RESUMEN
BACKGROUND: Optimal antibiotic dosing for Staphylococcus aureus bloodstream infections (BSI) is still controversial. One reason is inter-individual variation in pharmacokinetics, which may be influenced by various patient-related factors, particularly in critically ill patients. OBJECTIVES: To describe the population pharmacokinetics (PopPK) of the antibiotic flucloxacillin in patients with S. aureus BSI. Subsequently, we sought to translate the model into a user-friendly app for generating a priori and a posteriori time-concentration curves and dose recommendations to optimize dosing regimens. METHODS: Total and unbound flucloxacillin concentrations were included from 49 patients from a prospective cohort study conducted during clinical routine, including non-critically ill and critically ill individuals who received intermittent bolus applications. These data were analysed using non-linear mixed-effects modelling. RESULTS: Most patients (98%) were treated with 2 g of flucloxacillin every 4 h. We developed a joint model that simultaneously described total and unbound concentrations. The model included an allometric effect of glomerular filtration rate on clearance and albumin on the albumin dissociation constant. The latter was especially important, as in our population the unbound fraction was higher at 11.5% (16.7% for critically ill patients) compared with reported values of approximately 5%. Based on our joint model, we developed a web-based app for optimizing dosing regimens of flucloxacillin. CONCLUSIONS: By utilizing data from clinical routine, we were able to create a predictive PopPK model of flucloxacillin and identify influential covariates. The web-based app is currently being validated in a clinical trial.
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Antibacterianos , Bacteriemia , Floxacilina , Infecciones Estafilocócicas , Humanos , Floxacilina/farmacocinética , Floxacilina/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Anciano , Estudios Prospectivos , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Staphylococcus aureus/efectos de los fármacos , Anciano de 80 o más Años , Adulto , Enfermedad Crítica , Infusiones IntravenosasRESUMEN
OBJECTIVES: Flucloxacillin has the most narrow spectrum to treat staphylococcal infections, but has a large variability in bioavailability which hampers its intravenous (iv) to oral switch. To identify patients with adequate absorption, the use of an oral absorption test (OAT) measuring total plasma concentrations of flucloxacillin before and after an oral dose of 1 gram flucloxacillin, was previously published. The current pilot study aims to evaluate the fraction of patients with adequate absorption using a similar OAT; to assess the therapeutic consequences and to identify potential factors associated with adequate absorption. METHODS: Demographic data of adult patients treated with iv flucloxacillin and requiring prolonged therapy were collected retrospectively between May 2020 and November 2021 at Ghent University Hospital. A previously published OAT protocol was used, with addition of a protocol for intermittent dosing of iv flucloxacillin. Adequate absorption was defined as an increase in plasma concentration of at least 10 mg/L. RESULTS: The flucloxacillin OAT was performed in 99 patients, of which 62% were men, with a median age of 58 years and 95% received intermittent dosing of iv flucloxacillin. Of the 99 patients, 55% had a result indicating an adequate absorption and 49% of all patients were switched to oral flucloxacillin afterwards. Inadequate absorption was found to be associated with higher Body Mass Index and higher flucloxacillin baseline concentration, while co-administration of acetylsalicylic acid was associated with an adequate absorption. CONCLUSIONS: Based on the OAT, 49% of all patients were switched to oral flucloxacillin instead of broader-spectrum anti-staphylococcal antibiotics. This implicates that an OAT could be a valuable antimicrobial stewardship measure by restricting the use of broad-spectrum antibiotics. For each of the associations found, a hypothesis was formulated about the underlying reason or mechanism; these should be confirmed in future studies with prospective and multicentric design.
