Bacterial resistance to chlorhexidine in surgical dentistry

November 4, 2021
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Antiseptic agents are increasingly used for hand hygiene and skin decolonization as key tools for the prevention of healthcare-associated infections. Chlorhexidine, a divalent, cationic biguanide, has a broad spectrum of activity and is one of the most frequently used topical antiseptic agents. Notably, there are an increasing number of prevalence studies that report reduced levels of susceptibility to chlorhexidine. In contrast to bacterial resistance to antibiotics, using parameters such as the minimum inhibitory concentration to define resistance to antiseptics, including chlorhexidine, is not straightforward. A range of methods have been used for the detection of reduced susceptibility to chlorhexidine, but, importantly, there is no standardized method and no consensus on the definition of chlorhexidine resistance. In this review we have assessed the methods available for the detection of reduced susceptibility to chlorhexidine and the prevalence of coresistance to other antimicrobial agents. We have focused on the development of reduced susceptibility to chlorhexidine and the presence of efflux-mediated resistance genes in staphylococci, and have reviewed the clinical significance of this phenomenon. Lastly, we have identified unanswered questions to further our understanding of this emergent threat. We anticipate that clinical use of chlorhexidine will continue to increase, and it will be important to be alert to the possibility that this may lead to the emergence of new clones with reduced susceptibility. Indiscriminate chlorhexidine use in the absence of efficacy data should be discouraged.

References

  • 1. Salmanov A.G. (2011) Optimization of hand hygiene medical personnel surgical depertment. UMJ, 2(82): 85–91.
  • 2. Haley R.W., Culver D.H., White J.W. et al. (1985) The efficacy of infection surveillance and control programs in preventing nosocomial infections in US hospitals. Am. J. Epidemiol., 121: 182–205. doi: 10.1093/oxfordjournals.aje.a113990.
  • 3. Nystrom B. (1994) Impact of handwashing on mortality in intensive care: examination of the evidence. Infect. Control Hosp. Epidemiol., 15(7): 435–436. doi: 10.1086/646947.
  • 4. Reybrouck G. (1983) Role of hands in the spread of nosocomial infections. J. Hosp. Infect. 4(2): 103–110. doi: 10.1016/0195-6701(83)90040-3.
  • 5. Rotter M., Skopec M. (2003) Entwicklung der Händehygiene und die Bedeutung der Erkenntnisse von Ignaz Ph. Semmelweis, p. 1–27. In: G. Kampf (Еd.), Hände-Hygiene im Gesundheitswesen. Springer-Verlag KG, Berlin, Germany.
  • 6. Pittet D. (2000) Improving compliance with hand hygiene in hospitals. Infect. Control Hosp. Epidemiol., 21(6): 381–386. doi: 10.1086/501777.
  • 7. Boyce J.M., Pittet D. (2002) Guideline for hand hygiene in health-care settings. Recommendations of the healthcare infection control practices advisory committee and the HICPAC/SHEA/APIC/IDSA hand hygiene task force. Morb. Mortal. Wkly. Rep., 51: 1–45.
  • 8. Russell A.D. (1986) Chlorhexidine: antibacterial action and bacterial resistance. Infection, 14(5): 212–215. doi: 10.1007/BF01644264.
  • 9. Lowbury E.J., Lilly H.A. (1973) Use of 4 per cent chlorhexidine detergent solution (Hibiscrub) and other methods of skin disinfection. Br. Med. J., 1(5852): 510–515. doi:10.1136/bmj.1.5852.510.
  • 10. Lowbury E.J., Lilly H.A., Ayliffe G.A. (1974) Preoperative disinfection of surgeons’ hands: use of alcoholic solutions and effects of gloves on skin flora. Br. Med. J., 4(5941): 369–372. doi: 10.1136/bmj.4.5941.369.
  • 11. Linton K.B., George E. (1966) Inactivation of chlorhexidine («hibitane») by bark corks. Lancet, 1(7451): 1353–1355. doi: 10.1016/s0140-6736(66)92141-6.
