Clinical Pharmacokinetics

, Volume 43, Issue 6, pp 405–415 | Cite as

Teicoplanin in Patients with Acute Leukaemia and Febrile Neutropenia

A Special Population Benefiting from Higher Dosages
  • Federico Pea
  • Pierluigi Viale
  • Anna Candoni
  • Federica Pavan
  • Leonardo Pagani
  • Daniela Damiani
  • Marco Casini
  • Mario Furlanut
Original Research Article



To define the optimal dosage regimen of teicoplanin that ensures early therapeutically relevant trough concentrations (Cmin) [>10 mg/L at 24 hours and possibly close to 20 mg/L at 48 hours] in patients with acute leukaemia who develop febrile neutropenia after chemotherapy.


Prospective observational pharmacokinetic study.


Adult patients (n = 33) with normal renal function previously treated with antineoplastic chemotherapy because of acute lymphocytic or acute nonlymphocytic leukaemia, and subsequently developing febrile neutropenia treated with empirical antimicrobial therapy.


First, the standard dosage group (n= 11) was administered standard loading and maintenance doses of teicoplanin (400mg every 12 hours for three doses followed by 400mg once daily). Blood samples were collected at defined times as part of routine monitoring and assessed for teicoplanin plasma concentration by fluorescence polarisation immunoassay. Secondly, the high dosage group (n = 22) received a high loading regimen (800 + 400mg 12 hours apart on day 1, 600 + 400mg 12 hours apart on day 2) followed by a high maintenance regimen (400mg every 12 hours) from day 3 on.


In the standard dosage group, no patient had the recommended teicoplanin Cmin of ≥10 mg/L within the first 72 hours, and only five of the 11 patients (45%) had a Cmin of ≥10 mg/L after 120 hours. No patient had a Cmin of ≥20 mg/L. In the high dosage group, teicoplanin Cmin averaged ≥10 mg/L within 24 hours, and this value was achieved within 48 hours in all but one patient. Of note, Cmin at 72 hours exceeded 20 mg/L in ten of the 22 patients (45%). No patient experienced significant impairment of renal function.


In this patient group, therapeutically relevant Cmin may be achieved very early in the treatment period with loading doses of 12 mg/kg and 6 mg/kg 12 hours apart on day 1, and 9 mg/kg and 6 mg/kg 12 hours apart on day 2, regardless of renal function. Subsequently, in patients with normal renal function a maintenance dosage of 6 mg/kg every 12 hours may be helpful in ensuring Cmin close to 20 mg/L. Assessment of Cmin after 48–72 hours may be useful to individualise teicoplanin therapy. Factors increasing volume of distribution and/or renal clearance of teicoplanin (fluid load, hypoalbuminaemia, leukaemic status) may explain the need for higher dosages.


Therapeutic Drug Monitoring Normal Renal Function Teicoplanin Acute Leukaemia High Dosage Group 
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The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this study.


