KLINICKÁ FARMAKOLOGIE A FARMACIE / Klin Farmakol Farm 2023;37(3):86-88 / www.klinickafarmakologie.cz 88 EDITORIAL The importance of a fast-track pharmacology for the proper management of antibiotic therapy in intensive care units the potency of the given drug and provides no information regarding the time-course of antibiotic effect, nor whether the rate of bacterial killing may be altered in vivo by inadequate drug exposure (16). Accordingly, the best way to categorize an antibiotic is through the combination of the PK/PD characteristics, as it defines the individualized drug exposure necessary to ensure the optimal drug effectiveness for a given pathogen. In the past, this was considered merely a theoretical concept. Anyway, thanks to the identification of clinically relevant PK/PD targets measurable in hospital laboratories, individualized dosing strategies have been recently proposed [12]. Beta-lactam agents are examples of time dependent antibiotics (T>MIC), where the rate of killing is determined by the length of time necessary to kill, whereas aminoglycosides, daptomycin and fluoroquinolones are concentration-dependent antibiotics (Cmax/MIC), where killing is dependent on increasing concentrations of the drug. Some antimicrobial agents such as azithromycin, clindamycin, vancomycin, oxazolidinones and tetracycline exhibit mixed time-dependent and concentration dependent properties (AUC/MIC). A growing body of literature has been published in the last 2–3 years showing that licensed standard doses of antibiotics are often insufficient to achieve PK/PD targets in ICU patients. This has been demonstrated for linezolid, meropenem, ceftriaxone, piperacillin-tazobactam, and daptomycin. Patients at risk of not attaining these targets would benefit from drug dose intensification, with significant improvements in the clinical cure rates (12). Conclusions The current scenario of persisting poor outcomes for ICU patients with infection, as well as the documented association between suboptimal antimicrobial exposure and treatment failure, calls for an urgent and rapid optimization of drug dosing in this clinical setting. We, therefore, propose fast-track pharmacology as a branch of clinical pharmacology by direct analogy with what has been achieved in microbiology and enabled by improvements in analytical techniques. The concept of fast-track pharmacology facilitates the application of pharmacologic concepts at the bedside with the goal of improving the safety and efficacy of antimicrobial therapy for ICU patients. A fast pharmacology could help to address this issue by providing TDM results with a short turnaround time and by guiding physicians in the rational adjustment of antibiotic doses by proper identification and weight of the clinical variables eventually affecting drug PK in ICU (17). However, prospective clinical trials are required to determine whether a fast pharmacology-based approach (ideally combined with a fast microbiology to reach PK/PD targets) can significantly improve the treatment of infections in ICU patients. REFERENCES 1. Kollef MH, Bassetti M, Francois B, et al. The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship. Intensive Care Med. 2017;43:1187-1197. 2. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:775-777. 3. Law AC, Stevens JP, Walkey AJ. National Trends in Timing of Death Among Patients With Septic Shock, 1994–2014. Crit Care Med. 2019;47:1493-1496. 4. MacArthur RD, Miller M, Albertson T, et al. Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial. Clin Infect Dis. 2004;38:284-288. 5. Özenci V, Rossolini GM. Rapid microbial identification and antimicrobial susceptibility testing to drive better patient care: an evolving scenario. J Antimicrob Chemother 2019; 74 (Supplement_1) :i2-i5. 6. Mulatero F, Bonnardel V, Micolaud C. The way forward for fast microbiology. Clin Microbiol Infect. 2011;17:661-667. 7. De Waele JJ, Dhaese S. Antibiotic stewardship in sepsis management: toward a balanced use of antibiotics for the severely ill patient. Expert Rev Anti Infect Ther. 2019;17:89-97. 8. Leone M, Roberts JA, Bassetti M, et al. Update in antibiotic therapy in intensive care unit: report from the 2019 Nîmes International Symposium. Anaesth Crit Care Pain Med. 2019;38:647-656. 9. Sumi CD, Heffernan AJ, Lipman J, et al. What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review. Clin Pharmacokinet. 2019;58:1407-1443. 10. Heffernan AJ, Sime FB, Taccone FS, Roberts JA. How to optimize antibiotic pharmacokinetic/pharmacodynamics for Gram-negative infections in critically ill patients. Curr Opin Infect Dis. 2018;31:555-565. 11. Mula J, Chiara F, Manca A, et al. Analytical validation of a novel UHPLC-MS/MS method for 19 antibiotics quantification in plasma: Implementation in a LC-MS/MS Kit. Biomed Pharmacother. 2023;163:114790. 12. Abdul-Aziz MH, Alffenaar JC, Bassetti M, et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper. Intensive Care Med. 2020;46:1127-1153. 13. Imani S, Buscher H, Marriott D, et al. Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships. J Antimicrob Chemother. 2017;72:2891-2897. 14. Lau C, Marriott D, Gould M, et al. A retrospective study to determine the cefepime-induced neurotoxicity threshold in hospitalized patients. J Antimicrob Chemother. 2020; 75:718-725. 15. Cattaneo D, Marriott DJ, Gervasoni C. Hematological toxicities associated with linezolid therapy in adults: key findings and clinical considerations. Expert Rev Clin Pharmacol. 2023;16:219-230. 16. Onufrak NJ, Forrest A, Gonzalez D. Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing. Clin Ther. 2016;38:1930-1947. 17. Gatti M, Cojutti PG, Bartoletti M, et al. Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients. Crit Care. 2022;26:178.
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