  • 12. Walsh B., Blakemore P.H., Drabu Y.J. (1987) The effect of handcream on the antibacterial activity of chlorhexidine gluconate. J. Hosp. Infect., 9(1): 30–33. doi: 10.1016/0195-6701(87)90091-0.
  • 13. Burdon D.W., Whitby J.L. (1967) Contamination of hospital disinfectants with Pseudomonas species. Br. Med. J., 2(5545): 153–155. doi: 10.1136/bmj.2.5545.153.
  • 14. Hammond S.A., Morgan J.R., Russell A.D. (1987) Comparative susceptibility of hospital isolates of gram-negative bacteria to antiseptics and disinfectants. J. Hosp. Infect., 9(3): 255–264. doi: 10.1016/0195-6701(87)90122-8.
  • 15. Russell A.D., Day M.J. (1993) Antibacterial activity of chlorhexidine. J. Hosp. Infect., 25(4): 229–238. doi: 10.1016/0195-6701(93)90109-d.
  • 16. Richards R.M., Richards J.M. (1979) Pseudomonas cepacia resistance to antibacterials. J. Pharm. Sci., 68(11): 1436–1438. doi: 10.1002/jps.2600681127.
  • 17. Davies D.J. (1978) Agents as preservatives in eye-drops and contact lens solutions. J. Appl. Bacteriol., 44(3): Sxix–Sxxviii. doi: 10.1111/j.1365-2672.1978.tb04191.x.
  • 18. Hiom S.J., Furr J.R., Russell A.D. et al. (1992) Effects of chlorhexidine diacetate on Candida albicans. C. glabrata and Saccharomyces cerevisiae. J. Appl. Bacteriol., 72(4): 335–340. doi: 10.1111/j.1365-2672.1992.tb01844.x.
  • 19. Ekizoglu M.T., Özalp M., Sultan N. et al. (2003) An investigation of the bactericidal effect of certain antiseptics and disinfectants on some hospital isolates of gram-negative bacteria. Infect. Control Hosp. Epidemiol., 24(3): 225–227. doi: 10.1086/502194.
  • 20. Haley C.E., Marling-Cason M., Smith J.W. et al. (1985) Bactericidal activity of antiseptics against methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol., 21(6): 991–992. doi: 10.1128/jcm.21.6.991-992.1985.
  • 21. Kampf G., Höfer M., Wendt C. (1999) Efficacy of hand disinfectants against vancomycin-resistant enterococci in vitro. J. Hosp. Infect., 42(2): 143–150. doi: 10.1053/jhin.1998.0559.
  • 22. Goroncy-Bermes P., Schouten M.A., Voss A. (2001) In vitro activity of a nonmedicated handwash product, chlorhexidine, and an alcohol-based hand disinfectant against multiply resistant gram-positive microorganisms. Infect. Control Hosp. Epidemiol., 22(4): 194–196. doi: 10.1086/503398.
  • 23. Shimizu M., Okuzumi K., Yoneyama A. et al. (2002) In vitro antiseptic susceptibility of clinical isolates from nosocomial infections. Dermatology, 204 Suppl. 1: 21–27. doi: 10.1159/000057720.
  • 24. Guilhermetti M., Hernandes S.E., Fukushigue Y. et al. (2001) Effectiveness of hand-cleansing agents for removing methicillin-resistant Staphylococcus aureus from contaminated hands. Infect. Control Hosp. Epidemiol., 22(2): 105–108. doi: 10.1086/501872.
  • 25. Huang Y., Oie S., Kamiya A. (1994) Comparative effectiveness of hand-cleansing agents for removing methicillin-resistant Staphylococcus aureus from experimentally contaminated fingertips. Am. J. Infect. Control., 22(4): 224–227. doi: 10.1016/0196-6553(94)99000-x.
