Drug-related problems in patients admitted for SARS-CoV-2 infection during the COVID-19 pandemic.

Introduction: Drug-related problems (DRP) are events or circumstances in which drug therapy does or could interfere with desired health outcomes. In December 2019, a new coronavirus, SARS-CoV-2, appeared. Little knowledge about this type of infection resulted in the administration of various drugs with limited use in other pathologies. Evidence about DRP in patients with COVID-19 is lacking. Objective: The aim of the present study is to describe identified cases of DRP and those drugs involved in the first wave of patients with COVID-19, and evaluate associated risk factors. Material and methods: Observational, retrospective study performed in a tertiary university hospital between 14th March 2020 and 31 May 2020 (corresponding to the first COVID-19 wave). We recruited patients admitted during the study period. Exclusion criteria included age < 18 years; admission to critically ill units; and care received either in the emergency room, at-home hospitalization or a healthcare center. Results: A total of 817 patients were included. The mean age was 62.5 years (SD 16.4) (range 18-97), and 453 (55.4%) were male. A total of 516 DRP were detected. Among the patients, 271 (33.2%) presented at least one DRP. The mean DRP per patient with an identified case was 1.9. The prevailing DRPs among those observed were: incorrect dosage (over or underdosage) in 145 patients (28.2%); wrong drug combination in 131 (25.5%); prescriptions not in adherence to the then COVID-19 treatment protocol in 73 (14.1%); prescription errors due to the wrong use of the computerized physician order entry in 47 (9.2%); and incorrect dosage due to renal function in 36 (7%). The logistic regression analysis showed that patients who received only prescriptions of antibacterials for systemic use (J01 ATC group) faced a higher likelihood of experiencing a DRP (OR 2.408 (1.071-5.411), p = 0.033). Conclusion: We identified several factors associated with an increased risk of DRPs, similar to those reported in other pre-pandemic studies, including a prolonged length of stay, higher number of prescribed drugs and antimicrobial administration. The relevance of pharmacists and tools like pharmacy warning systems can help prevent, identify and resolve DRP efficiently.

Impact of the COVID-19 pandemic: Community and hospital shared pharmaceutical care model. Satisfaction and acceptability of patients with HIV infection on antiretroviral treatment.

OBJECTIVE: The health crisis due to the COVID-19 pandemic is a challenge in the dispensing of outpatient hospital medication (OHM). Models of Antiretroviral Therapy (ART) based on community pharmacy support (ARTCP) have proven to be successful. The aim was to evaluate the degree of satisfaction, acceptability and limitations of the implementation of ARTCP, in the context of a pandemic, in our environment. METHODS: Descriptive cross-sectional study carried out in a Barcelona hospital, during the months of July-November 2020. A telephone survey was carried out via a questionnaire on the quality dimensions of the model (degree of satisfaction, acceptability) and associated inconveniences. Data collected: demographics, antiretroviral treatment (ART), concomitant medication, drug interactions (DDIs), CD4 lymphocyte count and plasma viraemia. Data analysis included descriptive statistics. RESULTS: A total of 533 (78.0%) HIV patients receiving ART were included. 71.9% (383/533) of these patients were very satisfied and 76.2% preferred attending the community pharmacy rather than the hospital. The mean satisfaction rating was 9.3 (DS: 1.4). The benefits reported were: 1) proximity to home (406: 76.1%); 2) lower risk of contagion of COVID-19 (318: 59.7%); 3) shorter waiting time (201: 37.1%); 4) time flexibility (104: 19.5%); 5) reduction of financial expenses (35: 6.57%). A total of 11 (2%) patients reported no benefit. Only 22.9% reported disadvantages associated with ARTCP: 1) lack of privacy (65: 12.2%); 2) lack of coordinationorganization (57: 10.7%). CONCLUSIONS: The COVID-19 pandemic has had an impact on the provision of pharmaceutical care for HIV patients. The ARTPC model has proved efficient, with patients reporting a high degree of satisfaction.

Validation of a score to identify inpatients at risk of a drug-related problem during a 4-year period.

OBJECTIVE: Drug-related problems (DRP) produce high morbidity and mortality. It is therefore essential to identify patients at higher risk of these events. This study aimed to validate a DRP risk score in a large number of inpatients. MATERIAL AND METHODS: Validation of a previously designed score to identify inpatients at risk of experiencing at least one DRP in a tertiary university hospital from 2010 to 2013. DRP were detected by a pharmacy warning system integrated in the electronic medical record. The score included the following variables associated with a higher risk of DRP: prescription of a higher number of drugs, greater comorbidity, advanced age, specific ATC groups and certain major diagnostic categories. RESULTS: The study included a total of 52,987 admissions; of these, at least one DRP occurred in 14.9%. After validation of the score (period range, 2010-2013: 0.746-0.764), the area under the curve (AUC) was 0.751 (95% CI: 0.745-0.756). CONCLUSIONS: This value is higher than those reported in other studies describing validation of risk scores. The score showed good capacity to identify those patients at higher risk of DRP in a much larger sample of inpatients than previously described in the literature. This tool allows optimization of drug therapy monitoring in admitted patients.

