ABSTRACT
INTRODUCCIÓN: La monitorización de antimicrobianos mediante sus concentraciones plasmáticas permite determinar la posología óptima de éstos, conducta esencial en pediatría. OBJETIVOS: Describir la monitorización de concentraciones plasmáticas de antimicrobianos y el ajuste de dosis en población pediátrica para determinar si las dosis utilizadas alcanzan rangos terapéuticos. PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo, utilizando una base de datos con medición de concentraciones plasmáticas de amikacina y vancomicina en pacientes pediátricos del Hospital San Borja Arriarán, entre 2015-2018. Se determinó el número de pacientes que alcanzó rango terapéutico con dosis inicial, cuántos requirieron ajuste y sus características. RESULTADOS: Se monitorizó 104 concentraciones totales. Para vancomicina 65 concentraciones plasmáticas eran basales encontrándose fuera de rango terapéutico 56,5%; de los que requirieron ajuste, 25% fueron neonatos con mayor probabilidad de estar fuera de rango versus otros (p = 0,022). Para amikacina la Cpeak estuvo en rango en 60% de mediciones; 15,4% requirió ajuste incluyendo pacientes con fibrosis quística y oncológicos. No fue necesario efectuar ajustes en pacientes sin co-morbilidad. CONCLUSIÓN: La medición de concentraciones plasmáticas es necesaria para ajustar de forma individualizada la dosis, especialmente en pacientes pediátricos con fibrosis quística, oncológicos y en neonatología, donde es más probable no alcanzar rango terapéutico con las dosis iniciales.
BACKGROUND: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics. AIM: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges. METHODS: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined. RESULTS: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity. CONCLUSION: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Pediatrics , Amikacin/administration & dosage , Vancomycin/administration & dosage , Retrospective Studies , Drug Monitoring , Anti-Bacterial Agents/administration & dosageABSTRACT
El pioderma gangrenoso ampollar es una variedad infrecuente de pioderma gangrenoso, que se asocia en el 50-70% de los casos con trastornos oncohematológicos. Se comunica el caso de una paciente de 59 años, que consultó por fiebre y ampollas purpúricas de rápida progresión, con compromiso cutáneo mucoso. Con sospecha de una enfermedad neutrofílica, ampollar, o infección por gérmenes oportunistas, se realizó biopsia de piel para estudio histopatológico, inmunofluorescencia directa y cultivo. Los cultivos y la inmunofluorescencia directa fueron negativos, y la anatomía patológica reveló un denso infiltrado inflamatorio con predominio neutrofílico en dermis. Ante el diagnóstico de pioderma gangrenoso ampollar, se realizó una punción-aspiración de médula ósea cuyo resultado fue compatible con leucemia mieloide aguda. Se instauró tratamiento con corticosteroides sistémicos, a pesar de lo cual la paciente evolucionó desfavorablemente y falleció a los 15 días de su ingreso hospitalario. Este caso ilustra la asociación de esta enfermedad cutánea con trastornos oncohematológicos y el mal pronóstico que esto implica a corto plazo. (AU)
Bullous pyoderma gangrenosum is an infrequent type of pyoderma gangrenosum, associated with onco hematological diseases in 50-70% of cases. We present the case of a 59-year-old patient with fever and mucocutaneous hemorrhagic bullous of rapid progression. A biopsy for histopathology, direct immunofluorescence (DIF) and skin culture was made, considering the possibility of neutrophilic dermatoses, bullous dermatosis or an opportunistic infection. The results of both the culture and the DIF were negative. The histopathological examination of the specimen revealed a dense dermal polymorphic infiltrate composed primarily of neutrophils. Considering bullous pyoderma gangrenosum as a potential diagnosis, a bone-marrow biopsy was performed. This study revealed an acute myeloid leukemia. Although systemic corticosteroid therapy was begun, the patient presented an unfavorable evolution that led to her death 15 days after her admission at the hospital. This case shows the association between bullous pyoderma gangrenosum and onco hematological diseases. In addition, it highlights the poor prognosis related to these diseases in the short term. (AU)
