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Marie Pirotta, Jane Gunn, Patty Chondros, Sonia Grover, Paula O'Malley, Susan Hurley, and Suzanne Garland
Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial
BMJ 2004; 0: bmj.38210.494977.DEv1 [Abstract]
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Rapid Responses published:

[Read Rapid Response] POst-antibiotic probiotics
Gregor Reid   (5 September 2004)
[Read Rapid Response] Preventing vulvovaginal candidiasis
Sarah C Evans   (5 September 2004)
[Read Rapid Response] Re: Preventing vulvovaginal candidiasis
Marie Pirotta, Jane Gunn, Suzanne Garland   (9 September 2004)
[Read Rapid Response] Re: Post-antibiotic probiotics
Marie Pirotta, Jane Gunn, Suzanne Garland   (9 September 2004)
[Read Rapid Response] Re: Re: Post-antibiotic probiotics
Gregor Reid   (9 September 2004)

POst-antibiotic probiotics 5 September 2004
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Gregor Reid,
Director
Canadian R&D Centre for Probiotics, Lawson Inst, 268 Grosvenor Street, London, ON, N6A 4V2, Canada

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Re: POst-antibiotic probiotics

The recent study by Pirotta et al(1) unfortunately did not describe the antibiotics used nor their dosage or duration. As not all antibiotics induce yeast infections(2), this omission makes it difficult to analyse the significance of the findings. If we assume that all treatments were for 6 days and probiotics were not killed by simultaneous ingestion with the drugs, the antibiotics clearly had a severe and quick impact on the urogenital microbiota, similar to agents such as amoxacillin(3). In women prone to yeast vaginitis, agents such as fluoroquinolones or clarithromycin are better options to not disrupt the vaginal microbiota(2).

It is a pity the study did not identify and quantify indigenous Lactobacillus before, during and after treatment, as this would have better determined if their presence was associated with fewer yeast infections, or if the probiotic therapy led to heightened colonization, or if certain anti-yeast properties were expressed. Until these issues are clarified, all we can say from the present study is that an oral probiotic never shown to colonize the vagina or prevent urogenital infections, and a vaginal form shown in only one study to treat colpitis(4), do not prevent yeast vaginitis in patients treated with certain antibiotics. Fermalac likely functions by decreasing vaginal pH (thus the inclusion of S. thermophilus), a factor that is not restrictive to candidal growth. The use of probiotics such as L. rhamnosus GR-1 and L. fermentum RC-14 (not available commercially in Australia) known to colonize the vagina and significantly inhibit yeast growth(5) (Koehler G, personal communication), may have indeed reduced the incidence not only of candidiasis but also bacterial vaginosis2 post-antibiotic use. The authors are correct in that probiotics should not be used to treat vaginal candidiasis, however, the study provides insufficient evidence for health professionals to rule out all lactobacilli as adjunct therapeutics to prevent post-antibiotic urogenital infections.

1. Pirotta M, Gunn J, Chondros P, Grover S, O'Malley P, Hurley S, Garland S. Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. BMJ. 2004 Sep 4;329(7465):548 2. Reid G, Hammond J-A, Bruce AW. Effect of lactobacilli oral supplement on the vaginal microflora of antibiotic treated patients: randomized, placebo-controlled study. Nutraceut. Food. 2003, 8: 145-148. 3. Reid G, Bruce AW, Cook RL, Llano M. Effect on the urogenital flora of antibiotic therapy for urinary tract infection. Scand. J. Infect. Dis. 1990, 22: 43-47. 4. Chlebecek J, Reich I. [Fermalac Vaginal (Rougier Inc.) in the prevention of colpitis in pregnancy] Cesk Gynekol. 1993 Oct; 58(5):237-8. 5. Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R, Bruce AW. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol. Med. Microbiol. 2003, 35: 131-134.

Competing interests: I own patents on Lactobacillus strains GR-1 and RC-14

Preventing vulvovaginal candidiasis 5 September 2004
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Sarah C Evans,
General Practitiioner
Milton House Doctors Common Rd BERKHAMSTED Herts HP23 5PB

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Re: Preventing vulvovaginal candidiasis

It is very interesting and useful that Pirotta et al have had negative results fron their randomised controlled trial (RCT) using lactobacillus orally and vaginally with antibiotics . However, they are surely premature in telling us to inform our patients that lactobacillus is unlikely to prevent post-antibiotic vulvovaginitis. We may only tell women taking antibiotics that a four-day, concomitant course of lactobacillus in ineffective.

