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1.
Eur Rev Med Pharmacol Sci ; 25(10): 3923-3932, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34109607

RESUMEN

Angiotensin converting enzyme 2 (ACE2) has potentially conflicting roles in health and disease. COVID-19 coronavirus binds to human cells via ACE2 receptor, which is expressed on almost all body organs. Boosting the ACE2 receptor levels on heart and lung cells may provide more cellular enter to virus thereby worsening the infection. Therefore, among the drug targets, ACE2 is suggested as a vital target of COVID-19 therapy. This hypothesis is based on the protective role of the drugs acting on ACE2. Therefore, this review discusses the impact and challenges of using ACE2 as a target in the current therapy of COVID-19.


Asunto(s)
Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Antivirales/química , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/química , Adenosina Monofosfato/metabolismo , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/química , Alanina/metabolismo , Alanina/uso terapéutico , Enzima Convertidora de Angiotensina 2/metabolismo , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Antivirales/metabolismo , Antivirales/uso terapéutico , Azitromicina/química , Azitromicina/metabolismo , Azitromicina/uso terapéutico , COVID-19/tratamiento farmacológico , COVID-19/virología , Humanos , Hidroxicloroquina/química , Hidroxicloroquina/metabolismo , Hidroxicloroquina/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Vitamina D/química , Vitamina D/metabolismo , Vitamina D/uso terapéutico
3.
Cochrane Database Syst Rev ; 5: CD015043, 2021 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-34029377

RESUMEN

BACKGROUND: The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required. OBJECTIVES: To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA: We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS: We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7,  whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.


Asunto(s)
COVID-19/tratamiento farmacológico , Calcifediol/administración & dosificación , Colecalciferol/administración & dosificación , Vitaminas/administración & dosificación , 25-Hidroxivitamina D 2/sangre , Corticoesteroides/uso terapéutico , Adulto , Azitromicina/uso terapéutico , Sesgo , COVID-19/sangre , COVID-19/mortalidad , Causas de Muerte , Ceftriaxona/uso terapéutico , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapéutico , Persona de Mediana Edad , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Deficiencia de Vitamina D/diagnóstico
4.
J Nepal Health Res Counc ; 19(1): 1-9, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33934125

RESUMEN

BACKGROUND: The global spread of COVID-19 and the lack of definite treatment have caused an alarming crisis in the world. We aimed to evaluate the outcome and potential harmful cardiac effects of hydroxychloroquine and azithromycin compared to hydroxychloroquine alone for COVID-19 treatment. METHODS: PubMed, Medline, Google Scholar, Cochrane Library, clinicaltrials.gov, and World Health Organization clinical trial registry were searched using appropriate keywords and identified six studies using PRISMA guidelines. The quantitative synthesis was performed using fixed or random effects for the pooling of studies based on heterogeneities. RESULTS: The risk of mortality (RR=1.16; CI: 0.92-1.46) and adverse cardiac events (OR=1.06; CI: 0.82-1.37) demonstrated a small increment though of no significance. There were no increased odds of mechanical ventilation (OR=0.84; CI: 0.33-2.15) and significant QTc prolongation (OR=0.84, CI: 0.59-1.21). Neither the critical QTc threshold (OR=1.92, CI: 0.81-4.56) nor absolute ?QTc ?60ms (OR=1.95, CI:0.55-6.96) increased to the level of statistical significance among hydroxychloroquine and azithromycin arm compared to hydroxychloroquine alone, but the slightly increased odds need to be considered in clinical practice. CONCLUSIONS: The combination of hydroxychloroquine and azithromycin leads to small increased odds of mortality and cardiac events compared to hydroxychloroquine alone. The use of hydroxychloroquine and azithromycin led to increased odds of QT prolongation, although not statistically significant.


Asunto(s)
Azitromicina/uso terapéutico , COVID-19/tratamiento farmacológico , Enfermedades Cardiovasculares/inducido químicamente , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Azitromicina/efectos adversos , COVID-19/mortalidad , Enfermedades Cardiovasculares/mortalidad , Quimioterapia Combinada , Humanos , Hidroxicloroquina/efectos adversos , Neumonía Viral/mortalidad , Neumonía Viral/virología , SARS-CoV-2
5.
BMJ ; 373: n1038, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33975825

RESUMEN

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.


