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Evaluation of the Appropriateness of Antimicrobial Drug Dosages in Intensive Care Unit Patients

Year 2024, , 38 - 45, 01.03.2024
https://doi.org/10.52794/hujpharm.1302724

Abstract

The purpose of this study was to investigate the factors that required dose adjustments of antimicrobial drugs in intensive care unit (ICU) patients and to identify the drugs that required the most dose adjustments. The current prospective study was conducted in the reanimation ICU with 26-bed capacity of a university-affiliated hospital from September to December 2022. Two clinical pharmacists on duty examined patients’ antimicrobial drug dosages daily. The acceptance status of the recommendations and the patients’ demographic information were recorded. The study involved 133 ICU patients, and antimicrobial drug recommendations were made for 48 patients, 31 (64.6%) of whom were male. The median (IQR) age of the 48 patients was 67 (54–77). The count of recommendations was 94, and the acceptance rate was 100%. The recommendation rates were as follows: 71.3% for renal function, 11.7% for presence of continuous renal replacement therapy, 10.6% for indication, 4.3% for body weight, and 2.1% for loading dose. The top 3 drugs for which recommendations were made the most were colistin (21.3%), meropenem (18.1%), and piperacillin-tazobactam (12.8%). The most troublesome drug was colistin, which is frequently used to treat Acinetobacter pneumonia. Clinical pharmacist and physician collaboration may help rationalize ICU antimicrobial drug use.

