, Volume 64, Issue 9, pp 913–936 | Cite as

Glycopeptide Antibiotics

from Conventional Molecules to New Derivatives
  • Françoise Van BambekeEmail author
  • Yves Van Laethem
  • Patrice Courvalin
  • Paul M. Tulkens
Leading Article


Vancomycin and teicoplanin are still the only glycopeptide antibiotics available for use in humans. Emergence of resistance in enterococci and staphylococci has led to restriction of their use to severe infections caused by Gram-positive bacteria for which no other alternative is acceptable (because of resistance or allergy). In parallel, considerable efforts have been made to produce semisynthetic glycopeptides with improved pharmacokinetic and pharmacodynamic properties, and with activity towards resistant strains. Several molecules have now been obtained, helping to better delineate structure-activity relationships. Two are being currently evaluated for skin and soft tissue infections and are in phases II/ III. The first, oritavancin (LY333328), is the 4′-chlorobiphenylmethyl derivative of chloroeremomycin, an analogue to vancomycin. It is characterised by: i) a spectrum covering vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and to some extent glycopeptide-intermediate S. aureus (GISA); ii) rapid bactericidal activity including against the intracellular forms of enterococci and staphylococci; and iii) a prolonged half-life, allowing for daily administration. The second molecule is dalbavancin (BI397), a derivative of the teicoplanin analogue A40926. Dalbavancin has a spectrum of activity similar to that of oritavancin against vancomycin-sensitive strains, but is not active against VRE. It can be administered once a week, based on its prolonged retention in the organism. Despite these remarkable properties, the use of these potent agents should be restricted to severe infections, as should the older glycopeptides, with an extension towards resistant or poorly sensitive bacteria, to limit the risk of potential selection of resistance.


Minimum Inhibitory Concentration Vancomycin Glycopeptide Teicoplanin Glycopeptide Antibiotic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



F. Van Bambeke is Chercheur Qualifié of the Belgian Fonds National de la Recherche Scientifique. The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.


  1. 1.
    Reynolds PE. Structure, biochemistry and mechanism of action of glycopeptide antibiotics. Eur J Clin Microbiol Infect Dis 1989 Nov; 8(11): 943–50PubMedCrossRefGoogle Scholar
  2. 2.
    Arthur M, Reynolds P, Courvalin P. Glycopeptide resistance in enterococci. Trends Microbiol 1996 Oct; 4(10): 401–7PubMedCrossRefGoogle Scholar
  3. 3.
    Williams DH, Waltho JP. Molecular basis of the activity of antibiotics of the vancomycin group. Biochem Pharmacol 1988 Jan 1; 37(1): 133–41PubMedCrossRefGoogle Scholar
  4. 4.
    Loll PJ, Axelsen PH. The structural biology of molecular recognition by vancomycin. Annu Rev Biophys Biomol Struct 2000; 29: 265–89PubMedCrossRefGoogle Scholar
  5. 5.
    Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis 2001 Oct; 1(3): 147–55PubMedCrossRefGoogle Scholar
  6. 6.
    Schafer M, Schneider TR, Sheldrick GM. Crystal structure of vancomycin. Structure 1996 Dec 15; 4(12): 1509–15PubMedCrossRefGoogle Scholar
  7. 7.
    Groves P, Searle MS, Mackay JP, et al. The structure of an asymmetric dimer relevant to the mode of action of the glycopeptide antibiotics. Structure 1994 Aug 15; 2(8): 747–54PubMedCrossRefGoogle Scholar
  8. 8.
    Shiozawa H, Chia BC, Davies NL, et al. Cooperative binding interactions of glycopeptide antibiotics. J Am Chem Soc 2002 Apr 17; 124(15): 3914–9PubMedCrossRefGoogle Scholar
  9. 9.
    Mackay JP, Gerhard U, Beauregard DA, et al. Glycopeptide antibiotic activity and the possible role of dimerization: a model for biological signalling. J Am Chem Soc 1994; 116: 4581–90CrossRefGoogle Scholar
  10. 10.
    Mackay JP, Gerhard U, Beauregard DA, et al. Dissection of the contributions towards dimerization of glycopeptide antibiotics. J Am Chem Soc 1994; 116: 4573–80CrossRefGoogle Scholar
  11. 11.
    Beauregard DA, Williams DH, Gwynn MN, et al. Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics. Antimicrob Agents Chemother 1995 Mar; 39(3): 781–5PubMedCrossRefGoogle Scholar
  12. 12.
    Williams DH, Maguire AJ, Tsuzuki W, et al. An analysis of the origins of a cooperative binding energy of dimerization. Science 1998 May 1; 280(5364): 711–4PubMedCrossRefGoogle Scholar
  13. 13.
    Kaplan J, Korty BD, Axelsen PH, et al. The role of sugar residues in molecular recognition by vancomycin. J Med Chem 2001 May 24; 44(11): 1837–40PubMedCrossRefGoogle Scholar
  14. 14.
    Ge M, Chen Z, Onishi HR, et al. Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala. Science1999 Apr 16; 284(5413): 507–11PubMedCrossRefGoogle Scholar
  15. 15.
    Printsevskaya SS, Pavlov AY, Olsufyeva EN, et al. Role of the glycopeptide framework in the antibacterial activity of hydrophobic derivatives of glycopeptide antibiotics. J Med Chem 2003 Mar 27; 46(7): 1204–9PubMedCrossRefGoogle Scholar
  16. 16.
    Gholizadeh Y, Courvalin P. Acquired and intrinsic glycopeptide resistance in enterococci. Int J Antimicrob Agents 2000 Nov; 16 Suppl. 1: S11–7PubMedCrossRefGoogle Scholar
  17. 17.
