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Abstract

Introduction

This systematic review aimed to identify, evaluate, and critically analyze pharmacokinetic models of vancomycin in adult populations published in PubMed and EMBASE between 2020 and 2024.

Materials and Methods

Twenty-two studies were included, describing 24 models characterized by substantial heterogeneity in terms of study populations, methodological design, and covariate selection. Most models were developed in Asia and focused on hospitalized patients, particularly those in intensive care units (ICUs). Data from 2150 patients were analyzed, with an average of 93 patients per model.

Results

The models demonstrated high variability in pharmacokinetic parameters, such as vancomycin clearance (Cl) and volume of distribution (Vd), influenced by factors, such as renal function, weight, age, and comorbidities. The meta-analysis conducted on clearance and interindividual variability in clearance (IIV Cl) revealed high heterogeneity among the analyzed studies. The average vancomycin clearance was 4.23 L/h, with higher values observed in neurosurgical, oncohematologic patients, and those with increased renal function. The volume of distribution showed greater variability in obese patients and those undergoing continuous renal replacement therapy. Creatinine clearance (ClCr) was identified as a significant covariate in 66% of the models, while weight was significant in 33%. Other important covariates included age, sex, serum creatinine, serum urea, and the hospital admission unit. The meta-analysis of Cl and IIV Cl showed high heterogeneity among the studies, with I2 values of 0.83 for Cl and 0.98 for IIV Cl, indicating substantial variability.

Discussion

The limitations of this study included the diversity of the analyzed populations, which made it challenging to assess the model's suitability. While the models showed advances in precision, challenges, such as the lack of external validation and discrepancies in dosing recommendations, remain.

Conclusion

This review paper has highlighted the need to validate models in diverse populations and clinical settings to optimize personalized vancomycin therapy in adults. The findings have highlighted the importance of validating or adapting pharmacokinetic models to the specific characteristics of each hospital population.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-11-15
2025-11-29

