Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women Free

Abstract

Clinical management of bacterial vaginosis (BV) is difficult owing to inaccurate diagnostic tests, limited drug choices, and a high rate of recurrence. To our knowledge, there has not been a previous study of antimicrobial resistance (AMR) genes in community practice using next-generation sequencing (NGS). A case–control study (1 : 1 age-matched with and without BV) was undertaken in a series of 326 nongravid women of reproductive age with symptoms of BV to determine the prevalence of AMR genes. NGS was used to describe the complete vaginal microbiota and identify bacterial genes associated with resistance to: macrolides and/or lincosamides – , , , , and ; tetracyclines, β-lactams, streptomycin, gentamicin and/or tobramycin – , , , , , and ; 5-nitroimadazoles – and ; and triazoles – and . An evidence base was created to inform treatment decisions applicable to individual patients. AMR genes were identified in all drug classes: macrolides, 35.2 %; lincosamides, 35.6 %; tetracyclines, 21.8 %; aminoglycosides (streptomycin, gentamicin and tobramycin), 5.2 % each; 5-nitroimidazoles, 0.3 %; and triazoles, 18.7 %. There was more than a fourfold-higher frequency of AMR genes in pathogens from BV than from non-BV patients for macrolides (58.2 versus 12.3 %, respectively), lincosamides (58.9 versus 12.3 %) and tetracyclines (35.6 versus 8.0 %) (Fisher's exact test; all  < 0.001). For each patient with BV, the spectrum of resistance genes was matched to the pathogens present. AMR genes were present in the majority of vaginal microbiomes of patients with symptoms of BV.

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2016-05-01
2024-03-28
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References

  1. CLSI 2012 Performance Standards for Antimicrobial Susceptibility Testing 22nd Informational Supplement; Wayne, PA: Clinical and Laboratory Standards Institute;
    [Google Scholar]
  2. Boris J., Påhlson C., Larsson P. G. 1997; Six years observation after successful treatment of bacterial vaginosis. Infect Dis Obstet Gynecol 5:297–302 [View Article][PubMed]
    [Google Scholar]
  3. Bostwick D. G., Woody J., Budd W. T. 2016; Next-generation sequencing of bacterial vaginosis: case : control study with comprehensive species-level description.
    [Google Scholar]
  4. Boyanova L., Kolarov R., Gergova G., Dimitrova L., Mitov I. 2010; Trends in antibiotic resistance in Prevotella species from patients of the University Hospital of Maxillofacial Surgery, Sofia, Bulgaria, in 2003–2009. Anaerobe 16:489–492 [View Article][PubMed]
    [Google Scholar]
  5. Briselden A. M., Moncla B. J., Stevens C. E., Hillier S. L. 1992; Sialidases (neuraminidases) in bacterial vaginosis and bacterial vaginosis-associated microflora. J Clin Microbiol 30:663–666[PubMed]
    [Google Scholar]
  6. Brook I., Wexler H. M., Goldstein E. J. 2013; Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev 26:526–546 [View Article][PubMed]
    [Google Scholar]
  7. Budd W. T., Harwich M., Bostwick D. G., Meyers G., Dilts J., O'Hanlon K., Woody J., Mason L., Reynolds T. 2015; Metagenomics analysis using next generation sequencing of vaginal samples from community practices in the U.S. MOJ Cell Sci Rep 2:(2))
    [Google Scholar]
  8. Card R. M., Warburton P. J., MacLaren N., Mullany P., Allan E., Anjum M. F. 2014; Application of microarray and functional-based screening methods for the detection of antimicrobial resistance genes in the microbiomes of healthy humans. PLoS One 9:e86428 [View Article][PubMed]
    [Google Scholar]