    Centers for Disease Control and Prevention. Staphylococcus aureus resistant to vancomycin: United States, 2002. MMWR Morb Mortal Wkly Rep 2002; 51: 565–7Google Scholar
  18. 18.
    Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med 2003 Apr 3; 348(14): 1342–7PubMedCrossRefGoogle Scholar
  19. 19.
    Bozdogan B, Esel D, Whitener C, et al. Antibacterial susceptibility of a vancomycin-resistant Staphylococcus aureus strain isolated at the Hershey Medical Center. J Antimicrob Chemother 2003 Nov; 52(5): 864–8PubMedCrossRefGoogle Scholar
  20. 20.
    Tenover FC, Weigel LM, Appelbaum PC, et al. Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylvania. Antimicrob Agents Chemother 2004 Jan; 48(1): 275–80PubMedCrossRefGoogle Scholar
  21. 21.
    Poyart C, Pierre C, Quesne G, et al. Emergence of vancomycin resistance in the genus Streptococcus: characterization of a vanB transferable determinant in Streptococcus bovis. Antimicrob Agents Chemother 1997 Jan; 41(1): 24–9PubMedGoogle Scholar
  22. 22.
    Perichon B, Reynolds P, Courvalin P. VanD-type glycopeptide-resistant Enterococcus faecium BM 4339. Antimicrob Agents Chemother 1997 Sep; 41(9): 2016–8PubMedGoogle Scholar
  23. 23.
    Fines M, Perichon B, Reynolds P, et al. VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis BM 4405. Antimicrob Agents Chemother 1999 Sep; 43(9): 2161–4PubMedGoogle Scholar
  24. 24.
    McKessar SJ, Berry AM, Bell JM, et al. Genetic characterization of vanG, a novel vancomycin resistance locus of Enterococcus faecalis. Antimicrob Agents Chemother 2000 Nov; 44(11): 3224–8PubMedCrossRefGoogle Scholar
  25. 25.
    Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997 Jul; 40(1): 135–6PubMedCrossRefGoogle Scholar
  26. 26.
    Sieradzki K, Tomasz A. Gradual alterations in cell wall structure and metabolism in vancomycin-resistant mutants of Staphylococcus aureus. J Bacteriol 1999 Dec; 181(24): 7566–70PubMedGoogle Scholar
  27. 27.
    Leclercq R, Derlot E, Duval J, et al. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med 1988 Jul 21; 319(3): 157–61PubMedCrossRefGoogle Scholar
  28. 28.
    Uttley AH, Collins CH, Naidoo J, et al. Vancomycin-resistant enterococci. Lancet 1988 Jan 2; I(8575–6): 57–8CrossRefGoogle Scholar
  29. 29.
    Bonten MJ, Willems R, Weinstein RA. Vancomycin-resistant enterococci: why are they here, and where do they come from? Lancet Infect Dis 2001 Dec; 1(5): 314–25PubMedCrossRefGoogle Scholar
  30. 30.
    Kenner J, O’Connor T, Piantanida N, et al. Rates of carriage of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in an outpatient population. Infect Control Hosp Epidemiol 2003 Jun; 24(6): 439–44PubMedCrossRefGoogle Scholar
  31. 31.
    Schouten MA, Hoogkamp-Korstanje JA, Meis JF, et al. Prevalence of vancomycin-resistant enterococci in Europe. Eur J Clin Microbiol Infect Dis 2000 Nov; 19(11): 816–22PubMedCrossRefGoogle Scholar
  32. 32.
    van den Bogaard AE, Mertens P, London NH, et al. High prevalence of colonization with vancomycin- and pristinamycin-resistant enterococci in healthy humans and pigs in The Netherlands: is the addition of antibiotics to animal feeds to blame? J Antimicrob Chemother 1997 Sep; 40(3): 454–6PubMedCrossRefGoogle Scholar
  33. 33.
    van den Braak N, van Belkum A, van Keulen M, et al. Molecular characterization of vancomycin-resistant enterococci from hospitalized patients and poultry products in The Netherlands. J Clin Microbiol 1998 Jul; 36(7): 1927–32PubMedGoogle Scholar
  34. 34.
    Klare I, Badstubner D, Konstabel C, et al. Decreased incidence of VanA-type vancomycin-resistant enterococci isolated from poultry meat and from fecal samples of humans in the community after discontinuation of avoparcin usage in animal husbandry. Microb Drug Resist 1999; 5(1): 45–52PubMedCrossRefGoogle Scholar
  35. 35.
    Aarestrup FM, Seyfarth AM, Emborg HD, et al. Effect of abolishment of the use of antimicrobial agents for growth promotion on occurrence of antimicrobial resistance in fecal enterococci from food animals in Denmark. Antimicrob Agents Chemother 2001 Jul; 45(7): 2054–9PubMedCrossRefGoogle Scholar
  36. 36.
    van den Bogaard AE, Stobberingh EE. Epidemiology of resistance to antibiotics: links between animals and humans. Int J Antimicrob Agents 2000 May; 14(4): 327–35PubMedCrossRefGoogle Scholar
  37. 37.
    Bugg TD, Wright GD, Dutka-Malen S, et al. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry 1991 Oct 29; 30(43): 10408–15PubMedCrossRefGoogle Scholar
  38. 38.
    Arthur M, Molinas C, Depardieu F, et al. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM 4147. J Bacteriol 1993 Jan; 175(1): 117–27PubMedGoogle Scholar
  39. 39.
    Quintiliani Jr R, Courvalin P. Conjugal transfer of the vancomycin resistance determinant vanB between enterococci involves the movement of large genetic elements from chromosome to chromosome. FEMS Microbiol Lett 1994 Jun 15; 119(3): 359–63PubMedCrossRefGoogle Scholar
  40. 40.
    Baptista M, Depardieu F, Reynolds P, et al. Mutations leading to increased levels of resistance to glycopeptide antibiotics in VanB-type enterococci. Mol Microbiol 1997 Jul; 25(1): 93–105PubMedCrossRefGoogle Scholar
  41. 41.