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References

  1. Gu Q. Jones N. Drennan P. Peto T.E.A. Walker A.S. Eyre D.W. Assessment of an institutional guideline for vancomycin dosing and identification of predictive factors associated with dose and drug trough levels. J. Infect. 2022 85 4 382 389 10.1016/j.jinf.2022.06.029 35840011
    [Google Scholar]
  2. Cusumano J.A. Klinker K.P. Huttner A. Luther M.K. Roberts J.A. LaPlante K.L. Towards precision medicine: Therapeutic drug monitoring–guided dosing of vancomycin and β-lactam antibiotics to maximize effectiveness and minimize toxicity. Am. J. Health Syst. Pharm. 2020 77 14 1104 1112 10.1093/ajhp/zxaa128 32537644
    [Google Scholar]
  3. Rybak M.J. Le J. Lodise T.P. Levine D.P. Bradley J.S. Liu C. Mueller B.A. Pai M.P. Wong-Beringer A. Rotschafer J.C. Rodvold K.A. Maples H.D. Lomaestro B.M. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am. J. Health Syst. Pharm. 2020 77 11 835 864 10.1093/ajhp/zxaa036 32191793
    [Google Scholar]
  4. Drennan P.G. Begg E.J. Gardiner S.J. Kirkpatrick C.M.J. Chambers S.T. The dosing and monitoring of vancomycin: What is the best way forward? Int. J. Antimicrob. Agents 2019 53 4 401 407 10.1016/j.ijantimicag.2018.12.014 30599240
    [Google Scholar]
  5. Neely M.N. Kato L. Youn G. Kraler L. Bayard D. van Guilder M. Schumitzky A. Yamada W. Jones B. Minejima E. Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing. Antimicrob. Agents Chemother. 2018 62 2 e02042 e17 10.1128/AAC.02042‑17 29203493
    [Google Scholar]
  6. 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 77 50 57 10.1016/j.addr.2014.05.016 24910345
    [Google Scholar]
  7. Suzuki Y. Kawasaki K. Sato Y. Tokimatsu I. Itoh H. Hiramatsu K. Takeyama M. Kadota J. Is peak concentration needed in therapeutic drug monitoring of vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant staphylococcus aureus pneumonia. Chemotherapy 2012 58 4 308 312 10.1159/000343162 23147106
    [Google Scholar]
  8. Masich A.M. Kalaria S.N. Gonzales J.P. Heil E.L. Tata A.L. Claeys K.C. Patel D. Gopalakrishnan M. Vancomycin pharmacokinetics in obese patients with sepsis or septic shock. Pharmacotherapy 2020 40 3 211 220 10.1002/phar.2367 31957057
    [Google Scholar]
  9. Goyal R.K. Moffett B.S. Gobburu J.V.S. Al Mohajer M. Population pharmacokinetics of vancomycin in pregnant women. Front. Pharmacol. 2022 13 873439 10.3389/fphar.2022.873439 35734401
    [Google Scholar]
  10. Jing L. Liu T. Guo Q. Chen M. Lu J. Lv C. Development and comparison of population pharmacokinetic models of vancomycin in neurosurgical patients based on two different renal function markers. J. Clin. Pharm. Ther. 2020 45 1 88 96 10.1111/jcpt.13029 31463971
    [Google Scholar]
  11. Marsot A. Boulamery A. Bruguerolle B. Simon N. Vancomycin. Clin. Pharmacokinet. 2012 51 1 1 13 10.2165/11596390‑000000000‑00000 22149255
    [Google Scholar]
  12. Aljutayli A. Marsot A. Nekka F. An update on population pharmacokinetic analyses of vancomycin, part i: In adults. Clin. Pharmacokinet. 2020 59 6 671 698 10.1007/s40262‑020‑00866‑2 32020531
    [Google Scholar]
  13. Alqahtani S. Almatrafi A. Bin Aydan N. Alqahtani M. Alzamil F. Alsultan A. Asiri Y. Optimization of vancomycin dosing regimen in cancer patients using pharmacokinetic/pharmacodynamic modeling. Pharmacotherapy 2020 40 12 1192 1200 10.1002/phar.2475 33084059
    [Google Scholar]
  14. Lin Z. Chen D. Zhu Y.W. Jiang Z. Cui K. Zhang S. Chen L. Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units. Sci. Rep. 2021 11 1 2670 10.1038/s41598‑021‑82312‑2 33514803
    [Google Scholar]
