Staphylococcus aureus with reduced susceptibility to vancomycin in healthcare settings


Staphylococcus aureus


Glycopeptide resistance in Staphylococcus aureus is a source of great concern because, especially in hospitals, this class of antibiotics, particularly vancomycin, is one of the main resources for combating infections caused by methicillin-resistant Staphylococcus aureus strains (MRSA).

Reduced susceptibility to vancomycin (VISA) was first described in 1996 in Japan; since then, a phenotype with heterogeneous resistance to vancomycin (h-VISA) has emerged.
H-VISA isolates are characterised by the presence of a resistant subpopulation, typically at a rate of 1 in 105 organisms, which constitutes the intermediate stage between fully vancomycin-susceptible S. aureus (VSSA) and VISA isolates. As VISA phenotypes are almost uniformly cross-resistant to teicoplanin, they are also called Glycopeptides-intermediate Staphylococcus aureus strains (GISA) and, in the case of heterogeneous resistance to glycopeptides, h-GISA.

The overall prevalence of h-VISA is low, accounting for approximately 1.3% of all MRSA isolates tested.

Mortality due to h-GISA infections is very high (about 70%), especially among patients hospitalised in high-risk departments, such as intensive care units (ICU).
Given the great clinical relevance of strains that are heteroresistant to glycopeptides and the possible negative impact on treatment choices, it is important to draw up and implement infection control practices, including surveillance, the appropriate use of isolation precautions, staff training, hand hygiene, environmental cleansing and good antibiotic stewardship.


Acar JF, Kaplan EL, Brien, T.F. O' . Monitoring and management of bacterial resistance to antimicrobial agents, a World Health Organization symposium. Clin Infect Dis 1997;24. [Google Scholar]

Cristina ML, Spagnolo AM, Orlando P, Perdelli F. The role of the environment in the spread of emerging pathogens in at-risk hospital wards. Reviews in Medical Microbiology 2013;24(4):104-112. Available from: doi: 10.1097/MRM.0b013e328365c506. [Google Scholar]

Jevons MP, Coe AW, Parker MT. Methicillin resistance in staphylococci. Lancet 1963;1(7287):904-907. Available from: PubMed PMID: 13957735. [Google Scholar]

Manso E, Varaldo PE. La resistenza agli antibiotici negli stafilococchi. Website:

Epidemiology of methicillin-resistant Staphylococcus aureus infection in adults. Website:

Kluytmans J, Struelens M. Meticillin resistant Staphylococcus aureus in the hospital.. BMJ 2009 Feb;338. Available from: PubMed PMID: 19213761. [Google Scholar]

Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus.. Clin Infect Dis 2008 Jun;46 Suppl 5. Available from: PubMed PMID: 18462089. doi: 10.1086/533590. [Google Scholar]

Gould IM, David MZ, Esposito S, Garau J, Lina G, Mazzei T, et al. New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance.. Int J Antimicrob Agents 2012;39(2):96-104. Available from: PubMed PMID: 22196394. doi: 10.1016/j.ijantimicag.2011.09.028. [Google Scholar]

Staphylococcus aureus. Website:

Howden BP, Davies JK, Johnson PDR, Stinear TP, Grayson ML. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications.. Clin Microbiol Rev 2010;23(1):99-139. Available from: PubMed PMID: 20065327. doi: 10.1128/CMR.00042-09. [Google Scholar]

Tonin E, Tomasz A. Beta-lactam-specific resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother 1986;30(4):577-583. Available from: PubMed PMID: 3539012. doi: 10.1128/AAC.30.4.577. [Google Scholar]

van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis.. Clin Infect Dis 2012 Feb;54(6):755-771. Available from: PubMed PMID: 22302374. doi: 10.1093/cid/cir935. [Google Scholar]

Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997;40(1):135-136. Available from: doi: 10.1093/jac/40.1.135. [Google Scholar]

Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 1997;350(9092):1670-1673. Available from: PubMed PMID: 9400512. doi: 10.1016/S0140-6736(97)07324-8. [Google Scholar]

Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance.. Lancet Infect Dis 2001;1(3):147-155. Available from: PubMed PMID: 11871491. doi: 10.1016/S1473-3099(01)00091-3. [Google Scholar]

van Hal SJ, Paterson DL. Systematic review and meta-analysis of the significance of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates.. Antimicrob Agents Chemother 2010 Nov;55(1):405-410. Available from: PubMed PMID: 21078939. doi: 10.1128/AAC.01133-10. [Google Scholar]

van Hal SJ, Wehrhahn MC, Barbagiannakos T, Mercer J, Chen D, Paterson DL, et al. Performance of various testing methodologies for detection of heteroresistant vancomycin-intermediate Staphylococcus aureus in bloodstream isolates.. J Clin Microbiol 2011 Jan;49(4):1489-1494. Available from: PubMed PMID: 21270232. doi: 10.1128/JCM.02302-10. [Google Scholar]

Hal SJ, Jones M, Gosbell IB, et al. Vancomycin heteroresistance is associated with reduced mortality in ST239 methicillin- resistant Staphylococcus aureus blood stream infections. PLoS One. 2011;6:e21217–e21217.

