Advertisement

Clinical Drug Investigation

, Volume 19, Issue 3, pp 213–218 | Cite as

Optimisation of Vancomycin Regimen in Neutropenic Haematological Patients with Normal Renal Function

Multiple Daily Doses May Be Preferable
  • Federico Pea
  • Donatella Poz
  • Massimo Baraldo
  • Mario Furlanut
Clinical Pharmacokinetics

Abstract

Objective: To assess the appropriateness, on a pharmacokinetic basis, of a twice-daily regimen of vancomycin 1g in neutropenic patients with normal renal function, a regimen frequently used in the empirical treatment of this patient group. The study also used a Bayesian pharmacokinetic approach to predict vancomycin concentrations in order to determine the optimal dosage frequency of the drug (two or four daily doses) in this population.

Patients and Methods: Data were collected retrospectively as part of routine therapeutic drug monitoring (TDM) of vancomycin in 16 adult neutropenic patients. TDM of vancomycin peak (Cmax) and trough (Cmin) serum concentrations was performed after twice daily administration of vancomycin lg as a 1-hour intravenous infusion for 48 hours. According to TDM results (Cmin≥7 or <7 mg/L), the vancomycin regimen was individualised (total daily dose split into two or four divided doses) by means of a Bayesian-based pharmacokinetic computer programme. TDM was then repeated on day 7. Optimal Cmin were defined as with the range of 7 to 10 mg/L.

Results: On day 3 of therapy, nine patients had subtherapeutic Cmin (3.97 ± 0.59 mg/L; range 2.98 to 4.95 mg/L) according to ahigh estimated creatinine clearance (CLcr 1.79 ± 0.49 ml/kg/min; range 1.39 to 2.79 ml/kg/min), and another three patients had Cmin <7 mg/L. On day 7, higher vancomycin Cmin were achieved (8.92 ± 2.87 mg/L) in the 12 patients in whom their total daily dose was split into four (Cmin were optimal in nine and supratherapeutic in three patients), despite no major differences in the total daily dosage of vancomycin (29.77 ± 5.89 vs 30.85 ± 6.68 mg/kg; p = 0.79) and CLcr (1.63 ± 0.43 vs 1.90 ± 0.45 ml/kg/min; p = 0.19) versus day 3. Dose-normalised results suggested large interindividual pharmacokinetic variability.

Conclusion: Since the volume of distribution and/or clearance of vancomycin can be increased in patients with haematological malignancies and normal renal function, increasing the number of daily doses from two to four (with the same total daily dose) may increase t > MIC, an important determinant of vancomycin efficacy. However, because of interpatient variability, TDM of vancomycin is strongly recommended to individualise therapy in this subpopulation.

Keywords

Minimal Inhibitory Concentration Vancomycin Therapeutic Drug Monitoring Normal Renal Function Total Daily Dose 
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.

