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Vancomycin therapeutic drug monitoring is associated with reduced toxicity in ICU patients: a MIMIC-IV retrospective study
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  • Published: 11 March 2026

Vancomycin therapeutic drug monitoring is associated with reduced toxicity in ICU patients: a MIMIC-IV retrospective study

  • Jia Wang1,
  • Chuzhu Huang1,
  • Yan Chen1,
  • Yilin Huang1 &
  • …
  • Zhuomin Wu1 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Medical research
  • Nephrology
  • Risk factors

Abstract

Vancomycin is a first-line treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections but is associated with risks of nephrotoxicity (5–43%), hepatotoxicity, and hematotoxicity. Therapeutic drug monitoring (TDM) is recommended to optimize dosing, yet its impact on multi-organ toxicity and mortality in intensive care unit (ICU) patients remains controversial because of conflicting evidence and methodological limitations in prior studies. Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v3.1) database for a retrospective cohort analysis of 28,451 ICU patients receiving intravenous vancomycin. The primary outcomes were vancomycin-associated nephrotoxicity (AKI according to the KDIGO criteria), hepatotoxicity (ALT/AST ≥ 120 U/L or bilirubin ≥ 2.5 mg/dL), and hematotoxicity (thrombocytopenia, anemia, or leukopenia); secondary outcomes included ICU / hospital mortality. Propensity score matching (PSM, 1:1 nearest neighbor with caliper = 0.1) balanced 32 baseline covariates, including demographics. The associations between TDM and outcomes were evaluated via multivariable logistic regression and Cox proportional hazards models, with the results validated through subgroup analyses (stratified by comorbidities and concomitant medications) and sensitivity analyses. Data from 28,451 ICU patients receiving intravenous vancomycin were extracted from the MIMIC-IV database, with 10,758 (37.8%) receiving TDM and 17,693 (62.2%) not receiving TDM. Before PSM, the TDM group presented higher baseline illness severity scores (e.g., SOFA, APS III) and more comorbidities. Unadjusted analyses revealed increased risks of adverse outcomes in the TDM group (AKI: OR = 2.98, 95% CI: 2.83–3.15; hematotoxicity: OR = 1.97, 95% CI: 1.88–2.07; hepatotoxicity: OR = 2.34, 95% CI: 2.19–2.50; all P < 0.001). However, with progressive adjustment for confounders, these associations attenuated significantly (Model 3: AKI OR = 1.93, hematotoxicity OR = 1.55, hepatotoxicity OR = 1.25; all P < 0.001). After PSM, the TDM group demonstrated significantly reduced risks of AKI (OR = 0.580, 95% CI: 0.540–0.610, P = 0.001), hematotoxicity (OR = 0.760, 95% CI: 0.710–0.800, P = 0.001), and hepatotoxicity (OR = 0.800, 95% CI: 0.750–0.860, P = 0.001). Secondary outcomes also favored TDM, with lower in-hospital mortality (OR = 0.672, 95% CI: 0.570–0.790, P = 0.001) and ICU mortality (OR = 0.691, 95% CI: 0.580–0.820, P = 0.001). Kaplan-Meier analysis further confirmed the survival benefits of TDM in both ICU and hospital settings (log-rank P < 0.001). Subgroup analyses revealed that hypertension, type 2 diabetes mellitus (T2DM), cancer, cerebral bleeding (CB), and concomitant use of aspirin or antibiotics were significant risk factors for nephrotoxicity, hematotoxicity and hepatotoxicity. This study demonstrated that vancomycin TDM is significantly associated with reduced toxicity risks (nephrotoxicity, hepatotoxicity, hematotoxicity) and mortality in intensive care unit (ICU) patients, supporting its routine use in critically ill populations.

Data availability

The MIMIC-IV database used in this study is publicly available to researchers who meet the criteria for access. Detailed instructions for obtaining the data can be found at https://mimic-iv.mit.edu/.

