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Antimicrobial Resistance to Agents Used for Staphylococcus aureus Decolonization: Is There a Reason for Concern?

  • Gregory R. Madden
  • Costi D. Sifri
Antimicrobial Development and Drug Resistance (A Pakyz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Antimicrobial Development and Drug Resistance

Abstract

Purpose of Review

Chlorhexidine gluconate (CHG) and mupirocin are increasingly used for Staphylococcus aureus decolonization to prevent healthcare-associated infections; however, increased use of these agents has led to concerns for growing resistance and reduced efficacy. In this review, we describe current understanding of reduced susceptibility to CHG and mupirocin in S. aureus and their potential clinical implications.

Recent Findings

While emergence of S. aureus tolerant or resistant to topical antimicrobial agents used for decolonization is well described, the clinical impact of reduced susceptibility is not clear. Important challenges are that standardized methods of resistance testing and interpretation are not established, and the risk for selection for co- or cross-resistance using universal, as opposed to targeted decolonization, is unclear.

Summary

Evidence continues to support S. aureus decolonization in certain patient groups, although further studies are needed to determine the long-term impact of CHG and mupirocin resistance on efficacy. Strategies to mitigate further development of reduced susceptibility and the consequences of selection pressures through universal decolonization on resistance will benefit from further investigation.

Keywords

Antimicrobial resistance Antiseptic Chlorhexidine Mupirocin Decolonization Staphylococcus aureus 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Wertheim HFL, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 2005;5:751–62.  https://doi.org/10.1016/S1473-3099(05)70295-4.CrossRefPubMedGoogle Scholar
  2. 2.
    Bode LGM, Kluytmans JAJW, Wertheim HFL, Bogaers D, Vandenbroucke-Grauls CMJE, Roosendaal R, et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med. 2010;362:9–17.  https://doi.org/10.1056/NEJMoa0808939.CrossRefPubMedGoogle Scholar
  3. 3.
    Gorwitz RJ, Kruszon-Moran D, McAllister SK, McQuillan G, McDougal LK, Fosheim GE, et al. Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001–2004. J Infect Dis. 2008;197:1226–34.  https://doi.org/10.1086/533494.CrossRefPubMedGoogle Scholar
  4. 4.
    Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infect Control Hosp Epidemiol. 2005;26:166–74.  https://doi.org/10.1086/502522.CrossRefPubMedGoogle Scholar
  5. 5.
    Eiff v C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001;344:11–6.  https://doi.org/10.1056/NEJM200101043440102. CrossRefGoogle Scholar
  6. 6.
    Safdar N, Bradley EA. The risk of infection after nasal colonization with Staphylococcus aureus. Am J Med. 2008;121:310–5.  https://doi.org/10.1016/j.amjmed.2007.07.034.CrossRefPubMedGoogle Scholar
  7. 7.
    Nelson RE, Slayton RB, Stevens VW, Jones MM, Khader K, Rubin MA, et al. Attributable mortality of healthcare-associated infections due to multidrug-resistant gram-negative bacteria and methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2017;38:848–56.  https://doi.org/10.1017/ice.2017.83.CrossRefPubMedGoogle Scholar
  8. 8.
    Calfee DP. Prevention and control of health care-associated infections. Twenty-Fifth Edition. Elsevier Inc. 2016. pp. 1861–1863. doi: https://doi.org/10.1016/B978-1-4557-5017-7.00282-8.
  9. 9.
    Lowbury EJ, Lilly HA. Use of 4 percent chlorhexidine detergent solution (Hibiscrub) and other methods of skin disinfection. Br Med J. 1973;1:510–5.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198–208.  https://doi.org/10.1056/NEJMoa1306801.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ridenour G, Lampen R, Federspiel J, Kritchevsky S, Wong E, Climo M. Selective use of intranasal mupirocin and chlorhexidine bathing and the incidence of methicillin-resistant Staphylococcus aureus colonization and infection among intensive care unit patients. Infect Control Hosp Epidemiol. 2007;28:1155–61.  https://doi.org/10.1086/520102.CrossRefPubMedGoogle Scholar
  12. 12.