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Antibacterianos , Floxacilina , Humanos , Floxacilina/administración & dosificación , Floxacilina/farmacocinética , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Administración Oral , Anciano , Adulto , Proyectos Piloto , Infecciones Estafilocócicas/tratamiento farmacológico , Disponibilidad BiológicaAsunto(s)
Humanos , Masculino , Recién Nacido , Piel/lesiones , Exantema , Dermatitis Exfoliativa/tratamiento farmacológico , Staphylococcus aureus , Floxacilina/administración & dosificación , Síndrome Estafilocócico de la Piel Escaldada/tratamiento farmacológico , Resultado del Tratamiento , Pacientes Internos , Síndrome Estafilocócico de la Piel Escaldada/complicaciones , Examen Físico , Enfermedades del Recién NacidoRESUMEN
There has been a surging interest in using elastomeric infusion devices to deliver outpatient parenteral antimicrobial therapy (OPAT), which is more cost-effective than standard antibiotic administration, which requires multiple daily home visits. This has been particularly important since the outbreak of the coronavirus pandemic, because reducing patient contact can also help to minimise transmission of COVID-19 to outpatients who are at a high risk of COVID-19-triggered complications. In this retrospective study, the clinical effectiveness of intravenous (IV) infusion of flucloxacillin using an elastomeric device was explored in a convenience sample of patients. Patients with three primary infective diagnoses-bloodstream infection, non-vertebral osteomyelitis and vertebral osteomyelitis-were included in the analyses. In non-vertebral osteomyelitis patients, Accufuser antibiotic infusion shortened the course of OPAT care relative to standard antibiotic administration (p<.05). In contrast, in vertebral osteomyelitis patients, it prolonged the course of OPAT care relative to standard administration (p<.05). In patients with bloodstream infections, no significant difference was found between the treatment modes (p=.93). Thus, the clinical effectiveness of Accufuser antibiotic infusion varies among patients with different infective diagnoses, and there seems to be a complex relationship between the method of antibiotic delivery and the patient's condition.
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Antibacterianos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Enfermería en Salud Comunitaria/métodos , Floxacilina/administración & dosificación , Terapia de Infusión a Domicilio/métodos , Bombas de Infusión , Osteomielitis/tratamiento farmacológico , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/prevención & control , Atención a la Salud/métodos , Elastómeros , Humanos , Infusiones Intravenosas/instrumentación , Pandemias/prevención & control , Neumonía Viral/prevención & control , Estudios Retrospectivos , SARS-CoV-2RESUMEN
PURPOSE: Tacrolimus and everolimus are widely used to prevent allograft rejection. Both are metabolized by the hepatic cytochrome P450 (CYP) enzyme CYP3A4 and are substrate for P-glycoprotein (P-gp). Drugs influencing the activity or expression of CYP enzymes and P-gp can cause clinically relevant changes in the metabolism of immunosuppressants. Several case reports have reported that flucloxacillin appeared to decrease levels of drugs metabolized by CYP3A4 and P-gp. The magnitude of this decrease has not been reported yet. METHODS: In this single-center retrospective cohort study, we compared the tacrolimus and everolimus blood trough levels (corrected for the dose) before, during, and after flucloxacillin treatment in eleven transplant patients (tacrolimus n = 11 patients, everolimus n = 1 patient, flucloxacillin n = 11 patients). RESULTS: The median tacrolimus blood trough level decreased by 37.5% (interquartile range, IQR 26.4-49.7%) during flucloxacillin treatment. After discontinuation of flucloxacillin, the tacrolimus blood trough levels increased by a median of 33.7% (IQR 22.5-51.4%). A Wilcoxon signed-rank test showed statistically significantly lower tacrolimus trough levels during treatment with flucloxacillin compared with before (p = 0.009) and after flucloxacillin treatment (p = 0.010). In the only available case with concomitant everolimus and flucloxacillin treatment, the same pattern was observed. CONCLUSIONS: Flucloxacillin decreases tacrolimus trough levels, possibly through a CYP3A4 and/or P-gp-inducing effect. It is strongly recommended to closely monitor tacrolimus and everolimus trough levels during flucloxacillin treatment and up to 2 weeks after discontinuation of flucloxacillin.
