new test for M Genitalium, a frequent cause of STIs

The FDA just approved the 1^st test to aid in the diagnosis of the sexually transmitted infection Mycoplasma genitalium (see https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629746.htm  )

Details:

-- M genitalium is a bacterium associated with non-gonococcal urethritis in men, and cervicitis and PID in women

-- M genitalium is responsible for 15 to 30% of persistent or recurrent urethritis in men in the US, and 10 to 30% of cervicitis in women

-- the test that was approved is a nucleic acid amplification test (NAAT) which detects M. Genitalium in urine, urethral, penile meatal, endocervical or vaginal swab samples

-- efficacy data of the new assay for M genitalium, from 11,774 samples:

    -- correctly identified in 90% of vaginal, male urethral, male urine and penile samples

    -- correctly identified in 77.8% of female urine and 81.5% of endocervical samples (vaginal swabs did better than sampling these sites)

    -- specificity 97.8-99.6%

------------------------------------------------

There was an updated review of Mycoplama genitalium (see mycoplasma genitalium review InfDrugResist2017 in dropbox, or Sethi S. Infection and Drug Resistance 2017; 10: 283-92).  This review updates my prior blog  http://gmodestmedblogs.blogspot.com/2015/06/m-gentialium.html 

Details:

-- M genitalium is ubiquitous in the world, prevalence rates ranging from 0.4% in young adults in the US to 4.5% in the Netherlands. 40 to 75% of cases in women and 70% in men are asymptomatic (note: these numbers from this article do differ from some others i have seen)

-- in particular, the association between M genitalium and STIs in men:

    --18-46% of non-GC, non-chlamydial infection (NCNGU)

        -- a study in the UK showed that non-gonococcal urethritis was related to M genitalium, ranging from 6 to 50% of cases

        -- a meta-analysis found M genitalium in 21% of men with acute NCNGU vs 7% of controls

        -- M genitalium is particularly common in men with recurrent urethritis following treatment with doxycycline (see treatment below, noting high levels of resistance)

        -- the association in men for urethritis is clearer than the associations below in women

    -- complications of M genitalium in men include: sexually acquired reactive arthritis, epididymitis, balanitis, and rarely conjunctivitis

--in women:

        -- 3-fold increased risk of mucopurulent cervicitis, after controlling for other STIs

        -- 2-fold increase in risk of PID

    -- complications of M genitalium in women: sexually acquired reactive arthritis, adverse pregnancy outcomes, and perhaps tubal infertility

-- as with other STIs, co-infection is common: one study in men found M genitalium associated with chlamydia in 35%, gonorrhea in 14% and both in 19%

-- M genitalium seems to be easily transmitted sexually, a study of 39 couples found 58% concordance (which is higher than the rate for chlamydia). It has also been found in anorectal swabs, with perhaps higher transmission rate than with vaginal intercourse, and there is a significant relationship between positive urethral samples and dysuria in MSM. it has also been found in the respiratory tract of neonates (though vertical transmission is still unclear)

-- HIV: several studies suggest an association between M genitalium and HIV acquisition; eg, higher HIV rate in high-risk women who had M genitalium in the 3 months prior to HIV infection. this is postulated to be from M genitalium decreasing the integrity of the endocervial epithelial barrier. And, HIV-positive women may clear their M genitalium infections more slowly than HIV negative women. M genitalium, which adheres to HIV-infected cells, may also enhance HIV viral release from those cells (shown in vitro)

Treatment:

-- M genitalium lacks a cell wall and is therefore not sensitive to antibiotics that inhibit cell wall formation (e.g. penicillins)

-- tetracyclines: doxycycline has been the most used but has response rates now only in the 30 to 40% range

-- macrolides: azithromycin seems to be the best of them, initial cure rates with single dose of 1 g of 85% response, but this has decreased to the 40 to 50% range in many areas. A recent study of 946 patients in the US found macrolide-resistant M genitalium in 51% of women and 42% of men. In Europe, macrolides are still recommended as the first-line antibiotic.

-- fluoroquinolones: moxifloxacin 400mg daily for 7-14 days is recommended for treating macrolide-resistant M genitalium, with initial studies showing excellent eradication. But there is increasing fluoroquinolone resistance and treatment failure, up to 47% in Japan, 15% in Australia

-- there are intriguing data about spectinomycin, which has been used in the past as an alternative treatment for GC

--and there are a few other agents in the pipeline, including the well-tolerated but quite expensive pristinamycin, which is about 75% effective when prior treatment with azithromycin, moxifloxacin, and doxycycline fail (eg, see https://wwwnc.cdc.gov/eid/article/24/2/17-0902_article )  

Commentary:

-- the CDC considers M genitalium to be one of the emerging issues in their guidelines, in part because antibiotic resistance to M genitalium has been increasing dramatically

-- My interest in sending out this update is:

    -- M genitalium infections are not so well-known to many of us in primary care, and may need to be treated differently given this resistance pattern

    -- a more general concern is that with the ease of getting urinary gonorrhea/chlamydia testing, some providers may be just getting this test to diagnose an STI, including PID, and missing other important infections.  in fact, the STI guidelines from the CDC note that <50% of PID cases are associated with gonorrhea or chlamydia (see http://gmodestmedblogs.blogspot.com/2015/06/new-std-treatment-guidelines.html  ).

--my prior blog based on a Netherlands study suggest that the preferred treatment for M. genitalium is 1.5 gm of azithromycin (500 mg once, then followed by 250 mg daily for 4 days), vs the CDC recommendation for 1gm once, since this single-dose treatment "has been shown to lead to a greater development of resistance to macrolide antibiotics".  see http://gmodestmedblogs.blogspot.com/2015/06/m-gentialium.html 

so, Mycoplasma genitalium is being increasingly recognized as a sexually-transmitted infection, in many ways similar to chlamydia. The concerns have been with diagnosis (which may be easier now with the newly approved FDA test) and with treatment (especially since it may need different meds: doxycycline does not work well, and azithro is becoming less good over time). And, we should have a heightened suspicion for M genitalium infection in patients with apparently resistant or recurrent infections....

related older blogs:

http://gmodestmedblogs.blogspot.com/2018/10/congenital-syphilis-and-other-stis-on.html : 2017 CDC surveillance report noting increases in chlamydia, GC and syphilis in the US, with notable increases in congenital syphilis in newborns

http://gmodestmedblogs.blogspot.com/2016/07/gonorrhea-resistance-increasing.html  which also references many prior blogs on antimicrobial resistance, including the WHO report that there was >25% resistance of GC to ceftriaxone in 3 of the 6 regions in the world, and that we are moving to a time when GC may be resistant to the 2 major drugs (ceftriaxone and azithromycin)

geoff

If you would like to be on the regular email list for upcoming blogs, please contact me atgmodest@uphams.org

to get access to blogs since 8/15/17:

1. go to http://gmodestmedblogs.blogspot.com/ to see them in reverse chronological order

2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category

3. or you can just type in a name in the search box and get all the blogs with that name in them

to access older blogs from the BMJ website, from October 2013 until 8/15/17: go to http://blogs.bmj.com/bmjebmspotlight/category/archive/ 

please feel free to circulate this to others. also, if you send me their emails, i can add them to the list