Maybe now Pirotta and colleagues would consider an RCT using a 2-4 week course of lactobacillus after the antibiotics combined with a sugar- free diet.

Competing interests: None declared

Re: Preventing vulvovaginal candidiasis 9 September 2004
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Marie Pirotta,
Senior Lecturer
Department of General Practice, University of Melbourne, 200 Berkeley St, Carlton, Australia, 3053,
Jane Gunn, Suzanne Garland

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Re: Re: Preventing vulvovaginal candidiasis

The correspondent is mistaken - all participants were asked to take the lactobacillus during their antibiotics and for four days afterwards: that is for ten days in total. Longer courses of lactobacillus may be acceptable to women prone to post-antibiotics vulvovaginitis, but our trial was not selecting for this. Interestingly, though, the average time to the development of symptoms of vaginitis was five days. So that in our sample post-antibiotic vulvovaginitis usually occurred while women were still taking the antibiotics.

Competing interests: Authors of the article

Re: Post-antibiotic probiotics 9 September 2004
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Marie Pirotta,
Senior Lecturer
Dept of General Practice, University of Melbourne, 200 Berkeley St, Carlton, Australia, 3053,
Jane Gunn, Suzanne Garland

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Re: Re: Post-antibiotic probiotics

One of the main strengths of our trial design was that it was community based, had few exclusion criteria and attempted to replicate how women themselves were self-medicating for prevention of post-antibiotic vulvovaginitis. A wide range of antibiotics was used, as would be expected in a community sample. The largest single grouping was amoxycillin (n = 80), which was evenly spread across study groups. The lactobacillus interventions were generally commenced on the first day of antibiotic use and continued until four days after antibiotics were ceased.

To define the lactobacillus microbiological flora prior, during and after the interventions would have been an extensive study in itself and was beyond our primary aim of testing a commonly used intervention in the community.

Dr Reid's assertion that other types of lactobacillus may have been effective would be strengthened if a plausible biological mechanism to support this view were also offered.

Competing interests: Authors of the publication

Re: Re: Post-antibiotic probiotics 9 September 2004
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Gregor Reid,
Director
Canadian R&D Centre for Probiotics, Lawson Inst, 268 Grosvenor Street, London, ON N6A 4V2, Canada

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Re: Re: Re: Post-antibiotic probiotics

I agree that the study has strengths, that the two probiotics did not appear to be effective, and the findings are interesting and likely representative of other community practices. The inclusion of extensive Lactobacillus and microbiota identification is labour intensive, but without this it is difficult to support the concluding comments regarding all lactobacilli probiotic therapies. Lactobacillus GR-1 and RC-14 produce anti-fungal factors, not yet fully identified. If indigenous strains produced these or other inhibitory factors in women who acquired yeast vaginitis, then we might conclude that clinically such effects are not important. If women with candidiasis were colonized by Lactobacillus not producing any evidence of anti-yeast activity, while those who did not become infected did have such strains, then clearly this presents a different scenario.

As yet, we don't know how and why urogenital infections arise in women. One reason could involve antibiotics like amoxacillin killing or disrupting the indigenous microbiota. In cases of BV and UTI there is usually a depletion of lactobacilli, and rapid growth of pathogens shortly before symptomatic infection. A study of the flora prior to candidiasis might help us understand what happens, including the extent to which a given antibiotic adversely affects it. If probiotic strains are not killed by the antibiotic, and produce factors that inhibit yeast colonization (adhesion,and replication) or modulate immunity so that inflammation, discharge and symptoms do not arise, I believe they could be beneficial. I agree that the trigger for rapid yeast multiplication and induction of a host response may be irrespective of the lactobacilli, but this too needs to be proven. My point is not to rule out the potential for probiotic intervention based on a clinical study of two products.

Competing interests: I own patents on Lactobacillus strains GR-1 and RC-14