Nov. 8, 2004 PITTSBURGH, Nov. 1 – In the first study to directly compare the emergence of antibiotic resistance following topical treatment between two antibiotics routinely prescribed for a common vaginal infection, researchers from the Magee-Womens Research Institute have found antibiotic-resistant bacteria more likely to develop with the drug clindamycin than metronidazole. The study is being published in the October issue of the American Journal of Obstetrics and Gynecology.
Researchers followed 99 women between the ages of 18 and 45 who were being treated for bacterial vaginosis (BV), a common gynecological complaint that infects up to 50 percent of women in some populations. BV is characterized by an increase in vaginal alkalinity and substitution of certain beneficial bacteria, particularly those that produce hydrogen peroxide, with more toxic bacteria. Among the infection's more prominent symptoms is a milky, foul-smelling discharge.
"Symptoms of discharge are one of the most common reasons women visit a gynecologist," said Sharon Hillier, Ph.D., professor in the departments of obstetrics, gynecology and reproductive sciences and molecular genetics and biochemistry at the University of Pittsburgh School of Medicine and senior author of the study. "For years, clinicians have thought of BV infection as a minor problem, but studies have shown that women who have BV are more likely to get herpes and other sexually transmitted diseases, including HIV."
For the antibiotic-resistance study, investigators traced the frequency and median concentrations of vaginal microbes from women with BV before and after treatment with vaginal preparations of clindamycin or metronidazole, according to Richard Beigi, M.D., a former fellow in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine, who now is with MetroHealth Medical Center in Cleveland, and the study's first author. Dr. Beigi was part of the Magee program when the antibiotic-resistance study was completed. Vaginal specimens were collected before treatment began and were compared with those collected during three consecutive follow-up visits. Antibiotic resistance testing also was performed.
Specifically examined were 10 groups of bacteria, including Lactobacillus spp, Gardnerella vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, Escherichia coli, Enterococcus spp, Prevotella bivia, Prevotella spp (pigmented and non-pigmented) and Porphyromonas spp. Analysis included data for women in whom therapy failed as well as those whose infection was cured, he said.
While some bacterial concentrations decreased for both groups, women treated with clindamycin experienced more frequent increases in bacterial concentrations of E. coli than those who were treated with metronidazole. In addition, women treated with metronidazole showed more significant decreases in concentrations of other bacteria such as P. bivia, pigmented Prevotella spp and U. urealyticum compared to clindamycin treatment, Dr. Beigi said.
"Fewer than 1 percent of bacterial samples we tested demonstrated resistance to metronidazole," said Dr. Beigi. "In contrast, 12 percent demonstrated baseline clindamycin resistance, and 53 percent demonstrated resistance to clindamycin after therapy."
In addition, women treated with clindamycin (but not metronidazole) showed evidence of clindamycin-resistant bacteria that persisted for 90 days after treatment at rates as high as 80 percent, Dr. Beigi said.
Metronidazole therapy resulted in increased colonization by protective Lactobacillus species in the week following therapy compared to the women treated with clindamycin.
Testing of pigmented Prevotella spp and P. bivia also revealed significant resistance – 75 percent and 57 percent, respectively – to clindamycin following therapy. Metronidazole resistance was far more rare at 0.5 percent and did not increase after treatment.
"Study results suggest that metronidazole and clindamycin differ in their effects on microbes in women with BV," said Dr. Beigi. "Increased bacterial resistance following clindamycin treatment may account for persistence of some pathogens after therapy."
Dr. Hillier said she believes these study results have the possibility to significantly impact standard BV treatment. "I think any time you find out that use of an antibiotic results in a huge antibiotic resistance, it's important," she said. Treatment decisions, however, remain the province of individual physicians and patients, Dr. Hillier added.
In addition to Drs. Beigi and Hillier, other study authors include Michele Austin, B.S.; Leslie Meyn, M.S.; and Marijane Krohn, Ph.D., all of the University of Pittsburgh. The study was funded by an unrestricted grant from 3M Pharmaceuticals, manufacturer of MetroGel-Vaginal, a metronidazole-containing treatment for bacterial vaginosis, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
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