Abbreviations

AKI:

Acute kidney injury

APS III:

Acute Physiology Score III

APACHE II:

Acute Physiology and Chronic Health Evaluation II

ASHP:

American Society of Health-System Pharmacists

BMI:

Body mass index

BUN:

Blood urea nitrogen

CB:

Cerebral bleeding

CI:

Confidence interval

CKD:

Chronic kidney disease

Cr:

Serum creatinine

CVA:

Cerebrovascular accident

GCS:

Glasgow Coma Scale

HF:

Heart failure

Hosp Day:

Hospital length of stay

ICU Day:

ICU length of stay

IHD:

Ischemic heart disease

ICU:

Intensive care unit

IDSA:

Infectious Diseases Society of America

IQR:

Interquartile range

MIMIC-IV:

Medical Information Mart for Intensive Care IV

MI:

Myocardial infarction

MRSA:

Methicillin-resistant Staphylococcus aureus

OASIS:

Oxford Acute Severity of Illness Score

OR:

Odds ratio

PSM:

Propensity score matching

RDW:

Red cell distribution width

SAPS II:

Simplified Acute Physiology Score II

SIRS:

Systemic inflammatory response syndrome

SOFA:

Sequential Organ Failure Assessment

SQL:

Structured Query Language

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

TDM:

Therapeutic drug monitoring

References

  1. Levine, D. P. Vancomycin: understanding its past and preserving its future. South. Med. J. 101 (3), 284–291. https://doi.org/10.1097/SMJ.0b013e3181647037 (2008). PMID: 18364659.

    Google Scholar 

  2. Rybak, 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. Health Syst. Pharm. 66(1), 82–98. https://doi.org/10.2146/ajhp080434 (2009). Erratum in: Am J Health Syst Pharm. 2009;66(10):887. PMID: 19106348.

  3. Abramson, M. A. & Sexton, D. J. Nosocomial methicillin-resistant and methicillin-susceptible Staphylococcus aureus primary bacteremia: at what costs? Infect. Control Hosp. Epidemiol. 20(6), 408–411. (1999). PMID: 10395142. https://doi.org/10.1086/501641

    Google Scholar 

  4. Cosgrove, S. E. et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin. Infect. Dis. 36 (1), 53–59. https://doi.org/10.1086/345476 (2003). Epub 2002 Dec 13. PMID: 12491202.

    Google Scholar 

  5. Engemann, J. J. et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin. Infect. Dis. 36 (5), 592–598. https://doi.org/10.1086/367653 (2003). Epub 2003 Feb 7. PMID: 12594640.

    Google Scholar 

  6. Harbarth, S., Rutschmann, O., Sudre, P. & Pittet, D. Impact of methicillin resistance on the outcome of patients with bacteremia caused by Staphylococcus aureus. Arch. Intern. Med. 158(2), 182–189 (1998). https://doi.org/10.1001/archinte.158.2.182

    Google Scholar 

  7. Noskin, G. A. et al. The burden of Staphylococcus aureus infections on hospitals in the United States: an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database. Arch. Intern. Med. 165 (15), 1756–1761. (2005). https://doi.org/10.1001/archinte.165.15.1756

    Google Scholar 

  8. Rybak, M. J., Bailey, E. M. & Warbasse, L. H. Absence of ‘‘red man syndrome’’ in patients being treated with vancomycin or high-dose teicoplanin. Antimicrob. Agents Chemother. 36, 1204–1207 (1992).

    Google Scholar 

  9. Bergman, M. M., Glew, R. H. & Ebert, T. H. Acute interstitial nephritis associated with vancomycin therapy. Arch. Intern. Med. 148, 2139–2140 (1988).

    Google Scholar 

  10. Cimino, M. A., Rotstein, C., Slaughter, R. L. & Emrich, L. J. Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy. Am. J. Med. 83, 1091–1097 (1987).

    Google Scholar 

  11. Rybak, M. J., Albrecht, L. M., Boike, S. C. & Chandrasekar, P. H. Neph rotoxicity of vancomycin, alone and with an aminoglycoside. J. Antimicrob. Chemother. 25, 679–687 (1990).

    Google Scholar 

  12. Traber, P. G. & Levine, D. P. Vancomycin ototoxicity in patient with normal renal function. Ann. Intern. Med. 95, 458–460 (1981).

    Google Scholar 

  13. 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. 57 (2), 734–744. https://doi.org/10.1128/AAC.01568-12 (2013). Epub 2012 Nov 19. PMID: 23165462; PMCID: PMC3553731.

    Google Scholar 

  14. Sinha Ray, A., Haikal, A., Hammoud, K. A. & Yu, A. S. L. Vancomycin and the risk of AKI: a systematic review and meta-analysis. Clin. J. Am. Soc. Nephrol. 11 (12), 2132–2140. https://doi.org/10.2215/CJN.05920616 (2016). Epub 2016 Nov 28. PMID: 27895134; PMCID: PMC5142072.