  9. Catlin B. W. 1992; Gardnerella vaginalis: characteristics, clinical considerations, and controversies. Clin Microbiol Rev 5:213–237[PubMed]
    [Google Scholar]
  10. Chakravorty S., Lee J. S., Cho E. J., Roh S. S., Smith L. E., Lee J., Kim C. T., Via L. E., Cho S. N., other authors. 2015; Genotypic susceptibility testing of Mycobacterium tuberculosis isolates for amikacin and kanamycin resistance by use of a rapid sloppy molecular beacon-based assay identifies more cases of low-level drug resistance than phenotypic Lowenstein-Jensen testing. J Clin Microbiol 53:43–51 [View Article][PubMed]
    [Google Scholar]
  11. Copeland A., Sikorski J., Lapidus A., Nolan M., Del Rio T. G., Lucas S., Chen F., Tice H., Pitluck S., other authors. 2009; Complete genome sequence of Atopobium parvulum type strain (IPP 1246). Stand Genomic Sci 1:166–173 [View Article][PubMed]
    [Google Scholar]
  12. De Backer E., Verhelst R., Verstraelen H., Claeys G., Verschraegen G., Temmerman M., Vaneechoutte M. 2006; Antibiotic susceptibility of Atopobium vaginae . BMC Infect Dis 6:51 [View Article][PubMed]
    [Google Scholar]
  13. De Backer E., Dubreuil L., Brauman M., Acar J., Vaneechoutte M. 2010; In vitro activity of secnidazole against Atopobium vaginae, an anaerobic pathogen involved in bacterial vaginosis. Clin Microbiol Infect 16:470–472 [View Article][PubMed]
    [Google Scholar]
  14. Delgado S., Flórez A. B., Mayo B. 2005; Antibiotic susceptibility of Lactobacillus and Bifidobacterium species from the human gastrointestinal tract. Curr Microbiol 50:202–207 [View Article][PubMed]
    [Google Scholar]
  15. Elkins C. A., Mullis L. B. 2004; Bile-mediated aminoglycoside sensitivity in Lactobacillus species likely results from increased membrane permeability attributable to cholic acid. Appl Environ Microbiol 70:7200–7209 [View Article][PubMed]
    [Google Scholar]
  16. Enne V. I., Delsol A. A., Roe J. M., Bennett P. M. 2006; Evidence of antibiotic resistance gene silencing in Escherichia coli . Antimicrob Agents Chemother 50:3003–3010 [View Article][PubMed]
    [Google Scholar]
  17. Ferris M. J., Masztal A., Aldridge K. E., Fortenberry J. D., Fidel P. L. Jr., Martin D. H. 2004; Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis. BMC Infect Dis 4:5 [View Article][PubMed]
    [Google Scholar]
  18. Fettweis J. M., Serrano M. G., Sheth N. U., Mayer C. M., Glascock A. L., Brooks J. P., Jefferson K. K., Buck G. A., Vaginal Microbiome Consortium. 2012; Species-level classification of the vaginal microbiome. BMC Genomics 13:(Suppl. 8)S17[PubMed]
    [Google Scholar]
  19. Finegold S. M. 1996; Anaerobic Gram-negative bacilli. In Medical Microbiology, 4th edn. ch. 20 Edited by Baron S. Galveston, TX: University of Texas Medical Branch at Galveston;
    [Google Scholar]
  20. Fredricks D. N., Fiedler T. L., Marrazzo J. M. 2005; Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 353:1899–1911 [View Article][PubMed]
    [Google Scholar]
  21. Fredricks D. N., Fiedler T. L., Thomas K. K., Mitchell C. M., Marrazzo J. M. 2009; Changes in vaginal bacterial concentrations with intravaginal metronidazole therapy for bacterial vaginosis as assessed by quantitative PCR. J Clin Microbiol 47:721–726 [View Article][PubMed]
    [Google Scholar]
  22. Gad G. F., Abdel-Hamid A. M., Farag Z. S. 2014; Antibiotic resistance in lactic acid bacteria isolated from some pharmaceutical and dairy products. Braz J Microbiol 45:25–33 [View Article][PubMed]
    [Google Scholar]
  23. Guido M., Quattrocchi M., Zizza A., Pasanisi G., Pavone V., Lobreglio G., Gabutti G., De Donno A. 2012; Molecular approaches in the diagnosis of sepsis in neutropenic patients with haematological malignances. J Prev Med Hyg 53:104–108[PubMed]
