Diagnosis and antimicrobial treatment of Mycoplasma genitalium infection: sobering thoughts

Abstract

The discovery of Mycoplasma genitalium in 1980–1981 eventually led to it becoming recognized as an important cause of non-gonococcal urethritis in men and also some genital tract diseases in women. Subsequent to the original isolation, further attempts failed over the next decade and reliable detection only became possible with the use of nucleic acid amplification techniques. Although tetracyclines, particularly doxycycline, were the first choice for treatment of non-gonococcal urethritis prior to the finding of M. genitalium, they were unsatisfactory for the treatment of M. genitalium-associated disease; the organisms were often not eliminated leading, for example, to chronic urethritis. However, the introduction of azithromycin, used as single-dose therapy for chlamydial infections, resulted in clearance of the mycoplasmal organisms from the genital tract and clinical recovery without the development of chronic disease. Nevertheless, such success was short-lived as M. genitalium, through mutation, began to develop resistance to azithromycin and M. genitalium mutants also began to circulate in some populations. In an attempt to counteract this, clinicians should give extended therapy, and in the future, microbiologists, using real-time PCRs, might be able to determine the existence of resistant strains in the local population and so advise on the most appropriate antibiotic. Other than azithromycin, there are a few options, moxifloxacin being one, although the recently reported resistance to this antibiotic is disturbing. In the short to medium term, combination therapy and/or the advent of a new antibiotic might abate the spread of resistance, but in the long term, there is potential for increasing prevalence of untreatable M. genitalium disease. In the future, attempts to develop a vaccine and, of equal importance, one to Chlamydia trachomatis, would not be out of place.

Keywords::

• antimicrobials
• diagnosis
• Mycoplasma genitalium
• resistance
• sensitivity
• treatment

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The discovery of Mycoplasma genitalium and its recognition as a major cause of genital tract infection and disease in men and women has stimulated considerable interest in its pathogenicity, epidemiology and in various issues surrounding the best approach to antibiotic treatment.

• The difficulty in detecting M. genitalium after original isolation in culture was frustrating but eventually overcome by the use of nucleic acid amplification techniques. Real-time PCRs have been helpful in diagnosing infection and, to some extent, in defining antibiotic susceptibility. There are now commercially available kits, particularly in Europe, designed specifically to detect M. genitalium or multiplex kits available to the public. The latter raises the issue of whether there is sufficient sensitivity provided by a multiplex approach and the need for guidance regarding treatment, particularly when there is more than one positive result.

• The development of antibiotic resistance by M. genitalium, first to the tetracyclines, then to the macrolides and most recently to the fluoroquinolones, has an obvious and serious impact on treatment. Strains of M. genitalium that are resistant to macrolides are common and widespread. Thus, before the use of azithromycin, it is wise to have some knowledge of the antibiotic sensitivity of the infecting strain involved. This applies to any other antibiotic that is considered for treatment.

• The resistance to greater or lesser degree of all antibiotics tried so far is disturbing. However, there are others that have good activity in vitro, but have had little or no testing in vivo. These include pristinamycin, solithromycin and possibly sparfloxacin and gemifloxacin, all of which need clinical evaluation. Sitafloxacin has been found to be effective in some trials, but needs further clinical testing. The effect of more than one antibiotic in combination needs evaluation.

• All the antibiotics mentioned above could come into use in the next 5 years and slow the specter of resistance to all antibiotics. If the latter occurs and, indeed before it might occur, it will be prudent to make efforts to produce a vaccine against M. genitalium.