  1. 1.
    Viscoli C, Castagnola E. Treatment of febrile neutropenia: what is new?. Curr Opin Infect Dis 2002; 15(4): 377–82PubMedCrossRefGoogle Scholar
  2. 2.
    Horvathova Z, Spanik S, Sufliarsky J, et al. Bacteremia due to methicillin-resistant staphylococci occurs more frequently in neutropenic patients who received antimicrobial prophylaxis and is associated with higher mortality in comparison to methicillin-sensitive bacteriemia. Int J Antimicrob Agents 1998; 10(1): 55–8PubMedCrossRefGoogle Scholar
  3. 3.
    Pagano L, Tacconelli E, Tumbarello M, et al. Bacteremia in patients with hematological malignancies: analysis of risk factors, etiological agents and prognostic indicators. Haematologica 1997; 82(4): 415–9PubMedGoogle Scholar
  4. 4.
    Davies JM. A review of the use of teicoplanin in haematological malignancy. Eur J Haematol Suppl 1998; 62: 2–5PubMedGoogle Scholar
  5. 5.
    Egerer G, Goldschmidt H, Streich N, et al. Ceftazidime in combination with glycopeptide antibiotic is an effective first-line therapy for patients undergoing high-dose therapy with autologous peripheral blood stem cell support. Support Care Cancer 1999; 7(5): 336–42PubMedCrossRefGoogle Scholar
  6. 6.
    Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002; 34(6): 730–51PubMedCrossRefGoogle Scholar
  7. 7.
    Gonzalez-Barca E, Carratala J, Mykietiuk A, et al. Predisposing factors and outcome of staphylococcus aureus bacteremia in neutropenic patients with cancer. Eur J Clin Microbiol Infect Dis 2001; 20(2): 117–9PubMedGoogle Scholar
  8. 8.
    Kaojarern S, Maoleekoonpairoj S, Atichartakarn V. Pharmacokinetics of amikacin in hematologic malignancies. Antimicrob Agents Chemother 1989; 33(8): 1406–8PubMedCrossRefGoogle Scholar
  9. 9.
    Tod M, Lortholary O, Seytre D, et al. Population pharmacokinetic study of amikacin administered once or twice daily to febrile, severely neutropenic adults. Antimicrob Agents Chemother 1998; 42(4): 849–56PubMedGoogle Scholar
  10. 10.
    Romano S, Fernandez de Gatta MM, Calvo MV, et al. Population pharmacokinetics of amikacin in patients with haematological malignancies. J Antimicrob Chemother 1999; 44(2): 235–42PubMedCrossRefGoogle Scholar
  11. 11.
    Zeitany RG, el Saghir NS, Santhosh-Kumar CR, et al. Increased aminoglycoside dosage requirements in hematologic malignancy. Antimicrob Agents Chemother 1990; 34(5): 702–8PubMedCrossRefGoogle Scholar
  12. 12.
    Nyhlen A, Ljungberg B, Nilsson-Ehle I. Pharmacokinetics of ceftazidime in febrile neutropenic patients. Scand J Infect Dis 2001; 33(3): 222–6PubMedCrossRefGoogle Scholar
  13. 13.
    Fernandez de Gatta MM, Fruns I, Hernandez JM, et al. Vancomycin pharmacokinetics and dosage requirements in hematologic malignancies. Clin Pharm 1993; 12(7): 515–20Google Scholar
  14. 14.
    Lortholary O, Tod M, Rizzo N, et al. Population pharmacokinetic study of teicoplanin in severely neutropenic patients. Antimicrob Agents Chemother 1996; 40(5): 1242–7PubMedGoogle Scholar
  15. 15.
    Pea F, Brollo L, Viale P, et al. Teicoplanin therapeutic drug monitoring in the critically ill patients: a retrospective study emphasizing the importance of a loading-dose. J Antimicrob Chemother 2003; 51(4): 971–5PubMedCrossRefGoogle Scholar
  16. 16.
    Wilson APR, Gruneberg RN, Neu H. A critical review of the dosage of teicoplanin in Europe and the USA. Int J Antimicrob Agents 1994; 4 Suppl. 1: S1–S30CrossRefGoogle Scholar
  17. 17.
    Begg EJ, Barclay ML, Kirkpatrick CM. The therapeutic monitoring of antimicrobial agents. Br J Clin Pharmacol 2001; 52 Suppl. 1: 35S–43SPubMedCrossRefGoogle Scholar
  18. 18.
    Schaison G, Graninger W, Bouza E. Teicoplanin in the treatment of serious infection. J Chemother 2000; 12 Suppl. 5: 26–33PubMedGoogle Scholar
  19. 19.
    Wilson AP. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet 2000; 39(3): 167–83PubMedCrossRefGoogle Scholar
  20. 20.
    Wilson AP, Gruneberg RN, Neu H. Dosage recommendations for teicoplanin. J Antimicrob Chemother 1993; 32(6): 792–6PubMedCrossRefGoogle Scholar
  21. 21.
    MacGowan AP, White LO, Reeves DS, et al. A retrospective review of serum teicoplanin concentrations in clinical trials and their relationship to clinical outcome. J Infect Chemother 1998; 2: 197–208CrossRefGoogle Scholar
  22. 22.