    [Google Scholar]
  24. Gutman R. E., Peipert J. F., Weitzen S., Blume J. 2005; Evaluation of clinical methods for diagnosing bacterial vaginosis. Obstet Gynecol 105:551–556 [View Article][PubMed]
    [Google Scholar]
  25. Harwich M. D. Jr, Alves J. M., Buck G. A., Strauss J.F., III, Patterson J. L., Oki A. T., Girerd P. H., Jefferson K. K. 2010; Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies. BMC Genomics 11:375 [View Article][PubMed]
    [Google Scholar]
  26. Harwich M. D. Jr, Serrano M. G., Fettweis J. M., Alves J. M., Reimers M. A., Buck G. A., Jefferson K. K., Vaginal Microbiome Consortium. 2012; Genomic sequence analysis and characterization of Sneathia amnii sp. nov. BMC Genomics 13:(Suppl. 8)S4 [View Article][PubMed]
    [Google Scholar]
  27. Jumas-Bilak E., Jean-Pierre H., Carlier J. P., Teyssier C., Bernard K., Gay B., Campos J., Morio F., Marchandin H. 2005; Dialister micraerophilus sp. nov. and Dialister propionicifaciens sp. nov., isolated from human clinical samples. Int J Syst Evol Microbiol 55:2471–2478 [View Article][PubMed]
    [Google Scholar]
  28. Kharsany A. B., Hoosen A. A., Van den Ende J. 1993; Antimicrobial susceptibilities of Gardnerella vaginalis . Antimicrob Agents Chemother 37:2733–2735 [View Article][PubMed]
    [Google Scholar]
  29. Klare I., Konstabel C., Werner G., Huys G., Vankerckhoven V., Kahlmeter G., Hildebrandt B., Müller-Bertling S., Witte W., Goossens H. 2007; Antimicrobial susceptibilities of Lactobacillus, Pediococcus and Lactococcus human isolates and cultures intended for probiotic or nutritional use. J Antimicrob Chemother 59:900–912 [View Article][PubMed]
    [Google Scholar]
  30. Klebanoff M. A., Turner A. N. 2014; Bacterial vaginosis and season, a proxy for vitamin D status. Sex Transm Dis 41:295–299 [View Article][PubMed]
    [Google Scholar]
  31. Leitsch D., Sóki J., Kolarich D., Urbán E., Nagy E. 2014; A study on Nim expression in Bacteroides fragilis . Microbiology 160:616–622 [View Article][PubMed]
    [Google Scholar]
  32. Livermore D. M., Wain J. 2013; Revolutionising bacteriology to improve treatment outcomes and antibiotic stewardship. Infect Chemother 45:1–10 [View Article][PubMed]
    [Google Scholar]
  33. Löfmark S., Edlund C., Nord C. E. 2010; Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis 50:(Suppl. 1)S16–S23 [View Article][PubMed]
    [Google Scholar]
  34. Lopes dos Santos Santiago G., Grob P., Verstraelen H., Waser F., Vaneechoutte M. 2012; Susceptibility testing of Atopobium vaginae for dequalinium chloride. BMC Res Notes 5:151 [View Article][PubMed]
    [Google Scholar]
  35. Marrazzo J. M., Thomas K. K., Fiedler T. L., Ringwood K., Fredricks D. N. 2008; Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med 149:20–28 [View Article][PubMed]
    [Google Scholar]
  36. Mayer B. T., Srinivasan S., Fiedler T. L., Marrazzo J. M., Fredricks D. N., Schiffer J. T. 2015; Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial vaginosis. J Infect Dis 212:793–802 [View Article][PubMed]
    [Google Scholar]
  37. McCarthy L. R., Mickelsen P. A., Smith E. G. 1979; Antibiotic susceptibility of Haemophilus vaginalis (Corynebacterium vaginale) to 21 antibiotics. Antimicrob Agents Chemother 16:186–189 [View Article][PubMed]
    [Google Scholar]
  38. Mitchell C., Manhart L. E., Thomas K., Fiedler T., Fredricks D. N., Marrazzo J. 2012; Behavioral predictors of colonization with Lactobacillus crispatus or Lactobacillus jensenii after treatment for bacterial vaginosis: a cohort study. Infect Dis Obstet Gynecol 2012:706540 [View Article][PubMed]
