1887

Abstract

The high incidence of urinary tract infection (UTI) among women and children, in combination with a lack of antibiotic efficacy with regard to pathogen eradication and recurrence prevention, as well as the negative side effects associated with antibiotics, has led researchers to explore the role of non-steroidal anti-inflammatory drugs as a primary management strategy. The aim of this study was to determine whether ibuprofen (IBU) or one of its major metabolites, 2-carboxyibuprofen (CIBU), could affect the growth and adhesion of the two most common uropathogens, and . The bacterial growth and adhesion to the urothelial cells of UTI89 and 1131 in the presence of physiologically relevant concentrations of IBU and CIBU were assessed. The effect of IBU on bacterial adhesion to urothelial cells was also assessed following exposure to trimethoprim/sulfamethoxazole (TMP/SMX) and nitrofurantoin. Bacterial growth was not affected by IBU. Further, only at high levels of IBU not regularly found in the bladder was there a significant increase in 1131 attachment at growth inhibitory concentrations of TMP/SMX. There was no effect on the attachment of or to urothelial cells in the presence of nitrofurantoin. These studies indicate that the beneficial effects of IBU for UTI management are likely mediated through its anti-inflammatory properties rather than direct interactions with uropathogens in the bladder.

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2019-08-01
2019-08-20
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References

  1. Foxman B, Buxton M. Alternative approaches to conventional treatment of acute uncomplicated urinary tract infection in women. Curr Infect Dis Rep 2013;15:124–129 [CrossRef]
    [Google Scholar]
  2. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113:5–13 [CrossRef]
    [Google Scholar]
  3. Nicolle LE. The paradigm shift to non-treatment of asymptomatic bacteriuria. Pathogens 2016;5:38 [CrossRef]
    [Google Scholar]
  4. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the infectious diseases Society of America and the European Society for microbiology and infectious diseases. Clin Infect Dis 2011;52:e103–e120 [CrossRef]
    [Google Scholar]
  5. Robinson JL, Finlay JC, Lang ME, Bortolussi R et al. Urinary tract infections in infants and children: diagnosis and management. Paediatr Child Health 2014;19:315–319 [CrossRef]
    [Google Scholar]
  6. Mazzulli T. Diagnosis and management of simple and complicated urinary tract infections (UTIs). Can J Urol 2012;19:42–48
    [Google Scholar]
  7. Williams G, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children. Cochrane Database Syst Rev 2011;3:CD001534
    [Google Scholar]
  8. Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 2009;361:1748–1759 [CrossRef]
    [Google Scholar]
  9. Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 2008;122:1064–1071 [CrossRef]
    [Google Scholar]
  10. Dai B, Liu Y, Jia J, Mei C. Long-term antibiotics for the prevention of recurrent urinary tract infection in children: a systematic review and meta-analysis. Arch Dis Child 2010;95:499–508 [CrossRef]
    [Google Scholar]
  11. Goh EB, Yim G, Tsui W, McClure J, Surette MG et al. Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics. Proc Natl Acad Sci USA 2002;99:17025–17030 [CrossRef]
    [Google Scholar]
  12. Goneau LW, Yeoh NS, MacDonald KW, Cadieux PA, Burton JP et al. Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens. Antimicrob Agents Chemother 2014;58:2089–2097 [CrossRef]
    [Google Scholar]
