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1.
Rev Assoc Med Bras (1992) ; 67(3): 395-399, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34468604

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the efficacy of the use of four concomitant Chinese medicines with azithromycin in the treatment of mycoplasma pneumonia in children (MPC) by using network meta-analysis (NMA) and ranking them according to their performances. METHODS: There were a total of 130 randomly controlled trials of four different concomitant Chinese medicines with azithromycin for the treatment of MPC in many databases, and an NMA was conducted in them by using Stata (version 13.0) software to evaluate the odds ratio (OR) and sequence of the different combinations. The included studies were divided into two groups: control group (azithromycin alone) and observation group (one of four azithromycin combinations). RESULTS: A total of 13119 cases were included in this study, and the results showed that the pooled OR and 95% confidence interval (CI) of MPC improvement compared with azithromycin alone were 4.76 (3.18-7.14) for azithromycin and Reduning, 5.66 (4.50-7.12) for azithromycin and Tanreqing, 4.84 (3.35-7.01) for azithromycin and Xiyanping, and 4.58 (3.59-5.83) for azithromycin and Yanhuning, respectively. This study shows the significant efficacy of Chinese concomitant drug. The combination of azithromycin with Tanreqing is the best candidate of concomitant drug in terms of clinical efficacy. Its surface under the cumulative ranking (SUCRA) score was 85.5, while the SUCRA score for the azithromycin and Yanhuning combination was the worst, which is 48.4. CONCLUSIONS: The combination of azithromycin with Tanreqing is the most promising group among four combinations for the treatment of MPC.


Assuntos
Mycoplasma , Pneumonia por Mycoplasma , Ensaios Clínicos Controlados Aleatórios como Assunto , Azitromicina/uso terapêutico , Criança , China , Humanos , Metanálise em Rede , Pneumonia por Mycoplasma/tratamento farmacológico
2.
J Med Microbiol ; 70(9)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34494952

RESUMO

Introduction. Gonorrhoea is a sexually transmitted disease whose incidence has increased in recent years and adult gonococcal conjunctivitis (AGC) is a relatively uncommon complication.Hypothesis/Gap Statement. AGC is associated with increased incidence of genital gonorrhoea and must be treated correctly to avoid serious corneal complications.Aims. To report the prevalence, clinical features, and complications of AGC in a tertiary ophthalmology centre in Barcelona, Spain. Present epidemiological data, clinical features, ocular complications, and antibiotic susceptibility. Design: Single-centre, descriptive, retrospective case series.Methodology. Systematic case-defined search in medical records and further retrospective chart review study of microbiologically confirmed AGC attending outpatient clinic and/or emergency room from 2012 to 2020. We analysed the clinical presentation, treatments, antibiotic susceptibility, complications and ocular sequelae.Results. Thirteen patients were diagnosed of AGC. Eleven patients had unilateral presentation. Two patients had bilateral presentation. In ten cases there was abundant mucopurulent discharge, three cases presented periocular pain and periocular inflammation requiring a CT scan to rule out post-septal cellulitis. The diagnosis was confirmed by culture. In total, 100 % of strains were susceptible to ceftriaxone, 58 % were ciprofloxacin resistant and no beta-lactamase production was detected. Three patients required hospital admission. One patient developed a complication presenting with ptosis caused by superior symblepharon.Conclusion. AGC is a rare disease which is difficult to diagnose as it requires a high index of suspicion to prevent corneal perforation but in an important number of cases it may mimic orbital cellulitis. It is crucial that treatment starts as soon as possible to avoid serious corneal damage. Patients should promptly receive complete and correct treatment when admitted to the emergency room since an elevated number of patients do not attend their medical follow-up visit. Azithromycin or aminoglycoside eye drops are probably the best option to complete the treatment, due to high quinolone resistance.


Assuntos
Conjuntivite Bacteriana , Gonorreia , Neisseria gonorrhoeae/isolamento & purificação , Soluções Oftálmicas/uso terapêutico , Adolescente , Adulto , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Conjuntivite Bacteriana/tratamento farmacológico , Conjuntivite Bacteriana/epidemiologia , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
3.
Sci Rep ; 11(1): 16361, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381155