    MacGowan AP, Bowker KE. Pharmacodynamics of antimicrobial agents and rationale for their dosing. J Chemother 1997; 9 Suppl. 1: 64–73PubMedGoogle Scholar
  23. 23.
    Weinbren M, Struthers K. Emergence of Staphylococcus aureus (MRSA) with reduced susceptibility to teicoplanin during therapy. J Antimicrob Chemother 2002; 50(2): 306–7PubMedCrossRefGoogle Scholar
  24. 24.
    Cercenado E, Garcia-Leoni ME, Diaz MD, et al. Emergence of teicoplanin-resistant coagulase-negative staphylococci. J Clin Microbiol 1996; 34(7): 1765–8PubMedGoogle Scholar
  25. 25.
    Cunningham R, Gurnell M, Bayston R, et al. Teicoplanin resistance in Staphylococcus haemolyticus, developing during treatment. J Antimicrob Chemother 1997; 39(3): 438–9PubMedCrossRefGoogle Scholar
  26. 26.
    Pagano L, Tacconelli E, Tumbarello M, et al. Teicoplanin-resistant coagulase-negative staphylococcal bacteraemia in patients with haematological malignancies: a problem of increasing importance. J Antimicrob Chemother 1997; 40(5): 738–40PubMedCrossRefGoogle Scholar
  27. 27.
    Sloos JH, Dijkshoorn L, van Boven CP. Septicaemias caused by a strain of staphylococcus haemolyticus exhibiting intermediate susceptibility to teicoplanin in multiple intensive care unit patients. J Antimicrob Chemother 2000; 45(3): 410–1PubMedCrossRefGoogle Scholar
  28. 28.
    Torney HL, Balistreri FJ, Kenny MT, et al. Comparative therapeutic efficacy of teicoplanin and vancomycin in normal and in neutropenic mice infected with staphylococcus haemolyticus. J Antimicrob Chemother 1991; 28(2): 261–9PubMedCrossRefGoogle Scholar
  29. 29.
    Gimenez F, Leblond V, Nguyen J, et al. Variations of teicoplanin concentrations in neutropenic patients. J Clin Pharm Ther 1997; 22(3): 187–90PubMedCrossRefGoogle Scholar
  30. 30.
    Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16(1): 31–41PubMedCrossRefGoogle Scholar
  31. 31.
    Yamaoka K, Nakagawa T, Uno T. Application of Akaike’s information criterion ( AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 1978; 6(2): 165–75PubMedGoogle Scholar
  32. 32.
    Dykhuizen RS, Harvey G, Stephenson N, et al. Protein binding and serum bactericidal activities of vancomycin and teicoplanin. Antimicrob Agents Chemother 1995; 39(8): 1842–7PubMedCrossRefGoogle Scholar
  33. 33.
    Eriksson KM, Cederholm T, Palmblad JE. Nutrition and acute leukemia in adults: relation between nutritional status and infectious complications during remission induction. Cancer 1998; 82(6): 1071–7PubMedCrossRefGoogle Scholar
  34. 34.
    MacGowan AP. Pharmacodynamics, pharmacokinetics, and therapeutic drug monitoring of glycopeptides. Ther Drug Monit 1998; 20(5): 473–7PubMedCrossRefGoogle Scholar
  35. 35.
    Awni WM, St Peter WL, Guay DR, et al. Teicoplanin measurement in patients with renal failure: comparison of fluorescence polarization immunoassay, microbiological assay, and high-performance liquid chromatographic assay. Ther Drug Monit 1991; 13(6): 511–7PubMedCrossRefGoogle Scholar
  36. 36.
    Cox H, Whitby M, Nimmo G, et al. Evaluation of a novel fluorescence polarization immunoassay for teicoplanin. Antimicrob Agents Chemother 1993; 37(9): 1924–6PubMedCrossRefGoogle Scholar
  37. 37.
    Outman WR, Nightingale CH, Sweeney KR, et al. Teicoplanin pharmacokinetics in healthy volunteers after administration of intravenous loading and maintenance doses. Antimicrob Agents Chemother 1990; 34(11): 2114–7PubMedCrossRefGoogle Scholar
  38. 38.
    Pea F, Furlanut M, Poz D, et al. Pharmacokinetic profile of two different administration schemes of teicoplanin: single 400mg intravenous dose vs double-refracted 200mg intramuscular doses in healthy volunteers. Clin Drug Invest 1999; 18: 47–55CrossRefGoogle Scholar
  39. 39.
    Collin BA, Leather HL, Wingard JR, et al. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis 2001; 33(7): 947–53PubMedCrossRefGoogle Scholar
  40. 40.
    Sparrelid E, Hagglund H, Remberger M, et al. Bacteraemia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection. Bone Marrow Transplant 1998; 22(8): 795–800PubMedCrossRefGoogle Scholar
  41. 41.
    Tunkel AR, Sepkowitz KA. Infections caused by viridans streptococci in patients with neutropenia. Clin Infect Dis 2002; 34(11): 1524–9PubMedCrossRefGoogle Scholar
  42. 42.
    Schentag JJ. Antimicrobial management strategies for Grampositive bacterial resistance in the intensive care unit. Crit Care Med 2001; 29 (4 Suppl.): N100–7PubMedCrossRefGoogle Scholar
