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A review and new insights to antimicrobial action of local anesthetics

  • Bibi Marjan Razavi
  • Bibi Sedigheh Fazly BazzazEmail author
Review
  • 66 Downloads

Abstract

Local anesthetics (LAs) are medications which can provide analgesia in distinct body regions through the blockade of voltage-gated sodium channels. Besides pain management, the supplemental role of LAs as antimicrobial agents has been documented in several studies. Different databases including PubMed, Scopus, and Web of Science with the name of different local anesthetics and related names for antimicrobial keywords were searched without time limitation. This review summarized different in vitro and in vivo studies regarding antimicrobial effects of different LAs with focuses on antimicrobial applications of most studied LAs, interaction with different agents which combined with LAs, and mechanisms of action and structural dependence of LAs antibacterial effects. Among different LAs, lidocaine is the most studied preparation. Reduction of the incidence of endophthalmitis after intravitreal injection, prophylaxis for surgical wound infections, prevention of the incidence of catheter-associated infections, oral biofilm reduction on the buccal mucosa, and prevention against bacteria that produced nosocomial infection are some examples of lidocaine antimicrobial application. Studies showed that different factors including structure, concentration, duration of exposure, type of microorganism tested, and temperature affect the degree of LA antimicrobial activity. In addition, various agents such as antibiotics, preservatives, opioids, epinephrine, and propofol can combine with LAs and affect their antimicrobial properties through synergistic or antagonistic action. Due to antibacterial activities, LAs could be applied in a clinic for prophylaxis of surgical site infection. In the application of LAs prior to diagnostic procedures caution should be needed; otherwise, when culturing the specimen, they could lead to false negative results.

Keywords

Local anesthetic Antibacterial Antifungal Bactericidal Lidocaine Bupivacaine Ropivacaine Tetracaine 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Becker DE, Reed KL (2012) Local anesthetics: review of pharmacological considerations. Anesth Prog 59:90–102Google Scholar
  2. 2.
    Johnson SM, Saint John BE, Dine AP (2008) Local anesthetics as antimicrobial agents: a review. Surg Infect 9:205–213Google Scholar
  3. 3.
    Olsen KM, Peddicord TE, Campbell GD et al (2000) Antimicrobial effects of lidocaine in bronchoalveolar lavage fluid. J Antimicrob Chemother 45:217–219Google Scholar
  4. 4.
    Stratford AF, Zoutman DE, Davidson JS (2002) Effect of lidocaine and epinephrine on Staphylococcus aureus in a guinea pig model of surgical wound infection. Plast Reconstr Surg 110:1275–1279Google Scholar
  5. 5.
    Tustin A, Kim SJ, Chomsky A et al (2014) Antibacterial properties of 2% lidocaine and reduced rate of endophthalmitis after intravitreal injection. Retina 34:935–942Google Scholar
  6. 6.
    Lu CW, Lin TY, Shieh JS et al (2014) Antimicrobial effect of continuous lidocaine infusion in a Staphylococcus aureus-induced wound infection in a mouse model. Ann Plast Surg 73:598–601Google Scholar
  7. 7.
    Yang H, Guo X, Chen X et al (2013) Study on antibacterial effect of lidocaine. Chinese J Androl 27:14–16Google Scholar
  8. 8.
    Srisatjaluk RL, Klongnoi B, Wongsirichat N (2016) Antimicrobial effect of topical local anesthetic spray on oral microflora. J Dent Anesth Pain Med 16:17–24Google Scholar
  9. 9.
    Parr AM, Zoutman DE, Davidson JSD (1999) Antimicrobial activity of lidocaine against bacteria associated with nosocomial wound infection. Ann Plast Surg 43:239–245Google Scholar
  10. 10.
    Fazly Bazaz BS, Salt WG (1983) Local anaesthetics as antimicrobial agents: structure-action considerations. Microbios 37:45–64Google Scholar
  11. 11.
    Pere P, Lindgren L, Vaara M (1999) Poor antibacterial effect of ropivacaine: comparison with bupivacaine. Anesthesiology 91:884–886Google Scholar
  12. 12.
    Sakuragi T, Ishino H, Dan K (1998) Bactericidal activity of preservative-free bupivacaine on microorganisms in the human skin flora. Acta Anaesthesiol Scand 42:1096–1099Google Scholar
  13. 13.
    Rosenberg PH, Renkonen OV (1985) Antimicrobial activity of bupivacaine and morphine. Anesthesiology 62:178–179Google Scholar
  14. 14.