    Van Bambeke F, Chauvel M, Reynolds PE, et al. Vancomycin-dependent Enterococcus faecalis clinical isolates and revertant mutants. Antimicrob Agents Chemother 1999 Jan; 43(1): 41–7PubMedCrossRefGoogle Scholar
  42. 42.
    Hamilton-Miller JM. Vancomycin-resistant Staphylococcus aureus: a real and present danger? Infection 2002 Jun; 30(3): 118–24PubMedCrossRefGoogle Scholar
  43. 43.
    Hamilton-Miller JM. Glycopeptide-resistant staphylococci. Int J Antimicrob Agents 1999 Sep; 13(1): 63–5PubMedCrossRefGoogle Scholar
  44. 44.
    Cui L, Murakami H, Kuwahara-Arai K, et al. Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu 50. Antimicrob Agents Chemother 2000 Sep; 44(9): 2276–85PubMedCrossRefGoogle Scholar
  45. 45.
    Hiramatsu K, Okuma K, Ma XX, et al. New trends in Staphylococcus aureus infections: glycopeptide resistance in hospital and methicillin resistance in the community. Curr Opin Infect Dis 2002 Aug; 15(4): 407–13PubMedCrossRefGoogle Scholar
  46. 46.
    May J, Shannon K, King A, et al. Glycopeptide tolerance in Staphylococcus aureus. J Antimicrob Chemother 1998 Aug; 42(2): 189–97PubMedCrossRefGoogle Scholar
  47. 47.
    Johnson AP, Woodford N. Glycopeptide-resistant Staphylococcus aureus. J Antimicrob Chemother 2002 Nov; 50(5): 621–3PubMedCrossRefGoogle Scholar
  48. 48.
    Malabarba A, Ciabatti R. Glycopeptide derivatives. Curr Med Chem 2001 Dec; 8(14): 1759–73PubMedCrossRefGoogle Scholar
  49. 49.
    Candiani GP, Abbondi M, Borgonovi M, et al. In-vitro and in-vivo antibacterial activity of BI 397, a new semi-synthetic glycopeptide antibiotic. J Antimicrob Chemother 1999 Aug; 44(2): 179–92PubMedCrossRefGoogle Scholar
  50. 50.
    Biavasco F, Vignaroli C, Lupidi R, et al. In vitro antibacterial activity of LY333328, a new semisynthetic glycopeptide. Antimicrob Agents Chemother 1997 Oct; 41(10): 2165–72PubMedGoogle Scholar
  51. 51.
    Zeckel ML, Preston DA, Allen BS. In vitro activities of LY333328 and comparative agents against nosocomial gram-positive pathogens collected in a 1997 global surveillance study. Antimicrob Agents Chemother 2000 May; 44(5): 1370–4PubMedCrossRefGoogle Scholar
  52. 52.
    Garcia-Garrote F, Cercenado E, Alcala L, et al. In vitro activity of the new glycopeptide LY333328 against multiply resistant gram-positive clinical isolates. Antimicrob Agents Chemother 1998 Sep; 42(9): 2452–5PubMedGoogle Scholar
  53. 53.
    Jones RN, Biedenbach DJ, Johnson DM, et al. In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent. J Chemother 2001 Jun; 13(3): 244–54PubMedGoogle Scholar
  54. 54.
    Jones RN, Barrett MS, Erwin ME. In vitro activity and spectrum of LY333328, a novel glycopeptide derivative. Antimicrob Agents Chemother 1997 Feb; 41(2): 488–93PubMedGoogle Scholar
  55. 55.
    Noviello S, Ianniello F, Esposito S. In vitro activity of LY333328 (oritavancin) against gram-positive aerobic cocci and synergy with ciprofloxacin against enterococci. J Antimicrob Chemother 2001 Aug; 48(2): 283–6PubMedCrossRefGoogle Scholar
  56. 56.
    Aeschlimann JR, Allen GP, Hershberger E, et al. Activities of LY333328 and vancomycin administered alone or in combination with gentamicin against three strains of vancomycin-intermediate Staphylococcus aureus in an in vitro pharmacodynamic infection model. Antimicrob Agents Chemother 2000 Nov; 44(11): 2991–8PubMedCrossRefGoogle Scholar
  57. 57.
    Hackbarth CJ, Lopez S, Trias J, et al. In vitro activity of the glycopeptide BI 397 against Staphylococcus aureus and Staphylococcus epidermidis [abstract no. 1283]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–28; San Francisco (CA)Google Scholar
  58. 58.
    Tenover FC, Lancaster MV, Hill BC, et al. Characterization of staphylococci with reduced susceptibilities to vancomycin and other glycopeptides. J Clin Microbiol 1998 Apr; 36(4): 1020–7PubMedGoogle Scholar
  59. 59.
    Schwalbe RS, McIntosh AC, Qaiyumi S, et al. In vitro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci. Antimicrob Agents Chemother 1996 Oct; 40(10): 2416–9PubMedGoogle Scholar
  60. 60.
    Harland S, Tebbs SE, Elliott TS. Evaluation of the in-vitro activity of the glycopeptide antibiotic LY333328 in comparison with vancomycin and teicoplanin. J Antimicrob Chemother 1998 Feb; 41(2): 273–6PubMedCrossRefGoogle Scholar
  61. 61.
    Sillerstrom E, Wahlund E, Nord CE. In vitro activity of LY 333328 against anaerobic gram-positive bacteria. J Chemother 1999 Apr; 11(2): 90–2PubMedGoogle Scholar
  62. 62.
    Goldstein EJ, Citron DM, Merriam CV, et al. In vitro activities of Dalbavancin and nine comparator agents against anaerobic gram-positive species and corynebacteria. Antimicrob Agents Chemother 2003 Jun; 47(6): 1968–71PubMedCrossRefGoogle Scholar
  63. 63.
