Improving the Transition of Intravenous to Enteral Antibiotics in Pediatric Patients with Pneumonia or Skin and Soft Tissue Infections.

BACKGROUND: Despite national recommendations for early transition to enteral antimicrobials, practice variability has existed at our hospital. OBJECTIVE: The aim of this study was to increase the proportion of enterally administered antibiotic doses for Pediatric Hospital Medicine patients aged >60 days admitted for uncomplicated community-acquired pneumonia or skin and soft tissue infections from 44% to 75% in eight months. METHODS: This quality improvement study was conducted at a large, urban, academic children's hospital. The study population included Hospital Medicine patients aged >60 days with diagnoses of pneumonia or skin and soft tissue infections. Interventions included education on intravenous and enteral antibiotic charge differentials, documentation of transition plan, structured discussions of transition criteria, and real-time identification of failures with feedback. Our process measure was the total number of enteral antibiotic doses divided by all antibiotic doses in patients receiving enteral medications on the same day. An annotated statistical process control chart tracked the impact of interventions on the administration route of antibiotic doses over time. Additional outcome measures included antimicrobial costs per patient encounter using average wholesale prices and length of stay. RESULTS: The percentage of enterally administered antibiotic doses increased from 44% to 80% within eight months. Antimicrobial costs per patient encounter and the associated standard deviation of costs for our target diagnoses decreased by 70% and 84%, respectively. Average length of stay did not change. CONCLUSIONS: Standardized communication about criteria for transition from intravenous to enteral antibiotics can lead to earlier transitions for patients with pneumonia or skin and soft tissue infections, subsequently reducing costs and prescribing variability.

Introducing outpatient parenteral antimicrobial therapy in a children's hospital.

Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient care for delivering intravenous antibiotics in patients' homes or in a day care clinic setting. It was first introduced in North America in the 1970s and has evolved over the years, starting with the adult population and now moving to the paediatric population ( Chapman 2013 ). OPAT has the potential to offer excellent, patient-centred, high-quality care to treat a wide variety of infectious conditions in patients who are medically stable and do not need hospitalisation. For children and young people OPAT has the potential for families to resume their normal lives: returning to work, school and home. Paediatric OPAT (P-OPAT) is being implemented across the UK, with five centres now established. This article reports on the implementation of P-OPAT at Sheffield Children's NHS Foundation Trust (Sheffield Children's) in June 2016, highlighting the challenges and successes.

Trends and patterns of national antimicrobial consumption in Japan from 2004 to 2016.

Frequent use of broad-spectrum antimicrobial classes has been reported in Japan; however, little is known about the long-term trend of national antimicrobial consumption, and that of individual agents. This study analyzed the national sales data of systemic antimicrobials from 2004 to 2016, derived from the IMS Japan Pharmaceutical Market database, to assess the consumption patterns of antimicrobial classes and agents in Japan. The number of defined daily doses per 1000 inhabitants per day (DID) was calculated for each antimicrobial agent. During the last 13 years, total antimicrobial consumption fluctuated by only 5% around the average of 14.41 DID. In 2016, the most used class was macrolides (32%), followed by cephalosporins (28%) and fluoroquinolones (19%). Oral agents comprised a large proportion (93%) of antimicrobial consumption. The most used agent, clarithromycin, accounted for 25% of all oral compounds used in 2016. The consumption of oral agents with high bioavailability, such as fluoroquinolones, amoxicillin, and sulfamethoxazole/trimethoprim increased, whereas that of cephalosporins decreased. In 2016, ceftriaxone was the most consumed parenteral agent, followed by cefazolin. The consumption of parenteral agents increased after 2009 when high-dose regimens of piperacillin/tazobactam, meropenem, and ampicillin/sulbactam were approved by the health insurance system. National antimicrobial consumption has been stable over the last 13 years. Moreover, shifts in the use of agents with high bioavailability and those approved for high-dose regimens were observed. However, the increased use of broad-spectrum agents is worrisome. A multifaceted approach is required to reduce overall antimicrobial consumption.

