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

Overview

Journal Res Sq

Date 2024 Apr 25

PMID 38659968

Authors

D J Valint

Tina L Fiedler

Congzhou Liu

Sujatha Srinivasan

David N Fredricks

Affiliations

Soon will be listed here.

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., , spp., -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.

References

Srinivasan S, Hoffman N, Morgan M, Matsen F, Fiedler T, Hall R . Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One. 2012; 7(6):e37818. PMC: 3377712. DOI: 10.1371/journal.pone.0037818. View

van de Wijgert J, Verwijs M, Agaba S, Bronowski C, Mwambarangwe L, Uwineza M . Intermittent Lactobacilli-containing Vaginal Probiotic or Metronidazole Use to Prevent Bacterial Vaginosis Recurrence: A Pilot Study Incorporating Microscopy and Sequencing. Sci Rep. 2020; 10(1):3884. PMC: 7054572. DOI: 10.1038/s41598-020-60671-6. View

Schwebke J, Desmond R . A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis. 2006; 44(2):213-9. DOI: 10.1086/509577. View

Fredricks D, Fiedler T, Thomas K, Mitchell C, Marrazzo J . Changes in vaginal bacterial concentrations with intravaginal metronidazole therapy for bacterial vaginosis as assessed by quantitative PCR. J Clin Microbiol. 2009; 47(3):721-6. PMC: 2650913. DOI: 10.1128/JCM.01384-08. View

Gosmann C, Anahtar M, Handley S, Farcasanu M, Abu-Ali G, Bowman B . Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women. Immunity. 2017; 46(1):29-37. PMC: 5270628. DOI: 10.1016/j.immuni.2016.12.013. View

Bradshaw C, Tabrizi S, Fairley C, Morton A, Rudland E, Garland S . The association of Atopobium vaginae and Gardnerella vaginalis with bacterial vaginosis and recurrence after oral metronidazole therapy. J Infect Dis. 2006; 194(6):828-36. DOI: 10.1086/506621. View

Workowski K, Bachmann L, Chan P, Johnston C, Muzny C, Park I . Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021; 70(4):1-187. PMC: 8344968. DOI: 10.15585/mmwr.rr7004a1. View

Ahrens P, Andersen L, Lilje B, Johannesen T, Dahl E, Baig S . Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis. PLoS One. 2020; 15(7):e0236036. PMC: 7386580. DOI: 10.1371/journal.pone.0236036. View

McClelland R, Lingappa J, Srinivasan S, Kinuthia J, John-Stewart G, Jaoko W . Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study. Lancet Infect Dis. 2018; 18(5):554-564. PMC: 6445552. DOI: 10.1016/S1473-3099(18)30058-6. View

10.

Srinivasan S, Austin M, Fiedler T, Strenk S, Agnew K, Gowda G . gen. nov., sp. nov., and sp. nov., gen. nov.: novel bacteria from the family isolated from the female genital tract. Int J Syst Evol Microbiol. 2023; 73(10). PMC: 11318147. DOI: 10.1099/ijsem.0.006017. View

11.

Mayer B, Srinivasan S, Fiedler T, Marrazzo J, Fredricks D, Schiffer J . Rapid and Profound Shifts in the Vaginal Microbiota Following Antibiotic Treatment for Bacterial Vaginosis. J Infect Dis. 2015; 212(5):793-802. PMC: 4539900. DOI: 10.1093/infdis/jiv079. View

12.

Amsel R, Totten P, Spiegel C, Chen K, Eschenbach D, Holmes K . Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983; 74(1):14-22. DOI: 10.1016/0002-9343(83)91112-9. View

13.

Nugent R, Krohn M, Hillier S . Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991; 29(2):297-301. PMC: 269757. DOI: 10.1128/jcm.29.2.297-301.1991. View

14.

Aguin T, Akins R, Sobel J . High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study. Sex Transm Dis. 2014; 41(5):290-1. DOI: 10.1097/OLQ.0000000000000123. View

15.

Balkus J, Srinivasan S, Anzala O, Kimani J, Andac C, Schwebke J . Impact of Periodic Presumptive Treatment for Bacterial Vaginosis on the Vaginal Microbiome among Women Participating in the Preventing Vaginal Infections Trial. J Infect Dis. 2016; 215(5):723-731. PMC: 5853550. DOI: 10.1093/infdis/jiw622. View

16.

Sabo M, Lokken E, Srinivasan S, Kinuthia J, Richardson B, Fiedler T . Changes in Vaginal Bacteria and Inflammatory Mediators From Periconception Through the Early Postpartum Period in a Cohort of Kenyan Women Without HIV. J Infect Dis. 2023; 228(4):487-499. PMC: 10428199. DOI: 10.1093/infdis/jiad168. View

17.

Bradshaw C, Sobel J . Current Treatment of Bacterial Vaginosis-Limitations and Need for Innovation. J Infect Dis. 2016; 214 Suppl 1:S14-20. PMC: 4957510. DOI: 10.1093/infdis/jiw159. View

18.

Srinivasan S, Morgan M, Fiedler T, Djukovic D, Hoffman N, Raftery D . Metabolic signatures of bacterial vaginosis. mBio. 2015; 6(2). PMC: 4453549. DOI: 10.1128/mBio.00204-15. View

19.

Vodstrcil L, Muzny C, Plummer E, Sobel J, Bradshaw C . Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment. BMC Med. 2021; 19(1):194. PMC: 8411528. DOI: 10.1186/s12916-021-02077-3. View

20.

McGregor J, French J, Jones W, Milligan K, McKinney P, Patterson E . Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream. Am J Obstet Gynecol. 1994; 170(4):1048-59; discussion 1059-60. DOI: 10.1016/s0002-9378(94)70098-2. View