Subject(s)
Humans , Female , Middle Aged , Leukemia, Myeloid, Acute/pathology , Pyoderma Gangrenosum/diagnosis , Paraneoplastic Syndromes/pathology , Respiration, Artificial , Azacitidine/therapeutic use , Myelodysplastic Syndromes/pathology , Acyclovir/administration & dosage , Methylprednisolone/administration & dosage , Vancomycin/administration & dosage , Cardiotonic Agents/therapeutic use , Ceftazidime/administration & dosage , Amphotericin B/administration & dosage , Imipenem/administration & dosage , Sweet Syndrome/etiology , Pyoderma Gangrenosum/etiology , Pyoderma Gangrenosum/pathology , Pyoderma Gangrenosum/drug therapy , Adrenal Cortex Hormones/therapeutic use , Meropenem/administration & dosageABSTRACT
RESUMO Objetivo: Investigar a efetividade da vancomicina contra Gram-positivos com concentração inibitória mínima de 1mg/L em pacientes pediátricos com base na razão entre área sob a curva e concentração inibitória mínima > 400. Métodos: População de 22 pacientes pediátricos (13 meninos) internados no centro de terapia intensiva pediátrica, com função renal preservada, que foram distribuídos em dois grupos (G1 < 7 anos e G2 ≥ 7 anos). Após a quarta dose de vancomicina (10 - 15mg/kg a cada 6 horas), duas amostras de sangue foram colhidas (terceira e quinta horas), seguidas da dosagem sérica por imunoensaios para investigação da farmacocinética e da cobertura do antimicrobiano. Resultados: Não se registrou diferença entre os grupos com relação à dose, ao nível de vale ou ainda na área sob a curva. A cobertura contra Gram-positivos com concentração inibitória mínima de 1mg/L ocorreu em apenas 46% dos pacientes em ambos os grupos. A farmacocinética se mostrou alterada nos dois grupos diante dos valores de referência, mas a diferença entre grupos foi registrada pelo aumento da depuração total corporal e pelo encurtamento da meia-vida biológica, mais pronunciados nos pacientes mais novos. Conclusão: A dose empírica mínima de 60mg/kg ao dia deve ser prescrita ao paciente pediátrico de unidade de terapia intensiva com função renal preservada. A utilização da razão entre área sob a curva e concentração inibitória mínima na avaliação da cobertura da vancomicina é recomendada para se atingir o desfecho desejado, uma vez que a farmacocinética está alterada nesses pacientes, podendo impactar na efetividade do antimicrobiano.
Abstract Objective: To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods: A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results: There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion: A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.
Subject(s)
Humans , Male , Infant , Child, Preschool , Child , Adolescent , Vancomycin/administration & dosage , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/administration & dosage , Vancomycin/pharmacology , Vancomycin/pharmacokinetics , Intensive Care Units, Pediatric , Microbial Sensitivity Tests , Pilot Projects , Age Factors , Area Under Curve , Dose-Response Relationship, Drug , Half-LifeABSTRACT
Abstract Purpose The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. Methods Intermittent therapy was administered for 60 minutes and prescribed as a loading dose of 30 mg/kg and continued with 15 mg/kg q12 h. Continuous infusion was prescribed as a loading dose of 30 mg/kg followed by 30 mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1 h before third dose, 1 h, 8 h and 24 h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1 h after loading dose, 12 h, 24 h, 36 h, and 48 h after continuous infusion initiation. Results Median serum concentration of continuous infusion group at 24-hour was 23.59 µg/mL [14.52-28.97], while of intermittent infusion group at 23-hour was 12.30 µg/mL [7.27-18.12] and on 25-hour was 17.58 µg/mL [12.5-22.5]. Medians AUC24-48h were 357.2 mg.h/L and 530.2 mg.h/L for intermittent infusion and continuous infusion groups, respectively (p = 0.559). Conclusion Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.
