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Journals / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Cilt: 50 Sayı: 2

FACTORS AFFECTING MEROPENEM TROUGH LEVELS IN CRITICALLY ILL PATIENTS: A THERAPEUTIC DRUG MONITORING STUDY

KRİTİK HASTALARDA MEROPENEM SEVİYELERİNİ ETKİLEYEN FAKTÖRLER: TERAPÖTİK İLAÇ İZLEME ÇALIŞMASI

Ahmet Çakır(INONU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF CLINICAL PHARMACY)0000-0002-9843-1604
Hasan Memiş0000-0001-7158-1795
Zeynep Ülkü Gün(TRAKYA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF CLINICAL PHARMACY)0000-0002-7131-6585
Eren Demirpolat(ERCIYES UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PROFESSIONAL PHARMACEUTICAL SCIENCES, DEPARTMENT OF PHARMACOLOGY)0000-0003-4405-4660
Deccane Düzenci(MALATYA TURGUT OZAL UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF ANAESTHESIOLOGY AND REANIMATION)0000-0002-7572-2759
Murat Bıçakcıoğlu(MALATYA TURGUT OZAL UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF ANAESTHESIOLOGY AND REANIMATION)0000-0001-9101-6857
Çiğdem Karakükcü(ERCIYES UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF BASIC MEDICAL SCIENCES, DEPARTMENT OF MEDICAL BIOCHEMISTRY)0000-0001-9858-3272
Pages
265–276
Publication Date
2026-05-19
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In this study, the target 100% fT > MIC < 4×MIC was not achieved with standard or extended meropenem infusion, potentially limiting clinical cure in ICUs with resistant pathogens, highlighting the need for alternative dosing strategies.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: This study primarily aimed to determine meropenem the trough level (C min ) in intensive care unit (ICU), with an exploratory secondary aim of evaluating factors influencing C min and clinical cure.
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Key Findings & Data:Material and Method: This prospective study included adult ICU patients receiving meropenem for ≥48 hours, and C min levels were measured using a ready-to-use ELISA kit.
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Conclusion & Impact:In this study, the target 100% fT > MIC < 4×MIC was not achieved with standard or extended meropenem infusion, potentially limiting clinical cure in ICUs with resistant pathogens, highlighting the need for alternative dosing strategies.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:İlaç çukur düzeyi · meropenem · terapötik ilaç izlemi

Abstract

Objective: This study primarily aimed to determine meropenem the trough level (C min ) in intensive care unit (ICU), with an exploratory secondary aim of evaluating factors influencing C min and clinical cure. Material and Method: This prospective study included adult ICU patients receiving meropenem for ≥48 hours, and C min levels were measured using a ready-to-use ELISA kit. Result and Discussion: The study included 38 patients, 26 of whom were male. Mean meropenem C min value was found to be 0.40 ± 0.07 mg/l which is statistically different than the target value of 8 mg/l (p < 0.001). We found no statistically significant difference in mean C min between the patient groups whose creatinine clearance was smaller than 50 ml/min and not. Erythrocyte and hemoglobin values decreased after meropenem treatment compared to baseline (p < 0.05). C-Reactive Protein (CRP) decreased, and Sequential Organ Failure Assessment (SOFA) values increased after meropenem treatment (p < 0.001). Logistic regression in patients with Systemic Inflammatory Response Syndrome (SIRS) showed that only SOFA reduced the clinical cure rate (OR 0.534, 95% CI 0.311–0.917). In this study, the target 100% fT > MIC < 4×MIC was not achieved with standard or extended meropenem infusion, potentially limiting clinical cure in ICUs with resistant pathogens, highlighting the need for alternative dosing strategies.

Özet

Amaç: Bu çalışmanın öncelikli amacı yoğun bakım ünitesinde (YBÜ) meropenem çukur seviyesini (C min ) belirlemek, ikincil amacı ise C min ve klinik iyileşmeyi etkileyen faktörleri değerlendirmektir. Gereç ve Yöntem: Bu prospektif çalışmaya, ≥48 saat meropenem alan yetişkin yoğun bakım hastaları dahil edildi ve Cmin düzeyleri hazır kullanıma uygun ELISA kiti ile ölçüldü. Sonuç ve Tartışma: Çalışmaya 26’sı erkek toplam 38 hasta dahil edildi. Ortalama meropenem Cmin değerinin 0.40 ± 0.07 mg/l olduğu bulundu; bu değer, hedef değer olan 8 mg/l'den istatistiksel olarak farklıdır (p < 0.001). Kreatinin klirensi 50 ml/dk'dan az olan ve olmayan hasta grupları arasında ortalama C min açısından istatistiksel olarak anlamlı bir fark bulunmadı. Meropenem tedavisi sonrası eritrosit ve hemoglobin değerleri başlangıç değerlerine göre azaldı (p < 0.05). Meropenem tedavisi sonrasında C-reaktif protein (CRP) azaldı ve Sekansiyel Organ Yetmezliği Değerlendirmesi (SOFA) değerleri arttı (p < 0.001). Sistemik İnflamatuvar Yanıt Sendromu (SIRS) olan hastalarda yapılan lojistik regresyon analizinde yalnızca SOFA’nın klinik iyileşme oranını düşürdüğü görüldü (OR 0.534, %95 CI 0.311–0.917). Çalışmamızda, standart veya uzatılmış meropenem infüzyonu ile hedeflenen 100% fT >MIC < 4×MIC sağlanamadı; bu durum, dirençli patojenlerin sık görüldüğü yoğun bakım ünitelerinde klinik iyileşmeyi sınırlayabilir ve alternatif dozlama stratejilerinin geliştirilmesi gerektiğini göstermektedir.

