Intra-amniotic Candida albicans Infection Treated With Liposomal Amphotericin B With a Successful Neonatal Outcome.

Intra-amniotic infection with Candida species is an uncommon but severe condition with high fetal morbimortality and no established clinical guidelines for its management. We report a Candida albicans intra-amniotic infection diagnosed in a 25-week pregnant woman, successfully treated with high-dose liposomal amphotericin B. Pregnancy was prolonged until 30 weeks, and despite persistently positive Candida cultures in amniotic fluid, a healthy newborn was delivered without evidence of systemic infection. Amphotericin concentration was determined at birth, revealing levels over 30 times higher in mother's and cord blood than in the amniotic fluid, probably explaining the clinical protection despite failure in obtaining fungal clearance.

Implementación del Proceso Estandarizado de Evaluación Farmacoterapéutica en pacientes hospitalizados y ambulatorios / Implementation of the standardized process of Pharmacotherapeutic evaluation in inpatients and outpatients

Objetivos el seguimiento farmacoterapéutico (SFT) realizado por el farmacéutico clínico puede enmarcarse dentro de 3 actividades: la identificación, la resolución y la prevención de eventos adversos a medicamentos. Estas deben ajustarse a los requerimientos y los recursos de cada institución, generando la necesidad de desarrollar procedimientos que aumenten la eficiencia del SFT y garanticen la seguridad del paciente. Los farmacéuticos clínicos de la Red de Salud UC-CHRISTUS Chile desarrollamos un Proceso Estandarizado de Evaluación Farmacoterapéutica (PEEF). El objetivo principal del estudio fue evaluar el impacto de esta herramienta en términos del número de evaluaciones e intervenciones de los farmacéuticos clínicos y secundariamente determinar el ahorro de costos potenciales y directos asociados a las intervenciones en la Unidad de Cuidados Intensivos (UCI). Método estudio cuasi-experimental que evaluó la frecuencia y tipo de evaluaciones e intervenciones realizadas por los farmacéuticos clínicos en unidades de pacientes adultos de la Red UC-CHRISTUS, previo y posterior a la utilización del PEEF. La distribución de variables se evaluó mediante el test Shapiro–Wilk, la asociación entre el uso del PEEF y el número de evaluaciones e intervenciones fue realizada mediante el test Chi cuadrado. La evaluación de costos asociados a las intervenciones del farmacéutico clínico en UCI se realizó utilizando la metodología propuesta por Hammond et al.10. Resultados el total de pacientes evaluados pre- y pos-PEEF fue de 1.781 y 2.129, respectivamente. Las evaluaciones e intervenciones en el periodo pre-PEEF fueron 5.209 y 2.246, en el periodo pos-PEEF fueron 6.105 y 2.641, respectivamente. El aumento de las evaluaciones como de las intervenciones fue significativo solo en las unidades de mayor complejidad. La reducción potencial de costos estimados en el periodo pos-PEEF en UCI fue de 492.805 dólares americanos. ... (AU)

Objectives The Pharmacotherapeutic follow-up program (PFU) carried out by the clinical pharmacist can be categorized within 3 fundamental activities; identification, resolution and prevention of adverse drug events. These must be adjusted to the requirements and resources of each institution, developing procedures to increase PFU efficiency and to guarantee patient safety. The clinical pharmacists of UC-CHRISTUS Healthcare Network developed a Standardized Pharmacotherapeutic Evaluation Process (SPEP). The main goal of our study is to evaluate the impact of this tool through the pharmacist evaluation number and pharmacist interventions number. Secondarily to determine the potential and direct cost savings associated with the pharmacist interventions in an Intensive care unit (ICU). Methods A quasi-experimental study evaluated the frequency and type of pharmacist evaluation and pharmacist interventions performed by clinical pharmacists in adult patients units of UC-CHRISTUS Healthcare Network, before and after the implementation of SPEP. The distribution of variables was evaluated using the Shapiro–Wilk test and the association between the use of SPEP and the pharmacist evaluation and pharmacist interventions number was performed using the Chi-square test. The cost evaluation associated with pharmacist interventions in the ICU was carried out using methodology proposed by Hammond et al. Results A total number of 1,781 patients was evaluated before and 2,129 after the SPEP. The pharmacist evaluation and pharmacist interventions number in the before-SPEP period were 5,209 and 2,246. In the after-SPEP period were 6,105 and 2,641, respectively. The increase in both the pharmacist evaluation and pharmacist interventions number was significant only in critical care patients. The potential cost saving in after-SPEP period in the ICU was USD 492,805.... (AU)

Beta-Lactam Antibiotics Can Be Measured in the Exhaled Breath Condensate in Mechanically Ventilated Patients: A Pilot Study.