  13. Goneau LW, Hannan TJ, MacPhee RA, Schwartz DJ, Macklaim JM et al. Subinhibitory antibiotic therapy alters recurrent urinary tract infection pathogenesis through modulation of bacterial virulence and host immunity. mBio 2015;6:e00356–15 [CrossRef]
    [Google Scholar]
  14. Bleidorn J, Gágyor I, Kochen MM, Wegscheider K, Hummers-Pradier E. Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection? - Results of a randomized controlled pilot trial. BMC Med 2010;8:30–38 [CrossRef]
    [Google Scholar]
  15. Gágyor I, Hummers-Pradier E, Kochen MM, Schmiemann G, Wegscheider K et al. Immediate versus conditional treatment of uncomplicated urinary tract infection - a randomized-controlled comparative effectiveness study in general practices. BMC Infect Dis 2012;12:146–152 [CrossRef]
    [Google Scholar]
  16. Gágyor I, Bleidorn J, Kochen MM, Schmiemann G, Wegscheider K et al. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ 2015;351:h6544 [CrossRef]
    [Google Scholar]
  17. Bleidorn J, Hummers-Pradier E, Schiemann G, Wiese B, Gágyor I. Recurrent urinary tract infections and complications after symptomatic versus antibiotic treatment: follow-up of a randomised controlled trial. Ger Med Sci 2016;14:Doc01
    [Google Scholar]
  18. Hannan TJ, Roberts PL, Riehl TE, van der Post S, Binkley JM et al. Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis. EBioMedicine 2014;1:46–57 [CrossRef]
    [Google Scholar]
  19. O’Brien VP, Hannan TJ, Yu L, Livny J, Roberson EDO et al. A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease. Nat Microbiol 2017;2:16196 [CrossRef]
    [Google Scholar]
  20. Vik I, Bollestad M, Grude N, Bærheim A, Mölstad S et al. Ibuprofen versus mecillinam for uncomplicated cystitis - a randomized controlled trial study protocol. BMC Infect Dis 2014;14:693 [CrossRef]
    [Google Scholar]
  21. Elvers KT, Wright SJ. Antibacterial activity of the anti-inflammatory compound ibuprofen. Lett Appl Microbiol 1995;20:82–84 [CrossRef]
    [Google Scholar]
  22. Obad J, Šušković J, Kos B. Antimicrobial activity of ibuprofen: new perspectives on an "Old" non-antibiotic drug. Eur J Pharm Sci 2015;71:93–98 [CrossRef]
    [Google Scholar]
  23. Laudy AE, Mrowka A, Krajewska J, Tyski S. The influence of efflux pump inhibitors on the activity of non-antibiotic NSAIDs against Gram-negative rods. PLoS One 2016;11:e0147131 [CrossRef]
    [Google Scholar]
  24. Shirin H, Moss SF, Kancherla S, Kancherla K, Holt PR et al. Non-steroidal anti-inflammatory drugs have bacteriostatic and bactericidal activity against Helicobacter pylori. J Gastroenterol Hepatol 2006;21:1388–1393
    [Google Scholar]
  25. Zimmermann P, Curtis N. Antimicrobial effects of antipyretics. Antimicrob Agents Chemother 2017;61:e02268–16 [CrossRef]
    [Google Scholar]
  26. Główka FK, Karaźniewicz M. High performance capillary electrophoresis method for determination of ibuprofen enantiomers in human serum and urine. Anal Chim Acta 2005;540:95–102 [CrossRef]
    [Google Scholar]
  27. Mazaleuskaya LL, Theken KN, Gong L, Thorn CF, FitzGerald GA et al. PharmGKB summary: Ibuprofen pathways. Pharmacogenet Genomics 2015;25:96–106 [CrossRef]
    [Google Scholar]
  28. Ipe DS, Sundac L, Benjamin WH, Moore KH, Ulett GC. Asymptomatic bacteriuria: prevalence rates of causal microorganisms, etiology of infection in different patient populations, and recent advances in molecular detection. FEMS Microbiol Lett 2013;346:1–10 [CrossRef]
    [Google Scholar]
  29. Jia W, Li G, Wang W. Prevalence and antimicrobial resistance of Enterococcus species: a hospital-based study in China. Int J Environ Res Public Health 2014;11:3424–3442 [CrossRef]
    [Google Scholar]
  30. Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol 2010;7:653–660 [CrossRef]
    [Google Scholar]
