Population pharmacokinetics of amikacin in neonatal intensive care unit patients

Background Amikacin treatment requires close monitoring of blood concentrations to increase the probability that levels achieved are both effective and safe. Aims We described population pharmacokinetics parameters of amikacin in newborns from a Neonatal Intensive Care Unit with suspected or documented sepsis. Methods A nonlinear mixed-effect model approach was used to analyse the data. Results Twenty seven neonates were enrolled. Final parameter estimates were: Ke(h-1)=0.232x(CR) Exp-0.85; V(mL/kg)=497. Conclusion Weight and serum creatinine are associated with neonatal amikacin volume of distribution and elimination constant rate, respectively. The presence of sepsis may decrease amikacin elimination, although this observation should be further explored. These results could help to individualize amikacin dosage for neonates

Pharmacovigilance of calcineurin inhibitors in pediatric kidney and liver transplantation

Objetivo: Desarrollar un programa de farmacovigilancia de pacientes pediátricos trasplantados hepáticos y renales centrado en inmunosupresores calcineurínicos del Hospital de Pediatría JP Garrahan de Argentina. Métodos: Se evaluaron las reacciones adversas a medicamentos (RAM) de los pacientes pediátricos trasplantados renales y hepáticos de nuestro hospital tratados con inhibidores de calcineurina (ciclosporina y tacrolimus) por revisión retrospectiva de historias clínicas de pacientes trasplantados en 2010-2011, y análisis prospectivo por farmacovigilancia activa de trasplantados fuera de dicho período, cuyas complicaciones se hayan presentado en los ateneos semanales del Servicio de Trasplante desde marzo de 2011. Las RAM se notificaron a la autoridad sanitaria nacional. Resultados: Se analizaron un total de 59 pacientes, 28 trasplantados renales y 31 hepáticos. Se notificaron, en ambos trasplantes, 60 RAM a ciclosporina destacándose (número de casos) hipertensión arterial (19) y nefrotoxicidad (6). Asimismo, se registraron 46 RAM a tacrolimus, incluyendo hipomagnesemia (25), hipertensión (7) y nefrotoxicidad (5). El 95% y 96% de los eventos adversos a ciclosporina y a tacrolimus, respectivamente, han sido agrupados como probables o definitivos. El 70% y 98% de los eventos adversos a ciclosporina y a tacrolimus respectivamente, han sido de severidad moderada o grave. Conclusiones: Este es el primer proyecto en América Latina que propone y desarrolla el estudio cuali-cuantitativo intensivo de RAM a inhibidores de calcineurina en trasplante pediátrico renal y hepático. Es necesario estimular la notificación espontánea así como continuar el seguimiento de RAM a mediano y largo plazo para mejorar la calidad de vida del paciente trasplantado.Aim: To develop a pharmacovigilance program of calcineurin inhibitors used in pediatric renal and liver transplant patients at Hospital de Pediatría JP Garrahan, Argentina. Methods: Adverse drug reactions (ADRs) of pediatric patients with kidney and liver transplantation treated with calcineurin inhibitors (cyclosporine and tacrolimus) were evaluated by retrospective review of medical records of patients transplanted between 2010 and 2011. In addition, we carried out active pharmacovigilance since March, 2011. ADRs were reported to the National Health Authority. Results: A total of 59 patients, 28 kidney transplant and 31 liver tarnsplant patients were analyzed. In both transplants, 60 ADRs to cyclosporine were reported including (number of cases), hypertension (19) and nephrotoxicity (6). In addition, 46 ADRs to tacrolimus were registered as hypomagnesemia (25), hypertension (7) and nephrotoxicity (5). A total of 95% and 96% of the adverse events to cyclosporine and tacrolimus, respectively, were defined as probable or definitive. Lastly, 70% and 98% of the events to cyclosporine and tacrolimus respectively, have been moderately severe or severe. Conclusions: This is the first study in Latin America that developed an intensive qualitative and quantitative analysis of the ADRs to calcineruin inhibitors in pediatric kidney and liver transplant patients. Spontaneous reporting should be motivated as well as monitoring ADRs should continue in the medium and long term for improving patient's quality of life.Fil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Rousseau, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Dip, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Monteverde, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Imventarza, Oscar. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Mato, Gabriel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Diferencias en tamaños de frascos de ibuprofeno jarabe no afectan cantidades dispensadas: el tamaño no importa.

