M. genitalium appeared in 28 (18%) of 157 diagnosed women with acute PID who were enrolled in a study that had primarily focused on comparing two antibiotic regimens, and in 30% of those women with histologically proven acute PID. Using an in-house transcription-mediated assay for M. genitalium, researchers at the University of Pittsburgh found that endometrial identification of M. genitalium linked independently with a fourfold increased prevalence of histologically confirmed acute PID.
Those numbers for M. genitalium put it in the same ball park in the study with the two traditional heavy hitters of acute PID, N. gonorrhoeae and C. trachomatis. By establishing a significant role for M. genitalium in acute PID, the data immediately called into question the standard empiric therapies for acute PID.
"The PID treatments we use fall short for eradicating M. genitalium," said Dr. Wiesenfeld, an ob.gyn. and infectious diseases physician at the University of Pittsburgh, who reported the results. "Whether these findings [affect] treatment guidelines for acute PID remains to be seen; but if it is truly important to treat M. genitalium, it will completely turn around our treatment regimens."
The looming dilemma is that the azithromycin or doxycycline used for gonorrhea will not stop many of the infections by M. genitalium, while the moxifloxacin that can handle most M. genitalium today does not eradicate N. gonorrhoeae.
However, it’s premature to consider routinely testing or screening for M. genitalium in patients with PID or other possible forms of M. genitalium infection, Dr. Wiesenfeld cautioned. That’s in part because of the current logistical limitations on testing, and in part because the long-term impact of M. genitalium infection on reproductive health is not yet established. Longer follow-up of women in the study should shed more light on the natural history of the patients who received treatments that did not eradicate M. genitalium.
"If M. genitalium turns out to be associated with PID, it is the single organism that is not covered by current treatment with a cephalosporin, doxycycline, and metronidazole," said Sharon L. Hillier, Ph. D., in an interview during the meeting. "We are very concerned about it because it is a fairly sizable fraction of the STIs we’ve seen in these women with acute PID," said Dr. Hillier, professor of ob.gyn. and reproductive sciences at the University of Pittsburgh and a collaborator with Dr. Wiesenfeld on his study.
Dr. Hillier agreed that the key question to address is the fertility risk to women from having PID caused by M. genitalium.
"It’s so common that it might have a huge population impact," she said. "We know fertility outcomes are bad from gonorrhea and Chlamydia." The fertility risk from M. genitalium "will be what makes us decide if we need to add another treatment."
Adding moxifloxacin to routine, empiric treatment for acute PID would be an especially tough call if it also meant dropping doxycycline, a drug that is otherwise attractive because of its low cost and broad spectrum of activity against other PID pathogens.
"It remains to be seen what we should do for empiric therapy for women who walk in with PID, what is the best way to try to preserve her fertility," Dr. Hillier said. "We simply don’t know right now, but it’s been a huge topic of conversation."
Changing the treatment strategies
While the best initial management strategy for acute PID remains unclear, the specter of M. genitalium has already changed the management strategy used by Dr. Paddy Horner to treat men with NGU, said Dr. Horner, a physician in the school of social and community medicine at the University of Bristol, U.K.
These days, his preferred approach is what he calls "infection-specific" first-line therapy: Before treatment begins, he eliminates purely empiric therapy by employing a commercially available, nucleic-acid amplification test for gonorrhea and Chlamydia at the first encounter and getting the result in 30 minutes.
That means treating men who test positive for Chlamydia with a week of doxycycline first, or starting with a 5-day course of azithromycin for men who are Chlamydia negative. However, he advised using a single, 1-g dosage of azithromycin with caution, because of the prevalence of macrolide resistance. But Dr. Horner also admitted that no evidence has proven the superiority of the 5-day alternative that starts with a 1-g dose followed by 500 mg daily for 4 more days. Men who test positive for N. gonorrhoeae should receive 1 g of azithromycin plus 500 mg ceftriaxone.
If the urethritis persists 2 weeks later, Dr. Horner recommended treating patients empirically with a combination of moxifloxacin and metronidazole to cover possible infection by either M. genitalium or U. urealyticum.