Penyesuaian Dosis Antibiotik pada Pasien Sepsis dengan Acute Kidney Injury dan Continuous Renal Replacement Therapy
Keywords:
Acute kidney injury, antibiotic dosing, continuous renal replacement theraphy, pharmacokinetics, sepsisAbstract
Sepsis is a life-threatening condition frequently complicated by acute kidney injury (AKI), resulting in substantial alterations in antibiotic pharmacokinetics. In critically ill patients requiring continuous renal replacement therapy (CRRT), antibiotic dosing becomes increasingly challenging because drug disposition is affected by both sepsis-related physiological changes and extracorporeal drug removal. This narrative review aimed to summarize current evidence regarding antibiotic dose adjustment in septic patients with AKI receiving CRRT and to discuss strategies for optimizing antimicrobial therapy. A narrative literature review was conducted using publications retrieved from PubMed and Scopus within the last ten years. The selected literature was analyzed to evaluate pharmacokinetic alterations, CRRT-related factors affecting antibiotic clearance, and dosing recommendations for commonly prescribed antibiotics, including meropenem, piperacillin/tazobactam, sefepim, and vancomycin. The reviewed evidence demonstrated that increased volume of distribution, hypoalbuminemia, augmented renal clearance, CRRT modality, effluent rate, membrane characteristics, and protein binding substantially influence antibiotic exposure and pharmacokinetic/pharmacodynamic target attainment. Current evidence supports individualized dosing strategies using loading doses, prolonged or continuous infusion, and therapeutic drug monitoring to optimize therapeutic efficacy while minimizing toxicity and antimicrobial resistance. Appropriate antibiotic dose adjustment based on patient characteristics and CRRT parameters is essential to improve clinical outcomes in septic patients with AKI.
References
Al-Shaer, M. H., Alghamdi, W. A., Graham, E., & Peloquin, C. A. (2020). Meropenem, Sefepim, and Piperacillin Protein Binding in Patient Samples. Therapeutic Drug Monitoring, 42(1), 129–132. https://doi.org/10.1097/FTD.0000000000000675
Al-Shaer, M. H., Philpott, C. D., Droege, C. A., Courter, J. D., Healy, D. P., Droege, M. E., Ernst, N. E., Mueller, E. W., & Peloquin, C. A. (2021). Sefepim population pharmacokinetics and target attainment in critically ill patients on continuous renal replacement therapy. Antimicrobial Agents and Chemotherapy, 65(6). https://doi.org/10.1128/AAC.00144-21
Bilbao-Meseguer, I., Rodríguez-Gascón, A., Barrasa, H., Isla, A., & Solinís, M. Á. (2018). Augmented Renal Clearance in Critically Ill Patients: A Systematic Review. Clinical Pharmacokinetics 2018 57:9, 57(9), 1107–1121. https://doi.org/10.1007/S40262-018-0636-7
Choi, G., Gomersall, C. D., Tian, Q., Joynt, G. M., Freebairn, R., & Lipman, J. (2009). Principles of antibacterial dosing in continuous renal replacement therapy. Critical Care Medicine, 37(7), 2268–2282. https://doi.org/10.1097/CCM.0B013E3181AAB3D0
Corona, A., Cattaneo, D., & Latronico, N. (2022). Antibiotic Therapy in the Critically Ill with Acute Renal Failure and Renal Replacement Therapy: A Narrative Review. Antibiotics 2022, Vol. 11, Page 1769, 11(12), 1769. https://doi.org/10.3390/ANTIBIOTICS11121769
Hahn, J., Lok Min, K., Kang, S., Yang, S., Soo Park, M., Wi, J., Jung Chang, M., & Min Jung Chang, or. (2021). Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy. https://journals.asm.org/journal/spectrum
Jang, S. M., Infante, S., & Abdi Pour, A. (2020). Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy. Pharmacy, 8(1), 18. https://doi.org/10.3390/pharmacy8010018
Kuwana, T., Kinoshita, K., Kanai, Y., Yamaya, Y., Takahashi, K., Ishizuka, S., & Imai, T. (2026). Impact of High-Dose Sefepim During the Initial 48 h on Intensive Care Unit Survival in Sepsis: A Retrospective Observational Study. Antibiotics, 15(1), 88. https://doi.org/10.3390/antibiotics15010088
Lamamri, M., Rutman, C., Codorniu, A., Holleville, M., Sigaut, S., Weiss, E., & Jeantrelle, C. (2026). Safety concerns associated with high-dose continuous infusion of sefepim among critically ill patients with mild renal impairment to augmented renal clearance at a level 1 trauma center: CEFTOX study. Antimicrobial Agents and Chemotherapy, 70(3), e0173525. https://doi.org/10.1128/aac.01735-25
Levy, M. M., Evans, L. E., & Rhodes, A. (2018). The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Medicine, 44(6), 925–928. https://doi.org/10.1007/s00134-018-5085-0