Subject(s)
Humans , Vancomycin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Vancomycin/therapeutic use , Drug Monitoring , Critical Illness , Intensive Care Units , Anti-Bacterial Agents/therapeutic useABSTRACT
Resumen Introducción: Vancomicina es un antimicrobiano ampliamente utilizado para infecciones por Staphylococcus coagulasa negativa en neonatos; sin embargo, no existe claridad sobre la dosis empírica que asegure su eficacia terapéutica. Objetivo: Evaluar la relación entre las dosis iniciales de vancomicina utilizadas en una Unidad de Cuidado Intensivo Neonatal (UCIN) con la eventualidad de alcanzar el objetivo terapéutico de área bajo la curva sobre concentración inhibitoria mínima (ABC/CIM) mayor a 400 µg/h/mL. Materiales y Método: Estudio descriptivo y retrospectivo, realizado entre febrero 2016 y marzo 2018. Se incluyeron neonatos en tratamiento con vancomicina por sospecha/confirmación de infección por cocáceas grampositivas y medición de concentraciones plasmáticas de vancomicina al inicio del tratamiento. La probabilidad de alcanzar el objetivo terapéutico se evaluó mediante re-muestreo de valores de ABC y CIM. Resultados: Se incluyeron 38 pacientes con 49 concentraciones plasmáticas de vancomicina. Los aislados microbiológicos se confirmaron en 94,7% de los pacientes (n = 36). Los valores de ABC/CIM en dos grupos (según niveles valle de vancomicina < 10 µg/mL y ≥ 10 µg/mL), fueron de una mediana de 327 (IQ 25-75 = 174-395) y 494 (IQ 25-75 = 318-631), respectivamente (p = 0,035). Las dosis empíricas utilizadas logran logran un objetivo terapéutico (ABC/CIM > 400) de sólo 47,7% considerando CIMs en nuestra institución. Conclusiones: Teniendo en cuenta las sensibilidades institucionales, no es posible asegurar alcanzar ABC/CIM > 400 µg/h/mL. Se debe seguir investigando para replantear las actuales estrategias de dosificación y así determinar la más apropiada para neonatos.
Abstract Background: Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. Aim: To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. Methods: Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. Results: Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. Conclusions: It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.
Subject(s)
Humans , Infant, Newborn , Vancomycin/administration & dosage , Staphylococcal Infections , Microbial Sensitivity Tests , Retrospective Studies , Area Under Curve , Anti-Bacterial AgentsABSTRACT
Nas últimas décadas, o aumento das indicações para dispositivos cardíacos eletrônicos implantáveis tem sido acompanhado pela elevação dos casos de complicações relacionadas ao seu uso, dentre elas a endocardite infecciosa. Apesar dos avanços diagnósticos e terapêuticos da doença, esta mantém elevada morbimortalidade. Os casos relacionados aos dispositivos apresentam importantes limitações referentes aos critérios e aos métodos diagnósticos que implicam na tomada de decisão terapêutica sobre retirada do dispositivo, com risco de morte e outras complicações. Ainda assim, o ecocardiograma mantém um grande valor no diagnóstico da endocardite infecciosa relacionada a dispositivos cardíacos e de suas complicações. O entendimento das limitações e dos desafios acerca do diagnóstico reforça a necessidade de mais estudos sobre do tema. O presente artigo visa descrever a epidemiologia, a microbiologia, os fatores de risco, a patogenia, o diagnóstico e o tratamento da endocardite infecciosa associada aos dispositivos cardíacos eletrônicos implantáveis, visando demonstrar, principalmente, o valor dos exames de imagem na abordagem dessa condição clínica, com ênfase nos achados ao ecocardiograma.
In recent decades, the increase in indications for implantable electronic cardiac devices has been accompanied by an increase in cases of complications related to their use, including infectious endocarditis. Despite the diagnostic and therapeutic advances of the disease, it maintains high morbidity and mortality. The cases related to the devices have important limitations regarding the criteria and diagnostic methods that imply in making a therapeutic decision about removing the device, with risk of death and other complications. Still, echocardiography remains of great value in the diagnosis of infective endocarditis related to cardiac devices and their complications. Understanding the limitations and challenges regarding diagnosis reinforces the need for further studies on the topic. This article aims to describe the epidemiology, microbiology, risk factors, pathogenesis, diagnosis and treatment of infective endocarditis associated with implantable electronic cardiac devices, aiming to demonstrate, mainly, the value of imaging tests in addressing this clinical condition , with emphasis on echocardiogram findings.
