VIENNA – Mycoplasma genitalium is a new bad boy of sexually transmitted infections, prompting experts to rethink how to treat nongonococcal urethritis, pelvic inflammatory disease, and other infections caused by the pathogen.
The full scope of M. genitalium in sexually transmitted infections (STI) of men and women is just now becoming clear – as are the treatment demands of M. genitalium’s susceptibility profile. Given that it’s notoriously hard to culture and that genetic-based assays are only recently available and not yet sold commercially, reliable management of M. genitalium depends on the fluoroquinolone moxifloxacin. Yet the threat of widespread resistance to that drug looms, with no good back-up agents currently available.
Because successful treatment of M. genitalium differs sharply from that of gonorrhea and Chlamydia trachomatis – the other two pathogens most common in urethritis, cervicitis, and pelvic inflammatory disease – clinicians increasingly confront infections unresponsive to or persistent despite a course of doxycycline or azithromycin (Zithromax).
Podium talks from a series of researchers in the United States and Europe at the joint meeting of the International Society for Sexually Transmitted Diseases Research and the International Union Against Sexually Transmitted Infections documented the STI niche that M. genitalium occupies and how well various antibiotics work against the pathogen.
"M. genitalium is associated with 15%-22% of nongonococcal urethritis cases, and 10%-15% of cervicitis cases, and in many settings is more common that Neisseria gonorrhoeae with treatment outcomes often far worse," said Lisa E. Manhart, Ph.D., an epidemiologist at the University of Washington, Seattle. "There is no characteristic clinical syndrome for M. genitalium infections; they look very similar to Chlamydia. Clinical judgment is the only option for treatment decisions in many settings, and no FDA-approved diagnostic test [for M. genitalium] exists."
Persistent cases of nongonococcal urethritis, cervicitis, and possibly pelvic inflammatory disease could benefit from treatment with moxifloxacin (Avelox), Dr. Manhart noted. But "it is becoming clear that resistance in M. genitalium develops rapidly."
"M. genitalium is an important STI, and guidelines should reflect this; but there is no good evidence base for optimal treatment. Optimal treatment is a moving target," said Dr. Jørgen S. Jensen, a researcher at the Statens Serum Institut in Copenhagen.
"Widespread use of azithromycin and moxifloxacin will select for multidrug-resistant strains; the time for single-drug, one-dose regimens is probably over," said Dr. Jensen, specifically referring to the common practice of treating nongonococcal urethritis with a single dose of azithromycin.
M. genitalium invades U.S.
Dr. Manhart and a second U.S. researcher, Dr. Harold C. Wiesenfeld from the University of Pittsburgh, each reported new data at the meeting showing how common M. genitalium STI infections have become among U.S. patients.
Dr. Manhart presented new data from the MEGA (Mycoplasma Genitalium Antibiotic Susceptibility and Treatment) trial, which enrolled 606 men with nongonococcal urethritis (NGU) at an STI clinic in Seattle. The study’s primary endpoint was a comparison of 100 mg doxycycline b.i.d. for 7 days and a single 1-g dose of azithromycin.
The two regimens produced similar cure rates – 76% in the doxycycline arm, and 80% in the azithromycin arm, Dr. Manhart and her associates reported earlier this year (Clin. Infec. Dis. 2013;56:934-42). The initial report also identified M. genitalium in 13% of those men – identified using an in-house polymerase chain reaction assay – compared with 24% who tested positive for Chlamydia and 23% infected with Ureaplasma urealyticum biovar.
The new analyses Dr. Manhart reported tracked the outcomes of patients infected with M. genitalium. Treatment with either of the standard doxycycline or azithromycin regimens failed about half the time, Dr. Manhart said: 29% of men with doxycycline-resistant infections who were retreated with azithromycin as part of the study’s extended protocol carried M. genitalium, and 70% of the men who failed initial azithromycin treatment who were then retreated with doxycycline had persistent infection with M. genitalium.
Results from the extended portion of the study also showed that treatment with moxifloxacin was the answer for most of the otherwise unresponsive M. genitalium infections, but it wasn’t perfect. The M. genitalium infection persisted in 12%-15% of those men after a full course of moxifloxacin.
The full results suggest that moxifloxacin is potentially effective for treating various persistent STIs, not only NGU but also cervicitis and possibly pelvic inflammatory disease (PID). But resistance to moxifloxacin develops "rapidly," meaning that surveillance for resistance is needed, as well as new drug alternatives, she said.
New suspect in acute PID?
Although Dr. Manhart hedged on the role of M. genitalium in PID, results from a different U.S. study created a strong case for a role in acute PID.