Vancomycin Therapeutic Regime Adjustment in Newborns and Infants with Bacterial Infection: Case Series

Author(s): Nadielle S. Bidu, Bruno J.D. Fernandes, Eduardo J.C. Dias, Jucelino N.C. Filho, Regina E.A. Bastos, Ana L.P.C. Godoy, Francine J. Azeredo, Joice N.R. Pedreira, Ricardo D. Couto*.

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 4 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Vancomycin is used mostly to overcome infections caused by methicillinresistant microorganisms. There are no well-established administration protocols for neonates and infants, so the leak of a specific administration regime in that population may lead to serum concentrations beyond the specified range.

Objective: This case series evaluated the pharmacokinetics adjustment from a vancomycin therapeutic regimen prescribed to neonates and infants with bacterial infection at a neonatal public hospital intensive- care-unit, with the primary purpose to verify cases of nephrotoxicity.

Methods: Three neonates and four infants taking vancomycin therapy, hospitalized in a public hospital from November 2014 to March 2015, were included in the study. Vancomycin serum concentrations were determined by particle-enhanced-turbidimetric inhibition-immunoassay. The vancomycin concentrations were used for dose adjustment by USC*Pack-PC-Collection®, a non-parametric maximization program. The trough serum concentration range of 10 to 20mg.L-1 was considered therapeutic.

Results: Three patients had serum concentration outside the reference-range, one with subtherapeutic, and two with supratherapeutic concentrations. All patients had concomitant use of drugs which interfered with vancomycin distribution and excretion pharmacokinetics parameters, including drugs that may enhance nephrotoxicity. One patient showed signs of acute renal damage, by low vancomycin and creatinine estimated clearances.

Conclusion: The pharmacokinetic adjustment has been proven to be a useful and necessary tool to increase therapeutic efficacy and treatment benefits. The standard dose of vancomycin can be used to initiate therapy in neonates and infants admitted to the ICU, but after reaching the drug steady state, the dosing regimen should be individualized and guided by pharmacokinetic parameters.

Keywords: Vancomycin therapy, pharmacokinetics, drug monitoring, nephrotoxicity, neonates, infants.

