Gopalkrishna K Bhat, Jyoti Kumari, Shalini M Shenoy, Ashwini Hegde, Chakrapani M, Vidyalakshmi K


Vancomycin is used as the antibiotic of choice for severe infection caused by methicillin resistant Staphylococcus aureus. Increased use of vancomycin and the selective pressure has resulted in the emergence of S.aureus with reduced susceptibility to vancomycin and vancomycin resistant S.aureus. This review summarizes the definition, mechanism, clinical significance and epidemiology of S.aureus with reduced susceptibility to vancomycin. It also discusses laboratory methods for detection and treatment options available for these pathogens.


Vancomycin, Vancomycin intermediate Staphylococcus aureus, Heteroresistant vancomycin intermediate Staphylococcus aureus, Vancomycin resistant Staphylococcus aureus

| PDF |


Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998;339(8):520-32.

Clements MO, Foster SJ. Stress resistance in Staphylococcus aureus. Trends Microbiol 1999;7(11):458-62.

Ratnaraja NV, Hawkey PM. Current challenges in treating MRSA: What are the options? Expert Rev Anti Infect Ther 2008;6(5):601-18.

Jensen SO, Lyon BR. Genetics of antimicrobial resistance in Staphylococcus aureus. Future Microbiol 2009;4(5):565-82.

Grundmann H, Aires-de-Sousa M, Boyce J, Tiemersma E. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet 2006;368(9538):874-85.

Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997;40:135-6.

Bierbaum G, Fuchs K, Lenz W, Szekat C, Sahl HG. Presence of Staphylococcus aureus with reduced susceptibility to vancomycin in Germany. Eur J Clin Microbiol Infect Dis 1999;18(10):691-6.

Delgado A, Riordan JT, Lamichhane-Khadka R, Winnett DC, Jimenez J, Robinson K, et al. Hetero-vancomycin-intermediate methicillin-resistant Staphylococcus aureus isolate from a medical center in Las Cruces, New Mexico. J Clin Microbiol 2007;45(4):1325-9.

Krzyszton-Russjan J, Gniadkowski M, Polowniak-Pracka H, Hagmajer E, Hryniewicz W. The first Staphylococcus aureus isolates with reduced susceptibility to vancomycin in Poland. J Antimicrob Chemother 2002;50(6):1065-9.

Marchese A, Balistreri G, Tonoli E, Debbia EA, Schito GC. Heterogeneous vancomycin resistance in methicillin-resistant Staphylococcus aureus strains isolated in a large Italian hospital. J Clin Microbiol 2000;38(2):866-9.

Centers for Disease Control and Prevention. Investigation and Control of Vancomycin-Resistant Staphylococcus aureus (VRSA): 2015 Available from: [Last accessed on 2016 Aug].

CLSI. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard. 7th ed. Wayne, PA: CLSI Document M7-A8, CLSI; 2009.

Sader HS, Rhomberg PR, Jones RN. Nine-hospital study comparing broth microdilution and E test method results for vancomycin and daptomycin against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2009;53:3162-5.

Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: A new model of antibiotic resistance. Lancet Infect Dis 2001;1(3):147-55.

Wootton M. The need for accuracy in performing vancomycin intermediate resistant Staphylococcus aureus (VISA) and hetero – VISA detection methods. Int J Antimicrob Agents 2006;28(6):586.

Howden BP, Davies JK, Johnson PD, 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;10:100-29.

Liu C, Chambers HF. Staphylococcus aureus with heterogeneous resistance to vancomycin: Epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother 2003;47(10):3040-5.

Cui L, Murakami H, Kuwahara-Arai K, Hanaki H, Hiramatsu K. Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50. Antimicrob Agents Chemother 2000;44(9):2276-85.

Nelson JL, Rice KC, Slater SR, Fox PM, Archer GL, Bayles KW, et al. Vancomycin-intermediate Staphylococcus aureus strains have impaired acetate catabolism: Implications for polysaccharide intercellular adhesin synthesis and autolysis. Antimicrob Agents Chemother 2007;51(2):616-22.

Cázares-Domínguez V, Cruz-Córdova A, Ochoa SA, Escalona G, Arellano-Galindo J, Rodríguez-Leviz A, et al. Vancomycin tolerant, methicillin-resistant Staphylococcus aureus reveals the effects of vancomycin on cell wall thickening. PLoS One 2015;10(3):e0118791.

Gardete S, Tomasz A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest 2014;124(7):2836-40.

Périchon B, Courvalin P. VanA-type vancomycin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2009;53(11):4580-7.

Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis 2006;42 Suppl 1:S25-34.