  43. 43.
    Elsaghier AA, Aucken HM, Hamilton-Miller JM, et al. Resistance to teicoplanin developing during treatment of methicillin-resistant Staphylococcus aureus infection. J Antimicrob Chemother 2002; 49(2): 423–4PubMedCrossRefGoogle Scholar
  44. 44.
    Hassan IA, Chadwick PR, Johnson AP. Clinical isolates of methicillin-resistant staphylococcus aureus (MRSA) with reduced susceptibility to teicoplanin in Northwest England. J Antimicrob Chemother 2001; 48(3): 454–5PubMedCrossRefGoogle Scholar
  45. 45.
    Fridkin SK. Vancomycin-intermediate and -resistant staphylococcus aureus: what the infectious disease specialist needs to know. Clin Infect Dis 2001; 32(1): 108–15PubMedCrossRefGoogle Scholar
  46. 46.
    Spanik S, Trupl J, Studena M, et al. Breakthrough nosocomial bacteraemia due to teicoplanin-resistant staphylococcus haemolyticus in five patients with acute leukaemia. J Hosp Infect 1997; 35(2): 155–9PubMedCrossRefGoogle Scholar
  47. 47.
    Ronchera-Oms CL, Tormo C, Ordovas JP, et al. Expanded gentamicin volume of distribution in critically ill adult patients receiving total parenteral nutrition. J Clin Pharm Ther 1995; 20(5): 253–8PubMedCrossRefGoogle Scholar
  48. 48.
    Nyhlen A, Ljungberg B, Nilsson-Ehle I. Pharmacokinetics of meropenem in febrile neutropenic patients: Swedish Study Group. Eur J Clin Microbiol Infect Dis 1997; 16(11): 797–802PubMedCrossRefGoogle Scholar
  49. 49.
    Rowland M. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet 1990; 18(3): 184–209PubMedCrossRefGoogle Scholar
  50. 50.
    Pea F, Furlanut M. Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions. Clin Pharmacokinet 2001; 40(11): 833–68PubMedCrossRefGoogle Scholar
  51. 51.
    Pea F, Brollo L, Lugano M, et al. Therapeutic drug monitoringguided high teicoplanin dosage regimen required to treat a hypoalbuminemic renal transplant patient undergoing continuous venovenous hemofiltration. Ther Drug Monit 2001; 23(5): 587–8PubMedCrossRefGoogle Scholar
  52. 52.
    Le Normand Y, Milpied N, Kergueris MF, et al. Pharmacokinetic parameters of vancomycin for therapeutic regimens in neutropenic adult patients. Int J Biomed Comput 1994; 36 (1–2): 121–5PubMedCrossRefGoogle Scholar
  53. 53.
    Chang D. Influence of malignancy on the pharmacokinetics of vancomycin in infants and children. Pediatr Infect Dis J 1995; 14(8): 667–73PubMedCrossRefGoogle Scholar
  54. 54.
    Cirillo M, Anastasio P, Spitali L, et al. Effects of a meat meal on renal sodium handling and sodium balance. Miner Electrolyte Metab 1998; 24(4): 279–84PubMedCrossRefGoogle Scholar
  55. 55.
    Charbonneau P, Harding I, Garaud JJ, et al. Teicoplanin: a well-tolerated and easily administered alternative to vancomycin for gram-positive infections in intensive care patients. Intensive Care Med 1994; 20 Suppl. 4: S35–42PubMedCrossRefGoogle Scholar
  56. 56.
    Wood MJ. Comparative safety of teicoplanin and vancomycin. J Chemother 2000; 12 Suppl. 5: 21–5PubMedGoogle Scholar
  57. 57.
    Fanos V, Mussap M, Khoory BJ, et al. Renal tolerability of teicoplanin in a case of neonatal overdose. J Chemother 1998; 10(5): 381–4PubMedGoogle Scholar
  58. 58.
    Sidi V, Roilides E, Bibashi E, et al. Comparison of efficacy and safety of teicoplanin and vancomycin in children with antineoplastic therapy-associated febrile neutropenia and gram-positive bacteremia. J Chemother 2000; 12(4): 326–31PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Federico Pea
    • 1
  • Pierluigi Viale
    • 2
  • Anna Candoni
    • 3
  • Federica Pavan
    • 1
  • Leonardo Pagani
    • 4
  • Daniela Damiani
    • 3
  • Marco Casini
    • 5
  • Mario Furlanut
    • 1
  1. 1.Department of Experimental and Clinical Pathology and Medicine, Medical School, Institute of Clinical Pharmacology and ToxicologyUniversity of UdineUdineItaly
  2. 2.Department of Medical and Morphological Research, Medical School, Clinic of Infectious DiseasesUniversity of UdineUdineItaly
  3. 3.Department of Medical and Morphologic Research, and Division of Hematology, Medical School, Chair of HematologyUniversity of UdineUdineItaly
  4. 4.Division of Infectious DiseasesBolzano General HospitalBolzanoItaly
  5. 5.Division of HematologyBolzano General HospitalBolzanoItaly

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