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Cite This Article

Çakır, A., Memiş, H., Gün, Z. Ü., Demirpolat, E., Düzenci, D., Bıçakcıoğlu, M., Karakükcü, Ç. (2026). FACTORS AFFECTING MEROPENEM TROUGH LEVELS IN CRITICALLY ILL PATIENTS: A THERAPEUTIC DRUG MONITORING STUDY. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 50 Sayı: 2, 265–276. https://doi.org/10.33483/jfpau.1770074

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References (36)

  1. Srzic, I., Nesek Adam, V., Tunjic Pejak, D. (2022). Sepsis definition: What's new in the treatment guidelines. Acta Clinica Croatica, 61(Suppl 1), 67-72. [CrossRef]
  2. Evans, L., Rhodes, A., Alhazzani, W., et al. (2021). Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Medicine, 47(11), 1181-1247. [CrossRef]
  3. Kumar, A., Roberts, D., Wood, K.E., et al. (2006). Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine, 34(6), 1589-1596. [CrossRef]
  4. Abdul-Aziz, M.H., Alffenaar, J.C., Bassetti, M., et al. (2020). Antimicrobial therapeutic drug monitoring in critically ill adult patients: A Position Paper. Intensive Care Medicine, 46(6), 1127-1153. [CrossRef]
  5. Steffens, N.A., Zimmermann, E.S., Nichelle, S.M., et al. (2021). Meropenem use and therapeutic drug monitoring in clinical practice: A literature review. Journal of Clinical Pharmacy and Therapeutics, 46(3), 610-621. [CrossRef]
  6. Levison, M.E., Levison, J.H. (2009). Pharmacokinetics and pharmacodynamics of antibacterial agents. Infectious Disease Clinics of North America, 23(4), 791-815. [CrossRef]
  7. Onufrak, N.J., Forrest, A., Gonzalez, D. (2016). Pharmacokinetic and pharmacodynamic principles of anti-infective dosing. Clinical Therapeutics, 38(9), 1930-1947. [CrossRef]
  8. Liang, S.Y., Kumar, A. (2015). Empiric antimicrobial therapy in severe sepsis and septic shock: Optimizing pathogen clearance. Current Infectious Disease Reports, 17(7), 493. [CrossRef]
  9. Goncalves-Pereira, J., Povoa, P. (2011). Antibiotics in critically ill patients: A systematic review of the pharmacokinetics of beta-lactams. Critical Care, 15(5), R206. [CrossRef]
  10. Roberts, J.A., Abdul-Aziz, M.H., Lipman, J., et al. (2014). Individualised antibiotic dosing for patients who are critically ill: Challenges and potential solutions. Lancet Infectious Diseases, 14(6), 498-509. [CrossRef]
  11. Balakrishnan, I., Shorten, R.J. (2016). Therapeutic drug monitoring of antimicrobials. Annals of Clinical Biochemistry, 53(Pt 3), 333-346. [CrossRef]
  12. Gross, A.S. (1998). Best practice in therapeutic drug monitoring. British Journal of Clinical Pharmacology, 46(2), 95-99. [CrossRef]
  13. Scharf, C., Liebchen, U., Paal, M., et al. (2020). The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome. Journal of Intensive Care, 8(1), 86. [CrossRef]
  14. Fattouh, R., Tijet, N., McGeer, A., et al. (2015). What ıs the appropriate meropenem MIC for screening of carbapenemase-producing enterobacteriaceae in low-prevalence settings? Antimicrobial Agents and Chemotherapy, 60(3), 1556-1559. [CrossRef]
  15. Pea, F., Della Siega, P., Cojutti, P., et al. (2017). Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae? International Journal of Antimicrobial Agents, 49(2), 255-258. [CrossRef]
  16. Ulldemolins, M., Soy, D., Llaurado-Serra, M., et al. (2015). Meropenem population pharmacokinetics in critically ill patients with septic shock and continuous renal replacement therapy: Influence of residual diuresis on dose requirements. Antimicrobial Agents and Chemotherapy, 59(9), 5520-5528. [CrossRef]
  17. Jung, S., Chung, E.K., Jun, M.S., et al. (2019). Differences in colistin administration and bacterial and treatment outcomes in critically ill Patients. Scientific Reports, 9(1), 8781. [CrossRef]
  18. Roberts, J.A., Hope, W.W., Lipman, J. (2010). Therapeutic drug monitoring of beta-lactams for critically ill patients: Unwarranted or essential? International Journal of Antimicrobial Agents, 35(5), 419-420. [CrossRef]