Antecedentes, objetivos y metodología / Background, objectives, and methods

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Equinocandinas: aspectos aplicados de la farmacología / Echinocandins: applied pharmacology

Las equinocandinas comparten las propiedades farmacodinámicas pero presentan algunas diferencias en su comportamiento farmacocinético, cuestión de interés en la práctica asistencial. No se absorben por vía oral. Su distribución en el organismo es un tanto especial ya que alcanzan concentraciones intracelulares elevadas, aunque en alguno de los fármacos puede ser reducida. Se fijan en elevada proporción a proteínas plasmáticas, por lo que al menos en el caso de la anidulafungina y la caspofungina se recomienda la administración de una dosis de carga; es discutible que no se realice con la micafungina. Se eliminan a través del metabolismo no microsómico, por lo que la concentración urinaria es muy reducida. En el proceso de eliminación biliar participan algunas proteínas transportadoras que probablemente son el origen de las interacciones descritas con la caspofungina y la micafungina. Estos dos fármacos han de ser utilizados con precaución en pacientes con alteración grave de la función hepática, pero todos ellos pueden utilizarse sin precauciones especiales cuando existe insuficiencia renal o el paciente precisa la utilización de técnicas de depuración externa (AU)

The echinocandins share pharmacodynamic properties, although there are some interesting differences in their pharmacokinetic behaviour in the clinical practice. They are not absorbed by the oral route. They have a somewhat special distribution in the organism, as some of them can reach high intracellular concentrations while, with some others, the concentration is reduced. They are highly bound to plasma proteins, thus it is recommended to administer a loading dose for anidulafungin and caspofungin, although this procedure is not yet clear with micafungin. Echinocandins are excreted via a non-microsomal metabolism, so the urinary concentration is very low. Some carrier proteins that take part in the biliary clearance process are probably involved in the interactions described with caspofungin and micafungin. These two drugs must be used with caution in patients with severely impaired hepatic function, while all of them can be used without special precautions when there is renal impairment or the patient requires renal replacement therapy (AU)

The Sojourn from Parenteral to Oral Taxanes using Nanocarrier Systems: A Patent Review.

Natural diterpenoid taxanes and their semisynthetic analogues have already made an indelible mark in the chemotherapeutic world for treating various kinds of malignancies. However, due to the absence of any functional groups which could be ionized by pH alteration or which may participate in salt formation, these taxanes, exhibit low solubility. Parenteral administration of taxanes with solubilising agents such as Cremophor EL and Polysorbate 80 results in undesirable side effects like hypersensitivity reactions, myelosuppression and peripheral neuropathy. Nanoengineered drug delivery systems like nanoemulsions, nanocrystals, dendrimers, micelles, selfnanoemulsifying systems, liposomes, solid-lipid nanoparticles and biodegradable polymeric nanoparticles, in this regard, tend to surmount these ostensible challenges, when administered orally. The bare taxanes encounter several inadequacies, namely poor aqueous solubility, structural instability in physiological fluids, p-glycoprotein recognition, hepatic first-pass effect, gastrointestinal permeability, and Cytochrome P450 enzymatic metabolism, etc. In addition, nanoscaled oral delivery improves drug encapsulation, thus facilitating diffusion through intestinal epithelium, modification of pharmacokinetic and tissue distribution profile of the drug, eventually resulting in flexibility of dosing schedules, prevention of discomfort of the injection and hospitalization, and improved patient convenience. The current review paper endeavors to provide a bird's eye view on the significant headway made on orally-administered nanosystems of taxanes and their analogues through patent applications published till date since its discovery.

Development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy program.

PURPOSE: The development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy (OPAT) program in a county teaching hospital are described. SUMMARY: A pharmacist-managed OPAT program was developed and implemented at a county teaching hospital to provide consistent evaluation, approval, and monitoring of patients requiring OPAT for the treatment of infection. The developmental and implementation stages of the OPAT program included (1) a needs assessment, (2) the identification of resources necessary for program operation, (3) delineation of general OPAT program operations and activities of individual OPAT clinicians, (4) the development of patient selection criteria, including a plan of care algorithm, and (5) acquisition of administrative support to approve the program. In this program, the OPAT pharmacist plays an integral role in the management and oversight of OPAT patients, working under a collaborative agreement with infectious diseases physicians. The OPAT pharmacist assists with appropriate patient and regimen selection, confirmation of orders on discharge, assuring that laboratory tests for safety surveillance are performed and evaluated, performing routine monitoring for adverse events and line complications, and assuring the removal of the vascular access device upon the completion of OPAT. CONCLUSION: The OPAT program provides structured monitoring, patient follow-up, and led to improvements in patient outcome with minimization of treatment and line-related adverse events.