  • 26. Voss A., Goroncy-Bermes P. (2000) Elimination and post-disinfection transmission of Staphylococcus aureus from experimentally contaminated hands. Infect. Control Hosp. Epidemiol., 21: 106.
  • 27. Casewell M., Phillips I. (1977) Hands as route of transmission for Klebsiella species. Br. Med. J., 2(6098): 1315–1317. doi:10.1136/bmj.2.6098.1315.
  • 28. Marena C., Lodola L., Zecca M. et al. (2002) Assessment of handwashing practices with chemical and microbiological methods: preliminary results from a prospective crossover study. Am. J. Infect. Control., 30(6): 334–340. doi: 10.1067/mic.2002.125809.
  • 29. Bryce E.A., Spence D., Roberts F.J. (2001) An in-use evaluation of an alcohol-based pre-surgical hand disinfectant. Infect. Control Hosp. Epidemiol., 22(10): 635–639. doi: 10.1086/501835.
  • 30. Nakahara H., Kozukue H. (1982) Isolation of chlorhexidine-resistant Pseudomonas aeruginosa from clinical lesions. J. Clin. Microbiol., 15(1): 166–168. doi:10.1128/jcm.15.1.166-168.1982.
  • 31. Barry A.L., Fuchs P.C., Brown S.D. (1999) Lack of effect of antibiotic resistance on susceptibility of microorganisms to chlorhexidine gluconate or povidone iodine. Eur. J. Clin. Microbiol. Infect. Dis., 18(12): 920–921. doi: 10.1007/s100960050434.
  • 32. Järvinen H., Tenovuo J., Huovinen P. (1993) In vitro susceptibility of Streptococcus mutans to chlorhexidine and six other antimicrobial agents. Antimicrob. Agents Chemother., 37(5): 1158–1159. doi:10.1128/AAC.37.5.1158.
  • 33. Nakahara H., Kozukoe H. (1981) Chlorhexidine resistance in Escherichia coli isolated from clinical lesions. Zentralbl. Bakteriol. Mikrobiol. Hyg. A., 251(2): 177–184.
  • 34. Ismaeel N., El-Moug T., Furr J.R. et al. (1986) Resistance of Providencia stuartii to chlorhexidine: a consideration of the role of the inner membrane. J. Appl. Bacteriol., 60: 361–367. doi: 10.1111/j.1365-2672.1986.tb01744.x.
  • 35. Thomas L., Maillard J.Y., Lambert R.J. et al. (2000) Development of resistance to chlorhexidine diacetate in Pseudomonas aeruginosa and the effect of a «residual» concentration. J. Hosp. Infect., 46: 297–303. doi: 10.1053/jhin.2000.0851.
  • 36. Martone W.J., Tablan O.C., Jarvis W.R. (1987) The epidemiology of nosocomial epidemic Pseudomonas cepacia infections. Eur. J. Epidemiol., 3: 222–232. doi: 10.1007/BF00149728.
  • 37. Lannigan R., Bryan L.E. (1985) Decreased susceptibility of Serratia marcescens to chlorhexidine related to the inner membrane. J. Antimicrob. Chemother., 15: 559–565. doi: 10.1093/jac/15.5.559.
  • 38. Baillie L. (1987) Chlorhexidine resistance among bacteria isolated from urine of catheterized patients. J. Hosp. Infect., 10: 83–86. doi: 10.1016/0195-6701(87)90037-5.
  • 39. Stickler D.J., Clayton C.L., Chawla J.C. (1987) The resistance of urinary tract pathogens to chlorhexidine bladder washouts. J. Hosp. Infect., 10: 28–39. doi: 10.1016/0195-6701(87)90029-6.
  • 40. Walker E.M., Lowes J.A. (1985) An investigation into in vitro methods for the detection of chlorhexidine resistance. J. Hosp. Infect., 6: 389–397. doi: 10.1016/0195-6701(85)90055-6.