    Google Scholar 

  15. Khwaja, A. KDIGO clinical practice guidelines for acute kidney injury. Nephron. Clin. Pract. 120(4), c179–c184. https://doi.org/10.1159/000339789 (2012). Epub 2012 Aug 7. PMID: 22890468.

  16. Moellering, R. C. Jr. Monitoring serum vancomycin levels: climbing the mountain because it is there? Clin. Infect. Dis. 18 (4), 544–546. https://doi.org/10.1093/clinids/18.4.544 (1994). Erratum in: Clin Infect Dis 1994;19(2):379. PMID: 8038307.

    Google Scholar 

  17. Darko, W., Medicis, J. J., Smith, A., Guharoy, R. & Lehmann, D. E. Mississippi mud no more: cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity. Pharmacotherapy 23 (5), 643–650. (2003). https://doi.org/10.1592/phco.23.5.643.32199

    Google Scholar 

  18. Johnson, A. E. W. et al. MIMIC-IV, a freely accessible electronic health record dataset. Sci. Data. 10, 1. https://doi.org/10.1038/s41597-022-01899-x (2023).

    Google Scholar 

  19. Mehta, R. L. et al. Acute Kidney Injury Network. Acute kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit. Care. 11, R31 (2007).

    Google Scholar 

  20. Rybak, M. J. et al. 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. 77(11), 835–864. https://doi.org/10.1093/ajhp/zxaa036. (2020) PMID: 32191793.

  21. National Cancer Institute Common Terminology Criteria for Adverse Events. (CTCAE) Version 5.0. [(accessed on 19 November 2024)];2017 Available online: https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v5-5x7.pdf

  22. Yang, J. J. et al. The influence of a therapeutic drug monitoring service on vancomycin-associated nephrotoxicity. J. Clin. Pharmacol. 64 (1), 19–29. https://doi.org/10.1002/jcph.2363 (2024). Epub 2023 Oct 25. PMID: 37779493.

    Google Scholar 

  23. Ye, Z. K., Tang, H. L. & Zhai, S. D. Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis. PLoS One. 8 (10), e77169. https://doi.org/10.1371/journal.pone.0077169 (2013). PMID: 24204764; PMCID: PMC3799644.

    Google Scholar 

  24. Lodise, T. P., Lomaestro, B., Graves, J. & Drusano, G. L. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob. Agents Chemother. 52 (4), 1330–1336. https://doi.org/10.1128/AAC.01602-07 (2008). Epub 2008 Jan 28. PMID: 18227177; PMCID: PMC2292536.

    Google Scholar 

  25. Welty, T. E. & Copa, A. K. Impact of vancomycin therapeutic drug monitoring on patient care. Ann Pharmacother. 28(12), 1335–1339. https://doi.org/10.1177/106002809402801201 (1994). PMID: 7696720.

  26. Iwamoto, T., Kagawa, Y. & Kojima, M. Clinical efficacy of therapeutic drug monitoring in patients receiving vancomycin. Biol. Pharm. Bull. 26(6), 876–879. https://doi.org/10.1248/bpb.26.876 (2003). PMID: 12808304.

  27. Peng, H. et al. Monitoring vancomycin blood concentrations reduces mortality risk in critically ill patients: a retrospective cohort study using the MIMIC-IV database. Front. Pharmacol. 15, 1458600. https://doi.org/10.3389/fphar.2024.1458600 (2024). PMID: 39611174; PMCID: PMC11602295.

    Google Scholar 

  28. LiverTox. Clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. PMID: 31643176.

  29. Asif, B. A. et al. Vancomycin-induced liver injury, DRESS, and HLA-A∗32:01. J. Allergy Clin. Immunol. Pract. 12 (1), 168–174e2 (2024). Epub 2023 Sep 20. PMID: 37739311; PMCID: PMC10885131.

    Google Scholar 

  30. Littlehales, E., Murray, O. & Dunsmuir, R. Vancomycin-Induced DRESS Syndrome: an important concern in orthopedic surgery. Case Rep. Orthop. 2018, 1439073. https://doi.org/10.1155/2018/1439073 (2018). PMID: 30034896; PMCID: PMC6035812.

    Google Scholar 

  31. Minhas, J. S., Wickner, P. G., Long, A. A., Banerji, A. & Blumenthal, K. G. Immune-mediated reactions to vancomycin: a systematic case review and analysis. Ann. Allergy Asthma Immunol. 116 (6), 544–553. https://doi.org/10.1016/j.anai.2016.03.030 (2016). Epub 2016 May 4. PMID: 27156746; PMCID: PMC4946960.