  31. Cusumano CK, Hung CS, Chen SL, Hultgren SJ. Virulence plasmid harbored by uropathogenic Escherichia coli functions in acute stages of pathogenesis. Infect Immun 2010;78:1457–1467 [CrossRef]
    [Google Scholar]
  32. Mobley HLT, Green DM, Trifillis AL, Johnson DE, Chippendale GR et al. Pyelonephritogenic Escherichia coli and killing of cultured human renal proxiaml tubular epithelial cells: role of hemolysin in some strains. Infect Immun 1990;58:1281–1289
    [Google Scholar]
  33. McGroarty JA, Lee V, Bruce AW, Reid G. Modulation of adhesion of uropathogenic Enterococcus faecalis to human epithelial cells in vitro by Lactobacillus species. Microb Ecol Health Dis 1992;5:309–314 [CrossRef]
    [Google Scholar]
  34. Millsap K, Reid G, Van der Mei HC, Busscher HJ. Displacement of Enterococcus faecalis from hydrophobic and hydrophilic substrata by Lactobacillus and Streptococcus spp. as studied in a parallel plate flow chamber. Appl Environ Microb 1994;60:1867–1874
    [Google Scholar]
  35. Mclean R, Nickel J, Noakes V, Costerton J. An in vitro ultrastructural study of infectious kidney stone genesis. Infect Immun 1985;49:805–811
    [Google Scholar]
  36. Hutt V, Klingmann I, Pabst GU, Salama Z, Nieder M et al. Studies of the pharacokinetics and bioavailability of a new trimethoprim/sulfamethoxazole preparation in healthy volunteers. Arzneimittelforschung 1988;38:1347–1350
    [Google Scholar]
  37. Clinical and Laboratory Standards Institute Performance standards for antimicrobial susceptibility testing, 17th informational supplement. CLSI document M100-S17. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute; 2007
    [Google Scholar]
  38. Magiera S, Gülmez Ş. Ultrasound-assisted emulsification microextraction combined with ultra-high performance liquid chromatography-tandem mass spectrometry for the analysis of ibuprofen and its metabolites in human urine. J Pharm Biomed Anal 2014;92:193–202 [CrossRef]
    [Google Scholar]
  39. García-Vázquez A, Borrull F, Calull M, Aguilar C. Single-drop microextraction combined in-line with capillary electrophoresis for the determination of nonsteroidal anti-inflammatory drugs in urine samples. Electrophoresis 2016;37:274–281 [CrossRef]
    [Google Scholar]
  40. Sarafraz-Yazdi A, Amiri A, Rounaghi G, Eshtiagh-Hosseini H. Determination of non-steroidal anti-inflammatory drugs in urine by hollow-fiber liquid membrane-protected solid-phase microextraction based on sol–gel fiber coating. J Chromat B 2012;908:67–75 [CrossRef]
    [Google Scholar]
  41. Gallardo-Moreno AM, van der Mei HC, Busscher HJ, González-Martín ML, Bruque JM et al. Adhesion of Enterococcus faecalis 1131 grown under subinhibitory concentrations of ampicillin and vancomycin to a hydrophilic and a hydrophobic substratum. FEMS Microbiol Lett 2001;203:75–79 [CrossRef]
    [Google Scholar]
  42. Whiteside SA, Dave S, Seney SL, Wang P, Reid G et al. Enterococcus faecalis persistence in pediatric patients treated with antibiotic prophylaxis for recurrent urinary tract infections. Future Microbiol 2018;13:1095–1115 [CrossRef]
    [Google Scholar]
  43. Bateman DN. NSAIDs: time to re-evaluate gut toxicity. Lancet 1994;343:1051–1052 [CrossRef]
    [Google Scholar]
  44. Martins M, Dastidar SG, Fanning S, Kristiansen JE, Molnar J et al. Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities. Int J Antimicrob Ag 2008;31:198–208 [CrossRef]
    [Google Scholar]
  45. Tse BN, Adalja AA, Houchens C, Larsen J, Inglesby TV et al. Challenges and opportunities of nontraditional approaches to treating bacterial infections. Clin Infect Dis 2017;65:495–500 [CrossRef]
    [Google Scholar]
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