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      Pharmacokinetics and pharmacodynamics of beta-lactam antibiotics in critically ill patients Translated title: Farmacocinética y farmacodinámica de los antibióticos betalactámicos en pacientes críticos

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          Abstract

          Abstract Optimal antibiotic therapy for critically ill patients can be complicated by the altered physiology associated with critical illness. Antibiotic pharmacokinetics and exposures can be altered driven by the underlying critical illness and medical interventions that critically ill patients receive in the intensive care unit. Furthermore, pathogens that are usually isolated in the intensive care unit are commonly less susceptible and “resistant” to common antibiotics. Indeed, antibiotic dosing that does not consider these unique differences will likely fail leading to poor clinical outcomes and the emergence of antibiotic resistance in the intensive care unit. The aims of this narrative review were to describe the pharmacokinetics of beta-lactam antibiotics in critically ill patients, to highlight pharmacokinetic/pharmacodynamic targets for both non-critically ill and critically ill patients, and to discuss important strategies that can be undertaken to optimize beta-lactam antibiotic dosing for critically ill patients in the intensive care unit.

          Translated abstract

          Resumen La terapia antibiótica óptima en los pacientes en estado crítico puede complicarse por la alteración de la fisiología asociada a esta etapa de la enfermedad. La farmacocinética y la exposición a los antibióticos pueden verse alteradas por la enfermedad crítica subyacente y las intervenciones médicas que reciben estos pacientes en la unidad de cuidados intensivos. Además, las cepas que suelen encontrarse en la unidad de cuidados intensivos suelen ser menos susceptibles y “resistentes” a los antibióticos más habituales. De hecho, una dosificación de antibióticos que no tenga en cuenta estas diferencias únicas, probablemente fracasará y dará lugar a resultados clínicos deficientes y a la aparición de resistencia a los antibióticos en la unidad de cuidados intensivos. Los objetivos de esta revisión son describir la farmacocinética de los antibióticos betalactámicos en pacientes críticos, destacar los objetivos farmacocinéticos/farmacodinámicos para los pacientes y exponer algunas estrategias importantes que pueden optimizar la dosificación de los antibióticos betalactámicos en pacientes críticos en la unidad de cuidados intensivos.

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

            To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".
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              Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

              Background In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. Methods We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. Results Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). Conclusions More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
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                Author and article information

                Journal
                fh
                Farmacia Hospitalaria
                Farm Hosp.
                Grupo Aula Médica (Toledo, Toledo, Spain )
                1130-6343
                2171-8695
                June 2022
                : 46
                : 3
                : 182-190
                Affiliations
                [1] Kuala Lumpur Kuala Lumpur orgnameUniversity of Malaya orgdiv1Faculty of Medicine orgdiv2Department of Medicine Malaysia
                [4] Brisbane orgnameRoyal Brisbane and Women's Hospital orgdiv1Department of Pharmacy Australia
                [3] Brisbane orgnameRoyal Brisbane and Women's Hospital orgdiv1Department of Intensive Care Medicine Australia
                [5] Nîmes orgnameUniversity of Montpellier orgdiv1Nîmes University Hospital orgdiv2Division of Anaesthesiology Critical Care Emergency and Pain Medicine France
                [2] Brisbane Queensland orgnameUniversity of Queensland orgdiv1University of Queensland Centre for Clinical Research orgdiv2Faculty of Medicine Australia
                Article
                S1130-63432022000300012 S1130-6343(22)04600300012
                10.7399/fh.13170
                438213dc-686d-40ad-914b-38f9a4ac1ff0

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 06 February 2022
                : 04 December 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 112, Pages: 9
                Product

                SciELO Spain

                Categories
                Reviews

                Farmacocinética clínica,Paciente crítico,Beta-lactámicos,Antibióticos,Clinical pharmacokinetics,Criticaly ill patient,Beta-lactamics,Antibiotics

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