1. Implementing a test and treat pathway for Mycoplasma Genitalium (MG) in men with Non-Specific Urethritis (NSU) attending a GUM clinic
John Reynolds-Wright1, Fabienne Verrall1, Mohamed Hassan-Ibrahim2, Suneeta Soni1
1Genitourinary Medicine, Brighton and Sussex University Hospitals
2Virology, Brighton and Sussex University Hospitals
Good morning, I would like to thank BASHH for the opportunity to present our data.

2. Background
Mycoplasma genitalium (MG) accounts for 10-35% of NSU cases1
Men with NSU are routinely tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
Until recently poor access to MG testing and where available testing only done if NSU unresponsive to first line treatment
Mycoplasma accounts for between 10-35% of cases of NSU.
In UK, men with NSU are routinely only tested for CT and GC
This is mainly because access to MG testing has historically been poor. Until recently there were no commercially available assays and testing was only available through a reference service using in-house PCRs if NSU was unresponsive to first or second line therapy. However newer assays are imminently available and it is likely that testing will increase significantly in UK over the next few years.
1. Jensen et al European guideline on Mycoplasma Genitalium infections

3. Background
MG is routinely tested for in some countries eg. Denmark and Australia
Recent reports of macrolide resistance in MG are up to 40%1
In many UK clinics, Azithromycin 1g is still treatment of choice for NSU
Other countries already recognize the importance of MG and for example all patients in Denmark are screened; In Australia symptomatic individuals are Other countries have already been testing for MG for many years for example all in Denmark and Australia and there are a number of published studies showing macrolide resistance rates of %,.
Yet despite the lack of MG testing and paucity of epidemiological data from the UK, we know from some small studies that rates of macrolide resistance among MG isolates is just as high at around 40%.
Despite this and the increasing concern around macrolide resistance in other organisms such as GC and syphilis, the treatment of choice in many UK centres for NSU remains a single dose of Azithromycin. Interestingly Sweden, where first line treatment for NSU is doxycycline, has reported lower rates of resistance of around 10-15%.
1. Sadiq et al High Prevalence of Antibiotic-Resistant Mycoplasma genitalium in Nongonococcal Urethritis

4. Aims
To pilot a test and treat pathway for MG in a busy city GUM service
To determine MG prevalence among men diagnosed with NSU
To measure clearance rates of MG post-treatment
With this is mind we switched our first line treatment of NSU to doxycycline 100mg bd for 7 days and began a pilot of routine testing of men with NSU for MG
We aimed to determine the prevalence of MG among men with NSU and also to measure clearance of infection post treatment, as a proxy for possible resistance.

5. Method - Testing Pathway
Symptoms
Microscopy
NSU diagnosis
Doxycycline 100mg BD for 7 days
Test FVU for CT, NG and MG
MG detected
Recall Patient to clinic
Treat with azithromycin 500mg stat and 250mg od for 4 days
Abstinence
Partner notification
Test of Cure in 4 weeks
Positive Test of Cure
Determine whether risk of reinfection
Treat with Moxifloxacin 400mg od for 10 days
All men with a diagnosis of NSU were eligible for MG testing.
A diagnosis of NSU was based on symptoms of urethritis and/or the presence of >5 polymorphonuclear  lymphocytes/high power field on microscopy of a gram stained urethral smear.
Men were prescribed doxy 100mg bd 7 days unless allergic or intolerant and a FVU sample was tested for CT, GC and MG using the Fast Track Diagnostics urethritis multiplex PCR.
Men subsequently found to have MG were recalled to clinic and offered treatment with azithromycin 500mg stat followed by 250mg od for 4 days.
They were advised to abstain from sex for another week and to inform partners of the new diagnosis.
Patients were invited for test of cure at 4 weeks post treatment and treatment failures were then treated with moxifloxacin 400mg PO OD for 10 days. Following this treatment, men were again invited for TOC  

6. Results - Demographics
Number of cases of NSU
383
Number of Cases Tested for MG
277 (72.3%)
Cases tested for MG (n=277)
White
247 (92.1%)
Median Age
30 (IQR )
MSM
96 (34.4%)
HIV Negative
259 (92.8%)
Between 1st Sept 2015 and 1st April 2016 we saw 383 men with NSU and tested 277 of them for MG
The majority were white heterosexual men. Most were HIV negative and median age was 30 years

7. Rates of infection NG 9 (3.2%) MG CT 43 73 (15.5%) (26.4%) MG + CT = 8
15.5% of men tested positive for M gen compared with 26.4% with CT and 3.2% GC. There were 8 men with MG and CT co-infection, and 1 with MG GC co-infection
MG + CT = 8
MG + NG = 1

8. Comparison between MG & Non-MG NSU
No significant difference between groups regarding:
Variable
MG Pos
MG Neg
p-value
Age (Mean)
30.8
33.1
0.205☨
PMNLs under microscopy (Mean)
2.8
2.5
0.200☨
No. of partners in 3/12 (Mean)
2.4
2.7
0.619☨
Heterosexual
63.1%
62.2%
0.549*
?Remove slide or say:
The were no significant differences between the MG and non MG urethritis groups in terms of Age, PMLs, Sexual orientation or number of partners in the past 3 months.
☨Independent t-test *Chi squared

9. Treatment and Test of Cure
NSU tested for MG
277
NSU treated with Doxycycline
233 (84.1%)
MG identified
43 (15.5%)
Returned for MG treatment
32 (74.4%)
Returned for TOC
23 (71.9%)
Positive TOC
7/23 (30.4%)
Treated with Moxifloxacin 6
Not treated 1
Of those tested for MG, 233 were given the standard first line treatment of Doxycycline and 43 cases of MG were identified.
Following recall, 32 reattended for a prolonged course of azithromycin.
23 of those treated returned for TOC and 7 were subsequently found to have positive TOC.
4 of the seven were re-treated with longer course azithromycin and 3 were given Moxifloxacin.
Further TOC data are unavailable for these 7 individuals  either because they only recently tested and are still awaiting test of cure or because they did not return for follow up.

10. Discussion MG accounted for 15.5% of NSU
25% of men with MG did not return for MG- specific treatment
?responded to doxycycline
30% of all TOCs were positive
?antibiotic resistance or re-infection
We found the rate of MG to be high, comparable to that of CT and much higher than GC.
A quarter of men with MG did not return for treatment with longer course azithromycin possibly because their symptoms had improved with 7 days of doxycycline. Whilst some mycoplasma does respond to tetracyclines, the efficacy of this drug against MG is poor and clearance of the organism cannot be assumed without performing test of cure.
Despite a testing pathway designed to avoid treatment failure, 30% of all tests of cure were positive, the implications for this being that these individuals either already had macrolide resistant MG or were re-infected and therefore at risk of developing subsequent resistance.

11. Conclusion
Testing for MG should be routine in men presenting with urethritis
MG detection should be accompanied by antimicrobial resistance testing
Antibiotic stewardship must be a priority for the future
Consider alternatives to single dose azithromycin
In conclusion, these are the first UK data for routine testing of MG and TOC in a real life setting and will help to inform future testing pathways with the advent of newer assays.
We have shown that MG is prevalent among men with NSU and recommend that it should be routinely tested for; however the threat of widespread macrolide resistance remains real and there is an urgent need for better diagnostics which will allow for the identification of MG to be accompanied by resistance testing. Antibiotic stewardship remains a priority and whilst quinolones therapy in the management of MG should be preserved as much as possible, alternatives to single dose azithromycin should be considered in the management of all STIs where possible.
Thank you very much for listening.