Resistance Guided Therapy

Practical implementation guide to Resistance Guided Therapy for Mycoplasma genitalium within the diagnostic laboratory.

What is Resistance Guided Therapy?

Diagnostics that detect infection and genetic markers for antibiotic resistance.

  • The misuse and overuse of antibiotics has led to concerning levels of global resistance rates across diseases, resulting in a world-wide call to action.
  • Notably, antibiotic resistance in sexually transmitted infections (STIs) is a growing public health issue. STIs have the potential to become the first incurable bacterial infections since the introduction of antibiotics.
  • Diagnostic tests that detect bacterial infection and genetic markers for antibiotic resistance in a single test can address this looming issue by enabling resistance guided therapy. In diseases such as TB, the implementation of resistance guided therapy is now common practice.

Why is Resistance Guided Therapy important?

  • improve patient treatment outcomes
  • reduce re-admission and healthcare costs
  • minimise the spread of antibiotic resistant infections
  • maintain the efficacy of antibiotic treatment (antibiotic stewardship)
“Today, antibiotics are rarely prescribed based on a definitive diagnosis. Diagnostic tests can show whether or not an antibiotic is actually needed, and which one. Having rapid, low-cost, and readily available diagnostics is an essential part of the solution to this urgent problem.”

– Dr Margaret Chan, Director General of the World Health Organization

Treating Mycoplasma genitalium with Resistance Guided Therapy improved overall cure rates from below 67% to ≥92%

Resistance-Guided-Therapy-increases-cure-rate

*Data from Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation. Read the full article here.

The Melbourne Sexual Health Centre employed a Resistance Guided Therapy approach by switching from azithromycin to doxycycline for presumptive treatment of M. genitalium (MG) then testing with the ResistancePlus® MG test from SpeeDx to determine presence of resistance mutations. Differential treatments based on the results of the ResistancePlus® MG test resulted in a cure rate of ≥92% of infections, with infrequent selection of macrolide resistance. Previous cure rates from the clinic population exhibiting high levels of antibiotic resistance have been reported below 67% and as low as 40% when treating with standard front-line azithromycin therapy.

Implementing Resistance Guided Therapy for M. genitalium in your laboratory

Step 1: Testing algorithm for M. genitalium and macrolide resistance

resistance guided therapy_testing algorithm for MG & macrolide resistance

  • Who to test?*

Patients with symptoms you may include are: NGU, PID, cervicitis, urethritis, anorectal condition. In most labs, this number will be below 1,000 samples per annum.

Step 2: Treatment algorithm for M. genitalium based on macrolide resistance status

resistance guided therapy_treatment algorithm for MG based on macrolide resistance status*Recommendations by the Australian STI Management Guidelines for M. genitalium

  • Doxycycline only cures ~30% of MG infections, but can lower bacterial load in most cases.
  • Treatment of MG with macrolides is more successful in infections with lower bacterial load.
  • Greater confidence with sequential azithromycin treatment if prescribed based on macrolide-sensitivity.

Mycoplasma genitalium has emerged as a sexually transmitted infection with prevalence rates higher than gonorrhoea in many populations.5 Like gonorrhoea, this bacterium has developed a high frequency of resistance to frontline antibiotic treatment, and for resistance strains, we have limited treatment options.5 This situation necessitates rapid resistance assays which will enable secondary treatment options to be used sparingly. To this point, emerging resistance to secondary treatment options such as fluoroquinolones have already been reported.6 The time to act is now!

“Although antimicrobial resistance is a massive challenge, it is one that I believe is well within our ability to tackle effectively. The human and economic costs compel us to act: if we fail to do so, the brunt of these will be borne by our children and grandchildren, and felt most keenly in the poorest parts of the world.”

– Lord Jim O’Neill4

The misuse and overuse of antibiotics has led to concerning levels of global resistance rates, resulting in a world-wide call to action.4 In diseases such as TB, the implementation of resistance-guided therapy is now common practice.7 It is well recognized that disease causing bacteria such as Mycoplasma genitalium (MG) are on the path to becoming “super-bugs”.3 There is an urgent need for new strategies and treatments to manage STDs rather than relying on a traditional syndromic approach. Availability of molecular resistance testing introduces resistance-guided therapy to STD management.

Changing the way STIs are treated

jorgen-article

Dr Jorgen Skov Jensen

Consultant physician in microbiology & infection control,
Statens Serum Institut, Denmark | View full article at Media Planet

References

1. Read TRH, Fairley CK, Murray GL, Jensen JS et al. Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation. CID June 5 2018. doi: 10.1093/cid/ciy477
2. Manhart LE, Gillespie CW, Lowens MS, Khosropour CM, Colombara DV,
Golden MR, et al. Standard treatment regimens for nongonococcal urethritis have
similar but declining cure rates: a randomized controlled trial. CID 405 2013;56(7):934-42.

3. Unemo, M. & Jensen, J.S. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium. 2016. Nat. Rev. Urol. 268. Published online 10 Jan 2017. doi:10.1038/nrurol
4.O’Neill J. Tackling drug-resistant infections globally: final report and recommendations. The Review on Antimicrobial Resistance. May 2016:35.
5.Oakeshott P, Aghaizu A, Hay P, et al. Is Mycoplasma genitalium in women the “new chlamydia”? a community‐based prospective cohort study. Clin Infect Dis. 2010;51(10):1160–1166.
6.Tagg KA, Jeoffreys NJ, Couldwell DL., Donald JA, Gilbert GL. Fluoroquinolone and macrolide resistance-associated mutations in Mycoplasma genitalium. J Clin Microbiol. 2013;51(7):2245–2249.
7.World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. Geneva, Switzerland: World Health Organization; 2016.

Antimicrobial-resistant Neisseria gonorrhoeae is a serious public health threat and reports have been emerging of strains that are resistant to all known treatments.1 While new treatments are still in development, urgent action is needed to improve management strategies to control gonorrhoea, including improved diagnostics and better utilization of existing drugs. Traditional syndromic management of STDs requires >95% efficacy, however the availability of molecular tests which can diagnose infection and detect resistance markers will enable older treatments to be ‘recycled’ into use. Approximately 80% of N. gonorrhoeae infections in the US are susceptible to ciprofloxacin, and studies have shown that the gyrA genotype has >98% sensitivity and specificity to predict ciprofloxacin susceptibility.2,3

Tackling Drug-Resistant Infections Globally – 2016

gonorrhoea case study

Full Case Study
All credits towards AMR review and Lord Jim O’Neill

References

1.Terkelsen D., Tolstrup J., Johnsen C.H. et al. Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017. Euro Surveill. 2017 Oct;22(42).
2.Trembizki E., Guy R., Donovan B., Kaldor J.M., Lahra M.M., Whiley D.M. Further evidence to support the individualised treatment of gonorrhoea with ciprofloxacin.Lancet Infect Dis. 2016 Sep;16(9):1005-1006.
3.Allan-Blitz LT1, Wang X, Klausner JD. Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta-Analysis. Sex Transm Dis. 2017 May;44(5):261-265.

Dr. Catriona Bradshaw
Melbourne Sexual Health

M.genitalium management in the era of escalating antimicrobial resistance.

Click here for exclusive access to Dr. Bradshaw’s IUSTI presentation outlining her work with Mycoplasma genitalium and resistance guided therapy.


Simon Bone
SpeeDx

Implementation of Mycoplasma genitalium resistance testing within the diagnostic laboratory

Any lab can easily implement Mycoplasma genitalium testing with resistance determination. For a practical implementation of Resistance Guided Therapy with flexible solutions for low-medium throughput see this poster.


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