Roughly one out of three women ages 14-49 in the United States develop a vaginal bacterial imbalance known as bacterial vaginosis (BV) during their lifetime. BV is characterized by unpleasant odors, and potentially painful side effects, as well as the risk of associated health issues later in life. More than half of the patients who seek medical care do not respond to the first-line treatment, the antibiotic metronidazole, leading to recurrence.
Now Drexel researchers have developed a simple DNA PCR-based lab test — built on a more detailed genetic analysis of the main group of bacterial organisms that cause the infection — to help clinicians prescribe the right medicine for each patient. The results are published this week in the journal Genome Medicine.
“If this test becomes available to patients, they can avoid taking the wrong antibiotic, avoiding additional potential side effects and financial costs,” said lead author Katherine Innamorati, PhD, an instructor in Drexel University College of Medicine. “Faster treatment and better antibiotic stewardship is especially important for patients who may need to take multiple courses of antibiotics to fully eliminate the infection.”
The main bacterial pathogens associated with BV are a group of related bacterial species previously known as Gardnerella vaginalis. Earlier work by Garth Ehrlich, PhD, a professor of Microbiology and Immunology in the College of Medicine, and colleagues revealed that this group is actually composed of multiple species.
In the current paper, the authors built out this “family tree” much further. Using genome sequencing and genomic metrics on 129 Gardnerella spp. genomes, the team performed a detailed analysis revealing much greater diversity, including identifying 11 unique groups of organisms known as genospecies, which fall within several major clades, or groupings.
Using this data, the research team found that two of the clades are composed of five genospecies that are 100% resistant to metronidazole, but can be successfully treated with the antibiotic clindamycin. Both drugs are typically taken for a week and can be administered vaginally or by mouth. The team’s PCR test can distinguish among the strains, identifying ones that are highly resistant to metronidazole.
Symptomatic patients can experience vaginal itching, burning during urination, foul odor or gray, white or green discharge. BV is not considered a strictly sexually transmitted infection, but some sexual activities, including not using a condom, and other activities can increase the likelihood of developing BV.
An estimated half of BV cases show no noticeable symptoms, leading to many cases going untreated. Although about 30% of BV cases resolve without treatment, those with untreated cases may be at higher risk of sexually transmitted infections, greater likelihood of pregnancy complications and other negative impacts to quality of life resulting from inflammation of the mucosa in the reproductive tract.
“BV is a dysbiosis, meaning the whole microbiome of the lower reproductive tract is imbalanced,” said Ehrlich. “It’s possible that some patients may need both drugs — metronidazole might provide coverage for some microorganisms, particularly anerobic bacteria that grow in the absence of oxygen. So those with metronidazole resistant Gardnerella might benefit from treatment using both antibiotic drugs, but more research is needed to find out.”
The researchers have filed for a patent for the test. A commercial lab would be needed to offer this widely to patients. Demand from patients and patient support groups may help influence when such a test would become available. Right now, the test can help rule out metronidazole treatment based on highly resistant strains, and the team aims to expand its capabilities to also identify strains that have low resistance to metronidazole.
The team is also working on determining what gene(s) cause a resistant phenotype.
“It’s possible that expression of a gene could play a role in the resistance to an antibiotic, or help explain one aspect of how that resistance occurs, but our data suggests metronidazole resistance happens through multiple mechanisms, rather than one clear pattern,” said Ehrlich. “Much work remains to more fully understand the mechanisms by which different groups of genetic organisms become resistant to metronidazole.”
New randomized controlled trial data published this month in the New England Journal of Medicine suggested that women with BV who are in a monogamous relationship with a male partner may have a lower likelihood of BV coming back after 12 weeks if she takes the first line antibiotics while her male partner also takes the antibiotic and applies a topical antimicrobial clindamycin cream.
Additional authors on the study include Joshua P. Earl, Shirley C. Barrera, Rachel L. Ehrlich, Josephine Aiyeku, and Ari Gordon of Drexel, Evan Powell of University of Pittsburgh Medical Center, Adam C. Retchless of Allegheny Singer Research Institute, Azad Ahmed, Bhaswati Sen, Sergey Balashov, and Joshua Chang Mell of Drexel, and Sharon L. Hillier of the University of Pittsburgh.
