Repurposing of fluoxetine for antibacterial activities in catheter-associated urinary tract biofilm infections: an in vitro analysis
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Abstract
Background
Urinary tract infections are often initiated by indwelling catheters and bring about serious consequences, especially when they are caused by multidrug-resistant bacterial pathogens. The biofilms of uropathogens such as Enterococcus faecalis and Escherichia coli pose serious challenges. Therefore the scientific world is trying to experiment with alternative drugs to replace conventional antibiotics as the latter are more prone to cause the development of antibacterial resistance. Here, we evaluate the repurposing of the antidepressant fluoxetine as an antibacterial agent against the mentioned pathogens.
Methods
To repurpose fluoxetine for its antibacterial activity against Enterococcus faecalis and Escherichia coli, the agar diffusion method was used. The minimal inhibitory concentration was found by the microdilution method. The drug was also analyzed as a coating on catheters to evaluate its efficiency against biofilm formation by pathogens.
Results
The drug fluoxetine showed potential antibacterial and anti-biofilm activities. Its minimum inhibitory concentration was found to be 18.75 µg/mL and 37.5 µg/mL against Enterococcus faecalis and Escherichia coli respectively. The antibiofilm activity on polystyrene surfaces was also remarkable as it reduced the formation of Enterococcus faecalis and Escherichia coli biofilms by 70% and 74%, after being treated with 1x MICs and 2x MICs respectively.
Conclusions
Fluoxetine - one of the drugs of choice in treating depression, when repurposed, has shown considerable antibacterial and antibiofilm effects against two of the major catheter-associated urinary tract infection-causing bacteria - viz. Enterococcus faecalis and Escherichia coli. Therefore, further studies are needed to understand its applicability as an antibacterial agent.
Article Details
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References
Skelton-Dudley F, Doan J, Suda K, Holmes SA, Evans C, Trautner B. Spinal cord injury creates unique challenges in diagnosis and management of catheter-associated urinary tract infection. Top Spinal Cord Inj Rehabil 2019;25:331-9. doi: 10.1310/sci2504-331.
Medina M, Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol 2019;11:3-7. doi: 10.1177/1756287219832172.
Papanikolopoulou A, Maltezou HC, Stoupis A, et al. Catheter-associated urinary tract infections, bacteremia, and infection control interventions in a hospital: a six-year time-series study. J Clin Med 2022;11:5418. doi: 10.3390/jcm11185418.
Wooller KR, Backman C, Gupta S, Jennings A, Hasimja-Saraqini D, Forster AJ. A pre and post intervention study to reduce unnecessary urinary catheter use on general internal medicine wards of a large academic health science center. BMC Health Serv Res 2018;18:1-9. https://doi.org/10.1186/s12913-018-3421-2.
Saint S, Greene MT, Krein SL, et al. A program to prevent catheter-associated urinary tract infection in acute care. N Engl J Med 2016;374:2111-9. https://doi.org/10.1056/NEJMoa1504906.
Flores-Mireles A, Hreha TN, Hunstad DA. Pathophysiology, treatment, and prevention of catheter-associated urinary tract infection. Top Spinal Cord Inj Rehabil 2019 Summer;25:228-40. doi: 10.1310/sci2503-228.
Magill SS, O’Leary E, Janelle SJ, et al. Changes in prevalence of health care–associated infections in US hospitals. N Engl J Med 2018;379:1732-44. https://doi.org/10.1056/NEJMoa1801550.
Kim B, Pai H, Choi WS, et al. Current status of indwelling urinary catheter utilization and catheter-associated urinary tract infection throughout hospital wards in Korea: a multicenter prospective observational study. PLOS ONE 2017; 12:e0185369. https://doi.org/10.1371/journal. pone.0185369.
Bjarnsholt T. The role of bacterial biofilms in chronic infections. APMIS Suppl 2013 ;136:1-51. doi: 10.1111/apm.12099.
Sharma G, Sharma S, Sharma P, et al. Escherichia coli biofilm: development and therapeutic strategies. J Appl Microbiol 2016;121:309-19. https://doi.org/10.1111/jam.13078.
Sandhu R, Sayal P, Jakkhar R, Sharma G. Catheterization-associated urinary tract infections: epidemiology and incidence from tertiary care hospital in Haryana. J Health Res Rev 2018;1;5:135-41.
Walker JN, Flores-Mireles AL, Lynch AJ, et al. High-resolution imaging reveals microbial biofilms on patient urinary catheters despite antibiotic administration. World J Urol 2020;38: 2237-45. doi: 10.1007/s00345-019-03027-8.
Olivares E, Badel-Berchoux S, Provot C, Prévost G, Bernardi T, Jehl F. Clinical impact of antibiotics for the treatment of Pseudomonas aeruginosa biofilm infections. Front Microbiol 2020;10:2894. https://doi.org/10.3389/fmicb.2019.02894.
Hrvatin V. Combating antibiotic resistance: new drugs or alternative therapies? CMAJ 2017;189: E1199. doi: 10.1503/cmaj.109-5469.
Kamali E, Jamali A, Ardebili A, Ezadi F, Mohebbi A. Evaluation of antimicrobial resistance, biofilm forming potential, and the presence of biofilm-related genes among clinical isolates of Pseudomonas aeruginosa. BMC Res Notes 2020; 13:1-6. https://doi.org/10.1186/s13104-020-4890-z.
Karigoudar RM, Karigoudar MH, Wavare SM, Mangalgi SS. Detection of biofilm among uropathogenic Escherichia coli and its correlation with antibiotic resistance pattern. J Lab Physicians 2019;11:017-22. doi: 10.4103/JLP.JLP_98_18.