    • Huang SS, Septimus E, Kleinman K, Moody J, Hickok J, Avery TR, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368:2255–65.  https://doi.org/10.1056/NEJMoa1207290. The largest randomized trial to date examining universal versus targeted S. aureus decolonization of ICU patients. CrossRefPubMedGoogle Scholar
  13. 13.
    Yokoe DS, Anderson DJ, Berenholtz SM, Calfee DP, Dubberke ER, Ellingson KD, et al. A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates. Infect Control Hosp Epidemiol. 2014;35(Suppl 2):S21–31.  https://doi.org/10.1086/677216.CrossRefPubMedGoogle Scholar
  14. 14.
    Milstone AM, Elward A, Song X, Zerr DM, Orscheln R, Speck K, et al. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet. 2013;381:1099–106.  https://doi.org/10.1016/S0140-6736(12)61687-0.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Anderson DJ, Podgorny K, Berríos-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2016;35:S66–88.  https://doi.org/10.1017/S0899823X00193869.CrossRefGoogle Scholar
  16. 16.
    Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt). 2013;14:73–156.  https://doi.org/10.1089/sur.2013.9999.CrossRefGoogle Scholar
  17. 17.
    Allegranzi B, Bischoff P, de Jonge S, Kubilay NZ, Zayed B, Gomes SM, et al. New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis Elsevier. 2016;16:e276–87.  https://doi.org/10.1016/S1473-3099(16)30398-X.CrossRefGoogle Scholar
  18. 18.
    Kluytmans J, Manders MJ. Elimination of nasal carriage of Staphylococcus aureus in hemodialysis patients. Infect Control Hosp Epidemiol. 1996;17:793–7.  https://doi.org/10.1017/S0195941700003507. CrossRefPubMedGoogle Scholar
  19. 19.
    Mimoz O, Lucet J-C, Kerforne T, Pascal J, Souweine B, Goudet V, et al. Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial. Lancet. 2015;386:2069–77.  https://doi.org/10.1016/S0140-6736(15)00244-5.CrossRefPubMedGoogle Scholar
  20. 20.
    Huang SS, Septimus E, Kleinman K. Daily chlorhexidine bathing in general hospital units—results of the ABATE Infection Trial (Active BAThing to Eliminate Infection). Open Forum Infect Dis. 2017;(Suppl 1):S35–7.  https://doi.org/10.4103/0976-237X.188554.
  21. 21.
    Gantait S, Bhattacharyya J, Das S, Biswas S, Ghati A, Ghosh S, et al. Comparative assessment of the effectiveness of different cleaning methods on the growth of Candida albicans over acrylic surface. Contemp Clin Dent Medknow Publications. 2016;7:336–42.  https://doi.org/10.4103/0976-237X.188554.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Milstone AM, Passaretti CL, Perl TM. Chlorhexidine: expanding the armamentarium for infection control and prevention. Clin Infect Dis. 2008;46:274–81.  https://doi.org/10.1086/524736.CrossRefPubMedGoogle Scholar
  23. 23.
    Davies GE, Francis J, Martin AR, Rose FL, Swain G. 1: 6-DI-4′-Chlorhophenyldiguanidohexane (“Hibitane”). Laboratory investigation of a new antibacterial agent of high potency. Br J Pharmacol Chemother. 1954;9:192–6.  https://doi.org/10.1111/j.1476-5381.1954.tb00840.x.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Sharp G, Green S, Rose M. Chlorhexidine-induced anaphylaxis in surgical patients: a review of the literature. ANZ J Surg. 2016;86:237–43.  https://doi.org/10.1111/ans.13269.CrossRefPubMedGoogle Scholar
  25. 25.
    •• Williamson DA, Carter GP, Howden BP. Current and Emerging topical antibacterials and antiseptics: agents, action, and resistance patterns. Clin Microbiol Rev. 2017;30:827–60.  https://doi.org/10.1128/CMR.00112-16. A comprehensive review of patterns and mechanisms of resistance to topical biocides. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39(4Suppl 1):S1–S34.  https://doi.org/10.1016/j.ajic.2011.01.003.CrossRefPubMedGoogle Scholar
  27. 27.