RESUMO

Evidence on the efficacy of adding macrolides (azithromycin or clarithromycin) to the treatment regimen for COVID-19 is limited. We testify whether adding azithromycin or clarithromycin to a standard of care regimen was superior to standard of supportive care alone in patients with mild COVID-19.This randomized trial included three groups of patients with COVID-19. The azithromycin group included, 107 patients who received azithromycin 500 mg/24 h for 7 days, the clarithromycin group included 99 patients who received clarithromycin 500 /12 h for 7 days, and the control group included 99 patients who received standard care only. All three groups received only symptomatic treatment for control of fever and cough .Clinical and biochemical evaluations of the study participants including assessment of the symptoms duration, real-time reverse transcription-polymerase chain reaction (rRT-PCR), C-reactive protein (CRP), serum ferritin, D-dimer, complete blood count (CBC), in addition to non-contrast chest computed tomography (CT), were performed. The overall results revealed significant early improvement of symptoms (fever, dyspnea and cough) in patients treated with either azithromycin or clarithromycin compared to control group, also there was significant early conversion of SARS-CoV-2 PCR to negative in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).There was no significant difference in time to improvement of fever, cough, dyspnea, anosmia, gastrointestinal tract "GIT" symptoms and time to PCR negative conversion between patients treated with azithromycin compared to patients treated with clarithromycin (p > 0.05 for all). Follow up chest CT done after 2 weeks of start of treatment showed significant improvement in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).Adding Clarithromycin or azithromycin to the therapeutic protocols for COVID-19 could be beneficial for early control of fever and early PCR negative conversion in Mild COVID-19.Trial registration: (NCT04622891) www.ClinicalTrials.gov retrospectively registered (November 10, 2020).


Assuntos
Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Claritromicina/uso terapêutico , Adulto , COVID-19/fisiopatologia , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Resultado do Tratamento
4.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445055

RESUMO

BACKGROUND: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. METHODS: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. RESULTS: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. CONCLUSIONS: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients' survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.


Assuntos
COVID-19/terapia , Oxigênio/uso terapêutico , Probióticos/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Gasometria , Linhagem Celular , Feminino , Heparina , Humanos , Hipóxia , Itália , Pulmão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
Mymensingh Med J ; 30(3): 725-737, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226462

RESUMO

Multi-drug resistant Typhoid fever (resistant to previously used chloramphenicol, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole) has been commonly described in the South East Asia region and a recent report suggests that the salmonella typhi have reduced response to fluoroquinolones (nalidixic acid-resistant). The optimum treatment protocol for this type of serovar has not been established. This study compared different antimicrobial regimens for the treatment of uncomplicated typhoid fever which was conducted in the medicine ward of Dhaka Medical College Hospital (DMCH) and outdoor setting in private practice in Dhaka metropolitan city, Mymensingh and Sylhet town from January 2017 to December 2017. Bangladeshi adults with uncomplicated typhoid fever were included in this an open-label randomized controlled trial. Ciprofloxacin (20mg/kg of body weight/day for 14 days), azithromycin (20mg/kg/day for 14 days), and Cefixime (16mg/kg/day for 14 days) were compared. Of the 81 enrolled patients, 62 were eligible for analysis (61 S. enterica serovar Typhi, 1 Salmonella enterica serovar paratyphi A). Of the S enterica serovar Typhi isolates, 88.7% (55/62) were MDR and 93.5% (58/62) were nalidixic acid resistant (NAR). The clinical cure rate was 62% (13/21) with ciprofloxacin, 71% (15/21) with Cefixime, and 85% (17/20) with azithromycin (p=0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with cefixime (7.1 days [6.2 to 8.1 days]) and ciprofloxacin (8.2 days [7.2 to 9.2 days]) (p<0.001). All three antibiotics were well tolerated. A 7-day course of azithromycin can be successfully used in uncomplicated typhoid fever due to isolates of MDR S enterica serovar Typhi.


Assuntos
Azitromicina , Febre Tifoide , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Bangladesh/epidemiologia , Cefixima/uso terapêutico , Ciprofloxacina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Salmonella typhi , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia
6.
JAMA ; 326(6): 490-498, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34269813

RESUMO

Importance: Azithromycin has been hypothesized to have activity against SARS-CoV-2. Objective: To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Design, Setting, and Participants: Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Interventions: Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). Main Outcomes and Measures: The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Results: Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Conclusions and Relevance: Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. Trial Registration: ClinicalTrials.gov Identifier: NCT04332107.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , SARS-CoV-2 , Administração Oral , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , COVID-19/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Avaliação de Sintomas , Falha de Tratamento
7.
BMJ Open ; 11(6): e042893, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172543

RESUMO

OBJECTIVE: To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone. DESIGN: A modelling study. SETTING: England and Wales. PARTICIPANTS: Individuals accessing sentinel health services. INTERVENTION: Developing an Excel model which uses participants' demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015-2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme. MAIN OUTCOME MEASURES: Estimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation. RESULTS: Between 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%-51%) and penicillin (range: 6%-33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment. CONCLUSIONS: Using demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.


