Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia.

OBJECTIVES: To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded. RESULTS: Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed. CONCLUSIONS: In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

Comparison of two isocaloric parenteral nutrition regimens with different protein content - A propensity-score matched comparative study.

OBJECTIVE: this study aimed to assess the effects of two isocaloric parenteral nutrition (PN) regimens with different protein content and non-protein calorie to nitrogen ratio (NPCNR) on the evolution of nutritional parameters and outcomes in adult inpatients. METHODS: this was a retrospective quasi-experimental study performed in a 400-bed tertiary hospital. Adult inpatients were initially eligible if they had received ≥ 4 days of PN with NPCNR ≥ 100 or ≤ 90 in a period of three years. Patients were propensity-score matched to adjust for differences, resulting in two final cohorts: Cohort "Medium-P" included patients receiving PN with NCPCNR ≥ 100 and cohort "High-P", receiving PN with NCPCNR ≤ 90. The main variables were differences in plasma albumin, prealbumin, cholesterol, and lymphocyte count, days requiring PN, length of stay, and mortality at 90 days. RESULTS: 202 patients were finally recruited and divided into the two equal cohorts. Patients were mainly male (122; 60.4 %), surgical (149; 73.8 %), critically ill (100; 49.5 %), with high nutritional risk (141; 69.8 %) and with a neoplasm (145; 71.8 %). PN provided 25 kcal/kg/day, but protein intake was 0.25 g/kg/day higher in the "High-P" cohort. Baseline characteristics and biochemistry were not different between the two cohorts. The "High-P" cohort presented a smaller difference at the end of PN for lymphocytes, more days with hyperglycaemia, and more days requiring PN. The rest of variables did not differ. CONCLUSIONS: high doses of protein (lower NPCNR) did not present advantages compared to medium doses of protein (higher NPCNR) when providing isocaloric PN in adult inpatients.

Dispensation of outpatient hospital medicines by hospital only versus hospital-community pharmacies collaboration: a cross-sectional study and survey of patient's satisfaction.

Goal: To describe the experience of a dispensing model of outpatient hospital medicines (OHM) via collaboration of hospital and community pharmacies, and to explore patient satisfaction with the strategy as compared with the hospital pharmacy only service. Background: Patient satisfaction is an important component of the quality of health care. Study: A new model of dispensing OHM was conducted in the Outpatients Unit of the Service of Hospital Pharmacy of Hospital del Mar, in Barcelona, Spain. Participants were patients on stable chronic treatment with clinical or social fragility, immunocompromised patients, and those whose residence was located at a distance from the hospital that justified drug delivery through the community pharmacy. A cross sectional study was done using an ad hoc 14-item questionnaire collecting demographic data, duration of treatment, usual mode of collecting medication, and the degree of satisfaction regarding waiting time for the collection of medication, attention received by professionals, information received on treatment, and confidentiality. Results: The study population included a total of 4,057 patients (66.8% men) with a mean age of 53 (15.5) years, of whom 1,286 responded, with a response rate of 31.7%. Variables significantly associated with response to the survey were age over 44 years, particularly the age segment of 55-64 years (odds ratio [OR] 2.51) and receiving OHM via the community pharmacy (OR 12.76). Patients in the community pharmacy group (n = 927) as compared with those in the hospital pharmacy group (n = 359) showed significantly higher percentages of 'satisfied' and 'very satisfied' (p < 0.001) in the waiting time for the collection of OHM (88.1% vs. 66%), attention received by professionals (92.5% vs. 86.1%), and information received on treatment (79.4% vs. 77.4%). In relation to confidentiality, results obtained were similar in both pharmacy settings. Conclusion: Dispensing OHM through the community pharmacy was a strategy associated with greater patient satisfaction as compared with OHM collection at the hospital pharmacy service, with greater accessibility, mainly due to close distance to the patient's home. The participation of community pharmacists could further optimize the care received by patients undergoing OHM treatment.

Pharmacological management of antifungal agents in pulmonary aspergillosis: an updated review.