    Wilson AP. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet 2000 Sep; 39(3): 167–83PubMedCrossRefGoogle Scholar
  64. 64.
    Feketi R. Vancomycin, teicoplanin, and the streptogramins: quinupristin and dalfopristin. In: Mandell GE, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philadelphia (PA): Churchill Livingstone, 2000: 382–92Google Scholar
  65. 65.
    Rowe PA, Brown TJ. Protein binding of 14C-oritavancin [abstract no. A-2193]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–18; Chicago (IL)Google Scholar
  66. 66.
    Steiert M, Schmitz FJ. Dalbavancin (Biosearch Italia/Versicor). Curr Opin Investig Drugs 2002 Feb; 3(2): 229–33PubMedGoogle Scholar
  67. 67.
    Dowell JA, Gottlieb AB, Van Sanders C, et al. The pharmacokinetics and renal excretion of dalbavancin in healthy subjects [abstract no. A-1386]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  68. 68.
    Cavaleri M, Cooper A, Nutley MA, et al. Protein binding of dalbavancin using isothermal titration microcalorimetry [abstract no. A-1385]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  69. 69.
    Owen J. Population pharmacokinetic model. Brisbane (CA): InterMune, Inc., 2003. (Data on file)Google Scholar
  70. 70.
    Thomasson HR. Study ARKK. Brisbane (CA): InterMune, Inc., 1997. (Data on file)Google Scholar
  71. 71.
    Lowdin E, Odenholt I, Cars O. In vitro studies of pharmacodynamic properties of vancomycin against Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother 1998 Oct; 42(10): 2739–44PubMedGoogle Scholar
  72. 72.
    Houlihan HH, Stokes DP, Rybak MJ. Pharmacodynamics of vancomycin and ampicillin alone and in combination with gentamicin once daily or thrice daily against Enterococcus faecalis in an in vitro infection model. J Antimicrob Chemother 2000 Jul; 46(1): 79–86PubMedCrossRefGoogle Scholar
  73. 73.
    Fantin B, Carbon C. Importance of the aminoglycoside dosing regimen in the penicillin-netilmicin combination for treatment of Enterococcus faecalis-induced experimental endocarditis. Antimicrob Agents Chemother 1990 Dec; 34(12): 2387–91PubMedCrossRefGoogle Scholar
  74. 74.
    Lamp KC, Rybak MJ, Bailey EM, et al. In vitro pharmacodynamic effects of concentration, pH, and growth phase on serum bactericidal activities of daptomycin and vancomycin. Antimicrob Agents Chemother 1992 Dec; 36(12): 2709–14PubMedCrossRefGoogle Scholar
  75. 75.
    Drabu YJ, Blakemore PH. The post-antibiotic effect of teicoplanin: monotherapy and combination studies. J Antimicrob Chemother 1991 Apr; 27 Suppl. B: 1–7PubMedCrossRefGoogle Scholar
  76. 76.
    Chambers HF, Kennedy S. Effects of dosage, peak and trough concentrations in serum, protein binding, and bactericidal rate on efficacy of teicoplanin in a rabbit model of endocarditis. Antimicrob Agents Chemother 1990 Apr; 34(4): 510–4PubMedCrossRefGoogle Scholar
  77. 77.
    Peetermans WE, Hoogeterp JJ, Hazekamp-van Dokkum AM, et al. Antistaphylococcal activities of teicoplanin and vancomycin in vitro and in an experimental infection. Antimicrob Agents Chemother 1990 Oct; 34(10): 1869–74PubMedCrossRefGoogle Scholar
  78. 78.
    Craig WA. Does the dose matter? Clin Infect Dis 2001 Sep 15; 33 Suppl. 3: S233–7PubMedCrossRefGoogle Scholar
  79. 79.
    Knudsen JD, Fuursted K, Raber S, et al. Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection. Antimicrob Agents Chemother 2000 May; 44(5): 1247–54PubMedCrossRefGoogle Scholar
  80. 80.
    Cohen E, Dadashev A, Drucker M, et al. Once-daily versus twice-daily intravenous administration of vancomycin for infections in hospitalized patients. J Antimicrob Chemother 2002 Jan; 49(1): 155–60PubMedCrossRefGoogle Scholar
  81. 81.
    Klepser ME, Patel KB, Nicolau DP, et al. Comparison of bactericidal activities of intermittent and continuous infusion dosing of vancomycin against methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Pharmacotherapy 1998 Sep; 18(5): 1069–74PubMedGoogle Scholar
  82. 82.
    James JK, Palmer SM, Levine DP, et al. Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections. Antimicrob Agents Chemother 1996 Mar; 40(3): 696–700PubMedGoogle Scholar
  83. 83.
    Byl B, Jacobs F, Wallemacq P, et al. Vancomycin penetration of uninfected pleural fluid exudate after continuous or intermittent infusion. Antimicrob Agents Chemother 2003 Jun; 47(6): 2015–7PubMedCrossRefGoogle Scholar
  84. 84.
    Wysocki M, Delatour F, Faurisson F, et al. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother 2001 Sep; 45(9): 2460–7PubMedCrossRefGoogle Scholar
  85. 85.
    Basma V, Van Bambeke F, Mingeot-Leclercq MP, et al. Stability and compatibility of vancomycin for administration by continuous infusion in intensive care patients [abstract]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; Prague. In pressGoogle Scholar
  86. 86.
    Cheung RP, DiPiro JT. Vancomycin: an update. Pharmacotherapy 1986 Jul; 6(4): 153–69PubMedGoogle Scholar
  87. 87.
    Livermore DM. Antibiotic resistance in staphylococci. Int J Antimicrob Agents 2000 Nov; 16 Suppl. 1: S3–10PubMedCrossRefGoogle Scholar
  88. 88.