References

  • 1. Versporten A, Zarb P, Caniaux I, Gros M-F, Drapier N, Miller M, et al. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: Results of an internet-based global point prevalence survey. Lancet Glob Health. 2018;6(6):e619-e29. https://doi.org/10.1016/s2214-109x(18)30186-4
  • 2. Onufrak NJ, Forrest A, Gonzalez D. Pharmacokinetic and pharmacodynamic principles of anti-infective dosing. Clin Ther. 2016;38(9):1930-47. https://doi.org/10.1016/j.clinthera.2016.06.015
  • 3. Rawson TM, Wilson RC, O’Hare D, Herrero P, Kambugu A, Lamorde M, et al. Optimizing antimicrobial use: Challenges, advances and opportunities. Nat Rev Microbiol. 2021;19(12):747-58. https://doi.org/10.1038/s41579-021-00578-9
  • 4. Chai MG, Cotta MO, Abdul-Aziz MH, Roberts JA. What Are the current approaches to optimising antimicrobial dosing in the intensive care unit? Pharmaceutics. 2020;12(7). https://doi.org/10.3390/pharmaceutics12070638
  • 5. Timsit J-F, Bassetti M, Cremer O, Daikos G, De Waele J, Kallil A, et al. Rationalizing antimicrobial therapy in the ICU: A narrative review. Intensive Care Med. 2019;45(2):172-89. https://doi.org/10.1007/s00134-019-05520-5
  • 6. Roberts JA, Joynt GM, Choi GY, Gomersall CD, Lipman J. How to optimise antimicrobial prescriptions in the intensive care unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics. Int J Antimicrob Agents. 2012;39(3):187-92. https://doi.org/10.1016/j.ijantimicag.2011.11.002
  • 7. De Pascale G, Fortuna S, Tumbarello M, Cutuli SL, Vallecoccia M, Spanu T, et al. Linezolid plasma and intrapulmonary concentrations in critically ill obese patients with ventilatorassociated pneumonia: Intermittent vs continuous administration. Intensive Care Med. 2015;41(1):103-10. https://doi.org/10.1007/s00134-014-3550-y
  • 8. Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, et al. A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis. Am J Respir Crit Care Med. 2015;192(11):1298-305. https://doi.org/10.1164/rccm.201505-0857OC
  • 9. Patini R, Mangino G, Martellacci L, Quaranta G, Masucci L, Gallenzi P. The effect of different antibiotic regimens on bacterial resistance: A systematic review. Antibiotics (Basel). 2020;9(1). https://doi.org/10.3390/antibiotics9010022
  • 10. Jamal J-A, Economou CJ, Lipman J, Roberts JA. Improving antibiotic dosing in special situations in the ICU: burns, renal replacement therapy and extracorporeal membrane oxygenation. Curr Opin Crit Care. 2012;18(5):460-71. https://doi.org/10.1097/MCC.0b013e32835685ad
  • 11. Jiang SP, Zhu ZY, Ma KF, Zheng X, Lu XY. Impact of pharmacist antimicrobial dosing adjustments in septic patients on continuous renal replacement therapy in an intensive care unit. Scand J Infect Dis. 2013;45(12):891-9. https://doi.org/10.3109/00365548.2013.827338
  • 12. Leache L, Aquerreta I, Aldaz A, Monedero P, Idoate A, Ortega A. Clinical and economic impact of clinical pharmacist interventions regarding antimicrobials on critically ill patients. Res Social Adm Pharm. 2020;16(9):1285-9. https://doi.org/10.1016/j.sapharm.2019.07.006
  • 13. Díaz-Madriz JP, Zavaleta-Monestel E, Chaverri-Fernández JM, Arguedas-Chacón S, Arguedas-Herrera R, Leiva-Montero B, et al. Impact of a pharmacist-driven antimicrobial stewardship program on the prescription of antibiotics by intensive care physicians in a Latin American hospital: A retrospective study. J Am Coll Clin Pharm. 2022;5(11):1148-55. https://doi.org/10.1002/jac5.1708
  • 14. Huang H, Chen B, Liu G, Ran J, Lian X, Huang X, et al. A multi-center study on the risk factors of infection caused by multidrug resistant Acinetobacter baumannii. BMC Infect Dis. 2018;18(1):11. https://doi.org/10.1186/s12879-017-2932-5
  • 15. Murray G, Peleg A, Doi Y. Acinetobacter baumannii: Evolution of antimicrobial resistance-treatment options. Semin Respir Crit Care Med. 2015;36(01):085-98. https://doi.org/10.1055/s-0034-1398388
  • 16. Zhanel G, Clark N, Lynch J. Infections due to Acinetobacter baumannii in the ICU: Treatment options. Semin Respir Crit Care Med. 2017;38(03):311-25. https://doi.org/10.1055/s-0037-1599225
  • 17. Joannidis M, Druml W, Forni LG, Groeneveld ABJ, Honore PM, Hoste E, et al. Prevention of acute kidney injury and protection of renal function in the intensive care unit: Update 2017. Intensive Care Med. 2017;43(6):730-49. https://doi.org/10.1007/s00134-017-4832-y
  • 18. Fiaccadori E, Antonucci E, Morabito S, d’Avolio A, Maggiore U, Regolisti G. Colistin use in patients with reduced kidney function. Am J Respir Crit Care Med. 2016;68(2):296-306. https://doi.org/10.1053/j.ajkd.2016.03.421
  • 19. Stankowicz MS, Ibrahim J, Brown DL. Once-daily aminoglycoside dosing: An update on current literature. Am J Health Syst Pharm. 2015;72(16):1357-64. https://doi.org/10.2146/ajhp140564
  • 20. Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995;39(3):650-5. https://doi.org/10.1128/aac.39.3.650
  • 21. Abdul–Aziz MH, Brady K, Cotta MO, Roberts JA. Therapeutic drug monitoring of antibiotics: Defining the therapeutic range. Ther Drug Monit. 2022;44(1):19-31. https://doi.org/10.1097/FTD.0000000000000940
  • 22. Harding I, MacGowan A, White L, Darley E, Reed V. Teicoplanin therapy for Staphylococcus aureus septicaemia: Relationship between pre-dose serum concentrations and outcome. J Antimicrob Chemother. 2000;45(6):835-41. https://doi.org/10.1093/jac/45.6.835.
  • 23. Rowland M. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet. 1990;18:184-209. https://doi.org/10.2165/00003088-199018030-00002
  • 24. Sato M, Chida K, Suda T, Gemma H, Nakamura H, Muramatsu H, et al. Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level. J Infect Chemother. 2006;12(4):185-9. https://doi.org /10.1007/s10156-006-0446-y
  • 25. Wilson AP. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet. 2000;39(3):167-83. https://doi.org/10.2165/00003088-200039030-00001
  • 26. Tekosit (teicoplanin) [package insert]. Istanbul, TR: Kocak Pharmaceutical Company; 2007.
  • 27. Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic dosing for critically ill adult patients receiving intermittent hemodialysis, prolonged intermittent renal replacement therapy, and continuous renal replacement therapy: An update. Ann Pharmacother. 2020;54(1):43-55. https://doi.org/10.1177/1060028019865873
  • 28. Shaw AR, Chaijamorn W, Mueller BA. We underdose antibiotics in patients on CRRT. Semin Dial. 2016;29(4):278-80. https://doi.org/10.1111/sdi.12496
  • 29. Jiang S-P, Xu Y-Y, Yang P, Wu W-F, Zhang X-G, Lu X-Y, et al. Improving antimicrobial dosing in critically ill patients receiving continuous venovenous hemofiltration and the effect of pharmacist dosing adjustment. Eur J Intern Med. 2014;25(10):930-5. https://doi.org/10.1016/j.ejim.2014.08.001
  • 30. Jiang S-P, Zhu Z-Y, Ma K-F, Zheng X, Lu X-Y. Impact of pharmacist antimicrobial dosing adjustments in septic patients on continuous renal replacement therapy in an intensive care unit. Scand J Infect Dis. 2013;45(12):891-9. https://doi.org/10.3109/00365548.2013.827338
  • 31. Jiang S-P, Zhu Z-Y, Wu X-L, Lu X-Y, Zhang X-G, Wu B-H. Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: A comparative study. Ther Clin Risk Manag. 2014:405-12. https://doi.org/10.2147/TCRM.S59187