Polyethylene glycols in oral and parenteral formulations--A critical review.

Polyethylene glycols (PEGs) are frequently employed as vehicles in oral and parenteral dosage forms. PEGs have low toxicity, are miscible with aqueous fluids in all proportions, and dissolve many poorly aqueous soluble compounds. Compounds with poor aqueous solubility and resulting poor bioavailability and considerable individual variability in the absorption were shown to provide exceptionally high bioavailability and reduced inter-subject variability in plasma concentrations when dosed as solutions or suspensions in PEGs. The advantages offered by PEGs, however, are not without potential challenges that must also be considered and which are the focus of this review. First, PEGs often may have high solubilizing power for some poorly aqueous soluble compounds, the high affinity of these vehicles for water can potentially lead to precipitation of the dissolved compounds when the formulations encounter an aqueous environment in vitro or in vivo, resulting in reduced bioavailability of the compounds. Second, PEGs, due to the presence of hydroxyl groups in their structures, are reactive with compounds dissolved within, resulting in the formation of degradation products. Third, PEGs, due to the presence of recurring ether groups in their polymer chains, are also inherently susceptible to autooxidative reactions, resulting in the formation of highly reactive products, which degrade several compounds formulated with PEGs. The objective is to review the applications and limitations of PEGs in pharmaceutical dosage forms and discuss solutions to mitigate challenges that may potentially arise from their use.

Nanotechnology and the diagnosis/treatment of leishmaniasis / La nanotecnología y el diagnóstico/tratamiento de la leishmaniasis

Aim: The review article updates the current state of the art in the engineering of nanoplatforms against leishmaniasis. Special attention is devoted to the development of drug nanocarriers to be given to patients through the parenteral, topical, and oral routes of administration. Challenges and opportunities coming from advanced formulation methods/strategies introduced in the design of these nanosystems are emphasized. Finally, particular attention is also given to the use of nanoparticulate systems for vaccine delivery and for the diagnosis of the disease. Materials and Methods: To that aim, the Web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important preclinical results in the development of nanomedicines against leishmaniasis, as well considering vaccine delivery systems and nanoparticulate-based diagnosis. Results and Conclusion: The introduction of nanotechnology into the leishmaniasis arena is intended to optimize both the diagnosis and treatment (drug/vaccine therapy) of the disease. The objective is always to improve the selectivity of the imaging molecules or drugs/vaccines toward the parasite, especially when it is located inside phagocytic cells and neutrophils, while keeping to a very minimum the toxic side effects. Of course, only the wise engineering of the nanoparticulate delivery system will assure the best diagnostic/therapeutic outcomes

Objetivos: Este trabajo pretende actualizar la situación actual en el diseño de nanoplataformas contra la leishmaniasis. En este sentido, especial atención merecen los nanotransportadores de fármacos diseñados para ser administrados al paciente a través de las vías de administración parenteral, tópica y oral. Asimismo, se discuten las posibilidades que ofrecen las técnicas o estrategias de formulación más avanzadas en el diseño de estas nanoplataformas biomédicas. Finalmente, también se dedica especial atención a la utilización de estos nanosistemas en la administración de vacunas y en el diagnóstico de la leishmaniasis. Material y Métodos: Con este fin, se utilizaron las páginas Web PubMed, HCAplus, Thomson y Registry como principales fuentes para la búsqueda de los trabajos de investigación más interesantes publicados sobre la materia. La información así obtenida fue cuidadosamente analizada, resaltando aquellos resultados preclínicos más relevantes en cuanto al desarrollo de nanomedicamentos contra la leishmaniasis, y considerando también los nanosistemas transportadores de vacunas y las nanoplataformas de utilidad en el diagnóstico de esta enfermedad. Resultados y conclusiones: La nanotecnología es utilizada para mejorar el diagnóstico y tratamiento de la leishmaniasis. El objetivo es, en todos los casos, la mejora de la selectividad por el parásito de los fármacos, vacunas y moléculas utilizadas como agentes de contraste en técnicas de imagen, especialmente cuando este microorganismo se encuentra localizado en el interior de macrófagos y neutrófilos. Con esta interesante nanoherramienta, se puede también obtener una significativa reducción en la aparición y severidad de la toxicidad asociada a las técnicas de diagnóstico y tratamiento de la leishmaniasis. Es evidente que sólo con un inteligente diseño de estos nanosistemas se logran los mejores resultados de diagnóstico y terapia de la enfermedad