    Michel M, Gutmann L. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: therapeutic realities and possibilities. Lancet 1997 Jun 28; 349(9069): 1901–6PubMedCrossRefGoogle Scholar
  89. 89.
    Kirst HA, Thompson DG, Nicas TI. Historical yearly usage of vancomycin. Antimicrob Agents Chemother 1998 May; 42(5): 1303–4PubMedGoogle Scholar
  90. 90.
    Centers for Disease Control and Prevention. Nosocomial enterococci resistant to vancomycin: United States, 1989–1993. MMWR Morb Mortal Wkly Rep 1993 Aug 6; 42(30): 597–9Google Scholar
  91. 91.
    Fridkin SK, Edwards JR, Courval JM, et al. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 US adult intensive care units. Ann Intern Med 2001 Aug 7; 135(3): 175–83PubMedGoogle Scholar
  92. 92.
    Kumana CR, Ching TY, Kong Y, et al. Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections. Br J Clin Pharmacol 2001 Oct; 52(4): 427–32PubMedCrossRefGoogle Scholar
  93. 93.
    Shojania KG, Yokoe D, Platt R, et al. Reducing vancomycin use utilizing a computer guideline: results of a randomized controlled trial. J Am Med Inform Assoc 1998 Nov; 5(6): 554–62PubMedCrossRefGoogle Scholar
  94. 94.
    Goeckner BJ, Hendershot E, Scott K, et al. A vancomycin monitoring program at a community hospital. Jt Comm J Qual Improv 1998 Jul; 24(7): 379–85PubMedGoogle Scholar
  95. 95.
    Hamilton CD, Drew R, Janning SW, et al. Excessive use of vancomycin: a successful intervention strategy at an academic medical center. Infect Control Hosp Epidemiol 2000 Jan; 21(1): 42–5PubMedCrossRefGoogle Scholar
  96. 96.
    Linden PK. Treatment options for vancomycin-resistant enterococcal infections. Drugs 2002; 62(3): 425–41PubMedCrossRefGoogle Scholar
  97. 97.
    Eliopoulos GM. Quinupristin-dalfopristin and linezolid: evidence and opinion. Clin Infect Dis 2003 Feb 15; 36(4): 473–81PubMedCrossRefGoogle Scholar
  98. 98.
    Olsen KM, Rebuck JA, Rupp ME. Arthralgias and myalgias related to quinupristin-dalfopristin administration. Clin Infect Dis 2001 Feb 15; 32(4): e83–6PubMedCrossRefGoogle Scholar
  99. 99.
    Rubinstein E, Prokocimer P, Talbot GH. Safety and tolerability of quinupristin/dalfopristin: administration guidelines. J Antimicrob Chemother 1999 Sep; 44 Suppl. A: 37–46PubMedCrossRefGoogle Scholar
  100. 100.
    Gerson SL, Kaplan SL, Brass JB, et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 2002 Aug; 46(8): 2723–6PubMedCrossRefGoogle Scholar
  101. 101.
    Nilius AM. Have the oxazolidinones lived up to their billing?: future perspectives for this antibacterial class. Curr Opin Investig Drugs 2003 Feb; 4(2): 149–55PubMedGoogle Scholar
  102. 102.
    Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance: Hospital Infection Control Practices Advisory Committee (HICPAC). Infect Control Hosp Epidemiol 1995 Feb; 16(2): 105–13CrossRefGoogle Scholar
  103. 103.
    Gordts B, Firre E, Jordens P, et al. National guidelines for the judicious use of glycopeptides in Belgium. Clin Microbiol Infect 2000 Nov; 6(11): 585–92PubMedCrossRefGoogle Scholar
  104. 104.
    Nourse C, Byrne C, Leonard L, et al. Glycopeptide prescribing in a tertiary referral paediatric hospital and applicability of hospital infection control practices advisory committee (HICPAC) guidelines to children. Eur J Pediatr 2000 Mar; 159(3): 193–7PubMedCrossRefGoogle Scholar
  105. 105.
    Gruneberg RN, Antunes F, Chambers HF, et al. The role of glycopeptide antibiotics in the treatment of infective endocarditis. Int J Antimicrob Agents 1999 Aug; 12(3): 191–8PubMedCrossRefGoogle Scholar
  106. 106.
    Manley HJ, Bailie GR, Frye RF, et al. Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients. Perit Dial Int 2001 Jul; 21(4): 378–85PubMedGoogle Scholar
  107. 107.
    Stamatiadis D, Papaioannou MG, Giamarellos-Bourboulis EJ, et al. Pharmacokinetics of teicoplanin in patients undergoing continuous ambulatory peritoneal dialysis. Perit Dial Int 2003 Mar; 23(2): 127–31PubMedGoogle Scholar
  108. 108.
    Farber BF, Moellering Jr RC. Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob Agents Chemother 1983 Jan; 23(1): 138–41PubMedCrossRefGoogle Scholar
  109. 109.
    Wang LS, Liu CY, Wang FD, et al. Chromatographically purified vancomycin: therapy of serious infections caused by Staphylococcus aureus and other gram-positive bacteria. Clin Ther 1988; 10(5): 574–84PubMedGoogle Scholar
  110. 110.
    Sivagnanam S, Deleu D. Red man syndrome. Crit Care 2003 Apr; 7(2): 119–20PubMedCrossRefGoogle Scholar
  111. 111.
    Sorrell TC, Collignon PJ. A prospective study of adverse reactions associated with vancomycin therapy. J Antimicrob Chemother 1985 Aug; 16(2): 235–41PubMedCrossRefGoogle Scholar
  112. 112.
    Elting LS, Rubenstein EB, Kurtin D, et al. Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer 1998 Dec 15; 83(12): 2597–607PubMedCrossRefGoogle Scholar
  113. 113.