Objetivo: Estudiar si la disponibilidad, en una farmacia hospitalaria, de diferentes tamaños de frascos de un medicamento de alto consumo y bajo costo (ibuprofeno jarabe, 30 y 90 mililitros), afecta cuantitativamente su dispensación.Materiales y Métodos: Estudio observacional - retrospectivo basado en datos registrados por la Farmacia del Hospital de Pediatría Garrahan (Buenos Aires, Argentina) de enero/2011 a octubre/2014. Unidad de análisis principal: cantidad de frascos de ibuprofeno jarabe dispensadas (30 y 90 mL).Resultados: En octubre de 2014 sólo se dispensaron frascos de 30 mL (4113 unidades = 123390 mL). Los meses de octubre 2011, 2012 y 2013, se dispensaron 138330, 131220 y 98010 mL respectivamente (frascos x 90 mL).Conclusiones: Disponer de frascos de jarabe de diferentes tamaños no estaría relacionado con cambios en la cantidad total dispensada de un fármaco de alto consumo y bajo costo (ibuprofeno) desde la farmacia de un hospital pediátrico de alta complejidad

Emerging mupirocin resistance in methiciüin-resistant Staphylococcus aureus isolates at a tertiary care children's hospital in Argentina

En América Latina, existen escasos estudios sobre la resistencia a mupirocina y producción de bioflm en Staphylococcus aureus resistente a la meticilina (SARM). En este trabajo, se investigó la resistencia a mupirocina en SARM aislados de pacientes pediátricos con bacteremia y su capacidad para producir bioflm. Se estudió la resistencia a antibióticos por Kirby-Bauer y microdilución en caldo. Se cuantifcó el bioflm bacteriano por ensayo de cristal violeta. El 2,3 % (5/217) de los aislados de SARM presentaron un alto nivel de resistencia a mupirocina con una concentración inhibitoria mínima de >512 µg/ml, además de resistencia cruzada con clindamicina, eritromicina, gentamicina y ciprofoxacina. Notablemente, dichos aislados formaron bioflm en un nivel moderado-alto. Este primer reporte en Argentina de aislados clínicos de SARM resistentes a la mupirocina es clave para seguir su evolución en el tiempo a nivel local y en la región de América Latina.In Latin America, few studies have been done in mupirocin resistance and biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA). This study investigated mupirocin-resistance in MRSA isolates from pediatric patients with bacteremia and their ability to form bioflm. Antibiotic resistance was analyzed with the Kirby-Bauer test and the broth microdilution method. Bacterial bioflm formation was measured using the crystal violet assay. Among MRSA isolates, 2.3 % (5/217) exhibited a high level of mupirocin-resistance with a minimum inhibitory concentration of > 512 µg/mL, in addition to cross-resistance with clindamycin, erythromycin, gentamicin, and ciprofoxacin. Remarkably, bioflm formation in such isolates was moderate to high. This is the frst report published in Argentina on clinical isolates of mupirocinresistant MRSA and it is critical for following its evolution over time at a local level and in the Latin American region.Fil: Vázquez, Nicolás Martín. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Fiorilli, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Moreno, Silvia. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Pharmacoepidemiology of tacrolimus in pediatric liver transplantation

AEs during immunosuppressive treatment with tacrolimus are very common. We retrospectively evaluated FK safety and efficacy in a large pediatric liver transplant cohort in Latin America. During 2-year follow-up, we analyzed data from patients who underwent liver transplantation over the period 2010-2012 and recorded FK exposure, AEs, and AR episodes. AEs were classified according causality and severity. Tacrolimus exposure before and during AE was compared using Wilcoxon matched-pairs test. Kaplan-Meier curves were used for survival analysis. In total, 46 patients (out of 72 patients) experienced 69 AEs, such as hypomagnesemia (49%), PTLD (6%), hypertension (6%), and/or nephrotoxicity (22%). 43% of AEs were classified as moderate or serious, and 89% were assigned as probable or definitive. Patients who had one or more AR episodes accounted for 65%. The 12-month acute rejection-free survival was 41% (95% CI, 30.1%-53.1%). A significant difference was observed in FK trough concentrations before and during hypomagnesemia and nephrotoxicity (P<.05). This study is the first report of FK safety in a large group of pediatric liver transplant patients in Latin America. Children experience AEs, even in protocols with low FK doses. Therapeutic monitoring is an important tool to manage immunosuppressive schemes containing tacrolimus in vulnerable populations.Fil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Halac, Esteban. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Dip, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Imventarza, Oscar. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Medicinal cannabis in Latin America: History, current state of regulation, and the role of the pharmacist in a new clinical experience with cannabidiol oil

Objective: Cannabis sativa was introduced in Latin America in the 16th century. Nevertheless, many years have elapsed, and scientific progress and the medicinal use of C sativa have been restricted by the national laws of the countries in the region. Summary: In Argentina, the first law on medical cannabis, approved in 2017 (#17,350), establishes a regulatory framework for the medical use and scientific research of this plant and its derivatives. In 2018, the first clinical research protocol in Latin America was approved at Hospital de Pediatria Garrahan (Buenos Aires, Argentina) to evaluate the efficacy and safety of cannabidiol (CBD) oil for the treatment of pediatric patients with refractory epilepsy. In this context, the role of pharmacists in the health care system related to the study protocol and the medicinal use of CBD has evolved from dispensing to active participation in clinical follow-up and research protocols. Conclusion: Considering this experience, here we discuss the active role of the clinical pharmacist in the use of medicinal cannabis. Medicinal cannabis should be controlled in a legal framework based on clinical evidence, and the participation of the pharmacist in research and clinical protocols, as well as the dispensing and provision of information on the medicinal products should be emphasized in the clinical setting.Fil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; ArgentinaFil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Calle, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Dell'Orso, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gatto, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sberna, Norma. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Population pharmacokinetics of amikacin in neonatal intensive care unit patients