Gomez, D.S.; Campos, E.V.; Azevedo, R.P.; Silva, J.M.; Ferreira, M.C.; Sanches-Giraud, C.; Silva Júnior, C.V.; Santos, S.R. Individualised vancomycin doses for pediatric burn patients to achieve PK/PD targets. Burns, 2013, 39(3), 445-450.
Pacifici, G.; Allegaert, K. Clinical pharmacokinetics of vancomycin in the neonate: A review. Clinics, 2012, 67(7), 831-837.
Marqués-Miñana, M.R.; Saadeddin, A.; Peris, J.E. Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline. Br. J. Clin. Pharmacol., 2010, 70(5), 713-720.
Pai, M.P.; Neely, M.; Rodvold, K.A.; Lodise, T.P. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv. Drug Deliv. Rev., 2014, 20(77), 50-57.
Marsot, A.; Boulamery, A.; Bruguerolle, B.; Simon, N. Vancomycin: A review of population pharmacokinetic analyses. Clin. Pharmacokinet., 2012, 51(1), 1-13.
Radigan, E.A.; Gilchrist, N.A.; Miller, M.A. Management of aminoglycosides in the intensive care unit. J. Intensive Care Med., 2010, 25(6), 327-342.
Yamamoto, M.; Kuzuya, T.; Baba, B.; Yamada, K.; Nabeshima, T. Population pharmacokinetic analysis of vancomycin in patients with gram-positive infections and the influence of infectious disease type. J. Clin. Pharm. Ther., 2009, 34(4), 473-483.
Hwang, D.; Chiu, N.C.; Chang, L.; Peng, C.C.; Huang, D.T.; Huang, F.Y.; Chi, H. Vancomycin dosing and target attainment in children. J. Microbiol. Immunol. Infect., 2015, 50(4), 494-499.
Santos, L.; Torriani, M.S.; Barros, E. Medicamentos na Prática da Farmácia Clínica, 1st ed; Artmed Editora: Porto Alegre, 2013.
Broome, L.; So, T.Y. An Evaluation of Initial Vancomycin Dosing in Infants, Children, and Adolescents. Int. J. Pediatr., 2011, 2011, 470364.
Liu, C.; Bayer, A.; Cosgrove, S.E.; Daum, R.S.; Fridkin, S.K.; Gorwitz, R.J.; Kaplan, S.L.; Karchmer, A.W.; Levine, D.P.; Murray, B.E.; Rybak, M.J.; Talan, D.A.; Chambers, H.F. 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), e18-e55.
Alves, M.L.P.; Melo, G.A.N.; Yamada, S.S.; Nishiyama, P. Therapeutic monitoring of vancomycin. Acta Sci. Heal. Sci., 2012, 34(2), 199-204.
Rybak, M.J.; Lomaestro, B.M.; Rotschafer, J.C.; Moellering, R.C.; Craig, W.A.; Billeter, M.; Dalovisio, J.R.; Levine, D.P. 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(3), 325-327.
Touw, D.J.; Neef, C.; Thomson, A.H.; Vinks, A.A. Cost-effectiveness of therapeutic drug monitoring: A systematic review. Ther. Drug Monit., 2005, 27(1), 10-17.
Hoang, J.; Dersch-Mills, D.; Bresee, L.; Kraft, T.; Vanderkooi, O.G. Achieving therapeutic vancomycin levels in pediatric. Can. J. Hosp. Pharm., 2014, 67(6), 416-422.
Silva, D.C.B.; Seixas, G.T.F.; Araújo, O.R.; Arduini, R.G.; Carlesse, F.A.; Petrilli, A.S. Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients. Braz. J. Infect. Dis., 2012, 16(4), 361-365.
Benner, K.W.; Worthington, M.A.; Kimberlin, D.W.; Hill, K.; Buckley, K.; Tofil, N.M. Correlation of vancomycin dosing to serum concentrations in pediatric patients: A retrospective database review. J. Pediatr. Pharmacol. Ther., 2009, 14(2), 86-93.
Rybak, M.J. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin. Infect. Dis., 2006, 42(Suppl. 1), S35-S39.
DiPiro, J.T.; Spruill, W.J.; Wade, W.E.; Blouin, R.A.; Pruemer, J.M. Concepts in clinical pharmacokinetics, 4th ed; American Society of Health-System Pharmacists: Bethesda, 2005.
Schwartz, G.J.; Muñoz, A.; Schneider, M.F.; Mak, R.H.; Kaskel, F.; Warady, B.A.; Furth, S.L. New equations to estimate GFR in children with CKD. J. Am. Soc. Nephrol., 2009, 20(3), 629-637.
Gupta, A.; Biyani, M.; Khaira, A. Vancomycin nephrotoxicity: Myths and facts. Neth. J. Med., 2011, 69(9), 379-383.
James, C.W.; Gurk-Turner, C. Recommendations for monitoring serum vancomycin concentrations. Proc. Bayl. Univ. Med. Cent., 2011, 14(2), 189-190.
Dombroski, V.; Silva, M.M.G.; Silveira, M.E. Monitoramento terapêutico de vancomicina em uma unidade de terapia intensiva. Rev Médica UFPR, 2015, 2(2), 67-73.
Santos, A.B.; Duarte, A.; Saião, A.S. Vancomycin in clinical practice - a review. JBBR, 2011, 8(2), 321-327.
Van Hal, S.J.; Paterson, D.L.; Lodise, T.P. 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), 734-744.
Elyasi, S.; Khalili, H.; Hatamkhani, S.; Dashti-Khavidaki, S. Prevention of vancomycin induced nephrotoxicity: A review of preclinical data. Eur. J. Clin. Pharmacol., 2013, 69(4), 747-754.
Elyasi, S.; Khalili, H.; Dashti-Khavidaki, S.; Mohammadpour, A. Vancomycin-induced nephrotoxicity: Mechanism, incidence, risk factors and special populations. A literature review. Eur. J. Clin. Pharmacol., 2012, 68(9), 1243-1255.
Hazlewood, K.A.; Brouse, S.D.; Pitcher, W.D.; Hall, R.G. Vancomycin-Associated Nephrotoxicity: Grave Concern or Death by Character Assassination? Am. J. Med., 2010, 123(2), 182.e1-182.e7.
Kim, D.I.; Im, M.S.; Choi, J.H.; Lee, J.; Choi, E.H.; Lee, H.J. Therapeutic monitoring of vancomycin according to initial dosing regimen in pediatric patients. Korean J. Pediatr., 2010, 53(12), 1000-1005.
Pea, F.; Porreca, L.; Baraldo, M.; Furlanut, M. High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures. J. Antimicrob. Chemother., 2000, 45(3), 329-335.
Higgins, C. Urea and the clinical value of measuring blood urea concentration. 2016. Article downloaded from
Moffett, B.S.; Kim, S.; Edwards, M. Vancomycin nephrotoxicity may be overstated. J. Pediatr., 2011, 158(5), 865-866.
Zanotto, M.B.; Wappler, P.R.; d’Azevedo, P.A.; Carneiro, M.; Rauber, J.M.; Valim, A.R.M. Avaliação dos níveis séricos de vancomicina em pacientes internados em um hospital de ensino da região central do Rio Grande do Sul - Brasil. Rev. Jovens Pesqui., 2014, 4(3), 38-51.
Onwuchuruba, C.N.; Towers, C.V.; Howard, B.C.; Hennessy, M.D.; Wolfe, L.; Brown, M.S. Transplacental passage of vancomycin from mother to neonate. Am. J. Obstet. Gynecol., 2014, 210(4), 352.e1-352.e4.
Ringer, S.A. Acute renal failure in the neonate. Neoreviews, 2010, 11(5), e243-e251.
Rocha, M.J.S.P. Caracterização do perfil cinético de gentamicina e vancomicina em recém-nascidos prematuros., Doctor Thesis, Universidade de Coimbra: Coimbra. 2006.
Macdougall, C.; Chambers, H.F. Inibidores da síntese de proteínas e agentes antibacterianos diversos. In: Goodman & Gilman’s as bases farmacológicas da terapêutica, Laurence L. Brunton, Ed.; McGraw-Hill Interamericana do Brasil: Rio de Janeiro. 2012, 12 ed. pp. 1521-1547.
Ye, Z-K.; Tang, H-L.; Zhai, S-D. Benefits of therapeutic drug monitoring of vancomycin: A systematic review and meta-analysis. PLoS One, 2013, 8(10), e77169.
Levine, D.P. Vancomycin: A History. Clin. Infect. Dis., 2006, 42(Suppl. 1), S5-S12.
Bond, C.A.; Raehl, C.L. Clinical and economic outcomes of pharmacist-managed aminoglycoside or vancomycin therapy. Am. J. Health Syst. Pharm., 2005, 62(15), 1596-1605.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [346 - 351]
Pages: 6
DOI: 10.2174/1389201020666190319161511
Price: $65

Article Metrics

PDF: 33