  15. Wang C. Chen J. Yang B. Li S. Zhang Y. Chen L. Wang T. Dong Y. Determination of vancomycin exposure target and individualized dosing recommendations for critically ill patients undergoing continuous renal replacement therapy. Pharmacotherapy 2023 43 3 180 188 10.1002/phar.2771 36714991
    [Google Scholar]
  16. Fu X. Lin L. Huang L. Guo L. Clinical application of vancomycin population pharmacokinetics model in patients with hematological diseases and neutropenia. Biopharm. Drug Dispos. 2021 42 9 427 434 10.1002/bdd.2303 34651308
    [Google Scholar]
  17. Zhao S. He N. Zhang Y. Wang C. Zhai S. Zhang C. Population pharmacokinetic modeling and dose optimization of vancomycin in chinese patients with augmented renal clearance. Antibiotics 2021 10 10 1238 10.3390/antibiotics10101238 34680818
    [Google Scholar]
  18. Huang J. Wang X. Hao C. Yang W. Zhang W. Liu J. Qu H. Cystatin C and/or creatinine-based estimated glomerular filtration rate for prediction of vancomycin clearance in long-stay critically ill patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS): A population pharmacokinetics analysis. Intern. Emerg. Med. 2021 16 7 1883 1893 10.1007/s11739‑021‑02699‑8 33728578
    [Google Scholar]
  19. Belabbas T. Yamada T. Egashira N. Hirota T. Suetsugu K. Mori Y. Kato K. Akashi K. Ieiri I. Population pharmacokinetic model and dosing optimization of vancomycin in hematologic malignancies with neutropenia and augmented renal clearance. J. Infect. Chemother. 2023 29 4 391 400 10.1016/j.jiac.2023.01.010 36682608
    [Google Scholar]
  20. Oda K. Jono H. Kamohara H. Nishi K. Tanoue N. Saito H. Development of vancomycin dose individualization strategy by bayesian prediction in patients receiving continuous renal replacement therapy. Pharm. Res. 2020 37 6 108 10.1007/s11095‑020‑02820‑0 32468340
    [Google Scholar]
  21. Yamazaki S. Tatebe M. Fujiyoshi M. Hattori N. Suzuki T. Takatsuka H. Uchida M. Suzuki T. Ishii I. Population pharmacokinetics of vancomycin under continuous renal replacement therapy using a polymethylmethacrylate hemofilter. Ther. Drug Monit. 2020 42 3 452 459 10.1097/FTD.0000000000000721 31913865
    [Google Scholar]
  22. Bang J.Y. Kang H.I. Lee H.J. Chong Y.P. Hong S.K. Lee E.K. Choi B.M. Noh G.J. Development of a new pharmacokinetic model for target‐concentration controlled infusion of vancomycin in critically ill patients. Clin. Exp. Pharmacol. Physiol. 2022 49 2 202 211 10.1111/1440‑1681.13597 34596258
    [Google Scholar]
  23. Jung Y. Lee D.H. Kim H.S. Prospective cohort study of population pharmacokinetics and pharmacodynamic target attainment of vancomycin in adults on extracorporeal membrane oxygenation. Antimicrob. Agents Chemother. 2021 65 2 e02408 e02420 10.1128/AAC.02408‑20 33257444
    [Google Scholar]
  24. Jaisue S. Pongsakul C. D’Argenio D.Z. Sermsappasuk P. Population pharmacokinetic modeling of vancomycin in thai patients with heterogeneous and unstable renal function. Ther. Drug Monit. 2020 42 6 856 865 10.1097/FTD.0000000000000801 32947558
    [Google Scholar]
  25. Kanji S. Roberts J.A. Xie J. Zelenitsky S. Hiremath S. Zhang G. Watpool I. Porteous R. Patel R. Vancomycin population pharmacokinetics in critically ill adults during sustained low-efficiency dialysis. Clin. Pharmacokinet. 2020 59 3 327 334 10.1007/s40262‑019‑00817‑6 31471789
    [Google Scholar]
  26. Kovacevic T. Miljkovic B. Kovacevic P. Dragic S. Momcicevic D. Avram S. Jovanovic M. Vucicevic K. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. J. Crit. Care 2020 55 116 121 10.1016/j.jcrc.2019.10.012 31715528
    [Google Scholar]