Subject(s)
Humans , Male , Middle Aged , Arrhythmias, Cardiac/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/epidemiology , Heart Failure/drug therapy , Infections/therapy , Pacemaker, Artificial , Staphylococcus aureus/pathogenicity , Magnetic Resonance Imaging/methods , Vancomycin/administration & dosage , Comorbidity , Risk Factors , Defibrillators, Implantable , Echocardiography, Transesophageal/methods , Cardiac Resynchronization Therapy Devices , Floxacillin/administration & dosage , Positron Emission Tomography Computed Tomography/methodsABSTRACT
RESUMEN La meningitis infecciosa es una emergencia médica. Dentro del espectro de agentes infecciosos, el más importante es el Streptococcus pneumoniae, agente etiológico más frecuente de la meningitis bacteriana. El inicio de tratamiento antimicrobiano empírico es de gran importancia y considera a las cefalosporinas de tercera generación como la primera alternativa. Sin embargo, casos de resistencia a ceftriaxona han sido reportados en diversas partes del mundo, siendo un problema emergente, por lo que necesita una reconsideración de los esquemas antibióticos empíricos actuales. Presentamos el caso de un varón de 56 años que presenta meningitis aguda infecciosa por Streptococcus pneumoniae resistente a ceftriaxona, que respondió favorablemente al tratamiento empírico combinado con ceftriaxona y vancomicina y que durante su estadía hospitalaria se detectó la presencia de hipotiroidismo y megacisterna magna.
ABSTRACT Infectious meningitis is a medical emergency. Within the spectrum of infectious agents, the most important is Streptococcus pneumoniae, the most frequent etiological agent of bacterial meningitis. The initiation of empirical antimicrobial treatment bears great importance and considers third-generation cephalosporins as the first alternative. However, cases of ceftriaxone resistance have been reported in several regions of the world. This has become an emerging problem in need of reconsideration of the current empirical antibiotic treatment schemes. We present the case of a 56-year old man with acute infectious meningitis caused by ceftriaxone-resistant Streptococcus pneumoniae, who responded favorably to combined empirical treatment with ceftriaxone and vancomycin and to whom, during his hospital stay, the presence of hypothyroidism and mega cisterna magna was diagnosed.
Subject(s)
Humans , Male , Middle Aged , Ceftriaxone/administration & dosage , Vancomycin/administration & dosage , Meningitis, Pneumococcal/drug therapy , Anti-Bacterial Agents/administration & dosage , Streptococcus pneumoniae/isolation & purification , Microbial Sensitivity Tests , Treatment Outcome , Drug Resistance, Bacterial , Drug Therapy, Combination , Meningitis, Pneumococcal/microbiologyABSTRACT
ABSTRACT Objective Analyze the microbiological effectiveness, based on the pharmacokinetics/pharmacodynamics correlation of vancomycin in pediatric patients, and to propose dose adjustment. Methods This is an observational, cross-sectional study, conducted in a pediatric hospital, over a 1-year period (2016 to 2017). Children of both sexes, aged 2 to 12 years, were included in the study; burn children, and children in renal replacement therapy were excluded. For the pharmacokinetic analysis, two samples of 2mL of whole blood were collected, respecting the 2-hour interval between each withdrawal. Results Ten pediatric patients with median age of 5.5 years and interquartile range (IQR) of 3.2-9.0 years, median weight of 21kg (IQR: 15.5-24.0kg) and median height of 112.5cm (IQR: 95-133cm), were included. Only one child achieved trough concentrations between 10µg/mL and 15µg/mL. Conclusion The empirical use of vancomycin in the children studied did not achieve the therapeutic pharmacokinetic/pharmacodynamic target for minimum inhibitory concentration of 1µg/mL.