Asunto(s)
COVID-19/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Reposicionamiento de Medicamentos/métodos , Reclamos Administrativos en el Cuidado de la Salud/estadística & datos numéricos , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Azitromicina/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Ceftriaxona/uso terapéutico , Niño , Preescolar , China/epidemiología , Estudios de Cohortes , Combinación de Medicamentos , Registros Electrónicos de Salud/estadística & datos numéricos , Enoxaparina/uso terapéutico , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Lactante , Recién Nacido , Pacientes Internos , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Ritonavir/uso terapéutico , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , Seguridad , España/epidemiología , Resultado del Tratamiento , Estados Unidos/epidemiología , Vitamina D/uso terapéutico , Adulto Joven
7.
PLoS One ; 16(5): e0251048, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34033655

RESUMEN

BACKGROUND: COVID-19 is a multisystemic disorder that frequently causes acute kidney injury (AKI). However, the precise clinical and biochemical variables associated with AKI progression in patients with severe COVID-19 remain unclear. METHODS: We performed a retrospective study on 278 hospitalized patients who were admitted to the ward and intensive care unit (ICU) with COVID-19 between March 2020 and June 2020, at the University Hospital, São Paulo, Brazil. Patients aged ≥ 18 years with COVID-19 confirmed on RT-PCR were included. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We evaluated the incidence of AKI, several clinical variables, medicines used, and outcomes in two sub-groups: COVID-19 patients with AKI (Cov-AKI), and COVID-19 patients without AKI (non-AKI). Univariate and multivariate analyses were performed. RESULTS: First, an elevated incidence of AKI (71.2%) was identified, distributed across different stages of the KDIGO criteria. We further observed higher levels of creatinine, C-reactive protein (CRP), leukocytes, neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) in the Cov-AKI group than in the non-AKI group, at hospital admission. On univariate analysis, Cov-AKI was associated with older age (>62 years), hypertension, CRP, MCV, leucocytes, neutrophils, NLR, combined hydroxychloroquine and azithromycin treatment, use of mechanical ventilation, and vasoactive drugs. Multivariate analysis showed that hypertension and the use of vasoactive drugs were independently associated with a risk of higher AKI in COVID-19 patients. Finally, we preferentially found an altered erythrocyte and leukocyte cellular profile in the Cov-AKI group compared to the non-AKI group, at hospital discharge. CONCLUSIONS: In our study, the development of AKI in patients with severe COVID-19 was related to inflammatory blood markers and therapy with hydroxychloroquine/azithromycin, with vasopressor requirement and hypertension considered potential risk factors. Thus, attention to the protocol, hypertension, and some blood markers may help assist doctors with decision-making for the management of COVID-19 patients with AKI.


Asunto(s)
Lesión Renal Aguda/diagnóstico , COVID-19/patología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Azitromicina/uso terapéutico , Brasil/epidemiología , COVID-19/complicaciones , COVID-19/tratamiento farmacológico , COVID-19/virología , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Vasodilatadores/efectos adversos , Vasodilatadores/uso terapéutico , Adulto Joven
8.
Clin Dermatol ; 39(1): 107-117, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33972037

RESUMEN

The coronavirus disease 2019 pandemic has had a profound effect on our lives and careers; this presentation explores some of the lessons we have learned from it and others that it may yet teach us. Socioeconomic effects have been profound, not all of them favorable. Travel and meeting activities, as well as many other activities, have been severely restricted. Social unrest has become intense, and it may have questionable political consequences, as the United States is undergoing a contested election result.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19/prevención & control , COVID-19/terapia , Control de Enfermedades Transmisibles/métodos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Corticoesteroides/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , COVID-19/complicaciones , COVID-19/mortalidad , Vacunas contra la COVID-19/efectos adversos , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapéutico , SARS-CoV-2 , Estadística como Asunto , Zinc/uso terapéutico
9.
BMC Infect Dis ; 21(1): 411, 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33947344

RESUMEN

BACKGROUND AND OBJECTIVES: An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation. MATERIALS AND METHODS: Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated. RESULTS: A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group (p = 0.10). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group (p = 0.37). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period (p = 0.24); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group (p = 0.02, p = 0.005 and p = 0.03, respectively). CONCLUSIONS: According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.