Assuntos
Gonorreia , Minorias Sexuais e de Gênero , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Inglaterra/epidemiologia , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , País de Gales/epidemiologia
8.
PLoS One ; 16(6): e0252388, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34106964

RESUMO

BACKGROUND: Hydroxychloroquine combined with azithromycin (HCQ/AZI) has initially been used against coronavirus disease-2019 (COVID-19). In this retrospective study, we assessed the clinical effects of HCQ/AZI, with a 28-days follow-up. METHODS: In a registry-study which included patients hospitalized for COVID-19 between March 15 and April 2, 2020, we compared patients who received HCQ/AZI to those who did not, regarding a composite outcome of mortality and mechanical ventilation with a 28-days follow-up. QT was monitored for patients treated with HCQ/AZI. Were excluded patients in intensive care units, palliative care and ventilated within 24 hours of admission. Three analyses were performed to adjust for selection bias: propensity score matching, multivariable survival, and inverse probability score weighting (IPSW) analyses. RESULTS: Overall, 203 patients were included: 60 patients treated by HCQ/AZI and 143 control patients. During the 28-days follow-up, 32 (16.3%) patients presented the primary outcome and 23 (12.3%) patients died. Propensity-score matching identified 52 unique pairs of patients with similar characteristics. In the matched cohort (n = 104), HCQ/AZI was not associated with the primary composite outcome (log-rank p-value = 0.16). In the overall cohort (n = 203), survival and IPSW analyses also found no benefit from HCQ/AZI. In the HCQ/AZI group, 11 (18.3%) patients prolonged QT interval duration, requiring treatment cessation. CONCLUSIONS: HCQ/AZI combination therapy was not associated with lower in-hospital mortality and mechanical ventilation rate, with a 28-days follow-up. In the HCQ/AZI group, 18.3% of patients presented a prolonged QT interval requiring treatment cessation, however, control group was not monitored for this adverse event, making comparison impossible.


Assuntos
Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida , Resultado do Tratamento
9.
N Engl J Med ; 384(25): 2418-2427, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34161706

RESUMO

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis/isolamento & purificação , Doxiciclina/uso terapêutico , Doenças Retais/tratamento farmacológico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Infecções Assintomáticas , Austrália , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Método Duplo-Cego , Doxiciclina/administração & dosagem , Doxiciclina/efeitos adversos , Homossexualidade Masculina , Humanos , Análise de Intenção de Tratamento , Masculino , Técnicas de Amplificação de Ácido Nucleico , Doenças Retais/microbiologia , Reto/microbiologia
11.
Saudi J Kidney Dis Transpl ; 32(1): 218-222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34145134

RESUMO

Underlying comorbid illness is a known risk factor for severe coronavirus disease-2019 (COVID-19). Clinical course of COVID-19 in children with primary kidney disease is not well understood. We present the clinical profile and management of COVID-19 in three children at a COVID hospital in India. These children had nephrotic syndrome, hemolytic uremic syndrome, and chronic kidney disease, respectively. The first two were immunosuppressed, mandating to stop their immunosuppressive medications temporarily. Both had mild course of illness. Third child presented with respiratory distress requiring oxygen support, falling into moderate disease. Renal functions were normal in all of them. They all responded well to oral azithromycin and supportive management. None of them received chloroquine, corticosteroids, or monoclonal antibodies. All three recovered without complications.


Assuntos
COVID-19/complicações , COVID-19/terapia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Nefrótica/complicações , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Criança , Pré-Escolar , Feminino , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Síndrome Nefrótica/tratamento farmacológico , Oxigenoterapia , SARS-CoV-2
12.
Eur Rev Med Pharmacol Sci ; 25(10): 3923-3932, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34109607

RESUMO

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.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Antivirais/química , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/química , Alanina/metabolismo , Alanina/uso terapêutico , Enzima de Conversão de Angiotensina 2/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/metabolismo , Antivirais/uso terapêutico , Azitromicina/química , Azitromicina/metabolismo , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Humanos , Hidroxicloroquina/química , Hidroxicloroquina/metabolismo , Hidroxicloroquina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Vitamina D/química , Vitamina D/metabolismo , Vitamina D/uso terapêutico
13.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068694