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):1670-3.

Horne KC, Howden BP, Grabsch EA, Graham M, Ward PB, Xie S, et al. Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA. Antimicrob Agents Chemother 2009;53:3447-52.

Loomba PS, Taneja J, Mishra B. Methicillin and Vancomycin Resistant S. aureus in Hospitalized Patients. J Glob Infect Dis 2010;2(3):275-83.

Zhang S, Sun X, Chang W, Dai Y, Ma X. Systematic review and meta-analysis of the epidemiology of vancomycin-intermediate and heterogeneous vancomycin-intermediate Staphylococcus aureus Isolates. PLoS One 2015;10(8):e0136082.

Dubey D, Rath S, Sahu MC, Pattnaik L, Debata NK, Padhy RN. Surveillance of infection status of drug resistant Staphylococcus aureus in an Indian teaching hospital. Asian Pac J Trop Dis 2013;3:133-42.

Askari E, Tabatabai SM, Rian A. VanA-positive vancomycin–resistant Staphylococcus aureus: Systematic search and review of reported cases. Infect Dis Clin Pract 2013;21:91-3.

Thati V, Shivannavar CT, Gaddad SM. Vancomycin resistance among methicillin resistant Staphylococcus aureus isolates from intensive care units of tertiary care hospitals in Hyderabad. Indian J Med Res 2011;134(5):704-8.

Menezes GA, Harish BN, Sujatha S, Vinothini K, Parija SC. Emergence of vancomycin-intermediate Staphylococcus species in southern India. J Med Microbiol 2008;57:911-2.

Banerjee T, Anupurba S. Colonization with vancomycin-intermediate Staphylococcus aureus strains containing the vanA resistance gene in a tertiary-care center in north India. J Clin Microbiol 2012;50(5):1730-2.

Kumari J, Shenoy SM, Baliga S, Chakrapani M, Bhat GK. Healthcare-Associated Methicillin-Resistant Staphylococcus aureus: Clinical characteristics and antibiotic resistance profile with emphasis on macrolide-lincosamide-streptogramin B resistance. Sultan Qaboos Univ Med J 2016;16(2):e175-81.

Kumari J, Shenoy SM, Chakrapani M, Vidyalakshmi K, Bhat GK. In vitro activity of vancomycin and daptomycin against healthcare-associated methicillin-resistant Staphyloccocus aureus isolated from clinical specimen. Asian J Pharm Clin Res 2016;9:44-6.

Marlowe EM, Cohen MD, Hindler JF, Ward KW, Bruckner DA. Practical strategies for detecting and confirming vancomycin-intermediate Staphylococcus aureus: A tertiary-care hospital laboratory’s experience. J Clin Microbiol 2001;39:2637-9.

Hiramatsu K, Kayayama Y, Matsuo M, Aiba Y, Saito M, Hishinuma T, et al. Vancomycin-intermediate resistance in Staphylococcus aureus. J Glob Antimicrob Resist 2014;2(4):213-24.

Wootton M, Howe RA, Hillman R, Walsh TR, Bennett PM, MacGowan AP. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital. J Antimicrob Chemother 2001;47:399-403.

Hsu DI, Hidayat LK, Quist R, Hindler J, Karlsson A, Yusof A, et al. Comparison of method-specific vancomycin minimum inhibitory concentration values and their predictability for treatment outcome of meticillin-resistant Staphylococcus aureus (MRSA) infections. Int J Antimicrob Agents 2008;32(5):378-85.

Centers for Disease Control and Prevention (CDC). Laboratory capacity to detect antimicrobial resistance, 1998. MMWR Morb Mortal Wkly Rep 2000;48(51-52):1167-71.

Kumari J, Shenoy SM, Chakrapani M, Vidyalakshmi K, Bhat GK. Comparision of E-test and agar dilution for determining minimum inhibitory concentration of vancomycin to healthcare-associated methicillin resistant Staphylococcus aureus. Asian J Pharm ]Clin Res 2016;9:189-91.

Tenover FC, Moellering RC Jr. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus. Clin Infect Dis 2007;44(9):1208-15.

Chang FY, Peacock JE Jr, Musher DM, Triplett P, MacDonald BB, Mylotte JM, et al. Staphylococcus aureus bacteremia: Recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003;82(5):333-9.

Rose WE, Leonard SN, Rossi KL, Kaatz GW, Rybak MJ. Impact of inoculum size and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) on vancomycin activity and emergence of VISA in an in vitro pharmacodynamic model. Antimicrob Agents Chemother 2009;53(2):805-7.

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):1262-6.