Saito M, Katayama Y, Hishinuma T, Iwamoto A, Aiba Y, Kuwahara-Arai K, et al. "Slow VISA," a novel phenotype of vancomycin resistance, found in vitro in heterogeneous vancomycin-intermediate Staphylococcus aureus strain Mu3.. Antimicrob Agents Chemother 2014 May;58(9):5024-5035. Available from: PubMed PMID: 24841271. doi: 10.1128/AAC.02470-13. [Google Scholar]

Di Gregorio S, Perazzi B, Ordoñez AM, De Gregorio S, Foccoli M, Lasala MB, et al. Clinical, Microbiological, and Genetic Characteristics of Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Bacteremia in a Teaching Hospital. Microbial Drug Resistance 2015;21(1):25-34. Available from: doi: 10.1089/mdr.2014.0190. [Google Scholar]

Hanaki H, Cui L, Ikeda-Dantsuji Y, Nakae T, Honda J, Yanagihara K, et al. Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011. J Infect Chemother 2014;20(9):527-534. Available from: PubMed PMID: 25066429. doi: 10.1016/j.jiac.2014.06.012. [Google Scholar]

Chaudhari CN, Tandel K, Grover N, Sen S, Bhatt P, Sahni AK, et al. Heterogeneous vancomycin-intermediate among methicillin resistant Staphylococcus aureus.. Med J Armed Forces India 2015;71(1):15-18. Available from: PubMed PMID: 25609857. doi: 10.1016/j.mjafi.2014.03.008. [Google Scholar]

Monaco M, Sanchini A, Grundmann H, Pantosti A. Vancomycin-heteroresistant phenotype in invasive methicillin-resistant Staphylococcus aureus isolates belonging to spa type 041. Eur J Clin Microbiol Infect Dis 2010 Apr;29(7):771-777. Available from: PubMed PMID: 20401508. doi: 10.1007/s10096-010-0922-2. [Google Scholar]

Renzoni A, Kelley WL, Vaudaux P, Cheung AL, Lew DP. Exploring innate glycopeptide resistance mechanisms in Staphylococcus aureus. Trends Microbiol 2010;18(2):55-56. Available from: PubMed PMID: 20005114. doi: 10.1016/j.tim.2009.11.005. [Google Scholar]

Rybak M, Chin JN, Lau K, et al. Increasing prevalence of glycopeptide hetero-resistant S. aureus from the Detroit metropolitan area over a 20-year period (1986–2006) 17th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) and the 25th International Congress of Chemotherapy (ICC) 2007. [Abstract O32]

Appelbaum PC. MRSA--the tip of the iceberg.. Clin Microbiol Infect 2006;12:3-10. Available from: PubMed PMID: 16524422. doi: 10.1111/j.1469-0691.2006.01402.x. [Google Scholar]

Blot SI, Vandewoude KH, Hoste EA, Colardyn FA. Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus.. Arch Intern Med 2002 Oct;162(19):2229-2235. Available from: PubMed PMID: 12390067. doi: 10.1001/archinte.162.19.2229. [Google Scholar]

Chang F, MacDonald BB, Peacock Jr JE, Musher DM, Triplett P, Mylotte JM, et al. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance.. Medicine (Baltimore) 2003;82(5):322-332. Available from: PubMed PMID: 14530781. doi: 10.1097/ [Google Scholar]

Chang S, Sievert DM, Hageman JC, Boulton ML, Tenover FC, Downes FP, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene.. N Engl J Med 2003 Apr;348(14):1342-1347. Available from: PubMed PMID: 12672861. doi: 10.1056/NEJMoa025025. [Google Scholar]

Maor Y, Rahav G, Belausov N, Ben-David D, Smollan G, Keller N. Prevalence and Characteristics of Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Bacteremia in a Tertiary Care Center. Journal of Clinical Microbiology 2007;45(5):1511-1514. Available from: doi: 10.1128/JCM.01262-06. [Google Scholar]