Different techniques have been proposed to measure antibiotic levels within the lung parenchyma; however, their use is limited because they are invasive and associated with adverse effects. We explore whether beta-lactam antibiotics could be measured in exhaled breath condensate collected from heat and moisture exchange filters (HMEFs) and correlated with the concentration of antibiotics measured from bronchoalveolar lavage (BAL). We designed an observational study in patients undergoing mechanical ventilation, which required a BAL to confirm or discard the diagnosis of pneumonia. We measured and correlated the concentration of beta-lactam antibiotics in plasma, epithelial lining fluid (ELF), and exhaled breath condensate collected from HMEFs. We studied 12 patients, and we detected the presence of antibiotics in plasma, ELF, and HMEFs from every patient studied. The concentrations of antibiotics were very heterogeneous over the population studied. The mean antibiotic concentration was 293.5 (715) ng/mL in plasma, 12.3 (31) ng/mL in ELF, and 0.5 (0.9) ng/mL in HMEF. We found no significant correlation between the concentration of antibiotics in plasma and ELF (R2 = 0.02, p = 0.64), between plasma and HMEF (R2 = 0.02, p = 0.63), or between ELF and HMEF (R2 = 0.02, p = 0.66). We conclude that beta-lactam antibiotics can be detected and measured from the exhaled breath condensate accumulated in the HMEF from mechanically ventilated patients. However, no correlations were observed between the antibiotic concentrations in HMEF with either plasma or ELF.

Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-α2b in Healthy Adults: The IN2COVID Phase I Randomized Trial.

BACKGROUND AND OBJECTIVES: Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults. METHODS: A double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. RESULTS: Exposure to inhaled IFN-α2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-α concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons). CONCLUSIONS: Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. CLINICAL TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.

Implementation of the standardized process of Pharmacotherapeutic evaluation in inpatients and outpatients. / Implementación del Proceso Estandarizado de Evaluación Farmacoterapéutica en pacientes hospitalizados y ambulatorios.

OBJECTIVES: The Pharmacotherapeutic follow-up program (PFU) carried out by the clinical pharmacist can be categorized within 3 fundamental activities; identification, resolution and prevention of adverse drug events. These must be adjusted to the requirements and resources of each institution, developing procedures to increase PFU efficiency and to guarantee patient safety. The clinical pharmacists of UC-CHRISTUS Healthcare Network developed a Standardized Pharmacotherapeutic Evaluation Process (SPEP). The main goal of our study is to evaluate the impact of this tool through the pharmacist evaluation number and pharmacist interventions number. Secondarily to determine the potential and direct cost savings associated with the pharmacist interventions in an Intensive care unit (ICU). METHODS: A quasi-experimental study evaluated the frequency and type of pharmacist evaluation and pharmacist interventions performed by clinical pharmacists in adult patients units of UC-CHRISTUS Healthcare Network, before and after the implementation of SPEP. The distribution of variables was evaluated using the Shapiro-Wilk test and the association between the use of SPEP and the pharmacist evaluation and pharmacist interventions number was performed using the Chi-square test. The cost evaluation associated with pharmacist interventions in the ICU was carried out using methodology proposed by Hammond et al. RESULTS: A total number of 1,781 patients was evaluated before and 2,129 after the SPEP. The pharmacist evaluation and pharmacist interventions number in the before-SPEP period were 5,209 and 2,246. In the after-SPEP period were 6,105 and 2,641, respectively. The increase in both the pharmacist evaluation and pharmacist interventions number was significant only in critical care patients. The potential cost saving in after-SPEP period in the ICU was USD 492,805. Major adverse drug events prevention was the intervention that generated the most savings with a reduction of 60.2%. The total direct savings for sequential therapy was USD 8,072 in the study period. CONCLUSIONS: This study shows a clinical pharmacist developed tool called SPEP that increased the pharmacist evaluation and pharmacist interventions number in multiple clinical scenarios. These were significant only in critical care patients. Future investigations should make effort to evaluate the quality and clinical impact of these interventions.

