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Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure - 28/01/20

Doi : 10.1016/j.ajog.2019.08.008 
Marijn C. Verwijs, MD a, Stephen K. Agaba, MD b, Alistair C. Darby, MSc PhD c, Janneke H.H. M. van de Wijgert, MD, PhD, MPH a, d,
a Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom 
b Rinda Ubuzima, Kigali, Rwanda 
c Centre for Genomic Research, University of Liverpool, Liverpool, United Kingdom 
d Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands 

Corresponding author: Prof Janneke van de Wijgert.

Abstract

Background

Metronidazole is the first-line treatment for bacterial vaginosis, but cure rates are suboptimal and recurrence rates high.

Objectives

To evaluate the impact of a standard course of oral metronidazole treatment (500 mg twice per day for 7 days) on the vaginal microbiota of Rwandan bacterial vaginosis patients using microscopy and 16S rRNA gene sequencing, and to evaluate correlates of treatment failure.

Study Design

HIV-negative, nonpregnant women aged 18–45 years with bacterial vaginosis and/or Trichomonas vaginalis (N=68) were interviewed and sampled before and after metronidazole treatment. They were also screened, and treated if applicable, for other urogenital infections. The vaginal microbiota was assessed by Gram stain Nugent scoring, Illumina 16S rRNA HiSeq sequencing (relative abundances), and BactQuant 16S gene quantitative polymerase chain reaction (estimated concentrations). Only women with a pretreatment Nugent score of 7–10 and a valid posttreatment Nugent score (N=55) were included in metronidazole treatment failure analyses, with treatment failure defined as a posttreatment Nugent score of 4–10.

Results

The bacterial vaginosis cure rate by Nugent scoring was 54.5%. The mean total vaginal bacterial concentration declined from 6.59 to 5.85 log10/μL (P<.001), which was mostly due to a reduction in mean bacterial vaginosis-associated anaerobes concentration (all bacterial vaginosis-associated anaerobe taxa combined) from 6.23 to 4.55 log10/μL (P<.001). However, only 16.4% of women had a bacterial vaginosis anaerobes concentration reduction of more than 50%, and only 3 women had complete eradication. The mean concentration of lactobacilli (all species combined) increased from 4.98 to 5.56 log10/μL (P=.017), with L. iners being the most common species pre- and posttreatment. The mean concentration of pathobionts (defined as Proteobacteria, streptococci, staphylococci, enterococci, and a few others) did not change significantly: from 1.92 log10/μL pretreatment to 2.01 log10/μL posttreatment (P=.939). Pretreatment pathobionts concentration, and having a pretreatment vaginal microbiota type containing more than 50% Gardnerella vaginalis (compared with less than 50%), were associated with increased likelihood of treatment failure, but the latter did not reach statistical significance (P=.044 and P=.084, respectively).

Conclusions

Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments.

Le texte complet de cet article est disponible en PDF.

Key words : 16S rRNA gene sequencing, anaerobes, antibiotics, bacterial vaginosis, biofilm, Lactobacilli, metronidazole, trichomoniasis, vaginal dysbiosis, vaginal microbiota


Plan


 The authors report no conflict of interest.
 This work was supported by the DFID/MRC/Wellcome Trust Joint Global Health Trials Scheme as a Development Project (grant reference MR/M017443/1; grant title: “Preparing for a clinical trial of interventions to maintain normal vaginal microbiota for preventing adverse reproductive health outcomes in Africa”) and the University of Liverpool (Technology Directorate Voucher). The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the authors’ institutions or companies, or the funder. None of the authors were paid to write this article. The corresponding author had full access to the data and had final responsibility for the decision to submit for publication.
 Trial registration: Clinicaltrials.gov, reference number NCT02459665 (URL access on NCT02459665)
 Cite this article as: Verwijs MC, Agaba SK, Darby AC, et al. Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure. Am J Obstet Gynecol 2020;222:157.e1-13.


© 2019  The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 222 - N° 2

P. 157.e1-157.e13 - février 2020 Retour au numéro
Article précédent Article précédent
  • Defining the relationship between vaginal and urinary microbiomes
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