information on our advanced solutions.