    Safdar N, O'Horo JC, Ghufran A, Bearden A, Didier ME, Chateau D, et al. Chlorhexidine-impregnated dressing for prevention of catheter-related bloodstream infection. Crit Care Med. 2014;42:1703–13.  https://doi.org/10.1097/CCM.0000000000000319.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Rupp ME. Effect of a second-generation venous catheter impregnated with chlorhexidine and silver sulfadiazine on central catheter-related infections. Ann Intensive Care. 2005;143:570.  https://doi.org/10.7326/0003-4819-143-8-200510180-00007.CrossRefGoogle Scholar
  29. 29.
    Darouiche RO, Wall MJ, Itani KMF, Otterson MF, Webb AL, Carrick MM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362:18–26.  https://doi.org/10.1056/NEJMoa0810988.CrossRefPubMedGoogle Scholar
  30. 30.
    • Kampf G. Acquired resistance to chlorhexidine—is it time to establish an “antiseptic stewardship” initiative? J Hosp Infect. 2016;94:213–27.  https://doi.org/10.1016/j.jhin.2016.08.018. Proposal for an “antiseptic stewardship” initiative to limit CHG use. CrossRefPubMedGoogle Scholar
  31. 31.
    Smith K, Gemmell CG, Hunter IS. The association between biocide tolerance and the presence or absence of qac genes among hospital-acquired and community-acquired MRSA isolates. J Antimicrob Chemother. 2008;61:78–84.  https://doi.org/10.1093/jac/dkm395. CrossRefPubMedGoogle Scholar
  32. 32.
    Wang JT, Sheng WH, Wang JL, Chen D, Chen ML, Chen YC, et al. Longitudinal analysis of chlorhexidine susceptibilities of nosocomial methicillin-resistant Staphylococcus aureus isolates at a teaching hospital in Taiwan. J Antimicrob Chemother. 2008;62:514–7.  https://doi.org/10.1093/jac/dkn208.CrossRefPubMedGoogle Scholar
  33. 33.
    • Suwantarat N, Carroll KC, Tekle T, Ross T, Maragakis LL, Cosgrove SE, et al. High prevalence of reduced chlorhexidine susceptibility in organisms causing central line-associated bloodstream infections. Infect Control Hosp Epidemiol. 2014;35:1183–6. Study comparing prevalences of CHG resistance among CLABSI isolates in units with and without CHG bathing. CrossRefPubMedGoogle Scholar
  34. 34.
    •• Hayden MK, Lolans K, Haffenreffer K, Avery TR, Kleinman K, Li H, et al. Chlorhexidine and mupirocin susceptibility of methicillin-resistant Staphylococcus aureus isolates in the REDUCE-MRSA trial. J Clin Microbiol. 2016;54:2735–42.  https://doi.org/10.1128/JCM.01444-16. Largest published study to date assessing CHG and mupirocin resistance associated with implementation of universal versus targeted colonization. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Suller MTE, Russell AD. Antibiotic and biocide resistance in methicillin-resistant staphylococcus aureus and vancomycin-resistant Enterococcus. J Hosp Infect. 1999;43:281–91.  https://doi.org/10.1016/S0195-6701(99)90424-3.CrossRefPubMedGoogle Scholar
  36. 36.
    Cho O-H, Park K-H, Song JY, Hong JM, Kim T, Hong SI, et al. Prevalence and microbiological characteristics of qacA/B-positive methicillin-resistant Staphylococcus aureus isolates in a surgical intensive care unit. Microb. Drug Resist. 2017;00:1–7.  https://doi.org/10.1089/mdr.2017.0072. CrossRefGoogle Scholar
  37. 37.
    Warren DK, Prager M, Munigala S, Wallace MA, Kennedy CR, Bommarito KM, et al. Prevalence of qacA/B genes and mupirocin resistance among methicillin-resistant Staphylococcus aureus (MRSA) isolates in the setting of chlorhexidine bathing without mupirocin. Infect Control Hosp Epidemiol. 2016;37:590–7.  https://doi.org/10.1017/ice.2016.1.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Horner C, Mawer D, Wilcox M. Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter? J Antimicrob Chemother. 2012;67:2547–59.  https://doi.org/10.1086/677628. CrossRefPubMedGoogle Scholar
  39. 39.