RESUMO Objetivo Analisar a efetividade microbiológica considerando a correlação farmacocinética/farmacodinâmica de vancomicina em crianças e propor uma estimativa de ajuste na dose. Métodos Trata-se de um estudo observacional, transversal, realizado em hospital pediátrico, no período de 1 ano (2016 a 2017). Foram incluídas crianças de 2 a 12 anos de ambos os sexos, tendo sido excluídas crianças queimadas ou submetidas à terapia renal substitutiva. Para análise farmacocinética, foram coletadas duas amostras de 2mL de sangue total, respeitando o intervalo de 2 horas entre cada coleta. Resultados Foram incluídos dez pacientes pediátricos com idade de 5,5 anos (mediana) e intervalo interquartil (IQ) de 3,2-9,0 anos, peso de 21kg (mediana; IQ: 15,5-24,0kg) e altura de 112,5cm (mediana; IQ: 95-133cm). Apenas uma criança alcançou concentrações mínimas entre 10µg/mL e 15µg/mL. Conclusão A utilização empírica de vancomicina na população de crianças não alcançou o alvo farmacocinético/farmacodinâmico terapêutico para concentração inibitória mínima de 1μg/mL.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Vancomycin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Time Factors , Vancomycin/administration & dosage , Microbial Sensitivity Tests , Cross-Sectional Studies , Drug Monitoring/methods , Dose-Response Relationship, Drug , Anti-Bacterial Agents/administration & dosageABSTRACT
Resumen La presente revisión resume la evidencia sobre la monitorización terapéutica de tres antimicrobianos basada en datos regionales: vancomicina, amikacina y voriconazol en la población pediátrica. Estos datos coinciden con la literatura internacional en relación al requerimiento de dosis mayores que 40 mg/kg/día de vancomicina, la posibilidad de usar monodosis diarias de amikacina y el requerimiento de dosis mayores de voriconazol en relación a las iniciales recomendadas de 8 mg/kg/día. Contar con datos locales sobre el comportamiento farmacocinético/farmacodinámico de diversos antimicrobianos en la pediatría es de gran valor para adecuar la dosificación de los mismos en nuestra población. Se deberían incrementar los estudios de monitorización terapéutica en el uso de antimicrobianos en pediatría que permitan generar pautas de tratamiento adecuadas para este grupo etario.
This review summarizes recommendations of therapeutic monitoring of three antimicrobials based in regional data: vancomycin, amikacin and voriconazole in pediatric population. Regional evidence agrees with international literature regarding the requirement of higher daily doses than 40 mg/kg/day of vancomycin, as well as with the possibility of use one daily doses of amikacin and to recommend higher doses of voriconazole compared to the initially recommended doses of 8 mg/kg/day. Local data on the pharmacokinetic/pharmacodynamic behavior of various antimicrobials in pediatrics are of great value for dosing adjustment in our pediatric population. More studies in therapeutic monitoring in the use of antimicrobials in pediatrics should be performed in order to allow the generation of adequate treatment guidelines for this age group.
Subject(s)
Humans , Amikacin/administration & dosage , Amikacin/pharmacokinetics , Vancomycin/administration & dosage , Vancomycin/pharmacokinetics , Drug Monitoring/trends , Voriconazole/administration & dosage , Voriconazole/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacokinetics , Dose-Response Relationship, Drug , Latin AmericaABSTRACT
The management of Clostridium difficile (CD) infection has changed in recent years. The latest clinical guidelines and systematic reviews suggest the use of vancomycin orally as the first line of treatment regardless the severity of the crisis (main difference compared to previous recommendations), this is due to changes in its epidemiology, the decrease in effectiveness and the increase of recurrences with the use of metronidazole, particularly in severe crisis. In addition, the use of new agents such as fidaxomicin has been approved. Fulminant crisis require an aggressive management combining oral treatment, enemas and intravenous therapy in addition to a collaborative management with the surgery team. With respect to recurrences, the use of vancomycin in pulses and with extended therapy schemes is suggested; fecal microbiota transplantation (FMT) is also an attractive therapy for patients with multiple recurrences. The following is a summary of the latest recommendations and available evidence regarding the management of CD infection in the most frequent situations, both in first crisis and in its recurrences.