    Rocha JL, Kondo W, Baptista MI, et al. Uncommon vancomycin-induced side effects. Braz J Infect Dis 2002 Aug; 6(4): 196–200PubMedCrossRefGoogle Scholar
  114. 114.
    Wood MJ. The comparative efficacy and safety of teicoplanin and vancomycin. J Antimicrob Chemother 1996 Feb; 37(2): 209–22PubMedCrossRefGoogle Scholar
  115. 115.
    Boger DL. Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies. Med Res Rev 2001 Sep; 21(5): 356–81PubMedCrossRefGoogle Scholar
  116. 116.
    Malabarba A, Nicas TI, Thompson RC. Structural modifications of glycopeptide antibiotics. Med Res Rev 1997 Jan; 17(1): 69–137PubMedCrossRefGoogle Scholar
  117. 117.
    Axelsen PH, Li D. A rational strategy for enhancing the affinity of vancomycin towards depsipeptide ligands. Bioorg Med Chem 1998 Jul; 6(7): 877–81PubMedCrossRefGoogle Scholar
  118. 118.
    Hancock RE, Farmer SW. Mechanism of uptake of deglucoteicoplanin amide derivatives across outer membranes of Escherichia coli and Pseudomonas aeruginosa. Antimicrob Agents Chemother 1993 Mar; 37(3): 453–6PubMedCrossRefGoogle Scholar
  119. 119.
    Kenny MT, Brackman MA, Dulworth JK. In vitro activity of the semisynthetic glycopeptide amide MDL 63, 246. Antimicrob Agents Chemother 1995 Jul; 39(7): 1589–90PubMedCrossRefGoogle Scholar
  120. 120.
    Goldstein BP, Candiani G, Arain TM, et al. Antimicrobial activity of MDL 63,246, a new semisynthetic glycopeptide antibiotic. Antimicrob Agents Chemother 1995 Jul; 39(7): 1580–8PubMedCrossRefGoogle Scholar
  121. 121.
    Nagarajan R. Structure-activity relationships of vancomycintype glycopeptide antibiotics. J Antibiot (Tokyo) 1993 Aug; 46(8): 1181–95CrossRefGoogle Scholar
  122. 122.
    Cooper RD, Snyder NJ, Zweifel MJ, et al. Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity. J Antibiot (Tokyo) 1996 Jun; 49(6): 575–81CrossRefGoogle Scholar
  123. 123.
    Rodriguez MJ, Snyder NJ, Zweifel MJ, et al. Novel glycopeptide antibiotics: N-alkylated derivatives active against vancomycin-resistant enterococci. J Antibiot (Tokyo) 1998 Jun; 51(6): 560–9CrossRefGoogle Scholar
  124. 124.
    Nicas TI, Mullen DL, Flokowitsch JE, et al. Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci. Antimicrob Agents Chemother 1996 Sep; 40(9): 2194–9PubMedGoogle Scholar
  125. 125.
    Allen NE, Nicas TI. Mechanism of action of oritavancin and related glycopeptide antibiotics. FEMS Microbiol Rev 2003 Jan; 26(5): 511–32PubMedCrossRefGoogle Scholar
  126. 126.
    Printsevskaya SS, Pavlov AY, Olsufyeva EN, et al. Synthesis and mode of action of hydrophobic derivatives of the glycopeptide antibiotic eremomycin and des-(N-methyl-D-leucyl)eremomycin against glycopeptide-sensitive and -resistant bacteria. J Med Chem 2002 Mar 14; 45(6): 1340–7PubMedCrossRefGoogle Scholar
  127. 127.
    Debabov D, Pace J, Kaniga K, et al. A novel bactericidal antibiotic inhibits bacterial lipid synthesis [abstract no. F-364]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  128. 128.
    Leadbetter M, Linsell M, Fatheree P, et al. Difunctionalized vancomycin derivatives [abstract no. F-367]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  129. 129.
    Dong SD, Oberthur M, Losey HC, et al. The structural basis for induction of VanB resistance. J Am Chem Soc 2002 Aug 7; 124(31): 9064–5PubMedCrossRefGoogle Scholar
  130. 130.
    Nicolaou KC, Hughes R, Cho SY, et al. Synthesis and biological evaluation of vancomycin dimers with potent activity against vancomycin-resistant bacteria: target-accelerated combinatorial synthesis. Chemistry 2001 Sep 3; 7(17): 3824–43PubMedCrossRefGoogle Scholar
  131. 131.
    Griffin J, Linsell M, Nodwell M, et al. Multivalent drug design: vancomycin dimers [abstract no. F-369]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  132. 132.
    Sun B, Chen Z, Eggert US, et al. Hybrid glycopeptide antibiotics. J Am Chem Soc 2001 Dec 19; 123(50): 12722–3PubMedCrossRefGoogle Scholar
  133. 133.
    Chiosis G, Boneca IG. Selective cleavage of D-Ala-D-Lac by small molecules: re-sensitizing resistant bacteria to vancomycin. Science 2001 Aug 24; 293(5534): 1484–7PubMedCrossRefGoogle Scholar
  134. 134.
    Wu Z, Walsh CT. Phosphinate analogs of D-, D-dipeptides: slow-binding inhibition and proteolysis protection of VanX, a D-, D-dipeptidase required for vancomycin resistance in Enterococcus faecium. Proc Natl Acad Sci U S A 1995 Dec 5; 92(25): 11603–7PubMedCrossRefGoogle Scholar
  135. 135.
    Yang KW, Brandt JJ, Chatwood LL, et al. Phosphonamidate and phosphothioate dipeptides as potential inhibitors of VanX. Bioorg Med Chem Lett 2000 May 15; 10(10): 1085–7PubMedCrossRefGoogle Scholar
  136. 136.