Kirby A, Graham R, Williams NJ, Wootton M, Broughton CM, Alanazi M, et al. Staphylococcus aureus with reduced glycopeptide susceptibility in Liverpool, UK. J Antimicrob Chemother 2010 Feb;65(4):721-724. Available from: PubMed PMID: 20124288. doi: 10.7326/0003-4819-152-3-201002020-01002. [Google Scholar]

Liñares J. The VISA/GISA problem: therapeutic implications.. Clin Microbiol Infect 2001;7:8-15. Available from: PubMed PMID: 11688538. doi: 10.1046/j.1469-0691.2001.00054.x. [Google Scholar]

Ottria G, Dallera M, Aresu O, Manniello MA, Parodi B, Spagnolo AM, et al. Environmental monitoring programme in the cell therapy facility of a research centre: preliminary investigation.. J Prev Med Hyg 2010;51(4):133-138. PubMed PMID: 21553557. [Google Scholar]

Dietze B, Rath A, Wendt C, Martiny H. Survival of MRSA on sterile goods packaging. J Hosp Infect 2001;49(4):255-261. Available from: PubMed PMID: 11740873. doi: 10.1053/jhin.2001.1094. [Google Scholar]

Centers for Disease Control and Prevention/Healthcare Infection Control Practices Advisory Committee (HICPAC . author. Draft Guidelines for Environmental Infection Control in Healthcare Facilities. Atlanta, GA: Centers for disease Control and Prevention; 2001. [Google Scholar]

Farr BM, Salgado CD, Karchmer TB, Sherertz RJ. Can antibiotic-resistant nosocomial infections be controlled. Lancet Infect Dis 2001;1(1):38-45. Available from: PubMed PMID: 11871409. doi: 10.1016/S1473-3099(01)00020-2. [Google Scholar]

Perdelli F, Dallera M, Cristina ML, Sartini M, Ottria G, Spagnolo AM, et al. A new microbiological problem in intensive care units: environmental contamination by MRSA with reduced susceptibility to glycopeptides.. Int J Hyg Environ Health 2008;211(1-2):213-218. Available from: PubMed PMID: 17652023. doi: 10.1016/j.ijheh.2007.04.002. [Google Scholar]

Boccia D, D'Ancona F, Pantosti A. Resistenza alla Vancomicina in ceppi invasivi di Enterococcus faecalis ed enterococcus faecium. Dati preliminari Bollettino Epidemiologico Nazionale – Notiziario ISS. 2002;15(5)

Walsh TR, Howe RA, Wootton M, et al. Detection of glycopeptide resistance in Staphylococcus aureus. J Antimicrob Chemother 2001;47(3):357-358. Available from: doi: 10.1093/jac/47.3.357. [Google Scholar]

Ariza J, Pujol M, Cabo J, Peña C, Fernández N, Liñares J, et al. Vancomycin in surgical infections due to meticillin-resistant Staphylococcus aureus with heterogeneous resistance to vancomycin. The Lancet 1999;353(9164):1587-1588. Available from: doi: 10.1016/S0140-6736(99)01017-X. [Google Scholar]

Moore MR, Perdreau-Remington F, Chambers HF. Vancomycin treatment failure associated with heterogeneous vancomycin-intermediate Staphylococcus aureus in a patient with endocarditis and in the rabbit model of endocarditis.. Antimicrob Agents Chemother 2003;47(4):1262-1266. Available from: PubMed PMID: 12654656. doi: 10.1128/AAC.47.4.1262-1266.2003. [Google Scholar]

Liu C, Bayer A, Cosgrove SE, 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–e55.

Infection Prevention Working Party , author. MRSA Hospital. The Netherlands: 2007.

Rodríguez-Baño J, Bischofberger C, Álvarez-Lerma F, et al. Vigilancia y el control de Staphylococcus aureus resistente a meticilina en hospitales españoles. Documento de consenso GEIH-SEIMC y SEMPSPH. Enferm Infecc Microbiol Clin. 2008;26:285–298

Calfee DP, Salgado CD, Classen D, et al. SHEA/IDSA. Strategies to prevent transmission of methicillin-resistant Staphylococcus aureus in acute care hospitals. Infect Control Hosp Epidemiol 2008;29:62. [Google Scholar]

Cystic Fibrosis Trust , author. Methicillin-resistant Staphylococcus aureus (MRSA) Report of the UK Cystic Fibrosis Trust Infection Control Working Group. 2008.