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Floxacilina/farmacocinética , Rechazo de Injerto/prevención & control , Inmunosupresores/farmacocinética , Trasplante de Órganos/efectos adversos , Tacrolimus/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP/agonistas , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Adulto , Anciano , Niño , Preescolar , Citocromo P-450 CYP3A/metabolismo , Interacciones Farmacológicas , Everolimus/administración & dosificación , Everolimus/farmacocinética , Femenino , Floxacilina/administración & dosificación , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tacrolimus/administración & dosificaciónRESUMEN
INTRODUCTION: Although cellulitis is a relatively common condition, there is uncertainty about the benefit of intravenous (IV) over oral (PO) antibiotic therapy, and the appropriate duration of treatment. METHODS: Data extracted from a clinical trial (NCT01876628) of antibiotic therapy for cellulitis were used to assess the association between the route of administration and duration of treatment, and clinical outcome. RESULTS: Of 323 patients with antibiotic data, 114 received some IV therapy. IV antibiotic therapy was preferred in those who had received antibiotics prior to trial entry (P < 0.001). Patients characterised as having more severe cellulitis (C-reactive protein > 100 mg/L, affected skin surface area > 5% or systemic inflammatory response syndrome score ≥ 1) were more likely to have had IV therapy. Those given only PO therapy were more likely to have improved at day 5 compared with those given at least a single dose of IV therapy (P = 0.015), and were as likely to be back to their normal activities at day 10 (P = 0.90), and day 30 (P = 0.86). There was no association between initial severity and the duration of antibiotic therapy given within the trial. There was no association between duration of antibiotic therapy and outcome as measured at day 10 and day 30. CONCLUSIONS: This study provides evidence that recovery is not associated with the route of antibiotic administration for patients with cellulitis of similar severity, or that a course length of > 5 days results in any additional benefit.
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Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Clindamicina/uso terapéutico , Floxacilina/uso terapéutico , Administración Intravenosa , Administración Oral , Antibacterianos/farmacocinética , Celulitis (Flemón)/microbiología , Clindamicina/administración & dosificación , Clindamicina/farmacocinética , Quimioterapia Combinada , Duración de la Terapia , Femenino , Floxacilina/administración & dosificación , Floxacilina/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Infecciones Estafilocócicas/microbiología , Tenosinovitis/microbiología , Antibacterianos/administración & dosificación , Proteína C-Reactiva/análisis , Floxacilina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/cirugía , Staphylococcus aureus/aislamiento & purificación , Tenosinovitis/tratamiento farmacológico , Tenosinovitis/cirugía , TibiaAsunto(s)
Fracturas Óseas/etiología , Enfermedades Mandibulares/etiología , Osteomielitis/etiología , Parotiditis/complicaciones , Cálculos Salivales/complicaciones , Administración Intravenosa , Enfermedad Crónica , Femenino , Floxacilina/administración & dosificación , Fracturas Óseas/diagnóstico por imagen , Humanos , Enfermedades Mandibulares/diagnóstico por imagen , Metronidazol/administración & dosificación , Persona de Mediana Edad , Osteomielitis/tratamiento farmacológico , Parotiditis/diagnóstico por imagen , Parotiditis/tratamiento farmacológico , Combinación Piperacilina y Tazobactam/administración & dosificación , Cálculos Salivales/cirugía , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.
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Antibacterianos/normas , Citratos/normas , Elastómeros/normas , Floxacilina/normas , Medicina Estatal/normas , Antibacterianos/administración & dosificación , Tampones (Química) , Citratos/administración & dosificación , Embalaje de Medicamentos/métodos , Embalaje de Medicamentos/normas , Estabilidad de Medicamentos , Almacenaje de Medicamentos/métodos , Almacenaje de Medicamentos/normas , Elasticidad , Floxacilina/administración & dosificación , Humanos , Infusiones Intravenosas , Soluciones Farmacéuticas/administración & dosificación , Soluciones Farmacéuticas/normas , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. METHODS: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. RESULTS: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: -15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: -8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). CONCLUSIONS: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.