Anestesia total intravenosa en geriatría: el ejemplo del propofol / Total intravenous anaesthesia in geriatrics: The example of propofol

El objetivo de esta revisión es analizar los cambios en la farmacología del paciente anciano utilizando como ejemplo los modelos farmacocinéticos y farmacodinámicos del propofol existentes y los datos aportados por los autores(AU)

The aim of this review is to analyse the changes in the pharmacology of the elderly patient using, as examples, the existing pharmacokinetics and pharmacodynamics models of propofol and data provided in the literature(AU)

Epidural versus continuous preperitoneal analgesia during fast-track open colorectal surgery: a randomized controlled trial.

BACKGROUND: Effective postoperative analgesia is essential for early rehabilitation after surgery. Continuous wound infiltration (CWI) of local anesthetics has been proposed as an alternative to epidural analgesia (EA) during colorectal surgery. This prospective, double-blind trial compared CWI and EA in patients undergoing elective open colorectal surgery. METHODS: Fifty consecutive patients were randomized to receive EA or CWI for 48 h. In both groups, patients were managed according to Enhanced Recovery After Surgery recommendations. The primary outcome was the dynamic pain score measured during mobilization 24 h after surgery (H24) using a 100-mm verbal numerical scale. Secondary outcomes were time to functional recovery, analgesic technique-related side effects, and length of hospital stay. RESULTS: Median postoperative dynamic pain score was lower in the EA than in the CWI group (10 [interquartile range: 1.6-20] vs. 37 [interquartile range: 30-49], P < 0.001) and remained lower until hospital discharge. The median times to return of gut function and tolerance of a normal, complete diet were shorter in the EA than in the CWI group (P < 0.01 each). Sleep quality was also better in the EA group, but there was no difference in urinary retention rate (P = 0.57). The median length of stay was lower in the EA than in the CWI group (4 [interquartile range: 3.4-5.3] days vs. 5.5 [interquartile range: 4.5-7] days; P = 0.006). CONCLUSION: Within an Enhanced Recovery After Surgery program, EA provided quicker functional recovery than CWI and reduced length of hospital stay after open colorectal surgery.

Consenso sobre utilización de la vía parenteral en el deporte. Aspectos generales. Documento de consenso de la Federación Española de Medicina del Deporte / Consensus on use of parenteral via in sports. Document of Consensus of the Spanish Federation of Sports Medicine

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Contribution of infectious disease consultation toward the care of inpatients being considered for community-based parenteral anti-infective therapy.

BACKGROUND: In the acute care setting in a multidisciplinary healthcare environment, the contribution of infectious disease (ID) specialists to overall patient care is difficult to measure. This study attempts to quantify the contribution of ID specialists when consulted for an activity specific to ID practice, community-based parenteral anti-infective therapy (CoPAT). METHODS: In February 2010, an electronic form for requesting ID consultations was introduced in the computerized provider order entry (CPOE) system at the Cleveland Clinic. This allowed for easy identification of ID consultations for CoPAT. Hospital records for all patients with CoPAT consultation requests between February 11, 2010 and May 15, 2010 were reviewed for specific defined contributions in the domains of optimization of antimicrobial therapy, significant change in patient assessment, and additional medical care contribution. RESULTS: Over a 3-month period, there were 263 CoPAT consultation requests via CPOE, of which 172 were initial consultations and 91 reconsultations. Antimicrobial treatment was optimized in 84%, a significant change in patient assessment made in 52%, and additional medical care contribution provided in 71% of consultations. In 33% of consultations, there was contribution in all 3 domains. CoPAT was deemed not to be necessary in 27%. For patients requiring CoPAT, effective care transition from the inpatient to outpatient setting was assured at least 86% of the time. CONCLUSION: Infectious disease consultation before discharge on parenteral antibiotics adds value by contributing substantially to inpatient care, and providing antimicrobial stewardship and continuity of care at a critical patient care transition point.

Transitioning antimicrobial stewardship beyond the hospital: the Cleveland Clinic's community-based parenteral anti-infective therapy (CoPAT) program.

