Another look at local anesthetics: An overview of antimicrobial properties

Document Type : Review article

Authors

1 Mashhad University of Medical Sciences

2 گروه فارماکودینامی و سم شناسی دانشکده داروسازی مشهد

3 Department of Medicinal Chemistry, Mashhad University of Medical Sciences

Abstract

Loss of sensation in ​​the part of the body is called local anesthesia. Local anesthetics (LAs) can treat pain in specific areas of the body by blocking sodium channels. They have also been introduced in several studies as antimicrobial agents. In the present study, special attention has been paid to their role as antimicrobial agents and their effects in treatment.
By means of several databases, related key words for antimicrobial agents were searched until the end of 2021. Initially, by restricting the search, unrelated and duplicate studies were eliminated, and after reviewing the appropriate abstracts and complete texts,, they were appended to the present study.
This study is focusing on the antimicrobial application of LAs , their interfering with various agents in combination with them, the mechanism of action, and the structural dependence on the antimicrobial effects . The following results have been perceived:
1- Structure, concentration, duration of exposure, type of microorganism and temperature affect the antimicrobial activity.
2. Compounds such as opioids, antibiotics, etc. can be combined with them and affect the antimicrobial properties.
3- Lidocaine has been studied the most and has been effective in prevention and treatment.
4- Due to their antimicrobial activity, they can be used in the clinic to prevent infection at the surgical site.