Asunto(s)
Antivirales/uso terapéutico , COVID-19/tratamiento farmacológico , Ivermectina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anciano , Amidas/uso terapéutico , Antivirales/farmacocinética , Azitromicina/uso terapéutico , COVID-19/sangre , COVID-19/mortalidad , Citocromo P-450 CYP3A/genética , Quimioterapia Combinada , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Ivermectina/farmacocinética , Masculino , Persona de Mediana Edad , Neumonía Viral/sangre , Neumonía Viral/virología , Estudios Prospectivos , Pirazinas/uso terapéutico , Método Simple Ciego , Resultado del Tratamiento
10.
J Med Virol ; 93(7): 4411-4419, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33792956

RESUMEN

In late December 2019, an outbreak of a novel coronavirus which caused coronavirus disease 2019 (COVID-19) was initiated. Acute kidney injury (AKI) was associated with higher severity and mortality of COVID-19. We aimed to evaluate the effects of comorbidities and medications in addition to determining the association between AKI, antibiotics against coinfections (AAC) and outcomes of patients. We conducted a retrospective study on adult patients hospitalized with COVID-19 in a tertiary center. Our primary outcomes were the incidence rate of AKI based on comorbidities and medications. The secondary outcome was to determine mortality, intensive care unit (ICU) admission, and prolonged hospitalization by AKI and AAC. Univariable and multivariable logistic regression method was used to explore predictive effects of AKI and AAC on outcomes. Out of 854 included participants, 118 patients developed AKI in whom, 57 used AAC and 61 did not. Hypertension and diabetes were the most common comorbidities in patients developed AKI. AAC, lopinavir/ritonavir, ribavirin, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and corticosteroids had significant higher rate of administration in patients developed AKI. AAC were associated with higher deaths (odds ratio [OR] = 5.13; 95% confidence interval (CI): 3-8.78) and ICU admission (OR = 5.87; 95%CI: 2.81-12.27), while AKI had higher OR for prolonged hospitalization (3.37; 95%CI: 1.76-6.45). Both AKI and AAC are associated with poor prognosis of COVID-19. Defining strict criteria regarding indications and types of antibiotics would help overcoming concomitant infections and minimizing related adverse events.


Asunto(s)
Lesión Renal Aguda/epidemiología , Antivirales/uso terapéutico , COVID-19/tratamiento farmacológico , COVID-19/patología , SARS-CoV-2/efectos de los fármacos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/virología , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina , Azitromicina/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/prevención & control , Cuidados Críticos/estadística & datos numéricos , Combinación de Medicamentos , Femenino , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Humanos , Irán/epidemiología , Linezolid/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ribavirina/uso terapéutico , Ritonavir/uso terapéutico , Resultado del Tratamiento , Vancomicina/uso terapéutico
11.
BMJ Case Rep ; 14(4)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827889

RESUMEN

A 23-year-old primigravida at 20 weeks of gestation presented to our hospital with undifferentiated febrile illness and severe acute respiratory distress syndrome. She was intubated in the emergency department and transferred to the intensive care unit. Initial treatment included ventilatory care, vasopressor support and broad-spectrum antibiotics. Based on a positive PCR assay for scrub typhus, she was treated with intravenous doxycycline and azithromycin. Despite reduction in fever, her oxygenation further declined. Following a risk-benefits assessment, we decided to ventilate her in prone position for 8 hours a day for three consecutive days using a checklist-based protocol. Her oxygenation indices and lung compliance markedly improved over this period, and she was extubated a day later. She was eventually discharged home after 1 week.


Asunto(s)
Síndrome de Dificultad Respiratoria , Tifus por Ácaros , Adulto , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Doxiciclina , Femenino , Humanos , Embarazo , Síndrome de Dificultad Respiratoria/terapia , Tifus por Ácaros/tratamiento farmacológico , Tifus por Ácaros/terapia , Adulto Joven
12.
Travel Med Infect Dis ; 41: 102058, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33838319

RESUMEN

BACKGROUND: COVID-19 can be asymptomatic in a substantial proportion of patients. The assessment and management of these patients constitute a key element to stop dissemination. AIM: To describe the assessment and treatment of asymptomatic infection in patients with a confirmed diagnosis of COVID-19. METHODS: We searched five databases and search engines for preprints/preproofs, up to August 22, 2020. We included cohort, cross-sectional, and case series studies, reporting the assessment and management of asymptomatic individuals. We extracted data on total discharges with negative PCR, length of hospitalization, treatment, and number of patients who remained asymptomatic. A random-effects model with inverse variance method was used to calculate the pooled prevalence. RESULTS: 41 studies (nine cross-sectional studies, five retrospective studies and 27 reports/case series; 647 asymptomatic individuals), were included, of which 47% were male (233/501). The age of patients was between 1month and 73 years. In patients who became symptomatic, length of hospitalization mean was 13.6 days (SD 6.4). Studies used lopinavir/ritonavir, hydroxychloroquine plus ritonavir/lopinavir, hydroxychloroquine with and without azithromycin, ribavirin plus interferon and interferon alfa. The proportion of individuals who remained asymptomatic was 91% (463/588 patients; 95%CI: 78.3%-98.7%); and asymptomatic individuals discharged with negative PCR was 86% (102/124 individuals; 95%CI: 58.4%-100%). CONCLUSIONS: There is no standard treatment for asymptomatic COVID-19 individuals. There are no studies of adequate design to make this decision. It has been shown that most asymptomatic individuals who were followed have recovered, but this cannot be attributed to standard treatment.