BackgroundAmikacin treatment requires close monitoring of blood concentrations to increase the probability that levels achieved are both effective and safe.AimsWe described population pharmacokinetics parameters of amikacin in newborns from a Neonatal Intensive Care Unit with suspected or documented sepsis.Methods A nonlinear mixed-effect model approach was used to analyse the data.Results Twenty seven neonates were enrolled. Final parameter estimates were: Ke(h-1)=0.232x(CR) Exp-0.85; V(mL/kg)=497.ConclusionWeight and serum creatinine are associated with neonatal amikacin volume of distribution and elimination constant rate, respectively. The presence of sepsis may decrease amikacin elimination, although this observation should be further explored. These results could help to individualize amikacin dosage for neonates

Current status and regulation of bioanalytical laboratories engaged in quantifying immunosuppressants for transplant patients in Argentina

Objetivo. Establecer el estado de situación de los laboratorios analíticos que cuantifican inmunosupresores en pacientes con trasplantes que se encuentran bajo monitoreo terapéutico de drogas (TDM) de estos fármacos en Argentina, para establecer potenciales áreas de actuación perfectibles. Métodos. Se realizó una encuesta en centros clínicos y analíticos de TDM de Argentina, coordinada por la Unidad de Farmacocinética Clínica del Hospital Garrahan y el Instituto Nacional Central Único Coordinador de Ablación e Implante, desde setiembre de 2013 hasta noviembre de 2014. Resultados. Se incluyeron 27 centros clínicos y analíticos (muestra representativa nacional). El 45% fueron hospitales públicos. La mayoría (95%) monitorizan ciclosporina y tacrolimús; en menor medida, sirolimús y everolimús, y muy pocos el ácido micofenólico. La cantidad (mediana, rango) de muestras analizadas por mes para estos cinco fármacos fue de 251 (10 - 2024). Casi 60% de las muestras se analizaron en instituciones privadas. Solo cuatro (17%) de los encuestados informan valores del margen terapéutico. El 92% usa inmunoensayos como metodología analítica. El 68% de los encuestados que contaban con instalaciones bioanalíticas propias informaron poseer algún programa de garantía de calidad. Conclusiones. El TDM de inmunosupresores es una práctica recomendada para pacientes con trasplante en Argentina. Se requiere generar iniciativas nacionales que desarrollen guías armonizadas para laboratorios analíticos que incluyan procesos de garantía de calidad con alcance regulatorio relacionados con el TDM. Por otra parte, también es necesario capacitar al personal técnico y profesional, e invitar a participar a organizaciones públicas y privadas del ámbito regulatorio, sanitario y de la investigación.Objective. Determine the status of analytical laboratories that quantify immunosuppressants in transplant patients who are under therapeutic drug monitoring (TDM) for these drugs in Argentina in order to identify potential perfectible areas for action. Methods. A survey of the clinical and analytical TDM centers in Argentina was conducted between September 2013 and November 2014 under the direction of the Garrahan Hospital Clinical Pharmacokinetics Unit and the National Unified Central Institute for Ablation and Implant Coordination. Results. A nationally representative sample of 27 clinical and analytical centers was identified, of which 45% were public hospitals. Most of these centers (95%) monitor ciclosporin and tacrolimus, and to a lesser extent, sirolimus and everolimus; a small number of them also monitor mycophenolic acid. The median number of samples of these five drugs analyzed per month was 251 (range: 10-2024). Nearly 60% of the samples were analyzed in private institutions. Only four of the respondents (17%) reported values within the therapeutic margin. Of all the centers, 92% use immunoassay as the analytical methodology. Of the bioanalytical installations that have their own facilities, 68% reported that they also have their own quality assurance program. Conclusions. TDM of immunosuppressants is a recommended practice for transplant patients in Argentina. Initiatives need to be taken at the national level to develop uniform guidelines for analytical laboratories that include TDM-related quality assurance processes with regulatory force. There is also a need to train technical and professional personnel and to invite the participation of public and private organizations in the regulatory, public health, and research areas.Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leone, Francisco. Incucai; ArgentinaFil: Paternoster, Nora. Incucai; ArgentinaFil: Mato, Gabriel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentin

Population pharmacokinetics of amikacin in neonatal intensive care unit patients

Background Amikacin treatment requires close monitoring of blood concentrations to increase the probability that levels achieved are both effective and safe. Aims We described population pharmacokinetics parameters of amikacin in newborns from a Neonatal Intensive Care Unit with suspected or documented sepsis. Methods A nonlinear mixed-effect model approach was used to analyse the data. Results Twenty seven neonates were enrolled. Final parameter estimates were: Ke(h-1)=0.232x(CR) Exp-0.85; V(mL/kg)=497. Conclusion Weight and serum creatinine are associated with neonatal amikacin volume of distribution and elimination constant rate, respectively. The presence of sepsis may decrease amikacin elimination, although this observation should be further explored. These results could help to individualize amikacin dosage for neonates