Optimal aminoglycoside therapy following the sepsis: how much is too much?

Severe sepsis and septic shock are major problems as the result of high rates morbidity and mortality in intensive care units [ICUs]. In the presence of septic shock, each hour of delay in the administration of effective antibiotics is associated with a measurable increase in mortality. Aminoglycosides are effective broad-spectrum antibiotics that are commonly used in ICUs for the treatment of life-threatening Gram-negative infections and as a part of empiric therapy for severe sepsis and septic shock. Knowledge of the pharmacokinetic [PK] and pharmacodynamic [PD] properties of the antibiotics used for the management of critically ill patients is essential for selecting the antibiotic dosing regimens and improving patient outcome. Volume of distribution [Vd] and clearance [CL] of aminoglycosides in critically ill patients differs from general population and these parameters change considerably during the therapy. Pathophysiological changes during the sepsis alter the pharmacokinetic and pharmacodynamic profile of many drugs [increase in Vd and variable changes in CL have been reported for aminoglycosides during the sepsis], therefore, dosing regimen optimization is necessary for achieving therapeutic goal, and critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels and due to the considerable variation in kinetic parameters, the use of standard doses of aminoglycosides or dosing nomograms is not recommended in these populations

Uso de Aminoglucósidos en dos Hospitales Comunitarios de la ciudad de Cartagena de Enero a Diciembre de 1994 / Use of amiglycosides in two communitary Hospitals in Cartagena from January to December 1994

Se realizó un estudio descriptivo, retrospectivo en dos hospitales universitarios de tercer nivel de la ciudad de Cartagena, Colombia, con el objetivo de evaluar los parámetros usados en la dosificación de los aminoglucósidos. Se revisaron 251 historias clínicas de pacientes hospitalizados en los Servicios de Medicina Interna de enero a diciembre de 1994, que tuieran indicado y hubieran recibido un aminoglucósido. Fueron tomados los siguientes datos: Edad, peso, talla, sexo, determinación de creatinina sérica, tipo de aminoglucósido, dosis de carga y de mantenimiento, intervalo entre dosis, determinaciones plasmáticas del aminoglucósido, tipo y duración del tratamiento y vía de administración. Para facilitar la evaluación se consideraron como casos diferentes los paicentes en quienes hubo cambios en el tipo de aminoglucósido, dosis de mantenimiento o en la vía de administración. Para aquellos pacientes en los que todos los parámetros citados estuvieron anotados en la historia clínica, se calcularon los estimados de las concentraciones mínimas y máximas y se compararon con los datos reportados en la literatura. Se encontró que en 234 casos (93.23 por ciento) se dosificó sin tener en cuenta los datos de talla, peso o concentración de creatinina sérica inicial; sólo cuatro casos (1.59 por ciento) recibieron una dosis adecuada; en 110 casos (43.82 por ciento) no se monitorizó la función renal o por lo menos ete dato no se encontró en la historia clínica del paciente y en ningún caso se determinaron concentraciones plasmáticas del aminoglucósido utilizado. Se resalta la importancia de tener en cuenta parámetros claros para un mejor uso de estos fármacos

Therapeutic drug monitoring program

A therapeutic drug monitoring [TDM] program was initiated usimg clinical pharnacokinetic principles TDM was established in one patient -care clinical pharm acokinetic laboratory [LAB] which serves 350 medical / surgical beds and outpatient departments. Clinical pharmacokinetic guidelines regarding when and how to draw levels for TDM were made available and posted in each ward directives for LAB personnel were developed and rationale for each of the directive is explained. A clinical pharmacokineticist was actively involved in processing, interpreting, recommending and interacting with the clinician in 1996,5181 levels were received by the LAP from various wards. Those levels that would not yield any useful information towards bettei patient -care were not analyzed and termed as canceled. Toxic levels were those whose values were greater than the therapeutic range. Canceled and toxic levels were approximately 10% and 8% respectively. Antiepileptics represents 48% and gentamicin 21.5% of the total levels received by the LAB. Using basic pharmacokinetic concepts and abundance of clinical pharmacokinetic knowledge of various agents, allows the pharmacists to taks an active role in predicting proper dosage regimens and effectively using resources for better patient-care. TDM provides hospital pharmacists with an opportunity to use clinical pharmacokinetics in everyday practice