    Google Scholar 

  32. Yamanouchi, J. et al. Vancomycin-induced immune thrombocytopenia proven by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. Intern. Med. 55 (20), 3035–3038. https://doi.org/10.2169/internalmedicine.55.6902 (2016). Epub 2016 Oct 15. PMID: 27746445; PMCID: PMC5109575.

    Google Scholar 

  33. Shah, S., Sweeney, R., Rai, M. & Shah, D. A case of vancomycin-induced severe immune thrombocytopenia. Hematol. Rep. 15 (2), 283–289. https://doi.org/10.3390/hematolrep15020028 (2023). PMID: 37218820; PMCID: PMC10204526.

    Google Scholar 

  34. Yuan, K., Awan, K. S. & Long, J. Vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS). BMJ Case Rep. 13 (2), e232302. https://doi.org/10.1136/bcr-2019-232302 (2020). PMID: 32024716; PMCID: PMC7021173.

    Google Scholar 

  35. Obi, E. S. et al. Immune thrombocytopenia: a rare adverse event of vancomycin therapy. Cureus 15 (5), e39348. https://doi.org/10.7759/cureus.39348 (2023). PMID: 37351249; PMCID: PMC10284564.

    Google Scholar 

  36. Vandecasteele, S. J. & De Vriese, A. S. Recent changes in vancomycin use in renal failure. Kidney Int. 77, 760–764 (2010).

    Google Scholar 

  37. Wong-Beringer, A., Joo, J., Tse, E. & Beringer, P. Vancomycin associated nephrotoxicity: a critical appraisal of risk with high dose therapy. Int. J. Antimicrob. Agents. 37, 95–101 (2011).

    Google Scholar 

  38. Ingram, P. R. et al. Risk factors for nephrotoxicity associated with continuous vancomycin infusion in outpatient parenteral antibiotic therapy. J. Antimicrob. Chemother. 62, 168–171 (2008).

    Google Scholar 

  39. Jeffres, M. N., Isakow, W., Doherty, J. A., Micek, S. T. & Kollef, M. H. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin resistant Staphylococcus aureus pneumonia. Clin. Ther. 29, 1107–1115 (2007).

    Google Scholar 

  40. Long, C., Amin, N. C. & Manan, M. Population pharmacokinetics of vancomycin in hospitalized adult patients at a Malaysian tertiary care hospital. Eur. J. Pharm. Sci. 44, 195–196 (2011).

    Google Scholar 

  41. van de Vijsel, L. M. et al. Initial vancomycin dosing recommendations for critically ill patients undergoing continuous venovenous hemodialysis. Can. J. Hosp. Pharm. 63 (3), 196–206. https://doi.org/10.4212/cjhp.v63i3.915 (2010). PMID: 22478979; PMCID: PMC2901779.

    Google Scholar 

  42. Vázquez, M., Fagiolino, P., Boronat, A., Buroni, M. & Maldonado, C. Therapeutic drug monitoring of vancomycin in severe sepsis and septic shock. Int. J. Clin. Pharmacol. Ther. 46(3), 140–145. https://doi.org/10.5414/cpp46140 (2008). PMID: 18397685.

  43. Lau, A. H. & John, E. Elimination of vancomycin by continuous arteriovenous hemofiltration. Child Nephrol. Urol. 9(4), 232–235 (1988–1989). PMID: 3255486.

  44. Badran, E. F., Shamayleh, A. & Irshaid, Y. M. Pharmacokinetics of vancomycin in neonates admitted to the neonatology unit at the Jordan University Hospital. Int. J. Clin. Pharmacol. Ther. 49(4), 252–257. https://doi.org/10.5414/CP201456 (2011). PMID: 21429439.

  45. Golestaneh, L., Gofran, A., Mokrzycki, M. H. & Chen, J. L. Removal of vancomycin in sustained low-efficiency dialysis (SLED): a need for better surveillance and dosing. Clin. Nephrol. 72(4), 286–291. https://doi.org/10.5414/cnp72286 (2009). PMID: 19825334.

  46. Dolton, M. et al. Vancomycin pharmacokinetics in patients with severe burn injuries. Burns 36 (4), 469–476 (2010). Epub 2009 Oct 28. PMID: 19875238.