Asunto(s)
Infecciones Asintomáticas/terapia , COVID-19/diagnóstico , COVID-19/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Prueba de Ácido Nucleico para COVID-19/métodos , Niño , Preescolar , Quimioterapia Combinada , Femenino , Hospitalización , Humanos , Hidroxicloroquina/uso terapéutico , Lactante , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Ritonavir/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Adulto Joven
13.
Ann Palliat Med ; 10(5): 5098-5107, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33894712

RESUMEN

BACKGROUND: The current use of prophylactic antibiotics for lung cancer surgery requires modification in aging individuals with impaired lung function. A sustained-release formulation of azithromycin (AZM-SR) could help resolve some of these challenges with its sustained antibacterial and anti-inflammatory effects. The aim of this study was to examine the safety and efficacy of AZM-SR in lung cancer surgery as well as its anti-inflammatory effect. METHODS: Fifty patients were included in the study, and AZM-SR was administered 1 day prior to the surgery. The clinical course, including postoperative complications, was monitored, and the concentration of AZM, bacterial culture, and inflammatory cytokine levels of resected lung specimens were evaluated. RESULTS: No side effects related to AZM-SR were observed. Five cases of postoperative pneumonia (10%) were observed; technical issues were involved in 3 cases. All patients recovered well. Four cases showed positive bacterial culture upon lung tissue examination; however, this was not significantly correlated with postoperative complications. A negative correlation was observed between AZM concentration in lung tissue and interleukin-6 (IL-6) expression. CONCLUSIONS: Prophylactic utilization of AZM-SR in lung cancer surgery seems feasible. The anti-inflammatory effect of AZM might contribute additional beneficial effects in the perioperative management of lung cancer surgery.


Asunto(s)
Azitromicina , Neoplasias Pulmonares , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Preparaciones de Acción Retardada , Humanos , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía
14.
BMC Public Health ; 21(1): 822, 2021 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926403

RESUMEN

BACKGROUND: Biannual distribution of azithromycin to children 1-59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1-11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. METHODS: AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1-11: biannual azithromycin to children 1-11 months old with placebo to children 12-59 months old, 2) azithromycin 1-59: biannual azithromycin to children 1-59 months old, or 3) placebo: biannual placebo to children 1-59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1-59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1-59 months old comparing the azithromycin 1-59 and placebo arms, 2) children 1-11 months old comparing the azithromycin 1-11 and placebo arm, and 3) children 12-59 months in the azithromycin 1-11 and azithromycin 1-59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1-59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1-59 months old. DISCUSSION: As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. TRIAL REGISTRATION: This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).


Asunto(s)
Antibacterianos , Azitromicina , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Niño , Preescolar , Farmacorresistencia Bacteriana , Humanos , Lactante , Macrólidos , Administración Masiva de Medicamentos , Niger/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Microb Drug Resist ; 27(3): 281-290, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33729874

RESUMEN

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.


Asunto(s)
Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , COVID-19/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/farmacología , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Azitromicina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/farmacología , SARS-CoV-2
18.
Cochrane Database Syst Rev ; 3: CD004406, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33728634

RESUMEN

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications.  AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.


Asunto(s)
Antibacterianos/uso terapéutico , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/uso terapéutico , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Azitromicina/uso terapéutico , Cefalosporinas/efectos adversos , Cefalosporinas/uso terapéutico , Niño , Preescolar , Clindamicina/efectos adversos , Clindamicina/uso terapéutico , Humanos , Lactante , Macrólidos/efectos adversos , Macrólidos/uso terapéutico , Persona de Mediana Edad , Penicilinas/efectos adversos , Penicilinas/uso terapéutico , Faringitis/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Estreptocócicas/microbiología , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Adulto Joven
19.
J Pharmacol Exp Ther ; 377(2): 265-272, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674391