    McNeil JC, Kok EY, Vallejo JG, Campbell JR, Hulten KG, Mason EO, et al. Clinical and molecular features of decreased chlorhexidine susceptibility among nosocomial Staphylococcus aureus isolates at Texas Children’s Hospital. Antimicrob Agents Chemother. 2016;60:1121–8.  https://doi.org/10.1128/AAC.02011-15.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Best M, Sattar SA, Springthorpe VS, Kennedy ME. Efficacies of selected disinfectants against Mycobacterium tuberculosis. J Clin Microbiol. 1990;28:2234–9.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Bonez PC, Santos Alves dos CF, Dalmolin TV, Agertt VA, Mizdal CR, Flores VDC, et al. Chlorhexidine activity against bacterial biofilms. Am J Infect Control. 2013;41:E119–22.  https://doi.org/10.1016/j.ajic.2013.05.002.CrossRefPubMedGoogle Scholar
  42. 42.
    Skovgaard S, Larsen MH, Nielsen LN, Skov RL, Wong C, Westh H, et al. Recently introduced qacA/B genes in Staphylococcus epidermidis do not increase chlorhexidine MIC/MBC. J Antimicrob Chemother. 2013;68:2226–33.  https://doi.org/10.1093/jac/dkt182.PubMedCrossRefGoogle Scholar
  43. 43.
    Choudhury MA, Sidjabat HE, Rathnayake IU, Gavin N, Chan RJ, Marsh N, et al. Culture-independent detection of chlorhexidine resistance genes qacA/B and smr in bacterial DNA recovered from body sites treated with chlorhexidine-containing dressings. J MedMicrobiol. 2017;66:447–53.  https://doi.org/10.1099/jmm.0.000463.CrossRefGoogle Scholar
  44. 44.
    Fritz SA, Hogan PG, Camins BC, Ainsworth AJ, Patrick C, Martin MS, et al. Mupirocin and chlorhexidine resistance in Staphylococcus aureus in patients with community-onset skin and soft tissue infections. Antimicrob Agents Chemother. 2013;57:559–68.  https://doi.org/10.1128/AAC.01633-12.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Schlett CD, Millar EV, Crawford KB, Cui T, Lanier JB, Tribble DR, et al. Prevalence of chlorhexidine-resistant methicillin-resistant Staphylococcus aureus following prolonged exposure. Antimicrob Agents Chemother. 2014;58:4404–10.  https://doi.org/10.1128/AAC.02419-14.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lu Z, Chen Y, Chen W, Liu H, Song Q, Hu X, et al. Characteristics of qacA/B-positive Staphylococcus aureus isolated from patients and a hospital environment in China. J Antimicrob Chemother. 2014;70:653–7.  https://doi.org/10.1093/jac/dku456.CrossRefPubMedGoogle Scholar
  47. 47.
    Hasanvand A, Ghafourian S, Taherikalani M, Jalilian FA, Sadeghifard N, Pakzad I. Antiseptic resistance in methicillin sensitive and methicillin resistant Staphylococcus aureus isolates from some major hospitals, Iran. Recent Pat Antiinfect Drug Discov. 2015;10:105–12.CrossRefPubMedGoogle Scholar
  48. 48.
    Jennings MC, Minbiole KPC, Wuest WM. Quaternary ammonium compounds: an antimicrobial mainstay and platform for innovation to address bacterial resistance. ACS Infect Dis. 2015;1:288–303.  https://doi.org/10.1021/acsinfecdis.5b00047.CrossRefPubMedGoogle Scholar
  49. 49.
    Wayne PA.Methods for determining bactericidal activity of antimicrobial agents: approved guideline. CLSI document M26-A. Clinical and Laboratory Standards Institute1999.Google Scholar
  50. 50.
    Wuite J, Davies BI, Go M, Lambers J, Jackson D, Mellows G. Pseudomonic acid: a new topical antimicrobial agent. Lancet. 1983;2:394.  https://doi.org/10.1016/S0140-6736(83)90358-6.CrossRefPubMedGoogle Scholar
  51. 51.
