Enfermedad Hemato-Oncológica y Otros Factores Asociados con Niveles Subterapéuticos de Vancomicina en un Hospital de Alta Complejidad
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Introducción: La medición de niveles séricos valle de vancomicina es recomendada por las guías actuales para la monitorización del tratamiento, esperando valores entre 15-20mg/L en infección severas. Existen distintas variables que se asocian a no alcanzar niveles efectivos las cuales se buscan determinar en este estudio. El objetivo de este estudio fue determinar los factores asociados con niveles séricos subterapéuticos, su relación con la enfermedad hemato-oncológica y otras variables farmacocinéticas. Materiales y métodos: Estudio observacional de casos y controles en adultos hospitalizados a quienes se les midieron niveles séricos de vancomicina. Se analizaron un total de 857 historias clínicas, de las cuales 377 cumplieron con los criterios de inclusión. Se seleccionaron aleatoriamente 92 casos y 202 controles en una proporción 1:2, sin apareamiento. Resultados: La mediana de edad fue de 59 años, y el 56,8 % de los pacientes eran hombres. El 23,1 % presentó diagnóstico hemato-oncológico, siendo los más frecuentes los linfomas no Hodgkin y las leucemias agudas. Se encontraron cuatro variables estadísticamente significativas: enfermedad hemato-oncológica (OR 2,12; IC 95 % 1,53–4,88; p=0,004), índice de masa corporal mayor de 25 (OR 1,15; IC 95 % 1,07–1,21; p<0,001), edad mayor de 75 años (OR 0,96; IC 95 % 0,93–0,96; p<0,001) y creatinina mayor a 0,7 mg/dL (OR 0,08; IC 95 % 0,01–0,11; p<0,001). Discusión: La enfermedad hemato-oncológica y un mayor índice de masa corporal se asociaron significativamente con niveles subterapéuticos de vancomicina. Por el contrario, la edad avanzada y niveles más altos de creatinina actuaron como factores protectores, posiblemente debido a una menor depuración del fármaco. Estos hallazgos respaldan la necesidad de monitorización terapéutica y ajuste de dosis en pacientes oncológicos.
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Rodríguez-Rojas A, Rodríguez-Beltrán J, Couce A, Blázquez J. Antibiotics and antibiotic resistance: A bitter fight against evolution. Int J Med Microbiol. Elsevier GmbH.; 2013;303(6- 7):293-7. https://doi.org/10.1016/j.ijmm.2013.02.004
Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis. 2006;42 Suppl 1(Suppl 1):S35-9. https://doi.org/10.1086/491712
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3). https://doi.org/10.1093/cid/ciq146
Reardon J, Lau TTY, Ensom MHH. Vancomycin Loading Doses: A Systematic Review. Ann Pharmacother. 2015;29(5):557-65. https://doi.org/10.1177/1060028015571163
Hyuk M, Hwa Y, Lee S, Hoon S, Kim J. Neutropenia is independently associated with sub- therapeutic serum concentration of vancomycin. Clin Chim Acta. Elsevier B.V.; 2017;465:106- 11. https://doi.org/10.1016/j.cca.2016.12.021
Levine DP. Vancomycin : A History. Clin Infect Dis. 2006;48201:5-12. https://doi.org/10.1086/491709
Moellering RC. Vancomycin : A 50-Year Reassessment. Clin Infect Dis. 2006;42(Suppl 1):3-4. https://doi.org/10.1086/491708
Bruniera R. The use of vancomycin with its therapeutic and adverse effects: a review. Eur Rev Med Pharmacol Sci. 2015;19:694-700.
Mouton JW. Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics. 2014. 1- 467 p.