Keywords


1-Dranser K. Local Anesthetics. In: Katzung BG. Vanderah TW. Basic and Clinical Pharmacology. 15 th
ed. MC Graw Hill. 2021
2-Murphy J T, Allen H F, Mangiaracine AB, (1955) Preparation, sterilization, and preservation of
ophthalmic solutions¨experimental studies and a practical method. Arch Ophthalmol 53: 63-78.
3-Conte BA, Laforet EG (1962) The role of the topicall anaesthetics agents in modifying bacteriological
data obtained by bronchoscopy. New Eng J Med 267:957-960.
4-Silva MT, Sousa JCF, Polonia JJ, Macedo PM (1979) Effect of local anaesthetics on bacterial cells. J
Bact 137:461-468.
5. Johnson SM, Saint John BE, Dine AP (2008) Local anesthetics as antimicrobial agents: a review. Surg
Infect 9:205–213.
6-Razavi M, Fazly Bazzaz BS (2019) A review and new insights to antimicrobial action of local
anesthetics, Eur J Clin Microbiol Infect Dis. 38:991-1002.
7- Park KK, Sharon VR (2017) A review of local anesthetics: minimizing risk and side effects in
cutaneous surgery. Dermatol Surg 43:173–187.
8- Jung RM, Rybak MA, Milner PT et al (2017) Local anesthetics and advances in their administration:
an overview. J Pre-Clin Clin Res 11:94–101.
9- Keld DB, Hein L, Dalagaard M, Krogh L, Rodt SA (2000) The incidence of transient neurologic
symptoms (TNS). Acta Anaesthsiol Scand. 44: 285-290.
10-Ghaemi M, Ansari M, Mohammadi S (2006) Comparison of the sensory-motor block effects of low
dose hyperbaric bupivacaine and lidocaine in anorectal surgery with spinal anesthesia, J Advance Med
Biomed Res 14:1-5.
11-Adler DMT Damborg P, Verwilghen DR (2017) The antimicrobial activity of bupivacaine, lidocaine
and mepivacaine against equine pathogens: An investigation of 40 bacterial isolates, The Veterinary
Journal. 223: 27-31.
12-45. Rota S, Akcabay M, Emektas G et al (1993) Antibacterial activity of bupivacaine. Gazi Tip
Dergisi 4:69–71.
13. Pere P, Lindgren L, Vaara M (1999) Poor antibacterial effect of ropivacaine: comparison with
bupivacaine. Anesthesiology 91:884–886.
14. Grimmond TR, Brownridge P (1986) Antimicrobial activity of bupivacaine and pethidine. Anaesth
Intensive Care 14:418–420.
15- Rosenberg PH, Renkonen OV (1985) Antimicrobial activity of bupivacaine and morphine.
Anesthesiology 62:178–179.
16- Sakuragi T, Ishino H, Dan K (1998) Bactericidal activity of preservative-free bupivacaine on
microorganisms in the human skin flora, Acta Anaesthesiol Scand. 42:1096-9.
17- Sakuragi T, Ishino H, Dan K (1997) Bactericidal activity of 0.5% bupivacaine with preservatives on
microorganisms in the human skin flora. Reg Anesth 22:178–184.
18- Aydin ON, Eyigor M, Aydin N (2001) Antimicrobial activity of ropivacaine and other local
anaesthetics. Eur J Anaesthesiol 18:687–694.
19- 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 54:699–702.
21- Morrow ME, Berry CW (1988) Antimicrobial properties of topical anesthetic liquids containing
lidocaine or benzocaine. Anesth Prog 35:9–13.
22- Lagan G, McLure H (2004) Review of local anaesthetic agents. Curr Anaesth Crit Care 15:247–254.
23-Kerenyi M, Batai R, Juhasz V et al (2004) Lidocaine/prilocaine cream (EMLA) has antibacterial effect
in vitro. J Hosp Infect 55:75–76.
24-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 108:666–668.
25- Berg JO, Mössner BK, Skov MN et al (2006) Antibacterial properties of EMLA® and lidocaine in
wound tissue biopsies for culturing. Wound Repair Regen 14:581–525.
26-Meyler's, (2016) Side Effects of Drugs (Sixteenth Edition).
27- Fazly Bazaz BS, Salt WG (1983) Local anaesthetics as antimicrobial agents: structure-action
considerations. Microbios 37:45–64.
28-Fazly Bazaz BS, Salt WG (1983) Local anaesthetics as antibacterial agents: effects on cellular
respiration and the leakage of cytoplasmic constituents. Microbios 37:139–149.
29-Fazly Bazaz BS, Salt W (1983) Local anaesthetics induced turbidity increases: implications of
interactions with intact bacterial cells and with subcellular fractions. Microbios 36:135–147.
30-Beckett A, Patki SJ, Robinson AE (1959) The interaction of phenolic compoundswith bacteria, ll. The
effect of various substances on the interactionof hexylresorcinol with Escherichia coli, J Pharm
Pharmacol. 11:367-373
31-Hugo WB, Longwort AR (1964) some aspects of the mode of action of chlohexidine. J Pharm
Pharmacol. 16:655-662.
32- Batai I, Kerenyi M, Falvai J et al (2002) Bacterial growth in ropivacaine hydrochloride. Anesth Analg
94:729–731.
33- Gordh T, Gordh TE, Lindqvist K, Warner DS (2010) Lidocaine: The origin of a modern local
anesthetic, Anesthesiology. 113:1433–1437.
34-Neuwersch S, Kostenberger M, Sorschag S, Ilias W, Likar R (2017) Antimicrobial activity of
lidocaine, Bupivacaine, mepivacaine and ropivacaine on Staphylococcus epidermidis, Staphylococcus
aureus and Bacillus subtilis, The Open Pain Journal.10:1-4.
35- 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
117:2372–2378.
36- Tustin A, Kim SJ, Chomsky A et al (2014) Antibacterial propertiesof 2% lidocaine and reduced rate
of endophthalmitis after intravitreal injection. Retina 34:935–942.
37- Tabacov I, Tsatsova V (1970) The antibacterial effect of a chlorhexidine-lidocaine jelly upon the flora
of the anterior male urethra. Int Urol Nephrol 2:199–202.
38- Yang H, Guo X, Chen X et al (2013) Study on antibacterial effect of lidocaine. Chinese J Androl
27:14–16.
39- Srisatjaluk RL, Klongnoi B, Wongsirichat N (2016) Antimicrobial effect of topical local anesthetic
spray on oral microflora. J Dent Anesth Pain Med 16:17–24.
40- 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 77:554–557.
