Optimizing Vancomycin dosing in a sample of critically ill patients comparing current practices to individualized dose regimen: A Randomized study

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Noor Sameer Al-Khayyat https://orcid.org/0000-0002-0438-4692
Mowafaq Mohammed Ghareeb https://orcid.org/0000-0002-9968-7396
AbdulRasool Noori Al-Moosawi

Keywords

Vancomycin, Drug Monitoring, Area Under Curve, intensive care unit

Abstract

Background: In 2020, a revised consensus guideline of therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections was published, and reviewed by many regulatory authorities Stated that, in patients with suspected or definitive serious MRSA infections, an individualized dose targeting area under the curve over 24 hour (AUC24) to minimum inhibitory concentration (MIC) ratio of 400 to 600 mcg*hr/mL should be advocated to achieve clinical efficacy and improving patient safety, while many hospitals in Iraq utilize fixed manufacturer-recommended dose for vancomycin in patients with normal renal function which is 30 mg/kg/d given as two or four divided daily doses. Objective: Comparing vancomycin AUC24/MIC ratio of patients receiving conventional vancomycin doses to patients receiving individualized doses calculated by pharmacokinetic dosing methods. Methods: A prospective randomized study conducted in the Intensive Care Units (ICU) of two tertiary centers at Baghdad Medical Complex (Baghdad Teaching Hospital and Ghazi Al-Hariri Hospital for Surgical Specialties), Patients were assigned alternately, 30 patients who met inclusion criteria were assigned to the conventional group (group 1), receiving the conventional dose of 1 g of vancomycin every 12 hours or any other dose prescribed by ICU physicians, representing the current practice; and 30 patients were assigned to the interventional group (group 2), where vancomycin dose was calculated by pharmacokinetic dosing method. Results: The target AUC24/MIC Ratio of 400 – 600 mcg*hr/mL was achieved in 6 (20%) patients of group 1, and 16 (53.33%) patients of group 2, which was statistically significant with P-value 0.000. Conclusions: Individualized vancomycin dosing improved achievement of the therapeutic AUC24/MIC target versus conventional dosing (53.3% vs 20.0%) but was associated with increased nephrotoxicity.

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References

1. Katzung BG. Basic and Clinical Pharmacology 14th Edition: McGraw-Hill Education; 2018.
2. Laurence L. Brunton RH-D, Bjorn C. Knollmann. Goodman and Gilman’s, The Pharmacological Basis of Therapeutics, 13th Edition: McGraw-Hill Education; 2018.
3. Brayfield A. Martindale, The Complete Drug Reference 38th Edition: Pharmaceutical Press; 2014.
4. Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC, Jr., Craig WA, Billeter M, et al. Therapeutic monitoring of van- comycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2009;29(11):1275-9.
5. James M. Ritter RF, Graeme Henderson, Yoon Kong Loke, David MacEwan, Humphrey P. Rang. Rang and Dale’s Pharma- cology 9th Edition: Elsevier Ltd.; 2020.
6. Schäfer M, Schneider TR, Sheldrick GM. Crystal structure of vancomycin. Structure. 1996;4(12):1509-15.
7. Levine DP. Vancomycin: a history. Clin Infect Dis. 2006;42 Suppl 1:S5-12.
8. Moellering RC, Jr. Vancomycin: a 50-year reassessment. Clin Infect Dis. 2006;42 Suppl 1:S3-4.
9. Vandecasteele SJ, Boelaert JR, De Vriese AS. Staphylococcus aureus infections in hemodialysis: what a nephrologist should know. Clin J Am Soc Nephrol. 2009;4(8):1388-400.
10. Kan WC, Chen YC, Wu VC, Shiao CC. Vancomycin-Associated Acute Kidney Injury: A Narrative Review from Pathophysiolo- gy to Clinical Application. Int J Mol Sci. 2022;23(4).
11. Ye ZK, Li C, Zhai SD. Guidelines for therapeutic drug monitoring of vancomycin: a systematic review. PLoS One. 2014;9(6):e99044.
12. Rybak MJ. The Pharmacokinetic and Pharmacodynamic Properties of Vancomycin. Clinical Infectious Diseases. 2006;42(Supplement_1):S35-S9.
13. Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986;11(4):257-82.
14. Bauer LA. Applied Clinical Pharmacokinetics 3rd Edition: Mc Graw Hill Education; 2014.
15. Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, et al. Therapeutic monitoring of vancomycin for serious methi- cillin-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):835-64.
16. Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP. Vancomycin: we can’t get there from here. Clin Infect Dis. 2011;52(8):969-74.
17. Pai MP, Neely M, Rodvold KA, Lodise TP. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev. 2014;77:50-7.
18. Heil EL, Claeys KC, Mynatt RP, Hopkins TL, Brade K, Watt I, et al. Making the change to area under the curve-based vanco- mycin dosing. Am J Health Syst Pharm. 2018;75(24):1986-95.
19. Belavagi D, Bhandari RK, Shafiq N, Gota V, Patil A, Pandey AK, et al. A study to explore the appropriateness of dosing reg- imen of vancomycin in critically ill patients in a tertiary care unit of India. Germs. 2022;12(2):238-52.
20. Mali NB, Deshpande SP, Wandalkar PP, Gupta VA, Karnik ND, Gogtay NJ, et al. Single-dose and Steady-state Pharmaco- kinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India. Indian J Crit Care Med. 2019;23(11):513-7.
21. Shahrami B, Najmeddin F, Mousavi S, Ahmadi A, Rouini MR, Sadeghi K, et al. Achievement of Vancomycin Therapeutic Goals in Critically Ill Patients: Early Individualization May Be Beneficial. Crit Care Res Pract. 2016;2016:1245815.
22. Al-Sulaiti FK, Nader AM, Saad MO, Shaukat A, Parakadavathu R, Elzubair A, et al. Clinical and Pharmacokinetic Outcomes of Peak-Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Random- ized Controlled Trial. Eur J Drug Metab Pharmacokinet. 2019;44(5):639-52.
23. Roy AK, Mc Gorrian C, Treacy C, Kavanaugh E, Brennan A, Mahon NG, et al. A Comparison of Traditional and Novel Defi- nitions (RIFLE, AKIN, and KDIGO) of Acute Kidney Injury for the Prediction of Outcomes in Acute Decompensated Heart Failure. Cardiorenal Med. 2013;3(1):26-37.
24. Aljefri DM, Avedissian SN, Rhodes NJ, Postelnick MJ, Nguyen K, Scheetz MH. Vancomycin Area Under the Curve and Acute Kidney Injury: A Meta-analysis. Clin Infect Dis. 2019;69(11):1881-7.
25. Suzuki Y, Kawasaki K, Sato Y, Tokimatsu I, Itoh H, Hiramatsu K, et al. Is peak concentration needed in therapeutic drug monitoring of vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant staphylo- coccus aureus pneumonia. Chemotherapy. 2012;58(4):308-12.
26. Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49(4):507-14.