References

  1. 1.
    Wilhelm MR. Vancomycin. Mayo Clin Proc 1991; 66: 1165–70PubMedCrossRefGoogle Scholar
  2. 2.
    Healy DP, Polk RE, Garson ML, et al. Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers. Antimicrob Agents Chemother 1987; 31: 393–7PubMedCrossRefGoogle Scholar
  3. 3.
    Moellering Jr RC. Pharmacokinetics of vancomycin. J Antimicrob Chemother 1984; 14Suppl. D: 43–52PubMedCrossRefGoogle Scholar
  4. 4.
    Welty TE, Copa AK. Impact of vancomycin therapeutic drug monitoring on patient care. Ann Pharmacother 1994; 28: 1335–9PubMedGoogle Scholar
  5. 5.
    Marra F, Cairns B, Jewesson P. Vancomycin serum concentration monitoring. The middle ground is best. Clin Drug Invest 1996; 12: 105–18CrossRefGoogle Scholar
  6. 6.
    Leader WG, Chandler MHH, Castiglia M. Pharmacokinetic optimisation of vancomycin therapy. Clin Pharmacokinet 1995; 28: 327–42PubMedCrossRefGoogle Scholar
  7. 7.
    Pea F, Porreca P, Baraldo M, et al. High vancomycin dosage regimens required by intensive care unit admitted patients cotreated with drugs improving haemodynamics following cardiac surgical procedures. J Antimicrob Chemother. In pressGoogle Scholar
  8. 8.
    Pauly DJ, Musa DM, Lestico MR, et al. Risk of nephrotoxicity with combination vancomycin-aminoglycoside antibiotic therapy. Pharmacotherapy 1990; 10: 378–82PubMedGoogle Scholar
  9. 9.
    Rybak MJ, Albrecht LM, Boike SC, et al. Nephrotoxicity of vancomycin, alone and with an aminoglycoside. J Antimicrob Chemother 1990; 25: 679–87PubMedCrossRefGoogle Scholar
  10. 10.
    Craig W. Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. Eur J Microbiol Infect Dis 1993; 12Suppl. 1: 6–8Google Scholar
  11. 11.
    Ackerman BH, Vannier AM, Eudy EB. Analysis of vancomycin time-kill studies with Staphylococcus species by using a curve stripping program to describe the relationship between concentration and pharmacodynamic response. Antimicrob Agents Chemother 1992; 36: 1766–9PubMedCrossRefGoogle Scholar
  12. 12.
    Rotschafer JC, Zabinski RA, Walker KJ. Pharmacodynamic factors of antibiotic efficacy. Pharmacotherapy 1992; 12: Suppl.: 64S–70SPubMedGoogle Scholar
  13. 13.
    MacGowan AP. Pharmacodynamics, pharmacokinetics, and therapeutic drug monitoring of glycopeptides. Ther Drug Monitor 1998; 20: 473–7CrossRefGoogle Scholar
  14. 14.
    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 Entemcoccus faecalis. Pharmacotherapy 1998; 18: 1069–74PubMedGoogle Scholar
  15. 15.
    Soto J, Alsar MJ, Chantai P, et al. Correlation of vancomycin clearance and creatinine clearance: unreliability for predicting initial dosing in neutropenic haematological patients. J Antimicrob Chemother 1993; 32: 920–2PubMedCrossRefGoogle Scholar
  16. 16.
    Fernandez de Gatta MM, Fruns I, Hernandez JM, et al. Vancomycin pharmacokinetics and dosage requirements in hematologic patients. Clin Pharm 1993; 12: 515–20PubMedGoogle Scholar
  17. 17.
    Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41CrossRefGoogle Scholar
  18. 18.
    Schwenzer KS, Wang CHJ, Anhalt JP. Automated fluorescence polarization immunoassay for monitoring vancomycin. Ther Drug Monitor 1983; 5: 341–5CrossRefGoogle Scholar
  19. 19.
    Poirier TH, Gindici RA. Survey of clinical pharmacokinetic software for microcomputers. Hosp Pharm 1992; 27: 971–7PubMedGoogle Scholar
  20. 20.
    Saunders NJ. Vancomycin administration and monitoring reappraisal. J Antimicrob Chemother 1995; 36: 279–82PubMedCrossRefGoogle Scholar
  21. 21.
    Begg EJ, Barclay ML, Kirkpatrick CJM. The therapeutic monitoring of antimicrobial agents. Br J Clin Pharmacol 1999; 47: 23–30PubMedCrossRefGoogle Scholar
  22. 22.
    Zimmermann AE, Katona BG, Plaisance KI. Association of vancomycin serum concentrations with outcomes in patients with Gram-positive bacteriemia. Pharmacotherapy 1995; 15: 85–91PubMedGoogle Scholar
  23. 23.
    Mulhern JG, Braden GL, O’Shea MH, et al. Trough serum vancomycin levels predict the relapse of Gram-positive peritonitis in peritoneal dialysis patients. Am J Kidney Dis 1995; 25: 611–5PubMedCrossRefGoogle Scholar
  24. 24.
    Karam CM, McKinnon PS, Neuhauser MM, et al. Outcome assessment of minimizing vancomycin monitoring and dosage adjustments. Pharmacotherapy 1999; 19(3): 257–66PubMedCrossRefGoogle Scholar
  25. 25.
    Cimino MA, Rotstein C, Slaughter RL, et al. Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy. Am J Med 1987; 83: 1091–6PubMedCrossRefGoogle Scholar
  26. 26.
    Rybak MJ, Albrecht LM, Boike SC, et al. Nephrotoxicity of vancomycin, alone and with an aminoglycoside. J Antimicrob Chemother 1990; 25: 679–87PubMedCrossRefGoogle Scholar
  27. 27.
    Dufull SB, Begg EJ. Vancomycin toxicity. What is the evidence for dose dependency? Adverse Drug React Toxicol Rev 1994; 13: 103–14Google Scholar
  28. 28.
    Kralovicova K, Spanik S, Halko J, et al. Do vancomycin serum levels predict failures of vancomycin therapy or nephrotoxicity in cancer patients? J Chemother 1997; 9: 420–6PubMedGoogle Scholar
  29. 29.
    Fantin B, Ebert S, Leggett J, et al. Factors affecting duration of in vivo postantibiotic effect for aminoglycosides against Gram-negative bacilli. J Antimicrob Chemother 1991; 27: 829–36PubMedCrossRefGoogle Scholar
  30. 30.
    Gilbert DN. Once-daily aminoglycoside therapy. Antimicrob Agents Chemother 1991; 35: 399–405PubMedCrossRefGoogle Scholar
  31. 31.
    Dufull SB, Chambers ST, Begg EJ. How vancomycin is used in clinical practice — a survey. Aust NZ J Med 1993; 23: 662–6CrossRefGoogle Scholar
  32. 32.
    Saunders NJ. Why monitor peak vancomycin concentrations. Lancet 1994; 344: 1748–50PubMedCrossRefGoogle Scholar
  33. 33.
    Higa GM, Murray WE. Alterations in aminoglycoside pharmacokinetics in patients with cancer. Clin Pharm 1987; 6: 963–6PubMedGoogle Scholar
  34. 34.
    Kaojarern S, Maoleekoonpairoy S, Atichartakarn V Pharmacokinetics of amikacin in hematologic malignancies. Antimicrob Agents Chemother 1989; 33: 1406–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Federico Pea
    • 1
  • Donatella Poz
    • 1
  • Massimo Baraldo
    • 1
  • Mario Furlanut
    • 1
  1. 1.Institute of Clinical Pharmacology and ToxicologyDPMSC, University of UdineUdineItaly

Personalised recommendations