Borgman S, Stark M, Kaiser P, et al. MRSA in praxis, pflegeheim und häuslichem umfeld. Bayerisches Ärzteblatt 2008;3:176. [Google Scholar]

Tacconelli E. Screening and isolation for infection control. J Hosp Infect 2009;73(4):371-377. Available from: PubMed PMID: 19699554. doi: 10.1016/j.jhin.2009.05.002. [Google Scholar]

Harbarth S, Fankhauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, et al. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients.. JAMA 2008 Mar;299(10):1149-1157. Available from: PubMed PMID: 18334690. doi: 10.1001/jama.299.10.1149. [Google Scholar]

Robicsek A, Beaumont JL, Paule SM, Hacek DM, Thomson Jr RB, Kaul KL, et al. Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals.. Ann Intern Med 2008 Mar;148(6):409-418. Available from: PubMed PMID: 18347349. doi: 10.7326/0003-4819-148-6-200803180-00003. [Google Scholar]

Jeyaratnam D, Whitty CJM, Phillips K, Liu D, Orezzi C, Ajoku U, et al. Impact of rapid screening tests on acquisition of meticillin resistant Staphylococcus aureus: cluster randomised crossover trial.. BMJ 2008 Apr;336(7650):927-930. Available from: PubMed PMID: 18417521. doi: 10.1136/bmj.39525.579063.BE. [Google Scholar]

Raineri E, Crema L, Silvestri, A. De , Acquarolo A, Albertario F, Carnevale G, et al. Meticillin-resistant Staphylococcus aureus control in an intensive care unit: a 10 year analysis. Journal of Hospital Infection 2007;67(4):308-315. Available from: doi: 10.1016/j.jhin.2007.08.013. [Google Scholar]

Keshtgar MRS, Khalili A, Coen PG, Carder C, Macrae B, Jeanes A, et al. Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards.. Br J Surg 2008;95(3):381-386. Available from: PubMed PMID: 18041109. doi: 10.1002/bjs.6013. [Google Scholar]

Tacconelli E, De Angelis G, de Waure C, Cataldo MA, La Torre G, Cauda R. Rapid screening tests for meticillin-resistant Staphylococcus aureus at hospital admission: systematic review and meta-analysis.. Lancet Infect Dis 2009;9(9):546-554. Available from: PubMed PMID: 19695491. doi: 10.1016/S1473-3099(09)70150-1. [Google Scholar]

van Rijen M, Bonten M, Wenzel R, Kluytmans J. Mupirocin ointment for preventing Staphylococcus aureus infections in nasal carriers.. Cochrane Database Syst Rev 2008 Oct;4(4). Available from: PubMed PMID: 18843708. doi: 10.1002/14651858.CD006216.pub2. [Google Scholar]

Centers for Disease Control and Prevention , author . Interim guidelines for prevention and control of staphylococcal infection associated with reduced susceptibility to vancomycin. MMWR Morb Mortal Weekly Rep 1997;46:626. [Google Scholar]

Wenzel RP, Edmond MB. Vancomycin-resistant Staphylococcus aureus: infection control considerations.. Clin Infect Dis 1998;27(2):245-249. Available from: PubMed PMID: 9709870. doi: 10.1086/514646. [Google Scholar]

Kalenic S, Cookson B, Gallagher R, et al. Comparison of recommendations in national/regional Guidelines for the prevention and control of MRSA in thirteen European countries. Int J Infect Control 2010;v6. [Google Scholar]

Spagnolo AM, Orlando P, Panatto D, et al. An overview of carbapenem- resistant Klebsiella pneumoniae: Epidemiology and control measures. Rev Med Microbiol 2014;25(1):7-14. Available from: doi: 10.1097/MRM.0b013e328365c51e. [Google Scholar]

Cristina ML, Spagnolo AM, Cenderello N, Fabbri P, Sartini M, Ottria G, et al. Multidrug-resistant Acinetobacter baumannii outbreak: an investigation of the possible routes of transmission. Public Health 2013;127(4):386-391. Available from: doi: 10.1016/j.puhe.2013.01.025. [Google Scholar]

Cristina ML, Spagnolo AM, Ottria G, Sartini M, Orlando P, Perdelli F. Spread of multidrug carbapenem-resistant Acinetobacter baumannii in different wards of an Italian hospital. Am J Infect Control 2011;39(9):790-794. Available from: PubMed PMID: 21704428. doi: 10.1016/j.ajic.2011.01.016. [Google Scholar]

Cristina ML, Spagnolo AM, Sartini M, et al. Clostridium difficile infections: an emerging problem in healthcare facilities. Rev Med Microbiol 2012;23(4):67-75. Available from: PubMed PMID: 23715827. doi: 10.1097/MRM.0b013e3283573643. [Google Scholar]