Bosso J a., Nappi J, Rudisill C, Wellein M, Bookstaver PB, Swindler J, et al. Relationship between vancomycin trough concentrations and nephrotoxicity: A prospective multicenter trial. Antimicrob Agents Chemother. 2011;55(12):5475-9. https://doi.org/10.1128/AAC.00168-11
Van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin- induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57(2):734-44. https://doi.org/10.1128/AAC.01568-12
Leong J, Boro M, Winter M. Determining vancomycin clearance in an overweight and obese population. Am J Heal Pharm. 2011;68(119):599- 603. https://doi.org/10.2146/ajhp100410
Marsot A, Boulamery A, Bruguerolle B, Simon N. Vancomycin A Review of Population Pharmacokinetic Analyses. Clin Pharmacokinet 2012; 2012;51(1):1-13. https://doi.org/10.2165/11596390-000000000-00000
Buelga DS, Fernandez M, Herrera E V, Dominguez-gil A. Population Pharmacokinetic Analysis of Vancomycin in Patients with Hematological Malignancies. Antimicrob Agents Chemother. 2005;49(12):4934-41. https://doi.org/10.1128/AAC.49.12.4934-4941.2005
Soni SS, Ronco C, Katz N, Cruz DN. Early diagnosis of acute kidney injury: The promise of novel biomarkers. Blood Purif. 2009;28(3):165-74. https://doi.org/10.1159/000227785
Turnidge JD, Kotsanas D, Munckhof W, Roberts S, Bennett CM, Nimmo GR, et al. Staphylococcus aureus bacteraemia: a major cause of mortality in Australia and New Zealand. Med J Aust. 2009;191(7):368-73. https://doi.org/10.5694/j.1326-5377.2009.tb02841.x
Paul M, Kariv G, Goldberg E, Raskin M, Shaked H, Hazzan R, et al. Importance of appropriate empirical antibiotic therapy for methicillinresistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2010;65(12):2658-65. https://doi.org/10.1093/jac/dkq373
Robinson JO, Phillips M, Christiansen KJ, Pearson JC, Coombs GW, Murray RJ. Knowing prior methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization status increases the empirical use of glycopeptides in MRSA bacteraemia and may decrease mortality. Clin Microbiol Infect. European Society of Clinical Infectious Diseases; 2014;20(6):530-5. https://doi.org/10.1111/1469-0691.12388
Rodvold K a., Blum R a., Fischer JH, Zokufa HZ, Rotschafer JC, Crossley KB, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother. 1988;32(6):848-52. https://doi.org/10.1128/AAC.32.6.848
Matzke G, McGory R, Halstenson, Charles Keane W. Pharmacokinetics of Vancomycin in Patients with Various Degrees of Renal Function. Antimicrob Agents Chemother. 1984;25(5):433-7. https://doi.org/10.1128/AAC.25.4.433
Janson B, Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012;25(6):1. https://doi.org/10.1097/QCO.0b013e328359a4c1
Shimamoto Y, Fukuda T, Tanaka K, Komori K, Sadamitsu D. Systemic inflammatory response syndrome criteria and vancomycin doce requirement in patients with sepsis. Intensive Care Med. 2013;39(7):1247-52. https://doi.org/10.1007/s00134-013-2909-9
Matsumoto K, Takesue Y, Ohmagari N, Mochizuki T, Mikamo H, Seki M, et al. Practice guidelines for therapeutic drug monitoring of vancomycin: A consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. Elsevier; 2013;19(3):365-80. https://doi.org/10.1007/s10156-013-0599-4
Rybak M, Lomaestro B, Rotschafer JC, Moellering R, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Heal Pharm. 2009;66(1):82-98. https://doi.org/10.2146/ajhp080434
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: Executive summary. Clin Infect Dis. 2011;52(3):285- 92. https://doi.org/10.1093/cid/ciq146
Fernandez de gatta M, Buelga DS, Sánchez A, Dominguez-gil A, Garcia MJ. Vancomycin Dosage Optimization in Patients with Malignant Haematological Disease by Pharmacokinetic / Pharmacodynamic Analysis. 2009;48(4):273-80. https://doi.org/10.2165/00003088-200948040-00005
Minkute R, Briedis V, Steponaviciute R, Vitkauskiene a., Maciulaitis R. Augmented renal clearance - An evolving risk factor to consider during the treatment with vancomycin. J Clin Pharm Ther. 2013;38(6):462-7. https://doi.org/10.1111/jcpt.12088
Mohr JF, Murray BE. Point: Vancomycin is not obsolete for the treatment of infection caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2007;44(12):1536-42. https://doi.org/10.1086/518451
Steinmetz T, Eliakim-Raz N, Goldberg E, Leibovici L, Yahav D. Association of vancomycin serum concentrations with efficacy in patients with MRSA infections: a systematic review and meta-analysis. Clin Microbiol Infect. Elsevier Ltd; 2015;21(7):665-73. https://doi.org/10.1016/j.cmi.2015.04.003
Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N. Continuous versus intermittent infusion of vancomycin for the treatment of gram-positive infections: Systematic review and meta-analysis. J Antimicrob Chemother. 2012;67(1):17-24. https://doi.org/10.1093/jac/dkr442
Haeseker MB, Croes S, Neef C, Bruggeman CA, Stolk LML, Verbon A. Vancomycin Dosing in Neutropenic Patients. PLoS One. 2014;9(11):e112008. https://doi.org/10.1371/journal.pone.0112008
Amador JS, Vega A, Araos P, Quiñones LA, Amador CA. A Successful Experience of Individualized Vancomycin Dosing in Critically Ill Patients by Using a Loading Dose and Maintenance Dose. Pharmaceuticals (Basel). 2025;18(5):677. https://doi.org/10.3390/ph18050677
Parra González D, Pérez Mesa JA, Cuervo Maldonado SI, Díaz Rojas JA, Cortés JA, Silva Gómez E, et al. Pharmacokinetics of Vancomycin among Patients with Chemotherapy-Associated Febrile Neutropenia: Which Would Be the Best Dosing to Obtain Appropriate Exposure? Antibiotics (Basel). 2022;11(11):1523. https://doi.org/10.3390/antibiotics11111523