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Antibacterianos/administración & dosificación , Celulitis (Flemón)/tratamiento farmacológico , Administración Intravenosa , Anciano , Método Doble Ciego , Duración de la Terapia , Femenino , Floxacilina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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.
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Humanos , Masculino , Persona de Mediana Edad , Arritmias Cardíacas/complicaciones , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/epidemiología , Insuficiencia Cardíaca/tratamiento farmacológico , Infecciones/terapia , Marcapaso Artificial , Staphylococcus aureus/patogenicidad , Imagen por Resonancia Magnética/métodos , Vancomicina/administración & dosificación , Comorbilidad , Factores de Riesgo , Desfibriladores Implantables , Ecocardiografía Transesofágica/métodos , Dispositivos de Terapia de Resincronización Cardíaca , Floxacilina/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
BACKGROUND: The preferred treatment for severe methicillin-sensitive Staphylococcus aureus infections is flucloxacillin, a small-spectrum antibiotic administered intravenously (IV) and orally. However, clinicians switch to the less preferred broad-spectrum antibiotics because of the variable absorption after oral administration of flucloxacillin. A classical oral absorption test (OAT) requires overnight fasting and interruption of IV therapy, and is laborious. In the current study, we investigated whether a simplified OAT can be utilized in a clinical setting to guide antibiotic treatment in patients with severe S. aureus infections. For this, OAT IV therapy is continued and oral dosing is performed after a one-hour fast and implemented after a small study. METHODS: In 196 patients receiving IV flucloxacillin by continuous infusion, a classical OAT (test A) or simplified version of the OAT (test B) was performed. In both tests, 1 g oral flucloxacillin was given and serum samples were taken prior to intake and at one and two hours after administration. Flucloxacillin concentrations were determined by high-performance liquid chromatography. Adequate absorption was defined as an increase of flucloxacillin concentration of at least 10 mg/l after one or two hours compared to baseline. RESULTS: In a sample of 196 patients (85 F/111 M), test A was performed in 28 patients, and test B in 168 patients. Age, gender, and baseline values of creatinine and albumin were similar in both groups. The maximal increase of flucloxacillin absorption was highly variable between patients. In 26 (13%) of the 196 patients, the flucloxacillin increase did not reach the value of 10 mg/l. The median (interquartile range, IQR) maximal increase of flucloxacillin absorption was 22.0 (15-31.25) mg/l for test A and 21.5 (13-32.25) mg/l for test B. There was no significant difference in maximal increase of flucloxacillin absorption between test A and B (p = 0.74), nor between males and females (p = 0.95). Age, creatinine, and albumin were not correlated with flucloxacillin levels. CONCLUSIONS: The simplified version of the OAT is useful to identify patients with adequate oral flucloxacillin absorption, and to ensure the effective continuation of an oral small-spectrum treatment.
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Monitoreo de Drogas/métodos , Floxacilina , Absorción Gastrointestinal , Infecciones Estafilocócicas , Administración Oral , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Cromatografía Liquida/métodos , Relación Dosis-Respuesta a Droga , Femenino , Floxacilina/administración & dosificación , Floxacilina/farmacocinética , Humanos , Infusiones Intravenosas , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Reproducibilidad de los Resultados , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
We report a case of acute rheumatic fever with severe pancarditis occurring simultaneously with probable acute post-streptococcal glomerulonephritis in a previously well, Australian Aboriginal, 29-year-old male. These autoimmune streptococcal sequelae are usually considered pathogenetically distinct, and concurrence has not previously been reported from this high-burden setting. We hypothesize that a single type of infecting group A Streptococcus (Strep A) triggered both autoimmune sequelae. Salient features included mitral and aortic regurgitation that worsened during the acute illness, painful pericarditis, and high troponin; severe acute kidney injury with oliguria, hematuria, and macroalbuminuria; reduced complement (C3); and elevated streptococcal serology. The case highlights important diagnostic and management challenges. It also illustrates the serious morbidity impact of the complications of Strep A.