    Google Scholar 

  47. Fernández de Gatta, M. D. et al. Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clin. Pharmacol. Ther. 60(3):332–340. https://doi.org/10.1016/S0009-9236(96)90060-0 (1996). PMID: 8841156.

  48. Teramachi, H. et al. Evaluation of predictability for vancomycin dosage regimens by the Bayesian method with Japanese population pharmacokinetic parameters. Biol. Pharm. Bull. 25, 1333–1338 (2002).

    Google Scholar 

  49. Nunn, M. O. et al. Vancomycin dosing: assessment of time to therapeutic concentration and predictive accuracy of pharmacokinetic modeling software. Ann. Pharmacother. 45, 757–763 (2011).

    Google Scholar 

  50. Hazlewood, K. A., Brouse, S. D., Pitcher, W. D. & Hall, R. G. Vancomy cin-associated nephrotoxicity: grave concern or death by char acter assassination? Am. J. Med. 123, 182e1–182e7 (2010).

    Google Scholar 

  51. Wilhelm, M. P. & Estes, L. Symposium on antimicrobial agents–Part XII. Vancomycin. Mayo Clin. Proc. 74(9), 928–935. https://doi.org/10.4065/74.9.928 (1999). PMID: 10488798.

  52. Matsumoto, K. 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. 19 (3), 365–380. https://doi.org/10.1007/s10156-013-0599-4 (2013). Epub 2013 May 15. PMID: 23673472.

    Google Scholar 

  53. Geraci, J. E., Heilman, F. R., Nichols, D. R. & Wellman, W. E. Antibiotic therapy of bacterial endocarditis. VII. Vancomycin for acute micrococcal endocarditis; preliminary report. Proc. Staff Meet Mayo Clin. 33, 172–181 (1958).

    Google Scholar 

  54. Bailie, G. R. & Neal, D. Vancomycin ototoxicity and nephrotoxicity: a review. Med. Toxicol. Advers. Drug Exp. 3 (5), 376–386 (1988).

    Google Scholar 

  55. Forouzesh, A., Moise, P. A. & Sakoulas, G. Vancomycin ototoxicity: a reevaluation in an era of increasing doses. Antimicrob. Agents Chemother. 53, 483–486 (2009).

    Google Scholar 

  56. Humphrey, C., Veve, M. P., Walker, B. & Shorman, M. A. Long-term vancomycin use had low risk of ototoxicity. PLoS One. 14 (11), e0224561. https://doi.org/10.1371/journal.pone.0224561 (2019). PMID: 31693679; PMCID: PMC6834250.

    Google Scholar 

  57. Bruniera, F. R. et al. da Luz Gonçalves Pedreira FL. The use of vancomycin with its therapeutic and adverse effects: a review. Eur. Rev. Med. Pharmacol. Sci. 19(4), 694–700. PMID: 25753888. (2015).

  58. Pritchard, L. et al. Increasing vancomycin serum trough concentrations and incidence of nephrotoxicity. Am. J. Med. 123(12):1143–1149. https://doi.org/10.1016/j.amjmed.2010.07.025 (2010). PMID: 21183005.

  59. Farber, B. F. & Moellering, R. C. Jr Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob. Agents Chemother. ;23(1):138–141. doi: https://doi.org/10.1128/AAC.23.1.138. (1983). PMID: 6219616; PMCID: PMC184631.

  60. Bosso, J. A. et al. Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob. Agents Chemother. 55 (12), 5475–5479. https://doi.org/10.1128/AAC.00168-11 (2011). Epub 2011 Sep 26. PMID: 21947388; PMCID: PMC3232787.

    Google Scholar 

  61. Rybak, M. J. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin. Infect. Dis. 42(Suppl 1), S35–S39. https://doi.org/10.1086/491712 (2006). PMID: 16323118.

  62. Moise-Broder, P. A., Forrest, A., Birmingham, M. C. & Schentag, J. J. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin. Pharmacokinet. 43, 925–942 (2004).

    Google Scholar 

  63. Kullar, R., Davis, S. L., Levine, D. P. & Rybak, M. J. Impact of vanco mycin exposure on outcomes in patients with methicillin-resis tant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin. Infect. Dis. 52, 975–981 (2011).

    Google Scholar 

  64. Liu, C. et al. Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococ cus aureus infections in adults and children. Clin. Infect. Dis. 52, e18–55 (2011).