INTRODUCTION: Aspergillus may cause different types of lung infections: invasive, chronic pulmonary or allergic bronchopulmonary aspergillosis. Pharmacological management with antifungals poses as a challenge. Patients diagnosed with pulmonary aspergillosis are complex, as well as the problems associated with antifungal agents. AREAS COVERED: This article reviews the pharmacology of antifungal agents in development and currently used to treat pulmonary aspergillosis, including the mechanisms of action, pharmacokinetics, pharmacodynamics, dosing, therapeutic drug monitoring and safety. Recommendations to manage situations that arise in daily clinical practice are provided. A literature search of PubMed was conducted on November 15th, 2020 and updated on March 30th, 2021. EXPERT OPINION: Recent and relevant developments in the treatment of pulmonary aspergillosis have taken place. Novel antifungals with new mechanisms of action that extend antifungal spectrum and improve pharmacokinetic-related aspects, drug-drug interactions and safety are under current study. For those antifungals already marketed, new data related to pharmacokinetics, pharmacodynamics, dose adjustments in special situations, therapeutic drug monitoring and safety are available. To maximize efficacy and reduce the risk of associated toxicities, it is essential to choose the most appropriate antifungal; optimize its dose, interval, route of administration and length of treatment; and prevent side effects.

Azithromycin in the treatment of COVID-19: a review.

INTRODUCTION: SARS-CoV-2 is a novel virus that causes coronavirus disease-19 (COVID-19). Antiviral and immunomodulatory agents have been proposed as potential treatments. Azithromycin exhibits both properties and therefore may play a role. AREAS COVERED: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, and safety of azithromycin in viral infections, with emphasis on COVID-19. A literature search of PUBMED was conducted on May 30th and updated on July 28th. EXPERT OPINION: Azithromycin presents in vitro activity against SARS-CoV-2 and could act in different points of the viral cycle. Its immunomodulatory properties include the ability to downregulate cytokine production, maintain epithelial cell integrity or prevent lung fibrosis. Azithromycin use was associated with a reduction in mortality and ventilation days in other viral infections. These properties could be beneficial throughout the COVID-19. However, the evidence of its use is scarce and of low quality. Azithromycin has been assessed in retrospective observational studies mainly in combination with hydroxychloroquine, which has shown to provide no benefit. This macrolide presents a well-known safety profile. Upcoming clinical trials will determine the role of azithromycin in the COVID-19 (including the stage of the disease where it offers the greatest benefits and the effect of its combination with other drugs).

Personalized antimicrobial therapy in critical and elderly patients.

OBJECTIVE: Personalized therapy in the treatment of infections is essential to  ensure optimization of antimicrobial drug levels. This strategy, together with an  understanding of the activity of these drugs, decreases the risk of bacterial  resistance and improves the drugs' safety profile. Alternative  outes of administration, such as inhalation, and the information provided by  pharmacokinetic models, are essential given the limitation of antimicrobial  activity allowed by the new antimicrobials. METHOD: A non-systematic review of the literature is presented as a way of  tackling and finding solutions to the problem. A search for high-quality articles  on the research topic was conducted. Results: A total of 370 articles were  detected, which were subjected to a further selection to discard low quality  papers by a team of five clinical pharmacists and an intensivist. Finally, 153  articles were included in the review. CONCLUSIONS: The geriatric and the critical care patient population require the  administration of antimicrobials with close monitoring. The routes of  administration recommended for the first group are discouraged for the  second. The inhaled route often results in high plasma concentrations in  patients with respiratory infections. Pharmacokinetic models are a valuable tool  in the treatment of geriatric patients, who are often excluded  from clinical trials.

OBJETIVO: La terapia personalizada en el tratamiento de las infecciones es esencial para garantizar la optimización de los niveles de fármaco  lcanzados en el paciente tratado. Adicionalmente, esta estrategia, juntamente  con el conocimiento de la actividad antimicrobiana de estos fármacos,  isminuye la posibilidad de desarrollar resistencias bacterianas y mejora el perfil  de seguridad de estos fármacos. Las terapias por vías alternativas, como  la inhalada, y el soporte de la información facilitada por modelos  farmacocinéticos son esenciales debido a la limitación de la actividad aportada  por los nuevos antimicrobianos.Método: Se presenta una revisión no sistemática de la literatura como medida  de orientación de la problemática y soluciones a lo expuesto  anteriormente. Se ha efectuado una búsqueda de artículos de alta calidad  sobre el tópico planteado. RESULTADOS: Se detectaron 231 artículos que sufrieron una selección posterior,  en base a la calidad de los trabajos valorada por un equipo de cinco farmacéuticos clínicos y un médico intensivista. Finalmente, se incluyeron 153 artículos que soportan la revisión que se ha desarrollado. CONCLUSIONES: La población geriátrica y la integrada por pacientes críticos presenta la necesidad de utilización de los antimicrobianos con una  estrecha monitorización. Vías de administración recomendadas en la primera,  están desaconsejadas en la segunda. La vía inhalada es una vía que suele  relacionarse con elevadas concentraciones en pacientes con infecciones  respiratorias. Los modelos farmacocinéticos son un soporte de gran valor para poblaciones como la geriátrica debido a que es mayoritariamente excluida de los ensayos clínicos.

