Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial
BMJ. 2004 Sep 4;329(7465):548. Epub 2004 Aug 27.
Pirotta M, Gunn J, Chondros P, Grover S, O’Malley P, Hurley S, Garland S.
Pirotta and colleagues report on a randomized, placebo controlled trial to evaluate the effectiveness of two different probiotic preparations on preventing vulvovaginal candidiasis in women taking antibiotics. The supplements tested were: (1) Lactobac, an oral supplement comprised of Lactobacillus rhamnosus and Bifidobacterium longum; and (2) Femilac, an intravaginal application containing Streptococcus thermophilus, L. rhamnosus, L. delbreuckii and L. acidophilus.
The study was designed with four groups: (1) the oral product + vaginal placebo, (2) the vaginal product + oral placebo, (3) both placebos, or (4) both oral and vaginal products. The primary outcome was symptomatic vulvovaginal candidiasis (symptoms plusCandida isolated from vaginal swab). Symptom surveys and vaginal swabs were taken at days 0 and 14. Antibiotics + test product were administered for 6 days, followed by 4 additional days of probiotic supplementation. Subjects were off product for 4 days before final survey and swab were taken.
278 subjects were enrolled from 50 general practices in Melbourne, Australia. Results from 235 subjects were obtained. The trial was terminated early, as there was no indication of positive results. 23% of subjects developed vulvovaginitis, with no difference in incidence among any of the test groups. The authors concluded that lactobacilli does not prevent post-antibiotic vulvovaginitis.
This study is very well conducted from a clinical perspective. It is well-controlled and well-designed. However, the apparent naïveté of the investigators regarding microbiological issues prevents this study from being the final word on this line of research, in spite of their assertion that “further research on this subject is unlikely to be fruitful”. The most troubling aspect of this paper centers on the lack of definition of the products being tested. Neither strain designation nor viable levels were reported in the paper. Therefore, it is impossible to know what actually failed in this study.
If research over the past few years in probiotics has taught us anything, it is that different strains of even the same species may have different effects. There was no information provided in the paper that suggested that the bacteria used in these test products possessed any properties that might enable them to mediate an anti-Candida effect. There were no assessments conducted that demonstrate that strains used in the products were recovered alive from the vaginal swabs or, in the case of the oral product, from the feces. If these products contained strains that were biologically unable to transit the intestinal tract alive and exert an anti-fungal activity, there is no reason to believe that a clinical study using them would be positive.
The lack of awareness of these microbiological issues is evident by the title to the paper (and continued references in the body of the paper) solely to “lactobacillus” when the tested preparations contained Bifidobacterium and Streptococcus species as well. Because of the lack of characterization of the test products, the reader is not able to even determine if the test product was predominantly Lactobacillus. Since neitherBifidobacterium nor Streptococcus is important in the microecology of a healthy vaginal tract, this is a relevant point.
It is worth noting that although no effect was observed for probiotics on vulvovaginal candidiasis, there remains potential for the effectiveness of strains of lactobacilli on bacterial vaginosis. Although a recent double-blind placebo-controlled study was negative (Eriksson et al. 2005), other studies have documented the impact of certain orally-delivered strains of Lactobacillus on normalizing vaginal microbiota (Reid et al. 2004). However, controlled evaluation documenting symptom relief has not as yet been published.
Eriksson K, Carlsson B, Forsum U, Larsson PG. Acta Derm Venereol. 2005;85(1):42-6. A double-blind treatment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules.
Reid G, Burton J, Hammond JA, Bruce AW. Nucleic acid-based diagnosis of bacterial vaginosis and improved management using probiotic lactobacilli. J Med Food. 2004;7(2):223-8.