    Google Scholar 

  65. Christiansen, K. et al. Therapeutic guidelines: antibiotic 14th edn (Therapeutic Guidelines Limited, 2010).

  66. Tsutsuura, M. et al. The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing. BMC Infect. Dis. 21 (1), 153. https://doi.org/10.1186/s12879-021-05858-6 (2021). PMID: 33549035; PMCID: PMC7866743.

    Google Scholar 

  67. Patel, K., Crumby, A. S. & Maples, H. D. Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC? Paediatr Drugs. 17(2), 97–103. https://doi.org/10.1007/s40272-015-0117-5 (2015). PMID: 25644329.

  68. Frymoyer, A. et al. Association between vancomycin trough concentration and area under the concentration-time curve in neonates. Antimicrob. Agents Chemother. 58 (11), 6454–6461. https://doi.org/10.1128/AAC.03620-14 (2014). Epub 2014 Aug 18. PMID: 25136027; PMCID: PMC4249374.

    Google Scholar 

  69. McKamy, S. et al. Incidence and risk factors influencing the development of vancomycin nephrotoxicity in children. J. Pediatr. 158(3), 422–426. https://doi.org/10.1016/j.jpeds.2010.08.019. PMID: 20888013. (2011).

  70. Launay-Vacher, V., Izzedine, H., Mercadal, L. & Deray, G. Clinical review: use of vancomycin in haemodialysis patients. Crit. Care. 6 (4), 313–316. https://doi.org/10.1186/cc1516 (2002). Epub 2002 Jun 10. PMID: 12225605; PMCID: PMC137311.

    Google Scholar 

  71. Kang, J. S. & Lee, M. H. Overview of therapeutic drug monitoring. Korean J. Intern. Med. 24 (1), 1 (2009).

    Google Scholar 

  72. Ingram, P. R., Lye, D. C., Fisher, D. A., Goh, W. P. & Tam, V. H. Nephro toxicity of continuous versus intermittent infusion of vanco mycin in outpatient parenteral antimicrobial therapy. Int. J. Antimicrob. Agents. 34, 570–574 (2009).

    Google Scholar 

  73. Hutschala, D. et al. Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion. Anesthesiology 111, 356–365 (2009).

    Google Scholar 

  74. Cataldo, M. A., Tacconelli, E., Grilli, E., Pea, F. & Petrosillo, N. Con tinuous versus intermittent infusion of vancomycin for the treatment of gram-positive infections: systematic review and meta-analysis. J. Antimicrob. Chemother. 67, 17–24 (2012).

    Google Scholar 

  75. Wunderink, R. G. et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin. Infect. Dis. 54 (5), 621–629. (2012). https://doi.org/10.1093/cid/cir895

    Google Scholar 

  76. Filippone, E. J., Kraft, W. K. & Farber, J. L. The nephrotoxicity of vancomycin. Clin. Pharmacol. Ther. 102 (3), 459–469 (2017).

    Google Scholar 

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Acknowledgements

We appreciated the funders presented in the funding.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81801189) and the “Ying Cai Tuo Ju” Program at the First Affiliated Hospital of Shantou University Medical College (Grant No. YCTJ-2022-03).

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    Jia Wang, Chuzhu Huang, Yan Chen, Yilin Huang & Zhuomin Wu

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  3. Yan Chen
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  4. Yilin Huang
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Contributions

This short text acknowledges the contributions of specific colleagues, institutions, or agencies that aided the efforts of the authors. All the authors contributed to the study conception and design. Project design, patient information verification, and data cleaning, W.J.; paper writing and data checking, W.Z.M.; data inclusion and cleaning, H.C.Z.; data organization and statistical analysis, C.Y.; and data statistics, H.Y.L. All the authors have read and agreed to the published version of the manuscript.

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Correspondence to Zhuomin Wu.

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The authors declare no competing interests.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki. The MIMIC-IV database has received ethical approval from the Institutional Review Boards (IRBs) at Beth Israel Deaconess Medical Center and Massachusetts Institute of Technology. Because the database is publicly available and contains no protected health information, the requirement for ethical approval and informed consent for this study was waived.

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Wang, J., Huang, C., Chen, Y. et al. Vancomycin therapeutic drug monitoring is associated with reduced toxicity in ICU patients: a MIMIC-IV retrospective study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42395-1

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  • Received: 23 August 2025

  • Accepted: 25 February 2026

  • Published: 11 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-42395-1

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Keywords

  • Vancomycin
  • Therapeutic drug monitoring
  • ICU
  • Nephrotoxicity
  • Hepatotoxicity
  • Hematotoxicity
  • MIMIC-IV
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