Experimental injection of 'good' bacteria significantly cut bacterial vaginosis recurrence rate — study
Bacterial vaginosis (BV), an inflammatory condition caused by the proliferation of “bad” bacteria naturally found in the vagina, can affect up to half the women of reproductive age worldwide. Despite treatment with antibiotics, up to three in four women get recurrent infections within three months. But injecting a ‘good’ bacterium to subdue its deleterious peers can slash that high recurrence rate by a third, new clinical trial data suggest.
A 228-patient, placebo-controlled study funded by the NIH evaluated the effect of a ‘good’ bacterium product, called Lactin-V, which was packaged by California-based microbiome company Osel. The product, which is formulated as a powder containing a strain of the bacterium Lactobacillus crispatus, was injected into the vagina using a plastic device that resembles a tampon applicator — after patients were treated with a course of the antibiotic metronidazole in gel form.
At the three month mark, BV recurrence occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (confidence interval: 0.44 to 0.87; P=0.01) — meeting the main goal of the study. At week 24, there were 27% fewer cases of BV among those who got Lactin-V. No evidence emerged suggesting that Lactin-V causes any local or systemic side effects.
This is really the first major breakthrough in the field, providing adjuvant treatment as an option for women suffering from recurrent BV, if we can confirm the findings in a definitive pivotal phase III trial, the study’s lead investigator Craig Cohen, a professor of obstetrics, gynecology and reproductive sciences at the University of California, San Francisco, told Endpoints News.
Other efforts, such as fecal transplants for C. difficile, have bet on entire microbial communities to fight stubborn infections, he noted. “So for a single strain, to my knowledge, this may be the first live biotherapeutic to demonstrate efficacy.”
Trial data also showed that among women who injected Lactin-V, L. crispatus bacterium was detected in 79% of women at week 12 and 48% at week 24. In the placebo group, the bacterium was found in 6% of women during week 12 and 2% at week 24.
“Although combination metronidazole–probiotic regimens have been tested previously and some have been shown to reduce the risk of recurrence of bacterial vaginosis, the trials have generally been small and have lacked the use of standardized methods, including objective outcome measures for bacterial vaginosis recurrence and colonization by the active trial medication,” the researchers wrote in the New England Journal of Medicine, where the study was published on Wednesday.
The study was funded by the NIH, although Osel provided Lactin-V, which is also being tested as a treatment for recurrent urinary tract infections, in vitro fertilization and preterm birth by the company. A late-stage BV trial is also being planned by Osel, pending discussions with the FDA.
“We think this is a really important landmark in the field, it’s the first study to really show with a rigorously conducted trial, a statistically significant reduction (in BV recurrence rates). We also have been able to show the relationship between microbiota and prevention of BV recurrence, which in the past is something that in the microbiome field has been sort of in the realm of associations,” said Tom Parks, Osel’s director of product development said in an interview.
“So we’re putting a causal relationship together here to show that microbiota can be impacted by the introduction of an exogenous lactobacillus.”
The allure of L. crispatus
Lactin-V contains Lactobacillus crispatus, a strain of bacteria that has long known to be a beneficial component of the vaginal microbiome by primarily producing lactic acid. The resulting low pH constitutes a strong deterrent against the overgrowth of opportunistic pathogens. Data also suggest that these lactobacillus species are strongly associated with reproductive health, full-term birth and combating sexually transmitted infections.
In a recent study led by Jacques Ravel, who serves as the co-editor-in-chief of the journal Microbiome, found that the diversity of L. crispatus strains is in the region of 5,000. That finding, Ravel explained in a previous interview with Endpoints News, has major implications.
“From one woman to another, they might carry that same species, but it’s often not the same strain,” he said.
“What this means is that this concept of one strain solving all the problems is kind of gone. And that each woman actually has a microbiome, even though it’s dominated by a species, that species is represented by many, many different strains. So it’s almost like a little consortium of strains that are together — from the same species — but those strains work together in providing different functions. The whole consortium of all those strains together makes them stronger.”
When Osel started working on Lactin-V, scientists didn’t have the tools to interrogate the vaginal microbiome as they have now, Cohen said, adding that the strain of L. crispatus used in the product was taken from an African American woman in Seattle (BV has a relatively higher prevalence in women of color).
This trial data on Lactin-V “been a long time coming,” Parks said, explaining that the strain the company chose was determined by a number of factors including its ability to latch on vaginal epithelial cells and produce lactic acid.
“We’re hoping that this will basically put the vaginal microbiome on the map and lead to more and improved treatments for female reproductive health purposes.”