El manejo de la infección por Clostridium difficile (CD) ha tenido modificaciones los últimos años. Las últimas guías clínicas y revisiones sistemáticas sugieren el uso de vancomicina vía oral como primera línea de tratamiento independiente de la severidad de la crisis (diferencia principal con recomendaciones previas), esto debido a cambios en su epidemiología, la disminución de la efectividad y al aumento de las recurrencias con el uso de metronidazol, particularmente en crisis severas. Además, han sido aprobados el uso de nuevos agentes como la fidaxomicina. Las crisis de carácter fulminante requieren un manejo agresivo combinando terapia oral, vía enemas e intravenosa, además de un manejo en conjunto con el equipo de cirugía. Respecto a las recurrencias se sugiere el uso de vancomicina en pulsos y con esquemas de terapia extendida siendo además, el trasplante de microbiota fecal (FMT) una terapia atractiva para pacientes con múltiples recurrencias. A continuación se resumen las últimas recomendaciones y evidencia disponible respecto del manejo de la infección por CD en las situaciones más frecuentes, tanto en la primera crisis como en sus recurrencias.
Subject(s)
Humans , Vancomycin/therapeutic use , Clostridium Infections/drug therapy , Diarrhea/drug therapy , Fidaxomicin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Recurrence , Vancomycin/administration & dosage , Clostridioides difficile/drug effects , Clostridium Infections/complications , Diarrhea/microbiology , Fecal Microbiota Transplantation , Fidaxomicin/administration & dosage , Rifaximin/therapeutic use , Metronidazole/therapeutic use , Anti-Bacterial Agents/administration & dosageABSTRACT
Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.
Subject(s)
Adult , Female , Humans , Anti-Bacterial Agents/administration & dosage , Critical Illness , Extracorporeal Membrane Oxygenation , Hemofiltration , Pancreatitis/drug therapy , Vancomycin/administration & dosageSubject(s)
Humans , Female , Pregnancy , Adult , Anesthesia, Obstetrical/history , Coronary Disease/drug therapy , Coronary Disease/history , Endocarditis/prevention & control , Ampicillin/administration & dosage , Cesarean Section/methods , Electrocardiography , Prevalence , Radiography, Thoracic , Vancomycin/administration & dosageABSTRACT
RESUMO Objetivo: Avaliar se a posologia atualmente utilizada de vancomicina para tratamento de infecções bacterianas graves causadas por microrganismos Gram-positivos em pacientes admitidos à unidade de terapia intensiva proporcionam níveis plasmáticos de vale de vancomicina em nível terapêutico, e examinar possíveis fatores associados com níveis de vale de vancomicina adequados nesses pacientes. Métodos: Estudo prospectivo descritivo com amostra de conveniência. Os pacientes que cumpriam os critérios de inclusão tiveram seus dados coletados a partir das anotações da enfermagem e dos registros médicos entre setembro de 2013 e julho de 2014. Incluíram-se 83 pacientes. Os níveis plasmáticos de vale iniciais de vancomicina foram obtidos imediatamente antes da quarta dose de vancomicina. Definiu-se lesão renal aguda como um aumento de, pelo menos, 0,3mg/dL na creatinina sérica dentro de 48 horas. Resultados: Considerando os níveis de vale plasmáticos de vancomicina recomendados para o tratamento de infecções graves por Gram-positivos (15 - 20µg/mL), os pacientes foram categorizados em grupos como níveis de vale de vancomicina baixos, adequados e elevados, respectivamente divididos em 35 (42,2%), 18 (21,7%), e 30 (36,1%) pacientes. Os pacientes com lesão renal aguda tiveram níveis plasmáticos de vale de vancomicina significantemente mais elevados (p = 0,0055, com significância para tendência, p = 0,0023). Conclusão: Preocupantemente, mais de 40% dos pacientes não obtiveram níveis plasmáticos de vale de vancomicina considerados eficazes. São necessários estudos de farmacocinética e de regimes posológicos de vancomicina em pacientes admitidos em unidades de terapia intensiva, para contornar esta elevada proporção de falhas na obtenção de níveis de vale iniciais adequados de vancomicina. Deve ser desencorajado o uso de vancomicina sem monitoramento dos níveis de vale plasmáticos.