    Simor AE, Stuart TL, Louie L, Watt C, Ofner-Agostini M, Gravel D, et al. Mupirocin-resistant, methicillin-resistant Staphylococcus aureus strains in Canadian hospitals. Antimicrob Agents Chemother. 2007;51:3880–6.  https://doi.org/10.1128/AAC.00846-07.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Miller MA, Dascal A, Portnoy J, Mendelson J. Development of mupirocin resistance among methicillin-resistant Staphylococcus aureus after widespread use of nasal mupirocin ointment. Infect Control Hosp Epidemiol. 1996;17:811–3.  https://doi.org/10.1017/S019594170000357X. CrossRefPubMedGoogle Scholar
  53. 53.
    Vivoni AM, Santos K, de-Oliveira MP. Mupirocin for controlling methicillin-resistant Staphylococcus aureus: lessons from a decade of use at a university hospital. Infect Control Hosp Epidemiol. 2005;26:662–7.  https://doi.org/10.1086/502599.CrossRefPubMedGoogle Scholar
  54. 54.
    Hetem DJ, Bonten MJM. Clinical relevance of mupirocin resistance in Staphylococcus aureus. J Hosp Infect. 2013;85:249–56.  https://doi.org/10.1016/j.jhin.2013.09.006.CrossRefPubMedGoogle Scholar
  55. 55.
    Chaturvedi P, Singh AK, Shukla S, Agarwal L. Prevalence of mupirocin resistant Staphylococcus aureus isolates among patients admitted to a tertiary care hospital. N Am J Med Sci. 2014;6:403–7.  https://doi.org/10.4103/1947-2714.139293.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Upton A. Mupirocin and Staphylococcus aureus: a recent paradigm of emerging antibiotic resistance. J Antimicrob Chemother. 2003;51:613–7.  https://doi.org/10.1093/jac/dkg127.CrossRefPubMedGoogle Scholar
  57. 57.
    Walker ES, Levy F, Shorman M, David G, Abdalla J, Sarubbi FA. A decline in mupirocin resistance in methicillin-resistant Staphylococcus aureus accompanied administrative control of prescriptions. J Clin Microbiol. 2004;42:2792–5.  https://doi.org/10.1128/JCM.42.6.2792-2795.2004.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Williamson DA, Monecke S. High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale. Clin Infect Dis. 2014;59:1451–4.  https://doi.org/10.1093/cid/ciu658.CrossRefPubMedGoogle Scholar
  59. 59.
    Finlay JE, Miller LA, Poupard JA. Interpretive criteria for testing susceptibility of staphylococci to mupirocin. Antimicrob Agents Chemother. 1997;41:1137–9.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    European Committee On Antimicrobial Susceptibility Testing Website: Clinical Breakpoints [Internet]. eucast.org. [cited2017Nov 21]. Available from:http://www.eucast.org/clinical_breakpoints/
  61. 61.
    • Poovelikunnel T, Gethin G, Humphreys H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J Antimicrob Chemother. 2015;70:2681–92.  https://doi.org/10.1093/jac/dkv169. A review of potential alternative agents for mupirocin-based decolonization. CrossRefPubMedGoogle Scholar
  62. 62.
    • Patel JB, Gorwitz RJ, Jernigan JA. Mupirocin resistance. Clin Infect Dis. 2009;49:935–41.  https://doi.org/10.1086/605495. Guidelines defining high versus low-level mupirocin resistance. CrossRefPubMedGoogle Scholar
  63. 63.
    •• Wayne PA. Performance standards for antimicrobial susceptibility testing, 26th edition. CLSI Supplement M100S. Clinical and Laboratory Standards Institute 2016. CLSI definitions for antimicrobial resistance, including mupirocin. Google Scholar
  64. 64.
    Lee AS, Gizard Y, Empel J, Bonetti E-J, Harbarth S, François P. Mupirocin-induced mutations in ileS in various genetic backgrounds of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2014;52:3749–54.  https://doi.org/10.1128/JCM.01010-14.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Suwantarat N, Carroll KC, Tekle T, Ross T, Popoola VO, Milstone AM. Low prevalence of mupirocin resistance among hospital-acquired methicillin-resistant Staphylococcus aureus isolates in a neonatal intensive care unit with an active surveillance cultures and decolonization program. Infect Control Hosp Epidemiol. 2015;36:232–4.  https://doi.org/10.1017/ice.2014.17.CrossRefPubMedGoogle Scholar
  66. 66.
