Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades

  • E. AhlstrandEmail author
  • K. Svensson
  • L. Persson
  • U. Tidefelt
  • B. Söderquist


The aim of this study was to determine if there was a long-term increase in glycopeptide minimum inhibitory concentration (MIC) values, MIC creep, among bloodstream isolates of Staphylococcus epidermidis and S. haemolyticus isolated from patients with hematological malignancies. We conducted a retrospective single-center study where all positive blood cultures of S. epidermidis (n = 387) and S. haemolyticus (n = 19) isolated from patients with hematological malignancies during three decades, 1980 to 2009, were re-evaluated for the presence of reduced susceptibility to vancomycin and teicoplanin. Three different methods for the detection of reduced susceptibility to glycopeptides were used; standard Etest, macromethod Etest, and glycopeptide resistance detection (GRD) Etest. The median MIC value for vancomycin was 2 mg/L. MIC values for vancomycin and teicoplanin did not show any statistically significant increase during the study period. The presence of heterogeneously glycopeptide-intermediate staphylococci (hGIS) was analyzed among 405 coagulase-negative staphylococci (CoNS) isolates. hGIS were found in 31–45% of the CoNS isolates by the macromethod Etest and in 53–67% by the GRD Etest during the three decades. In conclusion, we did not observe any long-term glycopeptide MIC creep determined by the standard Etest, although a high and increasing proportion of heterogeneous vancomycin resistance was observed.


Minimum Inhibitory Concentration Vancomycin Hematological Malignancy Glycopeptide Teicoplanin 
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The study was supported by grants from the research committee of Örebro County Council, Sweden.

Transparency declarations

B. Söderquist has been a consultant for Pfizer and Janssen-Cilag.


Research Committee of Örebro County Council, Sweden.