    Taki Y, Ueno H, Murota K et al (1988) Effect of temperature on antibacterial activity of lidocaine to Staphylococcus aureus and Pseudomonas aeruginosa. Microbiol Immunol 32:429–434Google Scholar
  15. 15.
    Kose AA, Karabaggli Y, Kiremitci A et al (2010) Do local anesthetics have antibacterial effect on Staphylococcus aureus under in vivo conditions? An experimental study. Dermatol Surg 36:848–852Google Scholar
  16. 16.
    Kaya K, Rota S, Doǧan B et al (2007) Comparison of the antibacterial effects of two local anesthetics: lidocaine and articaine. Turk J Med Sci 37:7–10Google Scholar
  17. 17.
    Fazly Bazaz BS, Salt WG (1983) Local anaesthetics as antibacterial agents: effects on cellular respiration and the leakage of cytoplasmic constituents. Microbios 37:139–149Google Scholar
  18. 18.
    Schmidt RM, Rosenkranz HS (1970) Antimicrobial activity of local anesthetics: lidocaine and procaine. J Infect Dis 121:597–607Google Scholar
  19. 19.
    Ton That V, Nguyen S, Poon D et al (2010) Bioluminescent lux gene biosensors in oral streptococci: determination of complementary antimicrobial activity of minocycline hydrochloride with the anesthetic lidocaine/prilocaine or the antiseptic chlorhexidine. In Periodontitis: symptoms, treatment and prevention. Nova Science Publishers, Inc, p 141–165Google Scholar
  20. 20.
    Miller MA, Shelley WB (1985) Antibacterial properties of lidocaine on bacteria isolated from dermal lesions. Arch Dermatol 121:1157–1159Google Scholar
  21. 21.
    Pirbudak L, Karsligil T, Zer Y et al (2005) Antibacterial effect of bupivacaine and ropivacaine; effect of adjuvant drugs. Pain Clin 17:73–80Google Scholar
  22. 22.
    Won Keun S, Hyang Joon P, You Chan K et al (2000) The antimicrobial effects of lidocaine and epinephrine. Korean J Dermatol 38:635–642Google Scholar
  23. 23.
    Chandan SS, Faoagali J, Wainwright CE (2005) Sensitivity of respiratory bacteria to lignocaine. Pathology 37:305–307Google Scholar
  24. 24.
    Park KK, Sharon VR (2017) A review of local anesthetics: minimizing risk and side effects in cutaneous surgery. Dermatol Surg 43:173–187Google Scholar
  25. 25.
    Jung RM, Rybak MA, Milner PT et al (2017) Local anesthetics and advances in their administration – an overview. J Pre-Clin Clin Res 11:94–101Google Scholar
  26. 26.
    Drasner K (2015) Local anesthetics. In: Katzung B, Trevor A (eds) Basic and clinical pharmacology, 13th edn. Mc graw HillGoogle Scholar
  27. 27.
    Kim S, Toma H, Midha N et al (2010) Antibiotic resistance of conjunctiva and nasopharynx evaluation study: a prospective study of patients undergoing intravitreal injection. Ophthalmology 117:2372–2378Google Scholar
  28. 28.
    Filsoufi F, Castillo J, Rahmanian P et al (2009) Epidemiology of deep sternal wound infection in cardiac surgery. J Cardiothorac Vasc Anesth 23:488–494Google Scholar
  29. 29.
    Tabacov I, Tsatsova V (1970) The antibacterial effect of a chlorhexidine-lidocaine jelly upon the flora of the anterior male urethra. Int Urol Nephrol 2:199–202Google Scholar
  30. 30.
    Gocmen J, Buyukkocak U, Caglayan O (2008) In vitro antibacterial effects of topical local anesthetics. J Dermatol Treat 19:351–353Google Scholar
  31. 31.
    Mullin G, Rubinfeld R (1997) The antibacterial activity of topical anesthetics. Cornea 16:662–665Google Scholar
  32. 32.
    Morrow ME, Berry CW (1988) Antimicrobial properties of topical anesthetic liquids containing lidocaine or benzocaine. Anesth Prog 35:9–13Google Scholar
  33. 33.
    McCarthy P, Shklar G (1980) Diseases of the oral mucosa. Lea and Febiger, Philadelphia, p 101Google Scholar
  34. 34.
    Sculley PD, Dunley RE (1980) Antimicrobial activity of a lidocaine preparation. Anesth Prog 27:21–23Google Scholar
  35. 35.