    InterMune Inc. [online]. Available from URL: [Accessed 2004 Jan 1]
  137. 137.
    Nagarajan R. Antibacterial activities and modes of action of vancomycin and related glycopeptides. Antimicrob Agents Chemother 1991 Apr; 35(4): 605–9PubMedCrossRefGoogle Scholar
  138. 138.
    Sanchez-Silos RM, Perez-Giraldo C, Blanco MT, et al. Resistance to vancomycin, LY333328, ciprofloxacin and trovafloxacin of community-acquired and nosocomial strains of Enterococcus faecalis isolated in Badajoz (Spain) with and without high-level resistance to streptomycin and gentamicin. Chemotherapy 2001 Dec; 47(6): 415–20PubMedCrossRefGoogle Scholar
  139. 139.
    Arthur M, Depardieu F, Reynolds P, et al. Moderate-level resistance to glycopeptide LY333328 mediated by genes of the vanA and vanB clusters in enterococci. Antimicrob Agents Chemother 1999 Aug; 43(8): 1875–80PubMedGoogle Scholar
  140. 140.
    Aslangul E, Baptista M, Fantin B, et al. Selection of glycopeptide-resistant mutants of VanB-type Enterococcus faecalis BM4281 in vitro and in experimental endocarditis. J Infect Dis 1997 Mar; 175(3): 598–605PubMedCrossRefGoogle Scholar
  141. 141.
    Wilson P, Koshy C, Minassian M. An LY333328-dependent strain of Enterococcus faecalis isolated from a blood culture. J Antimicrob Chemother 1998 Sep; 42(3): 406–7PubMedCrossRefGoogle Scholar
  142. 142.
    Coyle EA, Rybak MJ. Activity of oritavancin (LY333328), an investigational glycopeptide, compared to that of vancomycin against multidrug-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model. Antimicrob Agents Chemother 2001 Mar; 45(3): 706–9PubMedCrossRefGoogle Scholar
  143. 143.
    Mercier RC, Houlihan HH, Rybak MJ. Pharmacodynamic eval-uation of a new glycopeptide, LY333328, and in vitro activity against Staphylococcus aureus and Enterococcus faecium. Antimicrob Agents Chemother 1997 Jun; 41(6): 1307–12PubMedGoogle Scholar
  144. 144.
    Hershberger E, Aeschlimann JR, Moldovan T, et al. Evaluation of bactericidal activities of LY333328, vancomycin, teico-planin, ampicillin-sulbactam, trovafloxacin, and RP59500 alone or in combination with rifampin or gentamicin against different strains of vancomycin-intermediate Staphylococcus aureus by time-kill curve methods. Antimicrob Agents Chemother 1999 Mar; 43(3): 717–21PubMedGoogle Scholar
  145. 145.
    Zelenitsky SA, Booker B, Laing N, et al. Synergy of an investigational glycopeptide, LY333328, with once-daily gentamicin against vancomycin-resistant Enterococcus faecium in a multiple-dose, in vitro pharmacodynamic model. An-timicrob Agents Chemother 1999 Mar; 43(3): 592–7Google Scholar
  146. 146.
    Baltch AL, Smith RP, Ritz WJ, et al. Comparison of inhibitory and bactericidal activities and postantibiotic effects of LY333328 and ampicillin used singly and in combination against vancomycin-resistant Enterococcus faecium. An-timicrob Agents Chemother 1998 Oct; 42(10): 2564–8Google Scholar
  147. 147.
    Mercier RC, Stumpo C, Rybak MJ. Effect of growth phase and pH on the in vitro activity of a new glycopeptide, oritavancin (LY333328), against Staphylococcus aureus and Enterococcus faecium. J Antimicrob Chemother 2002 Jul; 50(1): 19–24PubMedCrossRefGoogle Scholar
  148. 148.
    Zhanel GG, Kirkpatrick ID, Hoban DJ, et al. Influence of human serum on pharmacodynamic properties of an investiga-tional glycopeptide, LY28, and comparator agents against Staphylococcus aureus. Antimicrob Agents Chemother 1998 Sep; 42(9): 2427–30PubMedGoogle Scholar
  149. 149.
    Van Bambeke F, Snoeck AS, Chanteux H, et al. Is LY333328 glycopeptide a new cell-associated antibiotic?: comparative studies with vancomycin and azithromycin in a model of J774 mouse macrophages [abstract no. 1245]. 11th European Congress of Clinical Microbiology and Infectious Diseases; 2001 Apr 1–4; Istanbul, TurkeyGoogle Scholar
  150. 150.
    Kaatz GW, Seo SM, Aeschlimann JR, et al. Efficacy of LY333328 against experimental methicillin-resistant Staphylococcus aureus endocarditis. Antimicrob Agents Chemother 1998 Apr; 42(4): 981–3PubMedGoogle Scholar
  151. 151.
    Cabellos C, Fernandez A, Maiques JM, et al. Experimental study of LY333328 (oritavancin), alone and in combination, in therapy of cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 2003 Jun; 47(6): 1907–11PubMedCrossRefGoogle Scholar
  152. 152.
    Gerber J, Smirnov A, Wellmer A, et al. Activity of LY333328 in experimental meningitis caused by a Streptococcus pneumoniae strain susceptible to penicillin. Antimicrob Agents Chemother 2001 Jul; 45(7): 2169–72PubMedCrossRefGoogle Scholar
  153. 153.
    Rupp ME, Fey PD, Longo GM. Effect of LY333328 against vancomycin-resistant Enterococcus faecium in a rat central venous catheter-associated infection model. J Antimicrob Chemother 2001 May; 47(5): 705–7PubMedCrossRefGoogle Scholar
  154. 154.
    Saleh-Mghir A, Lefort A, Petegnief Y, et al. Activity and diffusion of LY333328 in experimental endocarditis due to vancomycin-resistant Enterococcus faecalis. Antimicrob Agents Chemother 1999 Jan; 43(1): 115–20PubMedCrossRefGoogle Scholar
  155. 155.