ABSTRACT Objective: This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. Methods: A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Results: Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Conclusion: Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged.
Subject(s)
Humans , Male , Female , Adult , Aged , Vancomycin/administration & dosage , Gram-Positive Bacterial Infections/drug therapy , Intensive Care Units , Anti-Bacterial Agents/administration & dosage , Vancomycin/pharmacokinetics , Prospective Studies , Drug Monitoring/methods , Creatinine/blood , Dose-Response Relationship, Drug , Acute Kidney Injury/complications , Middle Aged , Anti-Bacterial Agents/pharmacokineticsABSTRACT
Abstract Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m2/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m2/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m2/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p < 0.001). A dose of 27 mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Vancomycin/administration & dosage , Vancomycin/blood , Neonatal Sepsis/drug therapy , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Reference Values , Staphylococcus/drug effects , Drug Administration Schedule , Linear Models , Predictive Value of Tests , Retrospective Studies , Gestational Age , Statistics, Nonparametric , Dose-Response Relationship, Drug , Neonatal Sepsis/bloodSubject(s)
Humans , Infant , Bacteremia/drug therapy , Bacteremia/microbiology , Catheter-Related Infections/drug therapy , Catheter-Related Infections/microbiology , Cross Infection , Methicillin-Resistant Staphylococcus aureus , Parenteral Nutrition , Short Bowel Syndrome , Staphylococcal Infections/drug therapy , Vancomycin/administration & dosageABSTRACT
ABSTRACT INTRODUCTION: Appearance of isolated reports of resistance to anti-methicillin-resistantStaphylococcus aureus (MRSA) drugs is worrisome underscoring the need to continuously monitor the susceptibility of clinical MRSA isolates to these drugs. Hence, the present study is conducted to determine the susceptibility of MRSA isolates to various classes of anti-MRSA drugs such as vancomycin (glycopeptide), daptomycin (lipopeptide), tigecycline (glycylcycline), and linezolid (oxazolidinone) to determine the MIC50 and MIC90 values, and to observe MIC creep over a three year period, if any, with respect to these drugs. METHODS: A total of 200 isolates of MRSA obtained from clinical specimens were included. MIC was determined by E-test for anti-MRSA antibiotics vancomycin, linezolid, daptomycin, and tigecycline. Non-parametric methods (Kruskal-Wallis and Chi-square test) were used to assess MIC trends over time. In addition, MIC50 and MIC90 values were also calculated. RESULTS: No isolate was found resistant to vancomycin, daptomycin, or linezolid; five isolates were resistant to tigecycline. Seven VISA isolates were encountered with the MIC value for vancomycin of 4 µg/mL. MIC values for vancomycin, tigecycline, linezolid showed a definite increase over a 3-year period which was statistically significant with p-values <0.0001, 0.0032, 0.0242, respectively. When the percentage of isolates with a median MIC value less than or equal to that of the index year was calculated, the change was most striking with vancomycin. The proportion of isolates with higher MIC values was greater in 2014 than 2012 and 2013. CONCLUSION: MIC creep was notably observed with vancomycin, and to some extent with tigecycline and linezolid. Selection pressure may result in creeping MICs, which may herald the emergence of resistant organisms.