One of the tenets of value-based health care is a focus on providing benefits to patients, as measured by better health outcomes per dollar spent rather than minimizing costs. In fact, proponents of value-based health care argue that the best way to reduce health care costs is through a focused approach to improving health outcomes. Associated with this approach is the need to measure outcomes over the full cycle of care, not simply for services rendered while an inpatient. This article examines the community-based parenteral anti-infective therapy program at the Cleveland Clinic as a model for antimicrobial stewardship for patients requiring parenteral antimicrobial therapy at the time of discharge from the inpatient setting. The program is a patient needs-focused, coordinated team effort that mandates inpatient infectious disease consultation for patients requiring community-based parenteral anti-infective therapy. An examination of some of the features of the Cleveland Clinic program should provide guidance for other institutions seeking to improve the care of their patients requiring parenteral anti-infectives when transitioning care from the acute setting.

Considerations in developing a target product profile for parenteral pharmaceutical products.

A target product profile (TPP) describes how a product will be utilized by the end user. A systematically developed TPP can ensure alignment of objectives across company departments, accelerate development timelines, minimize development risks, and eventually lead to an optimal product. A TPP is particularly important for parenteral products due to the need for administration devices, the variety of possible end users (nurses, patients, pharmacists, and physicians), and requirements specific to sterile products. This manuscript describes key components of a TPP from a formulation development perspective and provides guidance on practical issues common to parenteral products.

Hidratación por vía subcutánea en pacientes con cáncer avanzado / No disponible

Introducción: La vía subcutánea se emplea con frecuencia en enfermosde cáncer avanzado o ancianos para administrar medicación por víaparenteral. Sin embargo, la hidratación por vía subcutánea es excepcionalen nuestro medio aunque ya se está utilizando en algunos centros. Pretendemosconocer si es factible administrar hidratación subcutánea enenfermos oncológicos, las características de la técnica y las difi cultadesque se pueden presentar en su aplicación.Pacientes, material y métodos: Se incluyeron pacientes oncológicos concáncer avanzado con deshidratación o riesgo de padecerla de la Unidadde Medicina Paliativa del Hospital Grey Nuns, Edmonton (Canadá) y delHospital Universitario de Valladolid que recibieron hidratación subcutáneacon volumen y ritmo de infusión adaptados a cada enfermo.Resultados: Se realizaron 101 punciones en 33 pacientes (Edmonton24; Valladolid 9), con un total de 314 días de infusión. El volumen fue1.000 cc/día durante una mediana de 10 días (1 a 21 días) y un ritmode 20 a 400 cc/hora. El punto de infusión se cambió cada tres días (1a 15 días), principalmente por acumulación en zona de punción. Solodos enfermos precisaron asociar hialuronidasa a la solución utilizadapor absorción defi ciente. Hubo diferencias entre Hospitales en las característicasde los pacientes (peor pronóstico: grupo español) y tipo deinfusión (mayor volumen y duración: grupo canadiense). La incidenciade complicaciones fue similar similares en ambos grupos y en generalde carácter leve.Conclusión: La vía subcutánea para la hidratación de pacientesoncológicos terminal es sencilla y parece exenta de complicacionesimportantes(AU)

Introduction: Subcutaneous infusion allows the administration of parenteraltreatments. However, subcutaneous hydration is exceptional in ourenvironment. We developed this trial in order to assess the feasibilityof such hydration in cancer patients, the procedures and potentialcomplications.Patients, material and methods: We included dehydrated terminally illcancer patients and patients at risk of developing dehydration from thePalliative Care Unit of The Grey Nuns Hospital, Edmonton (Canada)and Hospital Universitario de Valladolid (Spain). They received subcutaneoushydration; the volume and rhythm of infusion were adaptedto each patient.Results: We performed 101 clyses in 33 patients (Edmonton 24; Valladolid9), with a total of 314 days of infusion. Volume infused was1,000 cc/day over a median of three days (1 to 21 days) and a rhythmof 20 cc/hour. Clyses were changed every three days (1 to 15 days),mainly because of fl uid retention in the puncture area. Two patientsrequired hyaluronidase. There were differences between Hospitals incharacteristics of patients (worse prognosis in the Spanish group) andconditions of infusion (higher volume and duration in Canadians). Theincidence of complications was low, being similar in both groups.Conclusions: Subcutaneous hydration of terminally ill cancer patients iseasy and seems to be free of severe complications(AU)