Impact of HCV cure with drug-acting antivirals in the use of concomitant medication and lipid profile: follow-up data 2 years after the sustained virological response.

BACKGROUND AND AIM: Patients with chronic hepatitis C (CHC) frequently associated comorbidities and concomitant medication. Sustained virological response (SVR12) has been related to an increase in cholesterol serum levels and in peripheral vascular resistance. Our aim was to evaluate the impact of SVR12 on the use of concomitant medication and serum lipid profile. METHODS: Prospective study including patients treated with direct-acting antivirals who had achieved the SVR12. Clinical data and concomitant drugs were analysed at baseline and at least 1 year after SVR12. Differences from baseline to follow-up in the concomitant medication were evaluated by Stuart-Maxwell test and lipid profile by Wilcoxon signed-rank test. Patients were categorized according to the increase/decrease in the number of drugs included in each class (Anatomical Therapeutic Chemical classification system). RESULTS: Two hundred twenty-six patients with SVR12 were included, 73.5% were receiving concomitant drugs (49.6% with antihypertensive effect, 30.5% antacids, 16.4% anti-diabetic drugs, and 7.1% lipid-lowering agents). One year after SVR12, total cholesterol serum levels increased from 161 to 179 mg/dl (P < 0.001) and, after a median time of 25.7 months, the use of lipid-lowering drugs increased from 7.8 to 11.5% (P = 0.009). In addition, we observed a trend to use more antihypertensive drugs in older patients (P = 0.06), especially in those with cirrhosis. Anxiolytics decreased after SVR12 from 13.7 to 10.6% (P = 0.035). CONCLUSION: CHC cure is associated with a significant increase in cholesterol serum levels and the use of lipid-lowering agents, as well as the use of drugs with antihypertensive effect in older patients.

Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in critically-ill patients: systematic review.

INTRODUCTION: Community-acquired pneumonia (CAP) is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA) having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. OBJECTIVE: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. MATERIAL AND METHODS: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. RESULTS: A total of 70 articles were found to have been published, 13 (18.8%) having been included and 57 (81.4%) excluded. Cohort studies were predominant, having totaled 16 in number (20.7%) as compared to one sole cross-sectional study (3.5%). CONCLUSIONS: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics.

Introducción: La neumonía adquirida en la comunidad (NAC) está relacionada con unas tasas elevadas de morbi-mortalidad. A pesar de que Staphylococcus aureus resistente a meticilina (SARM) se ha relacionado frecuentemente con la neumonía nosocomial, algunos pacientes con NAC por este microorganismo revisten la suficiente gravedad como para precisar su ingreso en la UCI.Objetivos: Efectuar una revisión sistemática de la literatura sobre el tratamiento antibiótico de la NAC por SARM en pacientes críticos.Material y métodos: Se realizó una búsqueda de artículos sobre NAC por SARM en el paciente crítico. Se identificaron las publicaciones pertinentes en PUBMED, BestPractice database, UpTo-Date database y Cochrane Plus Library para artículos publicados en inglés desde diciembre del 2001 hasta abril del 2016. Resultados: Se encontraron 70 publicaciones, incluyendo 13 (18,8%) y excluyendo 57 (81,4%). Predominaron los estudios de cohortes con un total de 6 (20,7%), frente a una única publicación en forma de estudio transversal (3,5%). Conclusiones: La experiencia en el tratamiento de la NAC por SARM en pacientes que precisen ingreso en la UCI es muy limitada. La vancomicina o el linezolid parecen ser las terapias en las que se dispone de una mayor experiencia, aunque no existe ninguna recomendación específica al respecto. Puede ser útil la utilización de vías alternativas como la nebulizada, administración en perfusión continua o en asociación con otros antibióticos.