    Lefort A, Saleh-Mghir A, Garry L, et al. Activity of LY333328 combined with gentamicin in vitro and in rabbit experimental endocarditis due to vancomycin-susceptible or -resistant Enterococcus faecalis. Antimicrob Agents Chemother 2000 Nov; 44(11): 3017–21PubMedCrossRefGoogle Scholar
  156. 156.
    Al Nawas B, Swantes J, Shah PM. In vitro activity of LY333328, a new glycopeptide, against extracellular and intracellular vancomycin-resistant enterococci. Infection 2000 Jul; 28(4): 214–8PubMedCrossRefGoogle Scholar
  157. 157.
    Al Nawas B, Shah PM. Intracellular activity of vancomycin and LY333328, a new semisynthetic glycopeptide, against methicillin-resistant Staphylococcus aureus. Infection 1998 May; 26(3): 165–7CrossRefGoogle Scholar
  158. 158.
    Seral C, Van Bambeke F, Tulkens PM. Quantitative analysis of the activity of antibiotics (gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, oritavancin [LY333328]) against intracellular Staphylococcus aureus in mouse J774 macrophages. Antimicrob Agents Chemother 2003; 47(7): 2283–92PubMedCrossRefGoogle Scholar
  159. 159.
    Loutit JS. Mode of action and current status of the glycopeptide oritavancin [abstract no. 617]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  160. 160.
    Wasilewski MM, Disch DP, McGill JM, et al. Equivalence of shorter course therapy with oritavancin vs vancomycin/ cephalexin in complicated skin/skin structure infections [abstract no. UL-18]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–18; Chicago (IL)Google Scholar
  161. 161.
    Barrett JF. Oritavancin: Eli Lilly & Co. Curr Opin Investig Drugs 2001 Aug; 2(8): 1039–44PubMedGoogle Scholar
  162. 162.
    Van Bambeke F, Saffian J, Mingeot-Leclercq MP, et al. Oritavancin glycopeptide causes a lipid storage disorder and mixed morphological alterations of the vacuolar system in cultured rat embryo fibroblasts (FB) and J774 mouse macrophages (M) [abstract no. 2180]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  163. 163.
    Vicuron Pharmaceuticals, Inc. [online]. Available from URL: [Accessed 2004 Jan 1]
  164. 164.
    Malabarba A, Ciabatti R, Kettenring J, et al. Amides of deacetylglucosaminyl-deoxy teicoplanin active against highly glycopeptide-resistant enterococci: synthesis and antibacterial activity. J Antibiot (Tokyo) 1994 Dec; 47(12): 1493–506CrossRefGoogle Scholar
  165. 165.
    Malabarba A, Ciabatti R, Scotti R, et al. New semisynthetic glycopeptides MDL 63,246 and MDL 63,042, and other amide derivatives of antibiotic A-40,926 active against highly glycopeptide-resistant VanA enterococci. J Antibiot (Tokyo) 1995 Aug; 48(8): 869–83CrossRefGoogle Scholar
  166. 166.
    Lopez S, Hackbarth CJ, White R, et al. In vitro susceptibility and population analysis of staphylococci after serial passage at sub-MIC levels of dalbavancin and other glycopeptides [abstract no. P1539]. 13th European Congress of Clinical Microbiology and Infectious Diseases; 2003 May 10–13; GlasgowGoogle Scholar
  167. 167.
    Candiani GP, Romano G, Brunati C, et al. Efficacy of a single dalbavancin dose compared with multiple linezolid doses against penicillin-resistant pneumococci in a lobar pneumonia model in the immunocompetent rat [abstract no. 989]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–18; Chicago (IL)Google Scholar
  168. 168.
    Lefort A, Pavie J, Garry L, et al. Activity of dalbavancin (BI 397) in vitro and in experimental endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) susceptible or intermediate to glycopeptides (GISA) [abstract no. B-278]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  169. 169.
    Seltzer E, Dorr MB, Goldstein BP, et al., for the Dalbavancin Skin and Soft-Tissue Infection Study Group. Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. Clin Infect Dis 2003 Nov 15; 37(10): 1298–303PubMedCrossRefGoogle Scholar
  170. 170.
    Dowell JA, Seltzer E, Stogniew M, et al. Dalbavancin dosage adjustments not required for patients with mild renal impairment [abstract no. P1224]. 13th European Congress of Clinical Microbiology and Infectious Diseases; 2003 May 10–13; Glasgow, UKGoogle Scholar
  171. 171.
    Felmingham D, Reinert RR, Hirakata Y, et al. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and comparative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother 2002 Sep; 50 Suppl. S1: 25–37CrossRefGoogle Scholar
  172. 172.
    Vandecasteele SJ, Verhaegen J, Colaert J, et al. Failure of cefotaxime and meropenem to eradicate meningitis caused by an intermediately susceptible Streptococcus pneumoniae strain. Eur J Clin Microbiol Infect Dis 2001 Oct; 20(10): 751–2PubMedGoogle Scholar
  173. 173.
    Buckingham SC, Davis Y, English BK. Pneumococcal susceptibility to meropenem in a mid-south children’s hospital. South Med J 2002 Nov; 95(11): 1293–6PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Françoise Van Bambeke
    • 1
    Email author
  • Yves Van Laethem
    • 2
  • Patrice Courvalin
    • 3
  • Paul M. Tulkens
    • 1
  1. 1.Unité de Pharmacologie cellulaire et moléculaireUniversité Catholique de LouvainBrusselsBelgium
  2. 2.Service des Maladies InfectieusesHôpital Saint PierreBrusselsBelgium
  3. 3.Unité des Agents AntibactériensInstitut PasteurParisFrance

Personalised recommendations