Effect of Metronidazole on Concentrations of Vaginal Bacteria Associated with Risk of HIV Acquisition

Abstract

Several bacterial vaginosis (BV)-associated bacteria have been associated with elevated risk of HIV acquisition, however susceptibility of these bacteria to antibiotics is poorly understood. Vaginal samples were collected from 22 persons daily for two weeks following BV diagnosis. Metronidazole treatment was prescribed for 5-7 days. Changes in bacterial concentrations were measured with taxon-specific 16S rRNA gene quantitative PCR (qPCR) assays. A culture-based antimicrobial assay confirmed presence of antibiotics in vaginal swab samples. Bacterial DNA concentrations decreased during antibiotic administration for all thirteen bacterial taxa tested. Comparison of bacterial DNA concentrations in samples before administration of antibiotics to samples taken on the last day of antimicrobial assay-confirmed antibiotic presence showed a 2.3-4.5 log10-fold decrease across all taxa. Concentrations were frequently reduced to the qPCR assay's limit of detection, suggesting eradication of bacteria. Mean clearance time varied across taxa (1.2-8.6 days), with several bacteria (e.g., Gemella asaccharolytica, Sneathia spp., Eggerthella-like sp.) taking >7 days to suppress. Metronidazole reduces quantities of bacterial taxa associated with increased HIV acquisition risk. Eradication of high-risk vaginal bacteria using metronidazole is one promising avenue for reducing HIV acquisition risk. A 5-7-day treatment course may not be sufficient to suppress all bacteria.

Figure 1.

Concentrations of 13 vaginal bacteria over time during metronidazole treatment for a representative treatment course in one person with BV.

Figure 2.

Box plot displaying log-fold change in bacterial concentrations over course of antibiotic treatment for BV, for each of thirteen bacterial taxa. Total number of treatments in which a bacterial taxon appeared is indicated to the right of each bacterial taxon.

Figure 3.

Bar graph showing decreases in concentrations of bacterial DNA from baseline (1 day prior to confirmed antibiotic presence, black bar) to the last day of confirmed antibiotic presence (white bar) for each taxon assayed. Number of treatment courses in which a given taxa was observed is noted above each respective bar. Statistical significance assessed by Student’s t-test.

Figure 4.

Box plot (A) showing time to suppression for each bacterial taxon (total number of treatments in which a bacterial taxon appeared is indicated along base of x-axis); scatter plot (B) showing relationship between baseline bacterial concentration and time to suppression.

Figure 5.

Box plot showing time to suppression between different bacterial taxa, split by method of antibiotic administration (total number of treatments in which a bacterial taxon appeared is indicated along base of x-axis).