RESUMEN

Drug-induced long QT syndrome (LQTS) is an established cardiac side effect of a wide range of medications and represents a significant concern for drug safety. The rapidly and slowly activating delayed rectifier K+ currents, mediated by channels encoded by the human ether-a-go-go-related gene (hERG) and KCNQ1 + KCNE1, respectively, are two main currents responsible for ventricular repolarization. The common cause for drugs to induce LQTS is through impairing the hERG channel. For the recent emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, several drugs have been investigated as potential therapies; however, there are concerns about their QT prolongation risk. Here, we studied the effects of chloroquine, hydroxychloroquine, azithromycin, and remdesivir on hERG channels. Our results showed that although chloroquine acutely blocked hERG current (IhERG), with an IC50 of 3.0 µM, hydroxychloroquine acutely blocked IhERG 8-fold less potently, with an IC50 of 23.4 µM. Azithromycin and remdesivir did not acutely affect IhERG When these drugs were added at 10 µM to the cell culture medium for 24 hours, remdesivir increased IhERG by 2-fold, which was associated with an increased mature hERG channel expression. In addition, these four drugs did not acutely or chronically affect KCNQ1 + KCNE1 channels. Our data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns. SIGNIFICANCE STATEMENT: This work demonstrates that, among off-label potential COVID-19 treatment drugs chloroquine, hydroxychloroquine, azithromycin, and remdesivir, the former two drugs block hERG potassium channels, whereas the latter two drugs do not. All four drugs do not affect KCNQ1 + KCNE1. As hERG and KCNQ1 + KCNE1 are two main K+ channels responsible for ventricular repolarization, and most drugs that induce long QT syndrome (LQTS) do so by impairing hERG channels, these data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Azitromicina/farmacología , COVID-19/tratamiento farmacológico , Cloroquina/farmacología , Canal de Potasio ERG1/antagonistas & inhibidores , Hidroxicloroquina/farmacología , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/farmacología , Alanina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , COVID-19/metabolismo , Cloroquina/uso terapéutico , Relación Dosis-Respuesta a Droga , Canal de Potasio ERG1/metabolismo , Células HEK293 , Humanos , Hidroxicloroquina/uso terapéutico , Bloqueadores de los Canales de Potasio/farmacología , Bloqueadores de los Canales de Potasio/uso terapéutico
20.
J Trop Pediatr ; 67(1)2021 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-33684931

RESUMEN

BACKGROUND: Scrub typhus is typically associated with a rapid defervescence and clinical improvement within 48 h of initiation of appropriate antibiotics. But increasing reports of resistance to anti-rickettsial medications in scrub typhus are being reported in the literature. METHODS: This is a retrospective observational study of children up to the age of 14 years admitted between July 2017 and March 2020, to a private medical college hospital in southern part of India. The aim of this study was to compare the clinical response to antibiotic therapy with doxycycline and azithromycin in pediatric scrub typhus infection. RESULTS: One hundred thirty-eight children with scrub typhus infection were included for analysis. The median fever control time (h) was 12 (IQR = 6-29) and 24 (IQR = 10-52) with doxycycline and azithromycin respectively (p < 0.001*). Rapid fever control within 48 h was observed in 92% with doxycycline and in 74% with azithromycin (p < 0.001*). The clinical failure rate (defined by the necessity to change the antibiotics due to: (i) worsening of symptoms and signs of scrub typhus despite 48 h of antibiotics or (ii) persistence of fever and other symptoms of scrub typhus beyond 72 h), was significantly less with doxycycline (1%) compared with azithromycin (9.6%). CONCLUSION: There has been a significant delayed clinical response to azithromycin in the treatment of scrub typhus in India, when compared to doxycycline. Hence it is preferable to use doxycycline as the first line of antibiotic for undifferentiated fever in scrub typhus endemic areas. LAY SUMMARY: This retrospective study aims to compare the clinical response to doxycycline or azithromycin in the treatment of scrub typhus infection in children. The median fever control time, clinical failure rate and the proportion of children with rapid defervescence of fever within 48 h were significantly superior with doxycycline as compared to azithromycin. The findings of this study and those of similar studies in India represent a spectrum of delayed clinical response of Orientia tsutsugamushi to azithromycin as compared to doxycycline in this region.


Asunto(s)
Orientia tsutsugamushi , Tifus por Ácaros , Adolescente , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Niño , Humanos , India/epidemiología , Estudios Retrospectivos , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/tratamiento farmacológico , Tifus por Ácaros/epidemiología
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