    McDanel JS, Murphy CR, Diekema DJ, Quan V, Kim DS, Peterson EM, et al. Chlorhexidine and mupirocin susceptibilities of methicillin-resistant staphylococcus aureus from colonized nursing home residents. Antimicrob Agents Chemother. 2013;57:552–8.  https://doi.org/10.1128/AAC.01623-12.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kresken M, Hafner D, Schmitz F-J, Wichelhaus TA. Prevalence of mupirocin resistance in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis: results of the Antimicrobial Resistance Surveillance Study of the Paul-Ehrlich-Society for Chemotherapy, 2001. Int J Antimicrob Agent. 2004;23:577–81.  https://doi.org/10.1016/j.ijantimicag.2003.11.007.CrossRefGoogle Scholar
  68. 68.
    Hamed G-M, van Belkum A, Awang H, van Wamel W, Vasanthakumari N. Methicillin-susceptible and -resistant Staphylococcus aureus with high-level antiseptic and low-level mupirocin resistance in Malaysia. Microb Drug Resist. 2014;20:472–7.  https://doi.org/10.1089/mdr.2013.0222.CrossRefGoogle Scholar
  69. 69.
    Simor AE, Phillips E, McGeer A, Konvalinka A, Loeb M, Devlin HR, et al. Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization. Clin Infect Dis. 2007;44:178–85.  https://doi.org/10.1086/510392.CrossRefPubMedGoogle Scholar
  70. 70.
    Lee AS, Macedo-Vinas M, François P, Renzi G, Schrenzel J, Vernaz N, et al. Impact of combined low-level mupirocin and genotypic chlorhexidine resistance on persistent methicillin-resistant Staphylococcus aureus carriage after decolonization therapy: a case-control study. Clin Infect Dis. 2011;52:1422–30.  https://doi.org/10.1093/cid/cir233.CrossRefPubMedGoogle Scholar
  71. 71.
    Apisarnthanarak A, Yang Hsu L, Lim T-P, Mundy LM. Increase in chlorhexidine minimal inhibitory concentration of Acinetobacter baumannii clinical isolates after implementation of advanced source control. Infect Control Hosp Epidemiol. 2014;35:98–9.  https://doi.org/10.1086/674404.CrossRefPubMedGoogle Scholar
  72. 72.
    Wassenaar TM, Ussery D, Nielsen LN, Ingmer H. Review and phylogenetic analysis of qac genes that reduce susceptibility to quaternary ammonium compounds in Staphylococcus species. Eur J Microbiol Immunol. 2015;5:44–61.  https://doi.org/10.1556/EUJMI-D-14-00038.CrossRefGoogle Scholar
  73. 73.
    Azadpour M, Nowroozi J, Goudarzi GR, Mahmoudvand H. Presence of qacEΔ1 and cepA genes and susceptibility to a hospital biocide in clinical isolates of Klebsiella pneumoniae in Iran. Trop Biomed. 2015;32:109–15.PubMedGoogle Scholar
  74. 74.
    Pérez-Roth E, López-Aguilar C, Alcoba-Flórez J, Méndez-Álvarez S. High-level mupirocin resistance within methicillin-resistant Staphylococcus aureus pandemic lineages. Antimicrob Agents Chemother. 2006;50:3207–11.  https://doi.org/10.1128/AAC.00059-06.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Jensen SO, Apisiridej S, Kwong SM, Yang YH, Skurray RA, Firth N. Analysis of the prototypical Staphylococcus aureus multiresistance plasmid pSK1. Plasmid. 2010;64:135–42.  https://doi.org/10.1016/j.plasmid.2010.06.001.CrossRefPubMedGoogle Scholar
  76. 76.
    Kampf G, Jarosch R. Limited effectiveness of chlorhexidine based hand disinfectants against methicillin-resistant Staphylococcus aureus (MRSA). J Hosp Infect. 1998;38:297–303.  https://doi.org/10.1016/S0195-6701(98)90078-0.CrossRefPubMedGoogle Scholar
  77. 77.