Sieradzki K, Roberts RB, Haber SW, Tomasz A. The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. N Engl J Med 1999;340(7):517-23.

Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B, et al. Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus working group. N Engl J Med 1999;340(7):493-501.

Ariza J, Pujol M, Cabo J, Pena C, Fernandez N, Linares J, et al. Vancomycin in surgical infections due to methicillin resistant Staphylococcus aureus with heterogeneous resistance to vancomycin. Lancet 1999;353:1587-8.

Oliveira GA, Dell’Aquila AM, Masiero RL, Levy CE, Gomes MS, Cui L, et al. Isolation in Brazil of nosocomial Staphylococcus aureus with reduced susceptibility to vancomycin. Infect Control Hosp Epidemiol 2001;22:443-8.

Andrade-Baiocchi S, Tognim MC, Baiocchi OC, Sader HS. Endocarditis due to glycopeptide-intermediate Staphylococcus aureus: Case report and strain characterization. Diagn Microbiol Infect Dis 2003;45:149-52.

Howden BP, Ward PB, Charles PG, Korman TM, Fuller A, du Cros P, et al. Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis 2004;38(4):521-8.

Whitener CJ, Park SY, Browne FA, Parent LJ, Julian K, Bozdogan B, et al. Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure. Clin Infect Dis 2004;38(8):1049-55. 52. Casapao AM, Leonard SN, Davis SL, Lodise TP, Patel N, Goff DA, et al. Clinical outcome in patients with heterogenous vancomycin-intermediate Staphylococcus aureus bloodstream infection. Antimicrob Agents Chemother 2013;57:4252-9.

Gomes DM, Ward KE, LaPlante KL. Clinical implications of vancomycin heteroresistant and intermediately susceptible Staphylococcus aureus. Pharmacotherapy 2015;35(4):424-32.

Chen CJ, Huang YC, Chiu CH. Multiple pathways of cross-resistance to glycopeptides and daptomycin in persistent MRSA bacteraemia. J Antimicrob Chemother 2015;70(11):2965-72.

Tenover FC, Sinner SW, Segal RE, Huang V, Alexandre SS, McGowan JE Jr, et al. Characterisation of a Staphylococcus aureus strain with progressive loss of susceptibility to vancomycin and daptomycin during therapy. Int J Antimicrob Agents 2009;33(6):564-8.

Huang YT, Liao CH, Teng LJ, Hsueh PR. Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and tigecycline against blood isolates of Gram-positive bacteria in Taiwan. Clin Microbiol Infect 2008;14(2):124-9.

Jacqueline C, Caillon J, Le Mabecque V, Miègeville AF, Hamel A, Bugnon D, et al. In vivo efficacy of ceftaroline (PPI-0903), a new broad-spectrum cephalosporin, compared with linezolid and vancomycin against methicillin-resistant and vancomycin-intermediate Staphylococcus aureus in a rabbit endocarditis model. Antimicrob Agents Chemother 2007;51(9):3397-400.

Tarai B, Das P, Kumar D. Recurrent challenges for clinicians: Emergence of methicillin-resistant Staphylococcus aureus, vancomycin resistance, and current treatment options. J Lab Physicians 2013;5(2):71-8.

Voss A, Mouton JW, van Elzakker EP, Hendrix RG, Goessens W, Kluytmans JA, et al. A multi-center blinded study on the efficiency of phenotypic screening methods to detect glycopeptide intermediately susceptible Staphylococcus aureus (GISA) and heterogeneous GISA (h-GISA). Ann Clin Microbiol Antimicrob 2007;6:9.

About this article




Vancomycin, Vancomycin intermediate Staphylococcus aureus, Heteroresistant vancomycin intermediate Staphylococcus aureus, Vancomycin resistant Staphylococcus aureus





Additional Links

Manuscript Submission


Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 6 June 2017 Page: 32-38

Print ISSN


Online ISSN


Authors & Affiliations

Gopalkrishna K Bhat
Department of Microbiology, Kasturba Medical College, Mangalore, Karnataka, India

Jyoti Kumari
Department of Microbiology, Kasturba Medical College, Mangalore, Karnataka, India

Shalini M Shenoy
Department of Microbiology, Kasturba Medical College, Mangalore, Karnataka, India

Ashwini Hegde
Department of Microbiology, Kasturba Medical College, Mangalore, Karnataka, India

Chakrapani M
Department of Medicine, Kasturba Medical College, Mangalore, Karnataka, India.

Vidyalakshmi K
Department of Microbiology, Kasturba Medical College, Mangalore, Karnataka, India

Article Tools

Email this article (Login required)
Email the author (Login required)


  • There are currently no refbacks.