  • 41. Freney J., Husson M.O., Gavini F. et al. (1988) Susceptibilities to antibiotics and antiseptics of new species of the family Enterobacteriaceae. Antimicrob. Agents Chemother., 32(6): 873–876. doi: 10.1128/AAC.32.6.873.
  • 42. Chawner JA, Gilbert P. (1989). Interaction of the bisbiguanides chlorhexidine and alexidine with phospholipid vesicles: evidence for separate modes of action. J. Appl. Bacteriol., 66: 253–258. doi: 10.1111/j.1365-2672.1989.tb02476.x.
  • 43. Lambert R.J., Joynson J., Forbes B. (2001) The relationship and susceptibilities of some industrial laboratory and clinical isolates of Pseudomonas aeruginosa to some antibiotics and biocides. J. Appl. Microbiol., 91: 972–984. doi: 10.1046/j.1365-2672.2001.01460.x.
  • 44. Higgins C.S., Murtough S.M., Williamson E. et al. (2001) Resistance to antibiotics and biocides among nonfermenting gram-negative bacteria. Clin. Microbiol. Infect., 7: 308–315. doi: 10.1046/j.1198-743x.2001.00253.x.
  • 45. el Moug T., Rogers T.D., Furr J.R. et al. (1985) Antiseptic-induced changes in the cell surface of a chlorhexidine-sensitive and a chlorhexidine-resistant strain of Providencia stuartii. J. Antimicrob. Chemother., 16: 685–689. doi: 10.1093/jac/16.6.685.
  • 46. Tattawasart U., Hann A.C., Maillard J.-Y. J. et al. (2000) Cytological changes in chlorhexidine-resistant isolates of Pseudomonas stutzeri. J. Antimicrob. Chemother., 45: 145–152. doi: 10.1093/jac/45.2.145.
  • 47. Yamamoto T., Tamura Y., Yokota T. (1988) Antiseptic and antibiotic resistance plasmid in Staphylococcus aureus that possesses ability to confer chlorhexidine and acrinol resistance. Antimicrob. Agents Chemother., 32: 932–935. doi: 10.1128/AAC.32.6.932.
  • 48. Okuda T., Endo N., Osada Y. et al. (1984) Outbreak of nosocomial urinary tract infections caused by Serratia marcescens. J. Clin. Microbiol., 20(4): 691–695. doi:10.1128/jcm.20.4.691-695.1984.
  • 49. Gandhi P.A., Sawant A.D., Wilson L.A. et al. (1993) Adaption and growth of Serratia marcescens in contact lens disinfectant solutions containing chlorhexidine gluconate. Appl. Environ. Microbiol., 59(1): 183–188. doi:10.1128/aem.59.1.183-188.1993.
  • 50. Tattawasart U., Maillard J.-Y. Furr J.R. et al. (1999) Development of resistance to chlorhexidine diacetate and cetylpyridinium chloride in Pseudomonas stutzeri and changes in antibiotic susceptibility. J. Hosp. Infect., 42: 219–229. doi: 10.1053/jhin.1999.0591.
  • 51. Westergren G., Emilson C.-G. (1980) In vitro development of chlorhexidine resistance in Streptococcus sanguis and its transmissibility by genetic transformation. Scand. J. Dent. Res., 88(3): 236–243. doi: 10.1111/j.1600-0722.1980.tb01220.x.
  • 52. Brooks S.E., Walczak M.A. Hameed R. et al. (2002) Chlorhexidine resistance in antibiotic-resistant bacteria isolated from the surfaces of dispensers of soap containing chlorhexidine. Infect. Control Hosp. Epidemiol., 23(11): 692–695. doi: 10.1086/501996.
  • 53. Kampf G., Kramer A. (2004) Epidemiologic Background of Hand Hygiene and Evaluation of the Most Important Agents for Scrubs and Rubs. Clin. Microbiol. Rev., 17(4): 863–893. doi: 10.1128/CMR.17.4.863-893.2004.