Vancomycin Pharmacokinetic Parameters in Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT).
AbstractBackground: Vancomycin is used abundantly in patients undergoing HSCT, especially during neutropenic fever. Despite its widespread use little is known about vancomycin pharmacokinetics in HSCT patients. We conducted this study to investigate vancomycin pharmacokinetic parameters in our HSCT patients and to evaluate current dosing regimen based on trough vancomycin concentrations measurement.
Methods: Vancomycin serum concentration at steady-state was determined prospectively in 46 adult HSCT patients who received vancomycin as empirical treatment of neutropenic fever. Individual steady-steady pharmacokinetic parameters were also determined in 20 patients who had two vancomycin levels from an administered dose, assuming one-compartment model. Acute kidney injury was also evaluated in our patients during vancomycin therapy.
Results: Mean (±SD) apparent volume of distribution (L/kg) and clearance (mL/min) were 0.6 (± 0.33) and 109.7 (± 57.5) respectively. With mean (±SD) total daily dose of vancomycin 31.9 (±10.5) mg/kg/day that was administered, more than 90 % of measured vancomycin trough concentrations were outside the range of 15-20 mg/L and 54.3% of patients had trough concentrations below 10 mg/L. Of 46 patients, 21 patients (45.7%) developed acute kidney injury (AKI) during vancomycin therapy; among them 19 patients were receiving nephrotoxic drug(s) concomitantly.
Conclusion: Current vancomycin dosage regimen could not lead to recommended therapeutic serum concentrations in our patients. Large variation in vancomycin pharmacokinetic parameters observed among patients of this study along with difference of vancomycin pharmacokinetics in our study and other similar studies further explain the need for therapeutic drug monitoring and individualization of vancomycin dosing.
Majhail N, Weisdorf D. Complications after hematopoietic cell transplantation. In: Hoffmann R, Benz Jr EJ, Shattil SJ, Furie B, Silberstein LE, McGlave P, Heslop H. Hematology: Basic Principles and Practice. 5th ed. New York: Elsevier; 2009. p. 1755–70.
Engels EA, Ellis CA, Supran SE, Schmid CH, Barza M, Schenkein DP, et al. Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk. Clin Infect Dis; 1999. 28: 256–266.
Bock AM, Cao Q, Ferrieri P, Young JA, Weisdorf DJ. Bacteremia in blood or marrow transplantation patients: clinical risk factors for infection and emerging antibiotic resistance. Biol Blood Marrow Transplant; 2013. 19(1): 102–8.
Paul M, Borok S, Fraser A, Vidal L, Leibovici L. Empirical antibiotics against Gram positive infections for febrile neutropenia: systematic review and metaanatysis of randomized controlled trials. J Anlimicrob Chemother; 2005. 55: 436–44.
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis; 2011. 52: e56–e93.
de Naurois J, Novitzky-Basso I, Gill M, Marti M, Cullen M, Roila F, & ESMO Guidelines Working Group. Management of febrile neutropenia: ESMO clinical practice guidelines. Annals of Oncology; 2010. 21(5, Suppl.): v252–v256.
Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC, Craig WA, Billeter M, et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health–System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis; 2009. 49: 325–7.
Le Normand Y, Milpied N, Kergueris MF, Harousseau JL. Pharmacokinetic parameters of vancomycin for therapeutic regimens in neutropenic adult patients. Int JBiomed Comput; 1994. 36(1–2): 121–-5.
Pea F, Poz D, Baraldo M, Furlanut M. Optimisation of vancomycin regimen in neutropenic haematological patients with normal renal function: multiple daily doses may be preferable. Clin Drug Invest; 2000. 19(3): 213–8.
Fernández de Gatta MM, Fruns I, Hernández JM, Caballero D, San Miguel JF, Martínez Lanao J, Domínguez-Gil Hurlé A. Vancomycin pharmacokinetics and dosage requirements in hematologic malignancies. Clin Pharm; 1993. 12: 515–20.
Buelga DS, del Mar Fernandez de Gatta M, Herrera EV, Dominguez-Gil A, García MJ. Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies. Antimicrob Agents Chemother; 2005. 49(12): 4934–41.
Omote S, Yano Y, Hashida T, Masuda S, Yano I, Katsura T, Inui K. A retrospective analysis of vancomycin pharmacokinetics in Japanese cancer and non-cancer patients based on routine trough monitoring data. Biol Pharm Bull; 2009. 32(1): 99–104.
Lortholary O, Lefort A, Tod M, Chomat AM, Darras-Joly C, Cordonnier C; Club de Reflexion sur les Infections en Onco-Hématologie. Pharmacodynamics and pharmacokinetics of antibacterial drugs in the management of febrile neutropenia. Lancet Infect Dis. 2008; 8: 612–20.
Al-Kofide H, Zaghloul I, Al-Naim L. Pharmacokinetics of vancomycin in adult cancer patients. J Oncol Pharm Practice; 2010. 16: 245–250.
Teramachi H, Matsushita R and Tsuji A. Influence of malignancy on the pharmacokinetics of vancomycin hydrochloride in Japanese MRSA patients after dosage adjustment with the Bayesian method. Jpn J Chemotherapy; 2005. 53(6): 357–363 (in Japanese except Abstract ).
Cockcroft SW, Gault HM. Prediction of creatinine clearances from serum creatinine. Nephron; 1976. 16: 31–41.
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care; 2007. 11(2): R31.
Ambrose PJ, Winter ME. Vancomycin. In: Winter ME, Basic Clinical Pharmacokinetics. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 451–76.
Bauer LA. Applied clinical pharmacokinetics. 2end ed. New York: McGraw-Hill; 2008. p. 144–154.
Marra, F., B. Carins, and P. Jewesson. Vancomycin serum concentration monitoring. The middle ground is best. Clin Drug Investig; 1996. 12: 105–118.
NCCN CPGiO. Prevention and treatment of cancer-related infections. v.1 2012.
Hayatshahi A, Javadi M, Torkamandi M, Hadjibabaie M, Alahyari S, Gholami K, et al. Drug utilization review of vancomycin in febrile neutropenic patients hospitalized at a bone marrow transplantation center. IJHOSCR; 2010. 4(3): 10–13.
Vazin A, Japoni A, Shahbazi S, Davarpanah MA. Vancomycin utilization evaluation at hematology- oncology ward of a teaching hospital in Iran. IJPR; 2012. 11(1): 163–170.
Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol; 2009. 4(2): 481-508.
Harbarth S, Pestotnik SL, Lloyd JF, Burke JP, Samore MH. The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy. Am J Med; 2001. 111(7): 528–34.
Hodoshima N, Masuda S, Inui K. Decreased renal accumulation and toxicity of a new VCM formulation in rats with chronic renal failure. Drug Metab Pharmacokinet; 2007. 22: 419–427.
Elting LS, Rubenstein EB, Kurtin D. Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer; 1998. 83: 2597–607.
van Hal SJ, Paterson DL, Lodise TP. Vancomycin-induced nephrotoxicity in troughs of “15-20” mg/L era: a systematic review and meta-analysis. Antimicrob Agents Chemother; 2013. 57(2): 734–44.
Saddadi F, Najafi I, Hakemi MS, Falaknazi K, Attari F, Bahar B. Frequency, risk factors, and outcome of acute kidney injury following bone marrow transplantation at Dr Shariati hospital in Tehran. IJKD; 2010. 4(1): 20–6.
Schrier RW, Parikh CR. Comparison of renal injury in myeloablative autologous, myeloablative allogeneic and nonmyeloablative allogeneic haematopoietic cell transplantation. Nephrol Dial Transplant; 2005. 20: 678–683.
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