Craig Cohen, Bixby Center UCSF

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.”

J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

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