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease characterized by the proliferation of myofibroblasts and deposition of extracellular matrix that results in irreversible distortion of the lung structure and the formation of focal fibrosis. The molecular mechanism of IPF is not fully understood, and there is no satisfactory treatment. However, most studies suggest that abnormal activation of transforming growth factor-ß1 (TGF-ß1) can promote fibroblast activation and epithelial to mesenchymal transition (EMT) to induce pulmonary fibrosis. Deglycosylated azithromycin (Deg-AZM) is a compound we previously obtained by removing glycosyls from azithromycin; it was demonstrated to exert little or no antibacterial effects. Here, we discovered a new function of Deg-AZM in pulmonary fibrosis. In vivo experiments showed that Deg-AZM could significantly reduce bleomycin-induced pulmonary fibrosis and restore respiratory function. Further study revealed the anti-inflammatory and antioxidant effects of Deg-AZM in vivo. In vitro experiments showed that Deg-AZM inhibited TGF-ß1 signaling, weakened the activation and differentiation of lung fibroblasts, and inhibited TGF-ß1-induced EMT in alveolar epithelial cells. In conclusion, our findings show that Deg-AZM exerts antifibrotic effects by inhibiting TGF-ß1-induced myofibroblast activation and EMT.


Assuntos
Azitromicina/uso terapêutico , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Transdução de Sinais , Animais , Azitromicina/química , Azitromicina/farmacologia , Bleomicina , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glicosilação/efeitos dos fármacos , Inflamação/patologia , Pulmão/patologia , Camundongos , Modelos Biológicos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , Células NIH 3T3 , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo
14.
15.
s.l; CONETEC; 25 jun. 2021.
Não convencional em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-1254298

RESUMO

INTRODUCCIÓN: El SARS-CoV-2 puede conducir a un amplio espectro de enfermedades, que van desde síntomas muy leves de infección del tracto respiratorio superior hasta una neumonía potencialmente mortal. La enfermedad grave se asocia con frecuencia con altos niveles de marcadores inflamatorios. Por lo tanto, es un desafío definir si un paciente que cumple con criterios para una neumonía adquirida en la comunidad presenta además una coinfección bacteriana al ingreso. Por otro lado, durante la hospitalización puede ser difícil distinguir entre COVID-19 grave e infecciones secundarias bacterianas, siendo la coinfección infrecuentes.3-5 Dado que los pacientes con COVID-19 con frecuencia necesitan hospitalización prolongada y asistencia respiratoria, el uso innecesario de antibióticos en el momento de la hospitalización puede aumentar el riesgo individual de neumonía nosocomial posterior causada por bacterias resistentes y otros eventos adversos asociados al tratamiento. 4,5 En una población objetivo muy amplia, prescripciones de antibióticos universales para todos o la gran mayoría de los pacientes hospitalizados con COVID-19 pueden conducir a un fuerte aumento en uso de antibióticos durante una pandemia y, como resultado, un aumento potencial en las tasas de resistencia a los antimicrobianos. OBJETIVO: El objetivo del presente informe es evaluar parámetros de eficacia, seguridad, conveniencia y recomendaciones disponibles acerca del tratamiento emprírico con azitromicina en pacientes con COVID-19. MÉTODOS: Efectos en la salud: Se desarrolló un protocolo sustentado en proyectos que resume activamente la evidencia científica a medida que la misma se hace disponible. Con este fin se utilizó la plataforma Love de Epistemonikos para identificar revisiones sistemáticas "vivas". Se seleccionaron aquellas con una calidad metodológica apropiada evaluada a través de la herramienta AMSTAR-2, y que a su vez llevaran un proceso de actualización frecuente.7 De cada una de las revisiones sistemáticas identificadas se extractaron los efectos de la intervención sobre los desenlaces priorizados como importantes o críticos y la certeza en dichos efectos. Para la priorización de los desenlaces se adoptó una perspectiva desde el paciente considerando sus potenciales preferencias. La selección se realizó por consenso entre los autores y supervisores del informe considerando los resultados de múltiples ejercicios de priorización publicados, realizados en el marco del desarrollo de distintas guías de práctica clínica.8-11 Se seleccionaron "mortalidad" e "ingreso en asistencia ventilatoria mecánica" como desenlaces críticos y "duración de ventilación mecánica", "admisión hospitalaria", "duración de estadía hospitalaria", "mejoría clínica al día 7-28", "tiempo a la mejoría clínica", "eventos adversos graves" como desenlaces importantes. Adicionalmente, se extractaron datos relacionados con efectos de subgrupo potencialmente relevantes para la toma de decisión, con especial énfasis en el tiempo de evolución y la severidad de la enfermedad. Para confeccionar las conclusiones sobre el efecto de las intervenciones evaluadas sobre los desenlaces priorizados, utilizamos lineamientos publicados, específicamente desarrollados a tal fin. Implementación: Este dominio contempla dos subdominios: la existencia de barreras y facilitadores para la implementación de la tecnología evaluada no consideradas en los otros dominios analizados, y los costos comparativos en relación con otras intervenciones similares. Recomendaciones: Se utilizó la plataforma COVID recmap. Se seleccionaron aquellas guías con rigor metodológico apropiado según la herramienta AGREE II (> 70%) y se incorporaron sus recomendaciones al informe. RESULTADOS: Se identificaron tres revisiones sistemáticas que cumplen con los criterios de inclusión del presente informe. Se identificaron 11 ECAs que incluyeron 10.795 participantes en los que el tratamiento con azitromicina empírica se comparó con la atención estándar u otros tratamentos. CONCLUSIONES: El cuerpo de la evidencia disponible hasta el momento muestra que el tratamiento empírico con azitromicina no mejora desenlaces críticos como la muerte, el ingreso a ventilación mecánica o el tiempo transcurrido hasta resolución de los síntomas (alta certeza ⨁⨁⨁⨁). Adicionalmente, el tratamiento empírico con azitromicina podría no modificar la duración de la internación y su efecto sobre los eventos adversos graves en incierto (muy baja certeza ⨁◯◯◯). El tratamiento empírico antibióticos para todos, o la gran mayoría de los pacientes hospitalizados con COVID-19, podría resultar en un aumento en las infecciones por gérmenes resistentes a antimicrobianos y podría estar relacionada con la emergencia de cepas multiresistentes. El uso sistémico de antibióticos es fácilmente implementable, la azitromicina es accesible y su costo comparativo es bajo. Sin embargo, en el caso de ser utilizados en forma sistemática y en una población objetivo muy amplia, podría acarrear costos importantes. Los documentos identificados recomiendan no usar tratamiento empírico antibiótico, como la azitromicina, en forma sistemática o rutinaria en pacientes con COVID-19 sin sospecha de coinfección bacteriana o sobreinfección bacteriana.