Subject(s)
Humans , Anti-Bacterial Agents/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/administration & dosage , Daptomycin/administration & dosage , Daptomycin/pharmacology , India , Microbial Sensitivity Tests , Methicillin/administration & dosage , Methicillin/pharmacology , Minocycline/administration & dosage , Minocycline/analogs & derivatives , Minocycline/pharmacology , Tertiary Care Centers , Vancomycin/administration & dosage , Vancomycin/pharmacologyABSTRACT
Enterococos são ubíquos no ambiente e fazem parte da microbiota do trato gastrintestinal de humanos e animais. A importância dessas bactérias tem sido associada com infecções hospitalares e resistência a múltiplas drogas, principalmente à vancomicina. O objetivo do presente estudo foi realizar a caracterização molecular de cepas de Enterococcus spp. resistentes à vancomicina (VRE) isoladas a partir de amostras coletadas de pacientes hospitalizados, água superficial de rios urbanos e carne de frango comercializada no Brasil. A presença do gene vanA foi confirmada em 20 cepas multirresitentes isoladas durante 1997-2011. Dentre os isolados VRE, 12 cepas foram identificadas como E. faecium e oito como E. faecalis. Cepas de E. faecium isoladas de amostras clínicas e águas foram classificadas como clonalmente relacionadas pelo PFGE, com perfil virulência predominante (acm+, esp+). Adicionalmente, enquanto cepas de E. faecium isoladas dos rios pertenceram aos ST203, ST412 e ST478 (previamente caracterizados como endêmicos em hospitais brasileiros), novos STs foram identificados entre as cepas de E. faecalis (ST614, ST615 e ST616) e E. faecium (ST953 e ST954) isoladas de alimentos. Sequências completas do transposon Tn1546 das cepas clínicas VREfm 320/07 (ST478) e ambiental VREfm 11 (ST412) mostraram Tn1546-like element de ~12800 pb, com um ponto de mutação no gene vanA na posição 7.698 (substituição do nucleotídeo T pelo C) e uma no gene vanX na posição 8.234 (G pelo T). Além disso, uma deleção na extremidade esquerda do Tn1546, e as sequências IS1251 e IS1216E na região intergênica vanHS e vanYX, respectivamente, também foram detectados. A este respeito, a IS1216E na região intergênica vanXY constitui um conjunto de genes previamente relatado em cepas clínicas de VREfm no Brasil, denotando uma característica regional. IS1216E tem sido associada com os genes tcrB e aadE que conferem resistência ao cobre e aminoglicosídeos, em E. faecium e Streptococcus agalactiae, respectivamente. Portanto, essa IS pode contribuir para a rápida aquisição de resistência antimicrobiana entre as espécies de cocos Gram-positivos clinicamente importantes. Os tipos de Tn1546 indistiguíveis que foram identificados no atual estudo isolados de humano e ambientes aquáticos sugerem uma comum partilha de um pool de genes de resistência à vancomicina
Enterococci are ubiquitous in the environment and in the intestinal tract of humans and animals. The importance of these bacteria has been associated with nosocomial infection and multiple resistance to antimicrobial agents, mainly vancomycin. The aim of the present study was to perform molecular characterization of vancomycin-resistant Enterococcus spp. strains (VRE) isolated from hospitalized patients, surface water of urban rivers and retail chicken meat in Brazil. The presence of the vanA gene was confirmed in 20 multidrug-resistant strains isolated in 1997-2011. Among these VRE isolates, (n = 12) were identified as E. faecium and (n = 8) as E. faecalis. E. faecium strains isolated from water and clinical samples were classified as clonally related by PFGE, the predominant virulence profile being (acm+, esp+). Additionally, while E. faecium strains isolated from rivers belonging to ST203, ST412 and ST478 (previously characterized as endemic in Brazilian hospitals), new STs were identified among strains of E. faecalis (ST614, ST615 and ST616) and E. faecium (ST953 and ST954) isolated from food. Complete sequences of transposon Tn1546 from VREfm clinical strain 320/07 (ST478) and environmental strain VREfm 11 (ST412) showed a Tn1546-like element of ~12800 bp, with T7698C vanA and G8234T vanX mutations. Moreover, deletion of the Tn1546 left extremity, and the IS1251 and IS1216E sequence inside the vanHS and vanYX intergenic region, respectively, were also detected. In this regard, the IS1216E sequence inside the vanXY intergenic region constitutes a gene array previously reported for Brazilian VREfm clinical strains alone, denoting a regional characteristic. IS1216E has been associated with tcrB and aadE genes, which confer resistance to copper and aminoglycosides, in E. faecium and Streptococcus agalactiae, respectively. Therefore, IS1216E should contribute to rapid acquisition of antimicrobial resistance among species of the clinically important Gram-positive cocci. On the other hand, Tn1546-like elements were identical among clinical and environmental VREfm isolates, suggesting sharing of a common vancomycin resistance gene pool