    Aldous WK, Jensen R, Sieck BM (1998) Cocaine and lidocaine with phenylephrine as topical anesthetics: antimicrobial activity against common nasal pathogens. Ear Nose Throat J 77:554–557Google Scholar
  36. 36.
    Wimberley N, Willey S, Sullivan N et al (1979) Antibacterial properties of lidocaine. Chest 76:37–40Google Scholar
  37. 37.
    Sakuragi T, Ishino H, Dan K (1996) Bactericidal activity of clinically used local anesthetics on Staphylococcus aureus. Reg Anesth 21:239–242Google Scholar
  38. 38.
    Begec Z, Gulhas N, Toprak HI et al (2007) Comparison of the antibacterial activity of lidocaine 1% versus alkalinized lidocaine in vitro. Curr Ther Res Clin Exp 68:242–248Google Scholar
  39. 39.
    Feldman JM, Chapin-Robertson K, Turner J (1994) Do agents used for epidural analgesia have antimicrobial properties? Reg Anesth 19:43–47Google Scholar
  40. 40.
    Lagan G, McLure H (2004) Review of local anaesthetic agents. Curr Anaesth Crit Care 15:247–254Google Scholar
  41. 41.
    Maddi R, Horrow J, Mark J et al (1990) Evaluation of a new cutaneous topical anesthesia preparation. Reg Anesth 15:109–112Google Scholar
  42. 42.
    Kerenyi M, Batai R, Juhasz V et al (2004) Lidocaine/prilocaine cream (EMLA) has antibacterial effect in vitro. J Hosp Infect 55:75–76Google Scholar
  43. 43.
    Berg JO, Mössner BK, Skov MN et al (2006) Antibacterial properties of EMLA® and lidocaine in wound tissue biopsies for culturing. Wound Repair Regen 14:581–525Google Scholar
  44. 44.
    Batai I, Bogar L, Juhasz V et al (2009) A comparison of the antimicrobial property of lidocaine/prilocaine cream (EMLA®) and an alcohol-based disinfectant on intact human skin flora. Anesth Analg 108:666–668Google Scholar
  45. 45.
    Rota S, Akcabay M, Emektas G et al (1993) Antibacterial activity of bupivacaine. Gazi Tip Dergisi 4:69–71Google Scholar
  46. 46.
    Grimmond TR, Brownridge P (1986) Antimicrobial activity of bupivacaine and pethidine. Anaesth Intensive Care 14:418–420Google Scholar
  47. 47.
    Sakuragi T, Ishino H, Dan K (1997) Bactericidal activity of 0.5% bupivacaine with preservatives on microorganisms in the human skin flora. Reg Anesth 22:178–184Google Scholar
  48. 48.
    Batai I, Kerenyi M, Falvai J et al (2002) Bacterial growth in ropivacaine hydrochloride. Anesth Analg 94:729–731Google Scholar
  49. 49.
    Aydin ON, Eyigor M, Aydin N (2001) Antimicrobial activity of ropivacaine and other local anaesthetics. Eur J Anaesthesiol 18:687–694Google Scholar
  50. 50.
    Hodson M, Gajraj R, Scott NB (1999) A comparison of the antibacterial activity of levobupivacaine vs. bupivacaine: an in vitro study with bacteria implicated in epidural infection. Anaesthesia 54:699–702Google Scholar
  51. 51.
    Pelz K, Wiedmann-Al-Ahmad M, Bogdan C et al (2008) Analysis of the antimicrobial activity of local anaesthetics used for dental analgesia. J Med Microbiol 57:88–94Google Scholar
  52. 52.
    Pina-Vaz C, Rodrigues AG, Sansonetty F et al (2000) Antifungal activity of local anesthetics against Candida species. Infect Dis Obstet Gynecol 8:124–137Google Scholar
  53. 53.
    Rodrigues A, Pina-Vaz C, Mardh P et al (2000) Inhibition of germ tube formation by Candida albicans by local anesthetics: an effect related to ionic channel blockade. Curr Microbiol 40:145–148Google Scholar
  54. 54.
    Rodrigues AG, Araujo R, Pina-Vaz C (2006) Interaction of local anaesthetics with other antifungal agents against pathogenic aspergillus. Int J Antimicrob Agents 27:339–343Google Scholar
  55. 55.
    Abdelaziz AA, el-Nakeeb MA (1988) Sporicidal activity of local anaesthetics and their binary combinations with preservatives. J Clin Pharm Ther 13:249–256Google Scholar
  56. 56.
    Barza M, Ernst C, Baum J et al (1974) Effect of lidocaine on the antibacterial activity of seven antibiotics. Arch Ophthalmol 92:514–515Google Scholar
  57. 57.