  19. Alsultan, A., Dasuqi, S.A., Aljamaan, F., et al. (2021). Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia. Saudi Pharmaceutical Journal, 29(11), 1272-1277. [CrossRef]
  20. Zhao, H.Y., Gu, J., Lyu, J., et al. (2017). Pharmacokinetic and pharmacodynamic efficacies of continuous versus intermittent administration of meropenem in patients with severe sepsis and septic shock: A prospective randomized pilot study. Chinese Medical Journal, 130(10), 1139-1145. [CrossRef]
  21. Mattioli, F., Fucile, C., Del Bono, V., et al. (2016). Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients. European Journal of Clinical Pharmacology, 72(7), 839-848. [CrossRef]
  22. McWhinney, B.C., Wallis, S.C., Hillister, T., et al. (2010). Analysis of 12 beta-lactam antibiotics in human plasma by HPLC with ultraviolet detection. Journal of Chromatography B, 878(22), 2039-2043. [CrossRef]
  23. Udy, A.A., Varghese, J.M., Altukroni, M., et al. (2012). Subtherapeutic initial beta-lactam concentrations in select critically ill patients: Association between augmented renal clearance and low trough drug concentrations. Chest, 142(1), 30-39. [CrossRef]
  24. Krueger, W.A., Bulitta, J., Kinzig-Schippers, M., et al. (2005). Evaluation by monte carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers. Antimicrobial Agents and Chemotherapy, 49(5), 1881-1889. [CrossRef]
  25. Muller, A.E., Huttner, B., Huttner, A. (2018). Therapeutic drug monitoring of beta-lactams and other antibiotics in the intensive care unit: Which agents, which patients and which infections? Drugs, 78(4), 439-451. [CrossRef]
  26. Scharf, C., Paal, M., Schroeder, I., et al. (2020). Therapeutic drug monitoring of meropenem and piperacillin in critical illness-experience and recommendations from one year in routine clinical practice. Antibiotics (Basel), 9(3). [CrossRef]
  27. Nelson, N.R., Mendoza, C., Rhoney, D.H. (2023). Augmented renal clearance in the hematology and oncology populations: A scoping review for pharmacists. Journal of Pharmacy Practice, 36(6), 1485-1497. [CrossRef]
  28. Tilanus, A., Drusano, G. (2023). Optimizing the use of beta-lactam antibiotics in clinical practice: A test of time. Open Forum Infectious Diseases, 10(7), ofad305. [CrossRef]
  29. Zhao, Y., Xiao, C., Hou, J., et al. (2022). C/MIC > 4: A potential ınstrument to predict the efficacy of meropenem. Antibiotics (Basel), 11(5), 670. [CrossRef]
  30. Chytra, I., Stepan, M., Benes, J., et al. (2012). Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: A randomized open-label controlled trial. Critical Care, 16(3), R113. [CrossRef]
  31. Dulhunty, J.M., Roberts, J.A., Davis, J.S., et al. (2013). Continuous infusion of beta-lactam antibiotics in severe sepsis: A multicenter double-blind, randomized controlled trial. Clinical Infectious Diseases, 56(2), 236-244. [CrossRef]
  32. Wu, C.C., Su, Y.C., Wu, K.S., et al. (2021). Loading dose and efficacy of continuous or extended infusion of beta-lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta-analysis and meta-regression analysis. Journal of Clinical Pharmacy and Therapeutics, 46(2), 424-432. [CrossRef]
  33. Tournayre, S., Mathieu, O., Villiet, M., et al. (2023). Factors associated with meropenem pharmacokinetic/pharmacodynamic target attainment in septic critically ill patients treated with extended intermittent infusion or continuous infusion. International Journal of Antimicrobial Agents, 62(2), 106868. [CrossRef]
  34. Crass, R.L., Rodvold, K.A., Mueller, B.A., et al. (2019). Renal dosing of antibiotics: Are we jumping the gun?. Clinical Infectious Diseases, 68(9), 1596-1602. [CrossRef]
  35. Hassanpour, R., Ziaie, S., Kobarfard, F., et al. (2021). Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease. European Journal of Clinical Pharmacology, 77(6), 831-840. [CrossRef]
  36. Alobaid, A.S., Brinkmann, A., Frey, O.R., et al. (2016). What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients? Journal of Antimicrobial Chemotherapy, 71(3), 696-702. [CrossRef]