Population pharmacokinetics of amikacin in suspected cases of neonatal sepsis.

AIMS: This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure. METHODS: Newborns aged ≥3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM. RESULTS: Data from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl. CONCLUSION: Our main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.

[Surveillance of adverse effects of Tocilizumab for COVID-19]. / Tocilizumab en pacientes COVID-19: evaluación del perfil de seguridad en una indicación off label.

BACKGROUND: Tocilizumab (TCZ) is a new therapeutic alternative for severe cases of COVID-19 pneumonia. AIM: To evaluate the cumulative incidence (CI) of suspected adverse drug reactions (ADR) from TCZ in adult patients with COVID-19. MATERIAL AND METHODS: An active pharmacological surveillance protocol was carried out in patients older than 18 years old, who received at least one dose of TCZ between May and August 2020 at a clinical hospital. Non-infectious ADRs were categorized according to the Common Terminology Criteria for Adverse Events and the development of infection was classified as present or absent. Causality and preventability of ADRs were determined with the Naranjo Algorithm and the modified Schumock & Thornton criteria, respectively. RESULTS: The CI of ADRs caused by TCZ was 69.6% (95% confidence intervals (CI): 63.5-76.6). A rise in alanine and aspartate aminotransferases and the development of infections were the most frequent adverse events. Seventy-four percent were considered mild in severity. Sixty two percent of suspected non-infectious ADRs were classified as probable and all the infectious events as Possible. Of the ADRs observed, 33% were preventable. CONCLUSIONS: The occurrence of ADRs after the use of TCZ is frequent, of mild severity, and in one third of the cases, preventable. We suggest monitoring blood count, liver function tests and ruling out infection prior to TCZ administration.

Tocilizumab en pacientes COVID-19: evaluación del perfil de seguridad en una indicación off label / Surveillance of adverse effects of Tocilizumab for COVID-19

BAKCGROUND: Tocilizumab (TCZ) is a new therapeutic alternative for severe cases of COVID-19 pneumonia. AIM: To evaluate the cumulative incidence (CI) of suspected adverse drug reactions (ADR) from TCZ in adult patients with COVID-19. MATERIAL AND METHODS: An active pharmacological surveillance protocol was carried out in patients older than 18 years old, who received at least one dose of TCZ between May and August 2020 at a clinical hospital. Non-infectious ADRs were categorized according to the Common Terminology Criteria for Adverse Events and the development of infection was classified as present or absent. Causality and preventability of ADRs were determined with the Naranjo Algorithm and the modified Schumock & Thornton criteria, respectively. RESULTS: The CI of ADRs caused by TCZ was 69.6% (95% confidence intervals (CI): 63.5-76.6). A rise in alanine and aspartate aminotransferases and the development of infections were the most frequent adverse events. Seventy-four percent were considered mild in severity. Sixty two percent of suspected non-infectious ADRs were classified as probable and all the infectious events as Possible. Of the ADRs observed, 33% were preventable. CONCLUSIONS: The occurrence of ADRs after the use of TCZ is frequent, of mild severity, and in one third of the cases, preventable. We suggest monitoring blood count, liver function tests and ruling out infection prior to TCZ administration.

How far are we from predicting multi-drug interactions during treatment for COVID-19 infection?

Seriously ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hospitalized in intensive care units (ICUs) are commonly given a combination of drugs, a process known as multi-drug treatment. After extracting data on drug-drug interactions with clinical relevance from available online platforms, we hypothesize that an overall interaction map can be generated for all drugs administered. Furthermore, by combining this approach with simulations of cellular biochemical pathways, we may be able to explain the general clinical outcome. Finally, we postulate that by applying this strategy retrospectively to a cohort of patients hospitalized in ICU, a prediction of the timing of developing acute kidney injury (AKI) could be made. Whether or not this approach can be extended to other diseases is uncertain. Still, we believe it represents a valuable pharmacological insight to help improve clinical outcomes for severely ill patients.

[Acute phosphate nephropathy secondary to the use of oral sodium phosphate laxatives. Report of one case]. / Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico.

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.

A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19).

BACKGROUND: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. METHODS: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 µg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. DISCUSSION: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.

Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico / Acute phosphate nephropathy secondary to the use of oral sodium phosphate laxatives: report of one case

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.