Evaluation of the Appropriateness of Antimicrobial Drug Dosages in Intensive Care Unit Patients

Year 2024, , 38 - 45, 01.03.2024
https://doi.org/10.52794/hujpharm.1302724

Abstract

The purpose of this study was to investigate the factors that required dose adjustments of antimicrobial drugs in intensive care unit (ICU) patients and to identify the drugs that required the most dose adjustments. The current prospective study was conducted in the reanimation ICU with 26-bed capacity of a university-affiliated hospital from September to December 2022. Two clinical pharmacists on duty examined patients’ antimicrobial drug dosages daily. The acceptance status of the recommendations and the patients’ demographic information were recorded. The study involved 133 ICU patients, and antimicrobial drug recommendations were made for 48 patients, 31 (64.6%) of whom were male. The median (IQR) age of the 48 patients was 67 (54–77). The count of recommendations was 94, and the acceptance rate was 100%. The recommendation rates were as follows: 71.3% for renal function, 11.7% for presence of continuous renal replacement therapy, 10.6% for indication, 4.3% for body weight, and 2.1% for loading dose. The top 3 drugs for which recommendations were made the most were colistin (21.3%), meropenem (18.1%), and piperacillin-tazobactam (12.8%). The most troublesome drug was colistin, which is frequently used to treat Acinetobacter pneumonia. Clinical pharmacist and physician collaboration may help rationalize ICU antimicrobial drug use.

