Extended vs. Intermittent Beta-Lactam Infusion in ICU Sepsis

Официальное название

"The Impact of Beta-Lactam Infusion Strategy on Treatment Efficacy in Sepsis and Septic Shock : Extended vs. Intermittent Dosing in the ICU"

Обзор

This observational study compares extended versus intermittent beta-lactam infusion in sepsis patients, assessing survival, clinical cure rates, and practical ICU challenges. The findings will guide optimal antibiotic protocols, potentially improving sepsis outcomes through precision dosing strategies.

Подробное описание

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock should be considered a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities significantly increase mortality risk compared to sepsis alone.

Beta-lactam antibiotics exhibit broad-spectrum activity against most Gram-positive and Gram-negative bacteria, making them a key component of sepsis treatment. Their bactericidal effects are time-dependent, meaning efficacy depends on maintaining free drug concentrations above the minimum inhibitory concentration of the target pathogen for an optimal duration.

In clinical practice, beta-lactams are typically administered via intermittent infusion. However, critically ill patients often experience altered pharmacokinetics due to changes in renal clearance, protein binding, fluid balance, and volume distribution. This variability can lead to unpredictable drug concentrations, increasing the risk of subtherapeutic antibiotic exposure.

Existing studies suggest that continuous infusion may enhance beta-lactam efficacy by maintaining drug concentrations above the minimum inhibitory concentration for longer periods, optimizing pharmacokinetic and pharmacodynamic targets. Some meta-analyses and small randomized controlled trials report reduced mortality and improved clinical cure rates with continuous infusion, while others show no significant difference. However, differences in dosing regimens, patient populations, and pharmacokinetic variability in critically ill patients make it difficult to draw firm conclusions.

Вмешательства

• Препарат Extended beta-lactam antibiotics
  Group A will be receiving extended infusion of beta-lactam antibiotic over 4 hours.
• Препарат Intermittent Beta-lactam antibiotics
  Group B will be receiving intermittent infusion of beta-lactam antibiotic over 30 minutes.

Первичные конечные точки

• All-cause mortality at 90 days from the date of randomization. [Срок оценки: Baseline and 90 days]

Вторичные конечные точки (1)

• Clinical cure [Срок оценки: Baseline and 16 days]

Критерии участия

Критерии включения

• Aged: 18 - 65
• Patients admitted to critical care unit diagnosed with pneumonia or urinary tract infection with two of the following:

• Temperature: over 38 degree celsius
• Heart rate: over 100 beats per minute
• Respiratory rate: over 20 breaths per minute
• leucocyte count over than 12000 or less than 4000 microlitres or over 10% immature forms or bands
• Patients with positive sputum or urine cultures

Критерии исключения

• Hypersensitivity to Beta-lactams
• Pregnancy
• Very low probability of survival using APAACHE II score > 34 points.
• Immunodeficency or taking immunosuppressive medications
• Acute or chronic renal failure with creatinine clearance less than 30 ml/min according to Cockcroft-Gault formula.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, Shirwadkar C, Eastwood GM, Myburgh J, Paterson DL, Lipman J. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis. 2013 Jan;56(2):236-44. doi: 10.1093/cid/cis856. Epub 2012 Oct 16. PMID 23074313
• Guarino M, Perna B, Cesaro AE, Maritati M, Spampinato MD, Contini C, De Giorgio R. 2023 Update on Sepsis and Septic Shock in Adult Patients: Management in the Emergency Department. J Clin Med. 2023 Apr 28;12(9):3188. doi: 10.3390/jcm12093188. PMID 37176628
• Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29. PMID 3928249
• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580. PMID 1244564
• Li X, Long Y, Wu G, Li R, Zhou M, He A, Jiang Z. Prolonged vs intermittent intravenous infusion of beta-lactam antibiotics for patients with sepsis: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. Ann Intensive Care. 2023 Dec 5;13(1):121. doi: 10.1186/s13613-023-01222-w. PMID 38051467
• Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clin Infect Dis. 2023 Jul 18:ciad428. doi: 10.1093/cid/ciad428. Online ahead of print. PMID 37463564
• Povoa P, Coelho L, Dal-Pizzol F, Ferrer R, Huttner A, Conway Morris A, Nobre V, Ramirez P, Rouze A, Salluh J, Singer M, Sweeney DA, Torres A, Waterer G, Kalil AC. How to use biomarkers of infection or sepsis at the bedside: guide to clinicians. Intensive Care Med. 2023 Feb;49(2):142-153. doi: 10.1007/s00134-022-06956-y. Epub 2023 Jan 2. PMID 36592205
• Mirjalili M, Zand F, Karimzadeh I, Masjedi M, Sabetian G, Mirzaei E, Vazin A. The clinical and paraclinical effectiveness of four-hour infusion vs. half-hour infusion of high-dose ampicillin-sulbactam in treatment of critically ill patients with sepsis or septic shock: An assessor-blinded randomized clinical trial. J Crit Care. 2023 Feb;73:154170. doi: 10.1016/j.jcrc.2022.154170. Epub 2022 Oct 19. PMID 36272277

Идентификаторы

NCT: NCT07398703 · Beta-Lactam Infusion in sepsis

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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