    Udo EE. A chromosomal location of the mupA gene in Staphylococcus aureus expressing high-level mupirocin resistance. J Antimicrob Chemother. 2003;51:1283–6.  https://doi.org/10.1093/jac/dkg188.CrossRefPubMedGoogle Scholar
  78. 78.
    Bhardwaj P, Hans A, Ruikar K, Guan Z, Palmer KL. Reduced chlorhexidine and daptomycin susceptibility in vancomycin-resistant Enterococcus faecium after serial chlorhexidine exposure. Antimicrob Agents Chemother. 2018;62:e01235–17.  https://doi.org/10.1128/AAC.01235-17.PubMedCrossRefGoogle Scholar
  79. 79.
    Vali L, Davies SE, Lai LLG, Dave J, Amyes SGB. Frequency of biocide resistance genes, antibiotic resistance and the effect of chlorhexidine exposure on clinical methicillin-resistant Staphylococcus aureus isolates. J Antimicrob Chemother. 2008;61:524–32.  https://doi.org/10.1093/jac/dkm520.CrossRefPubMedGoogle Scholar
  80. 80.
    Otter JA, Patel A, Cliff PR, Halligan EP, Tosas O, Edgeworth JD. Selection for qacA carriage in CC22, but not CC30, methicillin-resistant Staphylococcus aureus bloodstream infection isolates during a successful institutional infection control programme. J Antimicrob Chemother. 2013;68:992–9.  https://doi.org/10.1093/jac/dks500.CrossRefPubMedGoogle Scholar
  81. 81.
    Cadilla A, David MZ, Daum RS, Boyle-Vavra S. Association of high-level mupirocin resistance and multidrug-resistant methicillin-resistant Staphylococcus aureus at an academic center in the midwestern United States. J Clin Microbiol. 2011;49:95–100.  https://doi.org/10.1128/JCM.00759-10.CrossRefPubMedGoogle Scholar
  82. 82.
    Farrand RJ, Williams A. Evaluation of single-use packs of hospital disinfectants. Lancet. 1973;1:591–3.  https://doi.org/10.1016/S0140-6736(73)90730-7.CrossRefPubMedGoogle Scholar
  83. 83.
    Sutherland R, Boon RJ, Griffin KE, Masters PJ, Slocombe B, White AR. Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother. 1985;27:495–8.  https://doi.org/10.1128/AAC.27.4.495.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    • Hetem DJ, Bootsma MCJ, Bonten MJM. Prevention of surgical site infections: decontamination with mupirocin based on preoperative screening for Staphylococcus aureus carriers or universal decontamination? Clin Infect Dis. 2016;62:631–6.  https://doi.org/10.1093/cid/civ990. One of two published mathematical models used to assess risk of mupirocin resistance associated with universal decolonization. CrossRefPubMedGoogle Scholar
  85. 85.
    Coates T, Bax R, Coates A. Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects. J Antimicrob Chemother. 2009;64:9–15.  https://doi.org/10.1093/jac/dkp159.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Hurdle JG. In vivo transfer of high-level mupirocin resistance from Staphylococcus epidermidis to methicillin-resistant Staphylococcus aureus associated with failure of mupirocin prophylaxis. J Antimicrob Chemother. 2005;56:1166–8.  https://doi.org/10.1093/jac/dki387.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    • Deeny SR, Worby CJ, Tosas Auguet O, Cooper BS, Edgeworth J, Cookson B, et al. Impact of mupirocin resistance on the transmission and control of healthcare-associated MRSA. J Antimicrob Chemother. 2015;70:3366–78.  https://doi.org/10.1093/jac/dkv249. One of two published mathematical models used to assess risk of mupirocin resistance associated with universal decolonization. PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    • Septimus EJ, Schweizer ML. Decolonization in prevention of health care-associated infections. Clin Microbiol Rev. 2016;29:201–22.  https://doi.org/10.1128/CMR.00049-15. A review of the current evidence for bacterial decolonization to prevent healthcare-associated infections. CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Steed LL, Costello J, Lohia S, Jones T, Spannhake EW, Nguyen S. Reduction of nasal Staphylococcus aureus carriage in health care professionals by treatment with a nonantibiotic, alcohol-based nasal antiseptic. Am J Infect Control. 2014;42:841–6.  https://doi.org/10.1016/j.ajic.2014.04.008.CrossRefPubMedGoogle Scholar
  90. 90.