Assuntos
Azitromicina/uso terapêutico , Vírus da SARS/efeitos dos fármacos , COVID-19/tratamento farmacológico , Análise Custo-Benefício
16.
Cochrane Database Syst Rev ; 5: CD015043, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34029377

RESUMO

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.


Assuntos
COVID-19/tratamento farmacológico , Calcifediol/administração & dosagem , Colecalciferol/administração & dosagem , Vitaminas/administração & dosagem , 25-Hidroxivitamina D 2/sangue , Corticosteroides/uso terapêutico , Adulto , Azitromicina/uso terapêutico , Viés , COVID-19/sangue , COVID-19/mortalidade , Causas de Morte , Ceftriaxona/uso terapêutico , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapêutico , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Deficiência de Vitamina D/diagnóstico
18.
J Infect Chemother ; 27(10): 1504-1507, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34052111

RESUMO

A 74-year-old man with diabetic nephropathy undergoing dialysis after total knee arthroplasty presented to our hospital with dyspnea and abnormal behavior such as wearing his pants on his head. The patient was in shock with ventricular tachycardia. Urine and blood cultures showed MAM with sterile pyuria. We administered amikacin and imipenem cilastatin, but repeated cultures were persistently positive. Although we initially chose not to administer azithromycin because of a higher risk of fatal arrhythmia, we had no choice but to administer azithromycin because of treatment failure. Upon close monitoring, we observed no arrhythmia, and the blood cultures became negative. The patient was discharged on day 106 without any symptoms. However, 2 months after discontinuation of antibiotics, he was readmitted and diagnosed with prosthetic joint infection due to MAM. He could not undergo total knee arthroplasty resection because of his low tolerance to surgery. We re-administered same antibiotics, and repeated draining and cleaning of his left knee for several weeks. The inflammation in the knee joint gradually improved, and the patient was discharged while treatment with azithromycin and amikacin was continued. After being discharged, the patient did not experience recurrent disease for at least 6 months. Our case suggests that MAM can cause sterile pyuria and infection in a patient with diabetic nephropathy. The macrolide agent is a key drug for MAM infection, and repeated joint lavage in addition to administering antibiotics may be an alternative treatment for prosthetic joint infection in patients with intolerance to surgery.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Idoso , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Diálise Renal/efeitos adversos
19.
J Nepal Health Res Counc ; 19(1): 1-9, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33934125

RESUMO

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.


Assuntos
Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Azitromicina/efeitos adversos , COVID-19/mortalidade , Doenças Cardiovasculares/mortalidade , Quimioterapia Combinada , Humanos , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , SARS-CoV-2
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