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Glomerulonefritis/etiología , Fiebre Reumática/complicaciones , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Ceftriaxona/administración & dosificación , Ceftriaxona/uso terapéutico , Floxacilina/administración & dosificación , Floxacilina/uso terapéutico , Cardiopatías/microbiología , Cardiopatías/patología , Humanos , Masculino , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Fiebre Reumática/diagnóstico , Fiebre Reumática/tratamiento farmacológicoAsunto(s)
Acrodermatitis/diagnóstico , Proteínas de Transporte de Catión/genética , Zinc/administración & dosificación , Zinc/deficiencia , Acrodermatitis/sangre , Acrodermatitis/tratamiento farmacológico , Acrodermatitis/genética , Administración Cutánea , Administración Intravenosa , Betametasona/administración & dosificación , Proteínas de Transporte de Catión/metabolismo , Análisis Mutacional de ADN , Quimioterapia Combinada/métodos , Femenino , Floxacilina/administración & dosificación , Pie , Mutación del Sistema de Lectura , Humanos , Recurrencia , Brote de los Síntomas , Adulto Joven , Zinc/sangre , Zinc/metabolismoRESUMEN
BACKGROUND: Outpatient parenteral antibiotic therapy after hospital admission is increasingly popular, but its use to avoid admission to hospital altogether by treating patients wholly as outpatients remains uncommon in children. One reason for the low use of treatment at home is the scarcity of evidence of its cost-effectiveness. In this planned follow-up analysis of the Cellulitis at Home or Inpatient in Children from the Emergency Department (CHOICE) trial, we aimed to assess the cost-effectiveness of an admission avoidance pathway, in which children were treated at home, compared with standard hospital care for the intravenous treatment of moderate or severe cellulitis. METHODS: We did a cost-effectiveness analysis to compare home treatment with intravenous ceftriaxone versus hospital treatment with intravenous flucloxacillin in children aged 6 months to 18 years who had presented to the emergency department at The Royal Children's Hospital, Melbourne, VIC, Australia, with moderate or severe uncomplicated cellulitis. We included costs from two sources: institutional costs at a patient level and expenses incurred by families. We measured effectiveness with quality-adjusted life years (QALYs), which we derived from the Child Health Utility 9D questionnaire, and a clinical outcome of treatment failure, which was the primary outcome of the CHOICE trial. We planned to calculate the incremental cost-effectiveness ratio, defined as the difference between groups in total cost divided by the difference between groups in effectiveness. The CHOICE trial is registered at ClinicalTrials.gov, number NCT02334124. FINDINGS: We included 180 children who comprised the per-protocol population in the CHOICE trial: 89 children in the home group and 91 children in the hospital group. The institutional cost per patient per episode was significantly lower in the home group than in the hospital group (AUS$1965 vs $3775; p<0·0001). The mean cost incurred per family was $182 for the home group and $593 for the hospital group (p<0·0001). Both measures of effectiveness were significantly better in the home group than in the hospital group: QALYs were 0·005 for the home group versus 0·004 for the hospital group (p<0·0001), and treatment failure occurred in one (1%) patient in the home group versus seven (8%) patients in the hospital group (risk difference -6·5%, 95% CI -12·4 to -0·7; p=0·029). Calculating the incremental cost-effectiveness ratio was thus deemed redundant. INTERPRETATION: Treatment at home was less costly and more effective than standard hospital care for children with moderate or severe cellulitis. These findings support development of this admission avoidance pathway in hospitals. FUNDING: The Royal Children's Hospital Foundation, Murdoch Children's Research Institute.