  27. Aljutayli A. Thirion D.J.G. Bonnefois G. Nekka F. Pharmacokinetic equations versus Bayesian guided vancomycin monitoring: Pharmacokinetic model and model‐informed precision dosing trial simulations. Clin. Transl. Sci. 2022 15 4 942 953 10.1111/cts.13210 35170243
    [Google Scholar]
  28. Munir M.M. Rasheed H. Khokhar M.I. Khan R.R. Saeed H.A. Abbas M. Ali M. Bilal R. Nawaz H.A. Khan A.M. Qamar S. Anjum S.M. Usman M. Dose tailoring of vancomycin through population pharmacokinetic modeling among surgical patients in Pakistan. Front. Pharmacol. 2021 12 721819 10.3389/fphar.2021.721819 34858169
    [Google Scholar]
  29. Jalusic K.O. Hempel G. Arnemann P.H. Spiekermann C. Kampmeier T.G. Ertmer C. Gastine S. Hessler M. Population pharmacokinetics of vancomycin in patients with external ventricular drain‐associated ventriculitis. Br. J. Clin. Pharmacol. 2021 87 6 2502 2510 10.1111/bcp.14657 33202067
    [Google Scholar]
  30. Yellepeddi V.K. Lindley B. Radetich E. Kumar S. Bhakta Z. Leclair L. Parrot M. Young D.C. Population pharmacokinetics and target attainment analysis of vancomycin after intermittent dosing in adults with cystic fibrosis. Antimicrob. Agents Chemother. 2024 68 1 e00992 e23 10.1128/aac.00992‑23 38059634
    [Google Scholar]
  31. Ahmed K. Ibrahim A. Gonzalez D. Nur A. Population pharmacokinetics and model-based dose optimization of vancomycin in sudanese adult patients with renal impairment. Drug Des. Devel. Ther. 2024 18 81 95 10.2147/DDDT.S432439 38260090
    [Google Scholar]
  32. Wei S. Zhang D. Zhao Z. Mei S. Population pharmacokinetic model of vancomycin in postoperative neurosurgical patients. Front. Pharmacol. 2022 13 1005791 10.3389/fphar.2022.1005791 36225566
    [Google Scholar]
  33. Kim A.J. Lee J.Y. Choi S.A. Shin W.G. Comparison of the pharmacokinetics of vancomycin in neurosurgical and non-neurosurgical patients. Int. J. Antimicrob. Agents 2016 48 4 381 387 10.1016/j.ijantimicag.2016.06.022 27546217
    [Google Scholar]
  34. Albanèse J. Léone M. Bruguerolle B. Ayem M.L. Lacarelle B. Martin C. Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob. Agents Chemother. 2000 44 5 1356 1358 10.1128/AAC.44.5.1356‑1358.2000 10770777
    [Google Scholar]
  35. Popa D. Loewenstein L. Lam S.W. Neuner E.A. Ahrens C.L. Bhimraj A. Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration. J. Hosp. Infect. 2016 92 2 199 202 10.1016/j.jhin.2015.10.017 26654472
    [Google Scholar]
  36. Mulla H. Lawson G. von Anrep C. Burke M.D. Upton D.U. Firmin R.K. Killer H. In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion 2000 15 1 21 26 10.1177/026765910001500104 10676864
    [Google Scholar]
  37. Donadello K. Roberts J.A. Cristallini Anrep S. Beumier M. Shekar K. Jacobs F. Belhaj A. Vincent J.L. de Backer D. Taccone F.S. Donadello, K.; Roberts, J.A.; Cristallini, S.; Beumier, M.; Shekar, K.; Jacobs, F.; Belhaj, A.; Vincent, J.L.; de Backer, D.; Taccone, F.S. Vancomycin population pharmacokinetics during extracorporeal membrane oxygenation therapy: A matched cohort study. Crit. Care 2014 18 6 632 10.1186/s13054‑014‑0632‑8 25416535
    [Google Scholar]
  38. Mousavi S. Levcovich B. Mojtahedzadeh M. A systematic review on pharmacokinetic changes in critically ill patients: Role of extracorporeal membrane oxygenation. Daru 2011 19 5 312 321 22615675
    [Google Scholar]
  39. Cheng V. Abdul-Aziz M.H. Burrows F. Buscher H. Cho Y.J. Corley A. Diehl A. Gilder E. Jakob S.M. Kim H.S. Levkovich B.J. Lim S.Y. McGuinness S. Parke R. Pellegrino V. Que Y.A. Reynolds C. Rudham S. Wallis S.C. Welch S.A. Zacharias D. Fraser J.F. Shekar K. Roberts J.A. Population pharmacokinetics of vancomycin in critically ill adult patients receiving extracorporeal membrane oxygenation (an ASAP ECMO Study). Antimicrob. Agents Chemother. 2022 66 1 e01377 e21 10.1128/AAC.01377‑21 34633852