Computerized pharmacy surveillance and alert system for drug-related problems.

WHAT IS KNOWN AND OBJECTIVE: Because of the impact of drug-related problems (DRPs) on morbidity and mortality, there is a need for computerized strategies to increase drug safety. The detection and identification of the causes of potential DRPs can be facilitated by the incorporation of a pharmacy warning system (PWS) in the computerized prescriber order entry (CPOE) and its application in the routine validation of inpatient drug therapy. A limited number of studies have evaluated a clinical decision support system to monitor drug treatment. Most of these applications have utilized a small range of drugs with alerts and/or types of alert. The objective of this study was to describe the implementation of a PWS integrated in the electronic medical record (EMR). METHODS: The PWS was developed in 2003-2004. Pharmacological information to generate drug alerts was entered on demographic data, drug dosage, laboratory tests related to the prescribed drug and drug combinations (interactions, duplications and necessary combinations). The PWS was applied in the prescription reviews conducted in patients admitted to the hospital in 2012. RESULTS AND DISCUSSION: Information on 83% of the drugs included in the pharmacopeia was introduced into the PWS, allowing detection of 2808 potential DRPs, representing 79·1% of all potential DRPs detected during the study period. Twenty per cent of PWS DRPs were clinically relevant, requiring pharmacist intervention. WHAT IS NEW AND CONCLUSION: The PWS detected most potential DRPs, thus increasing inpatient safety. The detection ability of the PWS was higher than that reported for other tools described in the literature.

Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections.

Linezolid is a valuable treatment option for central nervous system (CNS) infections caused by multidrug-resistant Gram-positive micro-organisms. Data regarding its penetration into the CNS have shown wide variability. The aim of this study was to describe the population pharmacokinetics of linezolid in plasma and cerebrospinal fluid (CSF) in critically ill patients with external CSF drainage and proven or suspected CNS infections. This was an observational pharmacokinetic (PK) study in 11 critically ill patients with proven or suspected CNS infection receiving linezolid. Serial blood and CSF samples were taken and were subject to population PK analysis. The median (interquartile range) of AUC(0-12h) was 47.6 (17.9-58.6) mgh/L in plasma and 21.1 (18.8-30.4) mgh/L in CSF, with a median CSF/plasma ratio of 0.77. At pre-dose at steady state, a strong positive correlation was observed between linezolid concentrations in CSF and plasma (Spearman's rho=0.758; P=0.011). For a minimum inhibitory concentration (MIC) of 2 mg/L, the median AUC(0-24h)/MIC values in plasma and CSF were <80 in all patients. A three-compartment linear model was found to be most appropriate. The mean value for linezolid clearance was 16.6L/h and mean volume of distribution was 101.3 L. No covariate relationships could be supported on any of the parameters. Linezolid demonstrated good penetration into the CNS but high interindividual PK variability. Administration of higher than standard doses of linezolid and therapeutic drug monitoring should therefore be considered as options to optimise linezolid dosing in critically ill patients with CNS infections.

[Mortality risk factors for bloodstream infections caused by extended-spectrum beta-lactamase-producing microorganisms]. / Factores de riesgo de mortalidad en pacientes con bacteriemia por cepas productoras de betalactamasas de espectro extendido.

OBJECTIVE: To identify risk factors for mortality in patients with bloodstream infection by extended-spectrum beta-lactamase (ESBL)-producing microorganisms. MATERIAL AND METHODS: A retrospective study in patients with bloodstream infection by ESBL-producing microorganisms from January 2000 to December 2006 was carried out. RESULTS: A total of 4,172 bloodstream infections were identified, 1,218 (29.2%) and 226 (5.4%) of which were caused by Escherichia coli and Klebsiella pneumoniae, respectively. The overall mortality rate was 50.9% in patients with bacteriema due to ESBL-producing strains. The binomial logistic regression model, adjusted for age and severity, identified admission to an intensive care unit (OR 38,631; 95%CI:3,375-424,618; P=.002) and a SAPS II severity index score >30 in the 24-48 h before obtaining blood culture (OR 17,980; 95% CI:2,193-170,439; P=.010) as factors associated to mortality, while the urinary tract as primary site of infection was an independent determinant for non-mortality (OR 0.184; 95% CI:0.034-0.975; P=.047). CONCLUSIONS: Patients with suspicion of bacteriema who have been admitted to the ICU with a score of elevated severity should be candidates for early empirical treatments as they have a greater risk of mortality. However, the benefit of this strategy may be limited due to the baseline severity of the patient.