Thangamani S, Younis W, Seleem MN. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections. Sci Rep 2015; 5:11596. doi: 10.1038/srep11596.
Gowri M, Sofi Beaula W, Biswal J, et al. â-lactam substituted polycyclic fused pyrrolidine/pyrrolizidine derivatives eradicate C. albicans in an ex vivo human dentinal tubule model by inhibiting sterol 14-á demethylase and cAMP pathway. Biochim Biophys Acta 2016;1860:636-47. doi: 10.1016/j.bbagen.2015.12.020.
Meiyazhagan G, Raju R, Winfred SB, et al. Bioactivity studies of â-lactam derived polycyclic fused pyrroli-dine/pyrrolizidine derivatives in dentistry: in vitro, in vivo and in silico studies. PLoS ONE 2015;10:e0131433. doi: 10.1371/journal.pone.0131433.
Gowri M, Jayashree B, Jeyakanthan J, Girija EK. Sertraline as a promising antifungal agent: inhibition of growth and biofilm of Candida auris with special focus on the mechanism of action in vitro. J Appl Microbiol 2020;128:426-37. https://doi.org/10.1111/jam.14490.
Goda RM, El-Baz AM, Khalaf EM, Elkhooly TA, Shohayeb MM. Combating bacterial biofilm formation in urinary catheter by green silver nanoparticle. Antibiotics (Basel) 2022;11:495. https://doi.org/10.3390/antibiotics11040495.
Jordan RP, Malic S, Waters MG, DJ Stickler, DW Williams. Development of an antimicrobial urinary catheter to inhibit urinary catheter encrustation. Microbiol Discov 2015; 3:1. http://dx.doi.org/10.7243/2052-6180-3-1.
Ansari MA, Albetran HM, Alheshibri MH, et al. Synthesis of electrospun TiO2 nanofibers and characterization of their antibacterial and antibiofilm potential against gram-positive and gram-negative bacteria. Antibiotics (Basel) 2020;9:572. doi: 10.3390/antibiotics9090572.
Shi D, Hao H, Wei Z, et al. Combined exposure to non-antibiotic pharmaceutics and antibiotics in the gut synergistically promote the development of multi-drug-resistance in Escherichia coli. Gut Microbes 2022;14:2018901. https://doi.org/10.1080/19490976.2021.2018901.
Jang HI, Eom YB. Antibiofilm and antibacterial activities of repurposing auranofin against Bacteroides fragilis. Arch Microbiol 2020;202: 473-82. https://doi.org/10.1007/s00203-019-01764-3.
Ayaz M, Subhan F, Ahmed J, et al. Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance. J Biol Res (Thessalon) 2015;22:4. doi: 10.1186/s40709-015-0028-1.
Kamurai B, Mombeshora M, Mukanganyama S. Repurposing of drugs for antibacterial activities on selected ESKAPE bacteria Staphylococcus aureus and Pseudomonas aeruginosa. Int J Microbiol 2020;2020. https://doi.org/10.1155/2020/8885338.
Abutaleb NS, Seleem MN. Repurposing the antiamoebic drug diiodohydroxyquinoline for treatment of Clostridioides difficile infections. Antimicrob Agents Chemother 2020;64e02115-19. doi: 10.1128/AAC.02115-19.
Pacios O, Fernández-García L, Bleriot I, et al. Enhanced antibacterial activity of repurposed mitomycin C and imipenem in combination with the lytic phage vB_KpnM-VAC13 against clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 2021;65:e0090021. doi: 10.1128/AAC.00900-21.
Zhu Z, Wang Z, Li S, et al. Antimicrobial strategies for urinary catheters. J Biomed Mater Res A 2019; 107:445-67. doi: 10.1002/jbm.a.36561.
Pelling H, Nzakizwanayo J, Milo S, et al. Bacterial biofilm formation on indwelling urethral catheters. Lett Appl Microbiol 2019;68:277-93. doi: 10.1111/lam.13144.
Ghosh A, Jayaraman N, Chatterji D. Small-molecule inhibition of bacterial biofilm. ACS Omega 2020;5:3108-15. doi: 10.1021/acsomega. 9b03695.
Muhammad MH, Idris AL, Fan X, et al. Beyond risk: bacterial biofilms and their regulating approaches. Front Microbiol 2020;11:928. doi: 10.3389/fmicb.2020.00928.
Ganesan V, Meiyazhagan G, Devaraj M, et al. Repurposing the antibacterial activity of etoposide% a chemotherapeutic drug in combination with eggshell-derived hydroxyapatite. ACS Biomater Sci Eng 2022;8: 682-93. doi: 10.1021/acsbiomaterials.1c01481.
Zeng X, She P, Zhou L, et al. Drug repurposing: antimicrobial and antibiofilm effects of penfluridol against Enterococcus faecalis. Microbiologyopen 2021;10:e1148. doi: 10.1002/mbo3.1148.
Rahuman HBH, Dhandapani R, Palanivel V, Thangavelu S, Paramasivam R, Muthupandian S. Bioengineered phytomolecules-capped silver nanoparticles using Carissa carandas leaf extract to embed on to urinary catheter to combat UTI pathogens. PloS One.2021;16:e0256748. doi: 10.1371/journal.pone.0256748.
Abbott IJ, Van Gorp E, van der Meijden A, et al. Oral fosfomycin treatment for enterococcal urinary tract infections in a dynamic in vitro model. Antimicrob Agents Chemother 2020;64:e00342-20. doi: 10.1128/AAC.00342-20.