References

  • 1. Versporten A, Zarb P, Caniaux I, Gros M-F, Drapier N, Miller M, et al. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: Results of an internet-based global point prevalence survey. Lancet Glob Health. 2018;6(6):e619-e29. https://doi.org/10.1016/s2214-109x(18)30186-4
  • 2. Onufrak NJ, Forrest A, Gonzalez D. Pharmacokinetic and pharmacodynamic principles of anti-infective dosing. Clin Ther. 2016;38(9):1930-47. https://doi.org/10.1016/j.clinthera.2016.06.015
  • 3. Rawson TM, Wilson RC, O’Hare D, Herrero P, Kambugu A, Lamorde M, et al. Optimizing antimicrobial use: Challenges, advances and opportunities. Nat Rev Microbiol. 2021;19(12):747-58. https://doi.org/10.1038/s41579-021-00578-9
  • 4. Chai MG, Cotta MO, Abdul-Aziz MH, Roberts JA. What Are the current approaches to optimising antimicrobial dosing in the intensive care unit? Pharmaceutics. 2020;12(7). https://doi.org/10.3390/pharmaceutics12070638
  • 5. Timsit J-F, Bassetti M, Cremer O, Daikos G, De Waele J, Kallil A, et al. Rationalizing antimicrobial therapy in the ICU: A narrative review. Intensive Care Med. 2019;45(2):172-89. https://doi.org/10.1007/s00134-019-05520-5
  • 6. Roberts JA, Joynt GM, Choi GY, Gomersall CD, Lipman J. How to optimise antimicrobial prescriptions in the intensive care unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics. Int J Antimicrob Agents. 2012;39(3):187-92. https://doi.org/10.1016/j.ijantimicag.2011.11.002
  • 7. De Pascale G, Fortuna S, Tumbarello M, Cutuli SL, Vallecoccia M, Spanu T, et al. Linezolid plasma and intrapulmonary concentrations in critically ill obese patients with ventilatorassociated pneumonia: Intermittent vs continuous administration. Intensive Care Med. 2015;41(1):103-10. https://doi.org/10.1007/s00134-014-3550-y
  • 8. Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, et al. A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis. Am J Respir Crit Care Med. 2015;192(11):1298-305. https://doi.org/10.1164/rccm.201505-0857OC
  • 9. Patini R, Mangino G, Martellacci L, Quaranta G, Masucci L, Gallenzi P. The effect of different antibiotic regimens on bacterial resistance: A systematic review. Antibiotics (Basel). 2020;9(1). https://doi.org/10.3390/antibiotics9010022
  • 10. Jamal J-A, Economou CJ, Lipman J, Roberts JA. Improving antibiotic dosing in special situations in the ICU: burns, renal replacement therapy and extracorporeal membrane oxygenation. Curr Opin Crit Care. 2012;18(5):460-71. https://doi.org/10.1097/MCC.0b013e32835685ad
  • 11. Jiang SP, Zhu ZY, Ma KF, Zheng X, Lu XY. Impact of pharmacist antimicrobial dosing adjustments in septic patients on continuous renal replacement therapy in an intensive care unit. Scand J Infect Dis. 2013;45(12):891-9. https://doi.org/10.3109/00365548.2013.827338
  • 12. Leache L, Aquerreta I, Aldaz A, Monedero P, Idoate A, Ortega A. Clinical and economic impact of clinical pharmacist interventions regarding antimicrobials on critically ill patients. Res Social Adm Pharm. 2020;16(9):1285-9. https://doi.org/10.1016/j.sapharm.2019.07.006
  • 13. Díaz-Madriz JP, Zavaleta-Monestel E, Chaverri-Fernández JM, Arguedas-Chacón S, Arguedas-Herrera R, Leiva-Montero B, et al. Impact of a pharmacist-driven antimicrobial stewardship program on the prescription of antibiotics by intensive care physicians in a Latin American hospital: A retrospective study. J Am Coll Clin Pharm. 2022;5(11):1148-55. https://doi.org/10.1002/jac5.1708
  • 14. Huang H, Chen B, Liu G, Ran J, Lian X, Huang X, et al. A multi-center study on the risk factors of infection caused by multidrug resistant Acinetobacter baumannii. BMC Infect Dis. 2018;18(1):11. https://doi.org/10.1186/s12879-017-2932-5
  • 15. Murray G, Peleg A, Doi Y. Acinetobacter baumannii: Evolution of antimicrobial resistance-treatment options. Semin Respir Crit Care Med. 2015;36(01):085-98. https://doi.org/10.1055/s-0034-1398388