    McConeghy KW, Mikolich DJ, LaPlante KL. Agents for the decolonization of methicillin-resistant Staphylococcus aureus. Pharmacotherapy. 2009;29:263–80.  https://doi.org/10.1592/phco.29.3.263.CrossRefPubMedGoogle Scholar
  91. 91.
    Phillips M, Rosenberg A, Shopsin B, Cuff G, Skeete F, Foti A, et al. Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution. Infect Cont Hosp Epidemiol. 2014;35:826–32.  https://doi.org/10.1086/676872.CrossRefGoogle Scholar
  92. 92.
    Miedzybrodzki R, Fortuna W, Weber-Dabrowska B, Górski A. Phage therapy of staphylococcal infections (including MRSA) may be less expensive than antibiotic treatment. Postepy Hig Med Dosw (Online). 2007;61:461–5.PubMedGoogle Scholar
  93. 93.
    Sikorska H, Smoragiewicz W. Role of probiotics in the prevention and treatment of meticillin-resistant Staphylococcus aureus infections. Int J Antimicrob Agent. 2013;42:475–81.  https://doi.org/10.1016/j.ijantimicag.2013.08.003.CrossRefGoogle Scholar
  94. 94.
    Alam F, Islam MA, Gan SH, Khalil MI. Honey: a potential therapeutic agent for managing diabetic wounds. Evid Based Complement Alternat Med. 2014;2014:169130–16.  https://doi.org/10.1155/2014/169130.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Fritz SA, Camins BC, Eisenstein KA, Fritz JM, Epplin EK, Burnham C-A, et al. Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and soft-tissue infections: a randomized trial. Infect Control Hosp Epidemiol. 2011;32:872–80.  https://doi.org/10.1086/661285.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Rohr U, Mueller C, Wilhelm M, Muhr G, Gatermann S. Methicillin-resistant Staphylococcus aureus whole-body decolonization among hospitalized patients with variable site colonization by using mupirocin in combination with octenidine dihydrochloride. J Hosp Infect. 2003;54:305–9.  https://doi.org/10.1016/S0195-6701(03)00140-3.CrossRefPubMedGoogle Scholar
  97. 97.
    Harris PNA, Le BD, Tambyah P, Hsu LY, Pada S, Archuleta S, et al. Antiseptic body washes for reducing the transmission of methicillin-resistant Staphylococcus aureus: a cluster crossover study. Open Forum Infect Dis. 2015;2:1–9.  https://doi.org/10.1093/ofid/ofv051.CrossRefGoogle Scholar
  98. 98.
    Parras F, Guerrero MC, Bouza E, Blázquez MJ, Moreno S, Menarguez MC, et al. Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1995;39:175–9.  https://doi.org/10.1128/AAC.39.1.175.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:e18–55.  https://doi.org/10.1093/cid/ciq146.CrossRefPubMedGoogle Scholar
  100. 100.
    Malani PN. National burden of invasive methicillin-resistant Staphylococcus aureus infection. JAMA. 2014;311:1438–9.  https://doi.org/10.1001/jama.2014.1666.CrossRefPubMedGoogle Scholar
  101. 101.
    Walker EM, Lowes JA. An investigation into in vitro methods for the detection of chlorhexidine resistance. J Hosp Infect. 1985;6:389–97.  https://doi.org/10.1016/0195-6701(85)90055-6.CrossRefPubMedGoogle Scholar
  102. 102.
    Morrissey I, Oggioni MR, Knight D, Curiao T, Coque T, Kalkanci A, et al. Evaluation of epidemiological cut-off values indicates that biocide resistant subpopulations are uncommon in natural isolates of clinically-relevant microorganisms. PLoS ONE. 2014;9:e86669.  https://doi.org/10.1371/journal.pone.0086669.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Infectious Diseases & International Health, Department of MedicineUniversity of Virginia Health SystemCharlottesvilleUSA
  2. 2.Office of Hospital Epidemiology/Infection Prevention & ControlUniversity of Virginia Health SystemCharlottesvilleUSA

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