41- Chandan SS, Faoagali J, Wainwright CE (2005) Sensitivity of respiratory bacteria to lignocaine.
Pathology 37:305–307.
42- Feldman JM, Chapin-RRoberison K, Tumer J (1994) Do agents used for epidural analgesia have
antimicrobial properties? Reg Anesth 19:43-47.
43- 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 68:242–248.
44- Pina-Vaz C, Rodrigues AG, Sansonetty F et al (2000) Antifungal activity of local anesthetics against
Candida species. Infect Dis Obstet Gynecol 8:124–137.
45- 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 40:145–148.
46- Rodrigues AG, Araujo R, Pina-Vaz C (2006) Interaction of local anaesthetics with other antifungal
agents against pathogenic aspergillus. Int J Antimicrob Agents 27:339–343.
47- Sakuragi T, Ishino H, Dan K (1996) Bactericidal activity of clinically used local anesthetics on
Staphylococcus aureus. Reg Anesth 21:239–242
48- Pal Sh, Sayana A, Joshi A, Juyal D (2019) Staphylococcus aureus: A predominant cause of surgical
site infections in a rural healthcare setup of Uttarakhand, J Family Med Prim Care. 8: 3600–3606.
49-Filsoufi F, Castillo J, Rahmanian P et al (2009) Epidemiology of deep sternal wound infection in
cardiac surgery. J Cardiothorac Vasc Anesth 23:488–494.
50- Parr AM, Zoutman DE, Davidson JSD (1999) Antimicrobial activity of lidocaine against bacteria
associated with nosocomial wound infection. Ann Plast Surg 43:239–245.
51- 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 73:598–601.
52-Allison C Scully, James R Boynton (2017) Antibiotics and Local Anesthetics: Drug Considerations
for the Child Patient, J Mich Dent Assoc 99:36-41, 71.
53- Rodrigues AG, Araujo R, Pina-Vaz C (2006) Interaction of local anaesthetics with other antifungal
agents against pathogenic aspergillus. Int J Antimicrob Agents 27:339–343.
54- 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. InPeriodontitis: symptoms, treatment and prevention.
Nova Science Publishers, Inc, p 141–165.
55- Barza M, Ernst C, Baum J et al (1974) Effect of lidocaine on the antibacterial activity of seven
antibiotics. Arch Ophthalmol 92:514–515.
56- Pöpping DM , Elia N, Marret E, Wenk M, Tramèr MR (2012) Opioids added to local anesthetics
for single-shot intrathecal anesthesia in patients undergoing minor surgery: a meta analysis of randomized
trials, Pain 153:784-793.
57-Sevgi Kesici, Mehmet Demirci, Ugur Kesici (2020) Antimicrobial effects of fentanyl and bupivacaine:
an in vitro study, Brazilian Journal of Anesthesiology 70:357-363.
58- Pirbudak L, Karsligil T, Zer Y et al (2005) Antibacterial effect of bupivacaine and ropivacaine; effect
of adjuvant drugs. Pain Clin 17:73–80.
59- Feldman JM, Chapin-Robertson K, Turner J (1994) Do agents used for epidural analgesia have
antimicrobial properties? Reg Anesth 19:43–47.
60- 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 97:409–411.
61- 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 24:634–639.
62-Tamanai-Shacoori Z, Shacoori V, Vo Van JM et al (2004) Sufentanil modifies the antibacterial
activity of bupivacaine and ropivacaine. Can J Anesth 51:911–914.
63- Yagiela JA (1995) Vasoconstrictor agents for local anesthesia. Anesth Prog 42:116–120.
64-Ugur Kesici, Mehmet Demirci, Sevgi Kesici (2019) Antimicrobial effects of local anaesthetics, Int
Wound 16:1029–1033.
65- Won Keun S, Hyang Joon P, You Chan K et al (2000) The antimicrobial effects of lidocaine and
epinephrine. Korean J Dermatol 38:635–642.
66- 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–
1279.
67- Sculley PD, Dunley RE (1980) Antimicrobial activity of a lidocaine preparation. Anesth Prog 27:21–
23.
68- Gajraj RJ, Hodson MJ, Gillespie JA et al (1998) Antibacterial activity of lidocaine in mixtures with
Diprivan. Br J Anaesth 81:444–448.
69- 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: Cd007874
70- 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 43:476–479.
71- Wachowski I, Jolly DT, Hrazdil J et al (1999) The growth of microorganisms in propofol and
mixtures of propofol and lidocaine. Anesth Analg 88:209–212.
72- Driver R, Granus V, Yassa Y (1998) Growth inhibition of Staphylococcus aureus by
propofol/lidocaine admixture. Anesth Analg 86:166S.
73- Curatolo M, Petersen-Felix S, Arendt-Nielsen L et al (1998) Adding sodium bicarbonate to lidocaine
enhances the depth of epidural blockade. Anesth Analg 86:341–347.
74- Snyders SP, James MFM (2008) Alkalinisation does not enhance the antimicrobial properties of local
anaesthetic solutions. S Afr J Anaesth Analg 14:25–28.
75- Thompson KD, Welykyj S, Massa MC (1993) Antibacterial activity of lidocaine in combination with
a bicarbonate buffer. J Dermatol Surg Oncol 19:216–220.
76- Begeç Z, Gülhaş N, Toprak HI et al (2007) Antibacterial effectiveness of alkalinized ropivacaine and
bupivacaine. Turk Anesteziyoloji ve Reanimasyon Dernegi Dergisi 35:11–15.
77- 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 57:88–94.
78- Wimberley N, Willey S, Sullivan N et al (1979) Antibacterial properties of lidocaine. Chest 76:37–40.
79- Schmidt RM, Rosenkranz HS (1970) Antimicrobial activity of local anesthetics: lidocaine and
procaine. J Infect Dis 121:597–607.
80- 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 38:429–434.
81- Leung Y, Rawal B (1977) Mechanism of action of tetracaine hydrochloride against Pseudomonas
aeruginosa. Infect Dis Obstet Gynecol 136:679–683.
82- 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 22:767–773.
83- Lamikanara A, Allwood M (1977) Effect of polyoxyalkylphenols on the optical density of
Staphylococcus aureus. J Appl Bacteriol 42:387–392.