    Kampe S, Poetter C, Buzello S et al (2003) Ropivacaine 0.1% with sufentanil 1 microg/mL inhibits in vitro growth of Pseudomonas aeruginosa and does not promote multiplication of Staphylococcus aureus. Anesth Analg 97:409–411Google Scholar
  58. 58.
    Tamanai-Shacoori Z, Shacoori V, Vo Van JM et al (2004) Sufentanil modifies the antibacterial activity of bupivacaine and ropivacaine. Can J Anesth 51:911–914Google Scholar
  59. 59.
    Guillier M, Boselli E, Bouvet L et al (2007) Levobupivacaine hydrochloride and sufentanil have no antimicrobial effect at 25°C in vitro. Eur J Anaesthesiol 24:634–639Google Scholar
  60. 60.
    Gajraj RJ, Hodson MJ, Gillespie JA et al (1998) Antibacterial activity of lidocaine in mixtures with Diprivan. Br J Anaesth 81:444–448Google Scholar
  61. 61.
    Euasobhon P, Dej-Arkom S, Siriussawakul A et al (2016) Lidocaine for reducing propofol-induced pain on induction of anaesthesia in adults. Cochrane Database Syst Rev 2:Cd007874Google Scholar
  62. 62.
    Sakuragi T, Yanagisawa K, Shirai Y et al (1999) Growth of Escherichia coli in propofol, lidocaine, and mixtures of propofol and lidocaine. Acta Anaesthesiol Scand 43:476–479Google Scholar
  63. 63.
    Wachowski I, Jolly DT, Hrazdil J et al (1999) The growth of microorganisms in propofol and mixtures of propofol and lidocaine. Anesth Analg 88:209–212Google Scholar
  64. 64.
    Driver R, Granus V, Yassa Y (1998) Growth inhibition of Staphylococcus aureus by propofol/lidocaine admixture. Anesth Analg 86:166SGoogle Scholar
  65. 65.
    Yagiela JA (1995) Vasoconstrictor agents for local anesthesia. Anesth Prog 42:116–120Google Scholar
  66. 66.
    Curatolo M, Petersen-Felix S, Arendt-Nielsen L et al (1998) Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade. Anesth Analg 86:341–347Google Scholar
  67. 67.
    Snyders SP, James MFM (2008) Alkalinisation does not enhance the antimicrobial properties of local anaesthetic solutions. S Afr J Anaesth Analg 14:25–28Google Scholar
  68. 68.
    Begeç Z, Gülhaş N, Toprak HI et al (2007) Antibacterial effectiveness of alkalinized ropivacaine and bupivacaine. Turk Anesteziyoloji ve Reanimasyon Dernegi Dergisi 35:11–15Google Scholar
  69. 69.
    Thompson KD, Welykyj S, Massa MC (1993) Antibacterial activity of lidocaine in combination with a bicarbonate buffer. J Dermatol Surg Oncol 19:216–220Google Scholar
  70. 70.
    Ohsuka S, Ohta M, Masuda K et al (1994) Lidocaine hydrochloride and acetylsalicylate kill bacteria by disrupting the bacterial membrane potential in different ways. Microbiol Immunol 38:429–434Google Scholar
  71. 71.
    Leung Y, Rawal B (1977) Mechanism of action of tetracaine hydrochloride against Pseudomonas aeruginosa. Infect Dis Obstet Gynecol 136:679–683Google Scholar
  72. 72.
    Fazly Bazaz BS, Salt W (1983) Local anaesthetics induced turbidity increases: implications of interactions with intact bacterial cells and with subcellular fractions. Microbios 36:135–147Google Scholar
  73. 73.
    Salt W, Wiseman D (1970) The effect of magnesium ions and Tris buffer on the uptake of cetyl trimethyl ammonium bromide by Escherichia coli. J Pharm Pharmacol 22:767–773Google Scholar
  74. 74.
    Lamikanara A, Allwood M (1977) Effect of polyoxyalkylphenols on the optical density of staphylococcus aureus. J Appl Bacteriol 42:387–392Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Bibi Marjan Razavi
    • 1
    • 2
  • Bibi Sedigheh Fazly Bazzaz
    • 3
    • 4
    Email author
  1. 1.Targeted Drug Delivery Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Pharmacodynamics and Toxicology, School of PharmacyMashhad University of Medical SciencesMashhadIran
  3. 3.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  4. 4.Pharmaceutical Control Department, School of PharmacyMashhad University of Medical SciencesMashhadIran

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