  • 16. Zhanel G, Clark N, Lynch J. Infections due to Acinetobacter baumannii in the ICU: Treatment options. Semin Respir Crit Care Med. 2017;38(03):311-25. https://doi.org/10.1055/s-0037-1599225
  • 17. Joannidis M, Druml W, Forni LG, Groeneveld ABJ, Honore PM, Hoste E, et al. Prevention of acute kidney injury and protection of renal function in the intensive care unit: Update 2017. Intensive Care Med. 2017;43(6):730-49. https://doi.org/10.1007/s00134-017-4832-y
  • 18. Fiaccadori E, Antonucci E, Morabito S, d’Avolio A, Maggiore U, Regolisti G. Colistin use in patients with reduced kidney function. Am J Respir Crit Care Med. 2016;68(2):296-306. https://doi.org/10.1053/j.ajkd.2016.03.421
  • 19. Stankowicz MS, Ibrahim J, Brown DL. Once-daily aminoglycoside dosing: An update on current literature. Am J Health Syst Pharm. 2015;72(16):1357-64. https://doi.org/10.2146/ajhp140564
  • 20. Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995;39(3):650-5. https://doi.org/10.1128/aac.39.3.650
  • 21. Abdul–Aziz MH, Brady K, Cotta MO, Roberts JA. Therapeutic drug monitoring of antibiotics: Defining the therapeutic range. Ther Drug Monit. 2022;44(1):19-31. https://doi.org/10.1097/FTD.0000000000000940
  • 22. Harding I, MacGowan A, White L, Darley E, Reed V. Teicoplanin therapy for Staphylococcus aureus septicaemia: Relationship between pre-dose serum concentrations and outcome. J Antimicrob Chemother. 2000;45(6):835-41. https://doi.org/10.1093/jac/45.6.835.
  • 23. Rowland M. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet. 1990;18:184-209. https://doi.org/10.2165/00003088-199018030-00002
  • 24. Sato M, Chida K, Suda T, Gemma H, Nakamura H, Muramatsu H, et al. Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level. J Infect Chemother. 2006;12(4):185-9. https://doi.org /10.1007/s10156-006-0446-y
  • 25. Wilson AP. Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet. 2000;39(3):167-83. https://doi.org/10.2165/00003088-200039030-00001
  • 26. Tekosit (teicoplanin) [package insert]. Istanbul, TR: Kocak Pharmaceutical Company; 2007.
  • 27. Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic dosing for critically ill adult patients receiving intermittent hemodialysis, prolonged intermittent renal replacement therapy, and continuous renal replacement therapy: An update. Ann Pharmacother. 2020;54(1):43-55. https://doi.org/10.1177/1060028019865873
  • 28. Shaw AR, Chaijamorn W, Mueller BA. We underdose antibiotics in patients on CRRT. Semin Dial. 2016;29(4):278-80. https://doi.org/10.1111/sdi.12496
  • 29. Jiang S-P, Xu Y-Y, Yang P, Wu W-F, Zhang X-G, Lu X-Y, et al. Improving antimicrobial dosing in critically ill patients receiving continuous venovenous hemofiltration and the effect of pharmacist dosing adjustment. Eur J Intern Med. 2014;25(10):930-5. https://doi.org/10.1016/j.ejim.2014.08.001
  • 30. Jiang S-P, Zhu Z-Y, Ma K-F, Zheng X, Lu X-Y. Impact of pharmacist antimicrobial dosing adjustments in septic patients on continuous renal replacement therapy in an intensive care unit. Scand J Infect Dis. 2013;45(12):891-9. https://doi.org/10.3109/00365548.2013.827338
  • 31. Jiang S-P, Zhu Z-Y, Wu X-L, Lu X-Y, Zhang X-G, Wu B-H. Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: A comparative study. Ther Clin Risk Manag. 2014:405-12. https://doi.org/10.2147/TCRM.S59187
There are 31 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Research Articles
Authors

Hasan Memiş 0000-0001-7158-1795

Ahmet Çakır 0000-0002-9843-1604

Nesligül Özdemir 0000-0003-2551-9549

Zeynep Ülkü Gün 0000-0002-7131-6585

Publication Date March 1, 2024
Acceptance Date August 15, 2023
Published in Issue Year 2024

Cite

Vancouver Memiş H, Çakır A, Özdemir N, Gün ZÜ. Evaluation of the Appropriateness of Antimicrobial Drug Dosages in Intensive Care Unit Patients. HUJPHARM. 2024;44(1):38-45.