    [Google Scholar]
  40. Moore J.N. Healy J.R. Thoma B.N. Peahota M.M. Ahamadi M. Schmidt L. Cavarocchi N.C. Kraft W.K. A population pharmacokinetic model for vancomycin in adult patients receiving extracorporeal membrane oxygenation therapy. CPT Pharmacometrics Syst. Pharmacol. 2016 5 9 495 502 10.1002/psp4.12112 27639260
    [Google Scholar]
  41. Matsumoto K. Takesue Y. Ohmagari N. Mochizuki T. Mikamo H. Seki M. Takakura S. Tokimatsu I. Takahashi Y. Kasahara K. Okada K. Igarashi M. Kobayashi M. Hamada Y. Kimura M. Nishi Y. Tanigawara Y. Kimura T. 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. 2013 19 3 365 380 10.1007/s10156‑013‑0599‑4 23673472
    [Google Scholar]
  42. Covajes C. Scolletta S. Penaccini L. Ocampos-Martinez E. Abdelhadii A. Beumier M. Jacobs F. de Backer D. Vincent J.L. Taccone F.S. Continuous infusion of vancomycin in septic patients receiving continuous renal replacement therapy. Int. J. Antimicrob. Agents 2013 41 3 261 266 10.1016/j.ijantimicag.2012.10.018 23312601
    [Google Scholar]
  43. Chu Y. Luo Y. Ji S. Jiang M. Zhou B. Population pharmacokinetics of vancomycin in Chinese patients with augmented renal clearance. J. Infect. Public Health 2020 13 1 68 74 10.1016/j.jiph.2019.06.016 31277936
    [Google Scholar]
  44. Udy A.A. Roberts J.A. Shorr A.F. Boots R.J. Lipman J. Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: Identifying at-risk patients. Crit. Care 2013 17 1 R35 10.1186/cc12544 23448570
    [Google Scholar]
  45. Bury D. ter Heine R. van de Garde E.M.W. Nijziel M.R. Grouls R.J. Deenen M.J. The effect of neutropenia on the clinical pharmacokinetics of vancomycin in adults. Eur. J. Clin. Pharmacol. 2019 75 7 921 928 10.1007/s00228‑019‑02657‑6 30877327
    [Google Scholar]
  46. Hochart C. Berthon C. Corm S. Gay J. Cliquennois M. Tricot S. Alfandari S. Vancomycin serum concentration during febrile neutropenia in patients with acute myeloid leukemia. Med. Mal. Infect. 2011 41 12 652 656 10.1016/j.medmal.2011.09.014 22056376
    [Google Scholar]
  47. Freifeld A.G. Bow E.J. Sepkowitz K.A. Boeckh M.J. Ito J.I. Mullen C.A. Raad I.I. Rolston K.V. Young J.A.H. Wingard J.R. 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 4 e56 e93 10.1093/cid/cir073 21258094
    [Google Scholar]
  48. Hong J. Krop L.C. Johns T. Pai M.P. Individualized vancomycin dosing in obese patients: A two-sample measurement approach improves target attainment. Pharmacotherapy 2015 35 5 455 463 10.1002/phar.1588 26011138
    [Google Scholar]
  49. Reynolds D.C. Waite L.H. Alexander D.P. DeRyke C.A. Performance of a vancomycin dosage regimen developed for obese patients. Am. J. Health Syst. Pharm. 2012 69 11 944 950 10.2146/ajhp110324 22610026
    [Google Scholar]
  50. Durand C. Bylo M. Howard B. Belliveau P. Vancomycin dosing in obese patients: Special considerations and novel dosing strategies. Ann. Pharmacother. 2018 52 6 580 590 10.1177/1060028017750084 29262697
    [Google Scholar]
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A Systematic Review of Pharmacokinetic Models of Vancomycin in Adult Patients (2020-2024): Trends, Variability, and Key Covariates
Bentham Science Publishers ; https://doi.org/10.2174/0113892002395979251015105103
/content/journals/cdm/10.2174/0113892002395979251015105103
/content/journals/cdm/10.2174/0113892002395979251015105103
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  • Article Type:     Review Article
Keywords: pharmacokinetics ; population models ; Vancomycin ; covariates ; critical care ; therapeutic drug monitoring

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