Factores de riesgo de mortalidad en pacientes con bacteriemia por cepas productoras de betalactamasas de espectro extendido / Mortality risk factors for bloodstream infections caused by extended-spectrum beta-lactamase-producing microorganisms

Objetivo. Identificar los factores de riesgo de mortalidad en pacientes con bacteriemia por microorganismos productores de betalactamasas de espectro extendido (BLEE). Material y métodos. Estudio retrospectivo de cohortes en pacientes con bacteriemia por microorganismos productores de BLEE desde enero de 2000 hasta diciembre de 2006. Resultados. Se identificaron 4.172 episodios de bacteriemia. De ellos, 1.218 (29,2%) fueron causados por Escherichia coli y 226 (5,4%) por Klebsiella pneumoniae, de los que en 42 y en 11 se aislaron cepas productoras de BLEE, respectivamente. La mortalidad cruda fue del 50,9% en los pacientes que presentaron bacteriemia por cepas productoras de BLEE. El modelo de regresión logística binomial, ajustado por edad y gravedad, identificó el ingreso en una unidad de cuidados intensivos (UCI) (odds ratio: 38,631; intervalo de confianza [IC] del 95%, 3,375-424,618; p=0,002) y un valor del índice de gravedad SAPS II superior a 30 en las 24-48h previas a la extracción de la muestra para hemocultivo que posteriormente resultó positivo (OR: 17,980; IC del 95%, 2,193-170,439; p=0,010) como factores asociados a mortalidad, mientras que el presentar bacteriemia de foco urinario resultó un factor protector (OR: 0,184; IC del 95%, 0,034-0,975; p=0,047). Conclusiones. Los pacientes con sospecha de bacteriemia y que hayan presentado un ingreso en la UCI y una puntuación de gravedad elevada deberían ser candidatos a recibir tratamiento empírico precoz al presentar un mayor riesgo de mortalidad. No obstante, el beneficio de esta estrategia puede verse limitado por la gravedad basal del paciente(AU)

Objective. To identify risk factors for mortality in patients with bloodstream infection by extended-spectrum beta-lactamase (ESBL)-producing microorganisms. Material and methods. A retrospective study in patients with bloodstream infection by ESBL-producing microorganisms from January 2000 to December 2006 was carried out. Results. A total of 4,172 bloodstream infections were identified, 1,218 (29.2%) and 226 (5.4%) of which were caused by Escherichia coli and Klebsiella pneumoniae, respectively. The overall mortality rate was 50.9% in patients with bacteriema due to ESBL-producing strains. The binomial logistic regression model, adjusted for age and severity, identified admission to an intensive care unit (OR 38,631; 95%CI:3,375-424,618; P=.002) and a SAPS II severity index score >30 in the 24-48h before obtaining blood culture (OR 17,980; 95% CI:2,193-170,439; P=.010) as factors associated to mortality, while the urinary tract as primary site of infection was an independent determinant for non-mortality (OR 0.184; 95% CI:0.034-0.975; P=.047). Conclusions. Patients with suspicion of bacteriema who have been admitted to the ICU with a score of elevated severity should be candidates for early empirical treatments as they have a greater risk of mortality. However, the benefit of this strategy may be limited due to the baseline severity of the patient(AU)

Enfuvirtida: primer fármaco de una nueva familia de antirretrovirales / Enfuvirtide: first drug of a new family of antiretroviral agents

Enfuvirtida o T-20 es el primer fármaco aprobado por la FDAy por la EMEA dentro del grupo de los inhibidores de la fusión. Sumecanismo de acción consiste en el bloqueo de la entrada del VIHen las células del organismo.Enfuvirtida está indicado en combinación con otros fármacosantirretrovirales, en el tratamiento de aquellos pacientes infectadospor el VIH que presentan resistencias o intolerancia a tratamientosantirretrovirales previos.Los ensayos clínicos han demostrado eficacia y seguridad deltratamiento con este fármaco. Los efectos adversos reportadoscon más frecuencia son las reacciones locales en el punto deadministración.Enfuvirtida contribuye a la ampliación del arsenal terapéuticodisponible para el tratamiento de la infección por VIH, permitiendouna terapia de rescate en aquellos pacientes con fracasos previosen el tratamiento

Enfuvirtide or T-20 is the first drug approved by the FDA andthe EMEA within the group of fusion inhibitors. Its mechanism ofaction is based on the blockade of the entry of the HIV to thebody cells.Enfuvirtide is recommended in combination with other antiretroviraldrugs for the treatment of patients infected by HIV thathave developed resistance or intolerance to other prior antirretroviraltherapies.Clinical trials have shown the effectiveness and safety of thetreatment with this drug. Side effects most commonly reportedare local reactions in the injection siteEnfuvirtide contributes to increase the therapeutic arsenal availablefor the management of the HIV infection, providing rescuetherapy for patients in which prior treatments have failed

[Enfuvirtide: first drug of a new family of antiretroviral agents]. / Enfuvirtida: primer fármaco de una nueva familia de antirretrovirales.

Enfuvirtide or T-20 is the first drug approved by the FDA and the EMEA within the group of fusion inhibitors. Its mechanism of action is based on the blockade of the entry of the HIV to the body cells. Enfuvirtide is recommended in combination with other antiretroviral drugs for the treatment of patients infected by HIV that have developed resistance or intolerance to other prior antiretroviral therapies. Clinical trials have shown the effectiveness and safety of the treatment with this drug. Side effects most commonly reported are local reactions in the injection site. Enfuvirtide contributes to increase the therapeutic arsenal available for the management of the HIV infection, providing rescue therapy for patients in which prior treatments have failed.