  1. 1.
    Rogers KL, Fey PD, Rupp ME (2009) Coagulase-negative staphylococcal infections. Infect Dis Clin North Am 23(1):73–98PubMedCrossRefGoogle Scholar
  2. 2.
    Wilson AP, O’Hare MD, Felmingham D, Grüneberg RN (1986) Teicoplanin-resistant coagulase-negative staphylococcus. Lancet 2(8513):973PubMedCrossRefGoogle Scholar
  3. 3.
    Schwalbe RS, Stapleton JT, Gilligan PH (1987) Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 316(15):927–931PubMedCrossRefGoogle Scholar
  4. 4.
    Henwood CJ, Livermore DM, Johnson AP, James D, Warner M, Gardiner A; The Linezolid Study Group (2000) Susceptibility of gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. J Antimicrob Chemother 46(6):931–940PubMedCrossRefGoogle Scholar
  5. 5.
    Santos Sanches I, Mato R, de Lencastre H, Tomasz A (2000) Patterns of multidrug resistance among methicillin-resistant hospital isolates of coagulase-positive and coagulase-negative staphylococci collected in the international multicenter study RESIST in 1997 and 1998. Microb Drug Resist 6(3):199–211PubMedCrossRefGoogle Scholar
  6. 6.
    de Neeling AJ, van Leeuwen WJ, Schouls LM, Schot CS, van Veen-Rutgers A, Beunders AJ, Buiting AG, Hol C, Ligtvoet EE, Petit PL, Sabbe LJ, van Griethuysen AJ, van Embden JD (1998) Resistance of staphylococci in The Netherlands: surveillance by an electronic network during 1989–1995. J Antimicrob Chemother 41(1):93–101PubMedCrossRefGoogle Scholar
  7. 7.
    Felmingham D, Brown DF, Soussy CJ; European Glycopeptide Resistance Survey Study Group (1998) European Glycopeptide Susceptibility Survey of gram-positive bacteria for 1995. Diagn Microbiol Infect Dis 31(4):563–571PubMedCrossRefGoogle Scholar
  8. 8.
    Froggatt JW, Johnston JL, Galetto DW, Archer GL (1989) Antimicrobial resistance in nosocomial isolates of Staphylococcus haemolyticus. Antimicrob Agents Chemother 33(4):460–466PubMedGoogle Scholar
  9. 9.
    Goldstein FW, Coutrot A, Sieffer A, Acar JF (1990) Percentages and distributions of teicoplanin- and vancomycin-resistant strains among coagulase-negative staphylococci. Antimicrob Agents Chemother 34(5):899–900PubMedGoogle Scholar
  10. 10.
    Grüneberg RN, Hryniewicz W (1998) Clinical relevance of a European collaborative study on comparative susceptibility of gram-positive clinical isolates to teicoplanin and vancomycin. Int J Antimicrob Agents 10(4):271–277PubMedCrossRefGoogle Scholar
  11. 11.
    Herwaldt L, Boyken L, Pfaller M (1991) In vitro selection of resistance to vancomycin in bloodstream isolates of Staphylococcus haemolyticus and Staphylococcus epidermidis. Eur J Clin Microbiol Infect Dis 10(12):1007–1012PubMedCrossRefGoogle Scholar
  12. 12.
    Luh KT, Hsueh PR, Teng LJ, Pan HJ, Chen YC, Lu JJ, Wu JJ, Ho SW (2000) Quinupristin-dalfopristin resistance among gram-positive bacteria in Taiwan. Antimicrob Agents Chemother 44(12):3374–3380PubMedCrossRefGoogle Scholar
  13. 13.
    Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S, Fukuchi Y, Kobayashi I (1997) Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 350(9092):1670–1673PubMedCrossRefGoogle Scholar
  14. 14.
    Sieradzki K, Roberts RB, Haber SW, Tomasz A (1999) The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. N Engl J Med 340(7):517–523PubMedCrossRefGoogle Scholar
  15. 15.
    Biavasco F, Vignaroli C, Lazzarini R, Varaldo PE (2000) Glycopeptide susceptibility profiles of Staphylococcus haemolyticus bloodstream isolates. Antimicrob Agents Chemother 44(11):3122–3126PubMedCrossRefGoogle Scholar
  16. 16.
    Sieradzki K, Roberts RB, Serur D, Hargrave J, Tomasz A (1998) Recurrent peritonitis in a patient on dialysis and prophylactic vancomycin. Lancet 351(9106):880–881PubMedCrossRefGoogle Scholar
  17. 17.
    Sieradzki K, Roberts RB, Serur D, Hargrave J, Tomasz A (1999) Heterogeneously vancomycin-resistant Staphylococcus epidermidis strain causing recurrent peritonitis in a dialysis patient during vancomycin therapy. J Clin Microbiol 37(1):39–44PubMedGoogle Scholar
  18. 18.
    Van Der Zwet WC, Debets-Ossenkopp YJ, Reinders E, Kapi M, Savelkoul PH, Van Elburg RM, Hiramatsu K, Vandenbroucke-Grauls CM (2002) Nosocomial spread of a Staphylococcus capitis strain with heteroresistance to vancomycin in a neonatal intensive care unit. J Clin Microbiol 40(7):2520–2525CrossRefGoogle Scholar
  19. 19.
    Gould IM (2008) Clinical relevance of increasing glycopeptide MICs against Staphylococcus aureus. Int J Antimicrob Agents 31(Suppl 2):1–9PubMedCrossRefGoogle Scholar
  20. 20.
    Bertin M, Muller A, Bertrand X, Cornette C, Thouverez M, Talon D (2004) Relationship between glycopeptide use and decreased susceptibility to teicoplanin in isolates of coagulase-negative staphylococci. Eur J Clin Microbiol Infect Dis 23(5):375–379PubMedCrossRefGoogle Scholar