Raccomandazioni sul controllo della diffusione nosocomiale dello Staphylococcus aureus resistente alla meticillina (MRSA) 2011. A cura di: Istituto Superiore di Sanità, Agenzia sanitaria e sociale regionale dell'Emilia-Romagna, Ministero della salute – Ufficio V Malattie infettive, Direzione generale della prevenzione sanitaria. Disponibile sul sito:

Kapil R, Bhavsar HK, Madan M. Hand hygiene in reducing transient flora on the hands of healthcare workers: an educational intervention.. Indian J Med Microbiol 2015;33(1):125-128. Available from:;year=2015;volume=33;issue=1;spage=125;epage=128;aulast=Kapil PubMed PMID: 25560015. doi: 10.4103/0255-0857.148409. [Google Scholar]

Monistrol O, López ML, Riera M, Font R, Nicolás C, Escobar MA, et al. Hand contamination during routine care in medical wards: the role of hand hygiene compliance. J Med Microbiol 2013 Jan;62(Pt 4):623-629. Available from: PubMed PMID: 23329322. doi: 10.1099/jmm.0.050328-0. [Google Scholar]

Al-Tawfiq JA, Abed MS, Al-Yami N, Birrer RB. Promoting and sustaining a hospital-wide, multifaceted hand hygiene program resulted in significant reduction in health care-associated infections. Am J Infect Control 2013;41(6):482-486. Available from: PubMed PMID: 23261346. doi: 10.1016/j.ajic.2012.08.009. [Google Scholar]

Sunkesula V, Kundrapu S, Macinga DR, Donskey CJ. Efficacy of alcohol gel for removal of methicillin-resistant Staphylococcus aureus from hands of colonized patients.. Infect Control Hosp Epidemiol 2015;36(2):229-231. Available from: PubMed PMID: 25633009. doi: 10.1017/ice.2014.34. [Google Scholar]

Hedin G, Blomkvist A, Janson M, Lindblom A. Occurrence of potentially pathogenic bacteria on the hands of hospital patients before and after the introduction of patient hand disinfection. APMIS 2012 May;120(10):802-807. Available from: PubMed PMID: 22958288. doi: 10.1111/j.1600-0463.2012.02912.x. [Google Scholar]

Orlando P, Cristina ML, Dallera M, Ottria G, Vitale A, Badolati G. Surface disinfection: evaluation of the efficacy of a nebulization system spraying hydrogen peroxide.. J Prev Med Hyg 2008;49(3):116-119. Available from: PubMed PMID: 19278138. [Google Scholar]

Gidengil CA, Gay C, Huang SS, et al. Cost-effectiveness of strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in an intensive care unit. Infect Control Hosp Epidemiol 2015;36(01):17-27. Available from: doi: 10.1017/ice.2014.12. [Google Scholar]

Huang SS, Septimus E, Avery TR, Lee GM, Hickok J, Weinstein RA, et al. Cost savings of universal decolonization to prevent intensive care unit infection: implications of the REDUCE MRSA trial.. Infect Control Hosp Epidemiol 2014;35 Suppl 3(Suppl 3). PubMed PMID: 25222894. doi: 10.1086/677819. [Google Scholar]

Borde JP, Batin N, Rieg S, Feik R, Reimling C, Kern WV, et al. Adherence to an antibiotic stewardship bundle targeting Staphylococcus aureus blood stream infections at a 200-bed community hospital. Infection 2014;42(4):713-719. Available from: doi: 10.1007/s15010-014-0633-1. [Google Scholar]

Cook PP, Gooch M. Long-term effects of an antimicrobial stewardship programme at a tertiary-care teaching hospital. International Journal of Antimicrobial Agents 2015;45(3):262-267. Available from: doi: 10.1016/j.ijantimicag.2014.11.006. [Google Scholar]

Pulcini C, Williams F, Molinari N, Davey P, Nathwani D. Junior doctors' knowledge and perceptions of antibiotic resistance and prescribing: a survey in France and Scotland. Clin Microbiol Infect 2011;17(1):80-87. Available from: PubMed PMID: 20132254. doi: 10.1111/j.1469-0691.2010.03179.x. [Google Scholar]

Chan Y, Lin T, Huang C, Deng S, Wu T, Leu H, et al. Implementation and outcomes of a hospital-wide computerised antimicrobial stewardship programme in a large medical centre in Taiwan. International Journal of Antimicrobial Agents 2011;38(6):486-492. Available from: doi: 10.1016/j.ijantimicag.2011.08.011. [Google Scholar]