Li, L., Li, X., Xia, Y., Chu, Y., Zhong, H., Li, J., Liang, P., Bu, Y., Zhao, R., Liao, Y., Yang, P., Lu, X., & Jiang, S. (2020). Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy. In Frontiers in Pharmacology (Vol. 11). Frontiers Media S.A. https://doi.org/10.3389/fphar.2020.00786
Mahmoud, S. H., & Shen, C. (2017). Augmented renal clearance in critical illness: An important consideration in drug dosing. In Pharmaceutics (Vol. 9, Number 3). MDPI AG. https://doi.org/10.3390/pharmaceutics9030036
Peng, Y., Liu, Y., Cheng, Z., Zhang, Q., Xie, F., Zhu, S., & Li, S. (2025). Population Pharmacokinetics of Prolonged Infusion for Meropenem: Tailoring Dosing Recommendations for Chinese Critically Ill Patients on Continuous Renal Replacement Therapy with Consideration for Renal Function. Drug Design, Development and Therapy, 19, 1105–1117. https://doi.org/10.2147/DDDT.S489603
Philpott, C. D., Droege, C. A., Droege, M. E., Healy, D. P., Courter, J. D., Ernst, N. E., Harger, N. J., Foertsch, M. J., Winter, J. B., Carter, K. E., Van Fleet, S. L., Athota, K., & Mueller, E. W. (2019). Pharmacokinetics and Pharmacodynamics of Extended-Infusion Sefepim in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open-Label Study. Pharmacotherapy, 39(11), 1066–1076. https://doi.org/10.1002/phar.2332
Pistolesi, V., Morabito, S., Di Mario, F., Regolisti, G., Cantarelli, C., & Fiaccadori, E. (2019). A guide to understanding antimicrobial drug dosing in critically ill patients on renal replacement therapy. Antimicrobial Agents and Chemotherapy, 63(8). https://doi.org/10.1128/AAC.00583-19;JOURNAL:JOURNAL:AAC;WGROUP:STRING:PUBLICATION
Roberts, J. A., & Roberts, D. M. (2014). Antibiotic dosing in critically ill patients with septic shock and on continuous renal replacement therapy: Can we resolve this problem with pharmacokinetic studies and dosing guidelines? In Critical Care (Vol. 18, Number 3). BioMed Central Ltd. https://doi.org/10.1186/cc13939
Rudd, K. E., Johnson, S. C., Agesa, K. M., Shackelford, K. A., Tsoi, D., Kievlan, D. R., Colombara, D. V., Ikuta, K. S., Kissoon, N., Finfer, S., Fleischmann-Struzek, C., Machado, F. R., Reinhart, K. K., Rowan, K., Seymour, C. W., Watson, R. S., West, T. E., Marinho, F., Hay, S. I., … Naghavi, M. (2020). Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. The Lancet, 395(10219), 200–211. https://doi.org/10.1016/S0140-6736(19)32989-7
Rungkitwattanakul, D., Chaijamorn, W., Charoensareerat, T., Charntrakarn, P., Khamkampud, O., Rattanaponpasert, N., Srisawat, N., & Pattharachayakul, S. (2021). Optimal levofloksasin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy. Journal of Critical Care, 63, 154–160. https://doi.org/10.1016/j.jcrc.2020.09.018
Singer, M., Deutschman, C. S., Seymour, C., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J. D., Coopersmith, C. M., Hotchkiss, R. S., Levy, M. M., Marshall, J. C., Martin, G. S., Opal, S. M., Rubenfeld, G. D., Poll, T. Der, Vincent, J. L., & Angus, D. C. (2016). The third international consensus definitions for sepsis and septic shock (sepsis-3). In JAMA - Journal of the American Medical Association (Vol. 315, Number 8, pp. 801–810). American Medical Association. https://doi.org/10.1001/jama.2016.0287
Sulaiman, H., Rozali, M. A., Adiraju, S. K. S., Hasan, M. S., Jamal, J. A., Liu, X., Mat-Nor, M. B., Mazlan, M. Z., Othman-Jailani, M. I., Salmuna, Z. N., Wallis, S. C., Roberts, J. A., & Abdul-Aziz, M. H. (2025). Meropenem dosing optimization on day 1 and steady state in critically ill patients without significant renal impairment. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-20630-5
Trotman, R. L., Williamson, J. C., Shoemaker, D. M., & Salzer, W. L. (2005). Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy. Clinical Infectious Diseases, 41(8), 1159–1166. https://doi.org/10.1086/444500
Vega Harwood, A. W., Fernández, M. M., Ezquer Garin, C., Álvarez, F. J., López Herrero, R., Tamayo, E., & Aguilar, G. (2025). Antimicrobial Dosing During Continuous Venovenous Hemodiafiltration in Septic Shock Patients: A Prospective, Multicenter Study Protocol. Antibiotics, 14(4). https://doi.org/10.3390/antibiotics14040420
Zarbock, A., Nadim, M. K., Pickkers, P., Gomez, H., Bell, S., Joannidis, M., Kashani, K., Koyner, J. L., Pannu, N., Meersch, M., Reis, T., Rimmelé, T., Bagshaw, S. M., Bellomo, R., Cantaluppi, V., Deep, A., De Rosa, S., Perez-Fernandez, X., Husain-Syed, F., … Forni, L. G. (2023). Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nature Reviews Nephrology, 19(6), 401–417. https://doi.org/10.1038/s41581-023-00683-3
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