    [Google Scholar]
  39. Morio F., Jean-Pierre H., Dubreuil L., Jumas-Bilak E., Calvet L., Mercier G., Devine R., Marchandin H. 2007; Antimicrobial susceptibilities and clinical sources of Dialister species. Antimicrob Agents Chemother 51:4498–4501 [View Article][PubMed]
    [Google Scholar]
  40. Nagy E., Sóki J., Urban E., Szoke I., Fodor E., Edwards R. 2001; Occurrence of metronidazole and imipenem resistance among Bacteroides fragilis group clinical isolates in Hungary. Acta Biol Hung 52:271–280 [View Article][PubMed]
    [Google Scholar]
  41. Olender A. 2013; Antibiotic resistance and detection of the most common mechanism of resistance (MLSB) of opportunistic Corynebacterium . Chemotherapy 59:294–306 [View Article][PubMed]
    [Google Scholar]
  42. Parma M., Stella Vanni V., Bertini M., Candiani M. 2014; Probiotics in the prevention of recurrences of bacterial vaginosis. Altern Ther Health Med 20:(Suppl. 1)52–57[PubMed]
    [Google Scholar]
  43. Piot P., van Dyck E., Goodfellow M., Falkow S. 1980; A taxonomic study of Gardnerella vaginalis (Haemophilus vaginalis) Gardner and Dukes 1955. J Gen Microbiol 119:373–396[PubMed]
    [Google Scholar]
  44. Polatti F. 2012; Bacterial vaginosis, Atopobium vaginae and nifuratel. Curr Clin Pharmacol 7:36–40 [View Article][PubMed]
    [Google Scholar]
  45. Robicsek A., Strahilevitz J., Jacoby G. A., Macielag M., Abbanat D., Park C. H., Bush K., Hooper D. C. 2006; Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 12:83–88 [View Article][PubMed]
    [Google Scholar]
  46. Salminen M. K., Rautelin H., Tynkkynen S., Poussa T., Saxelin M., Valtonen V., Järvinen A. 2004; Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 38:62–69 [View Article][PubMed]
    [Google Scholar]
  47. Schwebke J. R., Desmond R. A. 2007; A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis 44:213–219 [View Article][PubMed]
    [Google Scholar]
  48. Shanker S., Toohey M., Munro R. 1982; In vitro activity of seventeen antimicrobial agents against Gardnerella vaginalis . Eur J Clin Microbiol 1:298–300 [View Article][PubMed]
    [Google Scholar]
  49. Sobel J. D., Schmitt C., Meriwether C. 1993; Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J Infect Dis 167:783–784 [View Article][PubMed]
    [Google Scholar]
  50. Srinivasan S., Fredricks D. N. 2008; The human vaginal bacterial biota and bacterial vaginosis. Interdiscip Perspect Infect Dis 2008:750479[PubMed]
    [Google Scholar]
  51. Srinivasan S., Hoffman N. G., Morgan M. T., Matsen F. A., Fiedler T. L., Hall R. W., Ross F. J., McCoy C. O., Bumgarner R., other authors. 2012; Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One 7:e37818 [View Article][PubMed]
    [Google Scholar]
  52. Swidsinski A., Loening-Baucke V., Swidsinski S., Verstraelen H. 2015; Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report. Arch Gynecol Obstet 291:605–609[PubMed] [CrossRef]
    [Google Scholar]
  53. Taylor B. D., Darville T., Haggerty C. L. 2013; Does bacterial vaginosis cause pelvic inflammatory disease?. Sex Transm Dis 40:117–122[PubMed] [CrossRef]
    [Google Scholar]
  54. Tomusiak A., Strus M., Heczko P. B. 2011; [Antibiotic resistance of Gardnerella vaginalis isolated from cases of bacterial vaginosis]. Ginekol Pol 82:900–904 (in Polish)[PubMed]
    [Google Scholar]
  55. Tuite N., Reddington K., Barry T., Zumla A., Enne V. 2014; Rapid nucleic acid diagnostics for the detection of antimicrobial resistance in Gram-negative bacteria: is it time for a paradigm shift?. J Antimicrob Chemother 69:1729–1733 [View Article][PubMed]
    [Google Scholar]
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