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Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Análisis Costo-Beneficio/métodos , Floxacilina/uso terapéutico , Servicios de Atención de Salud a Domicilio/economía , Hospitalización/economía , Administración Intravenosa , Adolescente , Antibacterianos/administración & dosificación , Australia , Ceftriaxona/administración & dosificación , Niño , Preescolar , Servicio de Urgencia en Hospital , Femenino , Floxacilina/administración & dosificación , Estudios de Seguimiento , Humanos , Lactante , Masculino , Años de Vida Ajustados por Calidad de Vida , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Data indicate that codispensing flucloxacillin to patients already on warfarin may result in decreased warfarin efficacy. OBJECTIVES: This article investigates the effect of flucloxacillin on warfarin anticoagulation. PATIENTS AND METHODS: In a retrospective cohort study of warfarin users, using three nationwide registers we included 5,848 patients receiving 10 days flucloxacillin treatment and 201 with ≥30 days treatment. To assess the potential for confounding by indication, we also identified 21,430 individuals initiating phenoxymethylpenicillin. International normalized ratio (INR) values and warfarin doses were calculated day-by-day and proportion of patients with a subtherapeutic INR week-by-week during cotreatment. RESULTS: Following initiation of flucloxacillin with a planned treatment duration of 10 days and ≥30 days, the mean INR decreased from 2.36 (95% confidence interval [CI] 2.34; 2.37) to 2.20 (95% CI 2.19; 2.21) and from 2.24 (95% CI 2.16; 2.32) to 1.96 (95% CI 1.89; 2.02), respectively. Consequently, for individuals with 10 days treatment the proportion of patients with a subtherapeutic INR of < 2 increased from 22% in the week preceding flucloxacillin initiation to 35% in the third week after initiation of flucloxacillin. In patients with 30 days treatment, the proportion increased from 34 to 63% by week 6. In individuals initiating phenoxymethylpenicillin, INR levels did not decrease. CONCLUSION: One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect. To avoid unnecessary thromboembolic complications, the initiation of flucloxacillin should be accompanied by closer INR monitoring which may be especially important among individuals with lengthy treatments.
Asunto(s)
Anticoagulantes/administración & dosificación , Floxacilina/administración & dosificación , Tromboembolia/tratamiento farmacológico , Warfarina/administración & dosificación , Anciano , Anciano de 80 o más Años , Coagulación Sanguínea/efectos de los fármacos , Estudios de Cohortes , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Penicilina V/administración & dosificación , Sistema de Registros , Estudios Retrospectivos , Suecia/epidemiologíaRESUMEN
The purpose of this study was to develop a new similarity method to assess the drug-drug interaction between midazolam and flucloxacillin. Total quantum statistical moment (TQSM) of pharmacokinetic profiles were expressed by parameters AUCT, MRTT, VRTT et al. Statistical moment similarity (SMS) expressions were deduced to evaluate the similarity of the converted pharmacokinetic profiles. A trial of the pharmacokinetic interaction between midazolam and flucloxacillin by the SMS method was conducted. For midazolam, total quantum SMS (SMST) was 0.9582; total deviation was 0.0525; total variable probability was 4.18 %; total confidence of probability ß was 97.17 % under significance level 0.05; AUC0-∞ were 334.3±334.1 ngâ¢hâ¢mL-1 (after administration of midazolam alone) and 206.9±172.2 ngâ¢hâ¢mL-1 (after co-administration of midazolam and flucloxacillin), respectively. While, for 1'-hydroxy midazolam, SMST was 0.6920; total deviation was 0.3960; total variable probability was 30.80 %; total confidence of probability ß was 94.10 % under significance level 0.05; AUC0-∞ were 1364±810.7 ngâ¢hâ¢mL-1 (after administration of midazolam alone) and 1637±632.6 ngâ¢hâ¢mL-1 (after co-administration of midazolam and flucloxacillin), respectively. These results revealed that flucloxacillin might have weak pharmacokinetic interactions on midazolam metabolized into 1'-hydroxy midazolam, indicating that there was weak induction to CYP3A by flucloxacillin and that there was at least 30.80 % of metabolic behaviour in change with bioavailability decreased by 38.11 % that took effect to flucloxacillin metabolism for liver injury in CPY3A4 poor metabolic polymorphisms. SMS can be an optional method applied to characterize and analyze pharmacokinetic profiles.