  21. 21.
    Boisson K, Thouverez M, Talon D, Bertrand X (2002) Characterisation of coagulase-negative staphylococci isolated from blood infections: incidence, susceptibility to glycopeptides, and molecular epidemiology. Eur J Clin Microbiol Infect Dis 21(9):660–665PubMedCrossRefGoogle Scholar
  22. 22.
    Tacconelli E, Tumbarello M, Donati KG, Bettio M, Spanu T, Leone F, Sechi LA, Zanetti S, Fadda G, Cauda R (2001) Glycopeptide resistance among coagulase-negative staphylococci that cause bacteremia: epidemiological and clinical findings from a case–control study. Clin Infect Dis 33(10):1628–1635PubMedCrossRefGoogle Scholar
  23. 23.
    Biavasco F, Vignaroli C, Varaldo PE (2000) Glycopeptide resistance in coagulase-negative staphylococci. Eur J Clin Microbiol Infect Dis 19(6):403–417PubMedCrossRefGoogle Scholar
  24. 24.
    Hiramatsu K, Hanaki H (1998) Glycopeptide resistance in staphylococci. Curr Opin Infect Dis 11(6):653–658PubMedCrossRefGoogle Scholar
  25. 25.
    Cherif H, Kronvall G, Björkholm M, Kalin M (2003) Bacteraemia in hospitalised patients with malignant blood disorders: a retrospective study of causative agents and their resistance profiles during a 14-year period without antibacterial prophylaxis. Hematol J 4(6):420–426PubMedCrossRefGoogle Scholar
  26. 26.
    Walsh TR, Bolmström A, Qwärnström A, Ho P, Wootton M, Howe RA, MacGowan AP, Diekema D (2001) Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides. J Clin Microbiol 39(7):2439–2444PubMedCrossRefGoogle Scholar
  27. 27.
    Leonard SN, Rossi KL, Newton KL, Rybak MJ (2009) Evaluation of the Etest GRD for the detection of Staphylococcus aureus with reduced susceptibility to glycopeptides. J Antimicrob Chemother 63(3):489–492PubMedCrossRefGoogle Scholar
  28. 28.
    Maniati M, Petinaki E, Kontos, Maniatis AN, Spiliopoulou I, Petropoulou-Mylona D, Malamou-Lada H, Spaliara L, Koutsia-Carouzou C (2005) Rapid increase in numbers of Staphylococcus epidermidis strains with reduced susceptibility to teicoplanin in Greece. Int J Antimicrob Agents 25(4):346–348PubMedCrossRefGoogle Scholar
  29. 29.
    Trueba F, Garrabe E, Hadef R, Fabre R, Cavallo JD, Tsvetkova K, Chesneau O (2006) High prevalence of teicoplanin resistance among Staphylococcus epidermidis strains in a 5-year retrospective study. J Clin Microbiol 44(5):1922–1923PubMedCrossRefGoogle Scholar
  30. 30.
    Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP, Alamo D, Ortega M, Lopez J, Mensa J (2008) Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 46(2):193–200PubMedCrossRefGoogle Scholar
  31. 31.
    Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM, Stellrecht K (2008) Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother 52(9):3315–3320PubMedCrossRefGoogle Scholar
  32. 32.
    Srinivasan A, Dick JD, Perl TM (2002) Vancomycin resistance in staphylococci. Clin Microbiol Rev 15(3):430–438PubMedCrossRefGoogle Scholar
  33. 33.
    Cremniter J, Slassi A, Quincampoix JC, Sivadon-Tardy V, Bauer T, Porcher R, Lortat-Jacob A, Piriou P, Judet T, Herrmann JL, Gaillard JL, Rottman M (2010) Decreased susceptibility to teicoplanin and vancomycin in coagulase-negative staphylococci isolated from orthopedic-device-associated infections. J Clin Microbiol 48(4):1428–1431PubMedCrossRefGoogle Scholar
  34. 34.
    Natoli S, Fontana C, Favaro M, Bergamini A, Testore GP, Minelli S, Bossa MC, Casapulla M, Broglio G, Beltrame A, Cudillo L, Cerretti R, Leonardis F (2009) Characterization of coagulase-negative staphylococcal isolates from blood with reduced susceptibility to glycopeptides and therapeutic options. BMC Infect Dis 9:83PubMedCrossRefGoogle Scholar
  35. 35.
    Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC Jr, Craig WA, Billeter M, Dalovisio JR, Levine DP (2009) Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy 29(11):1275–1279PubMedCrossRefGoogle Scholar
  36. 36.
    Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS (2002) 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34(6):730–751PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • E. Ahlstrand
    • 1
    • 4
    Email author
  • K. Svensson
    • 2
  • L. Persson
    • 3
  • U. Tidefelt
    • 1
    • 4
  • B. Söderquist
    • 2
    • 3
    • 4
  1. 1.Department of Medicine, Division of HematologyÖrebro University HospitalÖrebroSweden
  2. 2.Department of Laboratory Medicine, Clinical MicrobiologyÖrebro University HospitalÖrebroSweden
  3. 3.Department of Infectious DiseasesÖrebro University HospitalÖrebroSweden
  4. 4.School of Health and Medical SciencesÖrebro UniversityÖrebroSweden

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