Two Fastidious Bacteria Linked to Pelvic Inflammatory Disease



MINNEAPOLIS – Evidence suggests that two novel fastidious bacteria linked to bacterial vaginosis are also associated with pelvic inflammatory disease.

Ureaplasma urealyticum biovar 2 (UU-2) and Leptotrichia sanguiengens/Leptotrichia amnionii (LS/LA) were significantly associated with PID after adjustment for age, race, chlamydia, and gonorrhea.

Ureaplasma parvum (UP), however, was not associated with PID in a substudy of women participating in the PEACH (PID Evaluation and Clinical Health) study.

Patrice Wendling/IMNG Medical Media

Dr. Catherine Haggerty

"This is the first study to demonstrate that [LS/LA] and UU-2, but not UP, are associated with PID," lead author Catherine Haggerty, Ph.D., said at the annual meeting of the Society for Pediatric and Perinatal Epidemiologic Research.

The results are consistent with studies showing that UU-2 is associated with nongonococcal urethritis in men, whereas UP is not. UU-2 and UP, also known as biovar 1, were recently designated as two distinct biovars. UP has not been consistently associated with bacterial vaginosis (BV) or PID.

The investigators used polymerase chain reaction (PCR) to measure select BV-associated, fastidious bacteria in cervical and endometrial specimens from 607 of 831 women recruited from emergency department and outpatient clinics during 1996-1999 for PEACH. The multicenter, randomized study compared the effectiveness of inpatient and outpatient treatment for PID.

The PEACH cohort was largely (75%) African-American, 40% were aged 20-24 years, half had an upper genital infection or inflammation, and 35% had gonorrhea or chlamydia.

Among the women in the subset, 22% had LS/LA only, 17% UP, 4% UU-2, 46% were coinfected with two or more bacteria, and 11% had no infection, said Dr. Haggerty, a reproductive epidemiologist with the University of Pittsburgh.

In adjusted logistic regression analysis, women who tested positive for LS/LA, UP, or UU-2 in the lower genital tract (cervix) were approximately 10, 13, and 20 times as likely, respectively, to test positive in the upper genital tract (endometrium).

Contamination during sampling is one possible explanation, but "still, the data provide intriguing evidence that there may be an upward transmission of these bacteria that may lead to the development of [PID]," she said.

Indeed, the likelihood of a woman having endometritis was significantly increased if she tested positive for UU-2 (adjusted odds ratio, 1.4) or LS/LA (OR, 2.2) in the endometrium, but not UP (OR, 0.8).

Among those women without gonorrheal or chlamydial infection, the risk of PID (histologically confirmed endometritis) was further increased with UU-2 (OR, 2.5) and LS/LA (OR, 2.7), but not UP (OR, 0.8).

The results may be important in guiding PID treatment, which currently consists of broad-spectrum antibiotics that may not target all the bacteria associated with the disorder, Dr. Haggerty said. UU-2 expresses tetracycline resistance in up to 45% of patients, while antimicrobial resistance to Leptotrichia is largely unknown because of the difficulty in culturing fastidious bacteria in vitro.

In addition, resistance to vaginal metronidazole has been reported among pregnant women with BV who carry the Leptotrichia or Sneathia species or BV-associated bacterium 1 (BVAB1) (BMC Infect. Dis. 2009;9:89). Metronidazole is a mainstay of BV treatment, but the Centers for Disease Control and Prevention still lists it as optional for PID, despite the frequent coexistence of the two conditions, Dr. Haggerty said.

"Studies are needed to determine treatment of these bacteria in general, as well as among PID patients," she said.

During a discussion of the study, an audience member questioned whether PCR is taking over as the diagnostic criterion for PID because many of the bacteria cannot be identified without it. Dr. Haggerty replied that we are moving in that direction, as a result of the "landmark study" by Dr. David Fredricks et al., reporting high sensitivities and specificities for several bacteria or combinations of bacteria identified using targeted PCR versus the Amsel (clinical) or Nugent (Gram stain) criteria (J. Clin. Microbiol. 2007;45:3270-6).

Dr. Haggerty and her coauthors reported no conflicts of interest. The substudy was funded by the National Institutes of Health/National Institute of Allergy and Infectious Diseases. PEACH was funded by the Agency for Health Care Policy and Research, now known as the Agency for Healthcare Research and Quality.

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