Asunto(s)
Antibacterianos/farmacología , Floxacilina/farmacología , Hipnóticos y Sedantes/farmacocinética , Midazolam/farmacocinética , Adulto , Antibacterianos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Citocromo P-450 CYP3A/metabolismo , Interacciones Farmacológicas , Floxacilina/administración & dosificación , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Midazolam/administración & dosificación , Modelos Estadísticos , Adulto JovenRESUMEN
We report a 36-year-old man who developed a large epidural and paraspinal abscess as a complication of infliximab therapy being used for underlying Crohn's disease. Cultures of the collection grew methicillin-susceptible Staphylococcus aureus, and treatment consisted of abscess drainage, prolonged intravenous and oral flucloxacillin and temporary withholding of his infliximab. While infection-related complications are well described with infliximab therapy, this is the first description of a large paraspinal abscess with epidural extension.
Asunto(s)
Absceso/microbiología , Enfermedad de Crohn/tratamiento farmacológico , Espacio Epidural/microbiología , Infliximab/efectos adversos , Absceso/diagnóstico por imagen , Absceso/tratamiento farmacológico , Absceso/cirugía , Adulto , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales , Enfermedad de Crohn/complicaciones , Drenaje/métodos , Espacio Epidural/diagnóstico por imagen , Floxacilina/administración & dosificación , Floxacilina/uso terapéutico , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Humanos , Infliximab/uso terapéutico , Masculino , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/aislamiento & purificación , Resultado del TratamientoRESUMEN
Intravenous flucloxacillin is one of the most frequently used high-dose penicillin therapies in hospitalized patients, forming the cornerstone treatment of invasive Staphylococcus aureus infection. Being a nonreabsorbable anion, flucloxacillin has been suggested to cause hypokalaemia, although the frequency and magnitude of this unwanted effect is unknown. In a retrospective cohort, we investigated the incidence and extent of hypokalaemia after initiation of intravenous flucloxacillin or ceftriaxone therapy. In total, 77 patients receiving flucloxacillin (62% male, mean age 70.5 years) and 84 patients receiving ceftriaxone (46% male, mean age 70.8 years) were included. Hypokalaemia occurred significantly more often in patients receiving flucloxacillin than ceftriaxone (42% vs 14%, p < 10-4 ). Moreover, follow-up potassium levels were significantly lower during flucloxacillin therapy. In general, women were more prone to develop hypokalaemia than men. In conclusion, intravenous flucloxacillin use is associated with a striking incidence of hypokalaemia. Therefore, standardized potassium measurements are necessary.
Asunto(s)
Antibacterianos/efectos adversos , Floxacilina/efectos adversos , Hipopotasemia/inducido químicamente , Infecciones Estafilocócicas/tratamiento farmacológico , Administración Intravenosa , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Estudios de Cohortes , Femenino , Floxacilina/administración & dosificación , Floxacilina/uso terapéutico , Humanos , Hipopotasemia/epidemiología , Incidencia , Masculino , Potasio/sangre , Estudios Retrospectivos , Infecciones Estafilocócicas/sangreRESUMEN
An ex-30-week gestation, preterm male baby was admitted to a tertiary neonatal unit and noted to have increased ventilator requirements and diagnosed with sepsis. The baby also developed an abscess over the left elbow and over the xiphisternum along with a decrease in movement of the left hand and the right leg. Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus (SA) was isolated from the blood culture. A whole body MRI showed disseminated abscess with multiple foci in the lung, left elbow and over the xiphisternum. Disseminated sepsis with multiple septic foci has not been previously reported in neonates. We would like to highlight the fact that sepsis due to PVL toxin-producing SA can cause significant morbidity and mortality in neonates. Proper screening should be done to rule out septic foci in neonates. MRI is a good non-invasive investigation to document septic foci in a neonate and rule out multiorgan involvement.