RESUMO
PURPOSE: The absence of specific treatments for COVID-19 leads to an intense global effort in the search for new therapeutic interventions and better clinical outcomes for patients. This review aimed to present a selection of accepted studies that reported the activity of antidepressant drugs belonging to the selective serotonin receptor inhibitor (SSRI) class for treating the novel coronavirus. METHODS: A search was performed in PubMed and SciELO databases using the following search strategies: [(coronavirus) OR (COVID) OR (SARS-CoV-2) AND (antidepressant) OR (serotonin) OR (selective serotonin receptor inhibitors)]. In the end, eleven articles were included. We also covered information obtained from ClinicalTrials.gov in our research. RESULTS: Although several clinical trials are ongoing, only a few drugs have been officially approved to treat the infection. Remdesivir, an antiviral drug, despite favorable preliminary results, has restricted the use due to the risk of toxicity and methodological flaws. Antidepressant drugs were able to reduce the risk of intubation or death related to COVID-19, decrease the need for intensive medical care, and severely inhibit viral titers by up to 99%. Among the SSRIs studied so far, fluoxetine and fluvoxamine have shown to be the most promising against SARS-CoV-2. CONCLUSION: If successful, these drugs can substantially reduce hospitalization and mortality rates, as well as allow for fully outpatient treatment for mild-to-moderate infections. Thus, repositioning SSRIs can provide benefits when faced with a rapidly evolving pandemic such as COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , Inibidores Seletivos de Recaptação de Serotonina , Antidepressivos/uso terapêutico , Antivirais/uso terapêutico , Fluoxetina , Fluvoxamina , Humanos , Receptores de Serotonina , SARS-CoV-2 , Serotonina , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
Infectious diseases are among the main causes of morbidity and mortality today. In facing this crisis, the development of new drug options and combat strategies is necessary. In this sense, drug repositioning or drug redirection has emerged for the faster identification of effective drugs. In this "Commentary," the anti-infective properties of the class of proton pump inhibitors (PPIs) are emphasized. Studies report activities against bacterial, fungal, parasitic, and viral agents. In addition, we have provided in a table a summary of the specific characteristics of PPIs and some of their anti-infective activities.
Assuntos
Anti-Infecciosos , Inibidores da Bomba de Prótons , Anti-Infecciosos/farmacologiaRESUMO
WHAT IS KNOWN AND OBJECTIVE: The widespread use of antibiotics as therapeutic agents caused an increase of multidrug resistant bacteria (MDR) appearance. Regarding MDRs, we highlight the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.., which are the ESKAPE group. COMMENT: New treatment alternatives for infections caused by ESKAPE are under current scientific research. The main suggestions are the use of actinomycetes that produce promising substances with antibiotic activity, the synergistic effect between antimicrobials and peptides, photoinactivation, peptide rich in cationic histidine, association of new antimicrobials; besides the repositioning of drugs already approved for the treatment of other diseases. WHAT IS NEW AND CONCLUSION: These selected studies showed that researchers from many countries are focused on the development of effective alternative strategies for the treatment of infections caused by these microorganisms.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Enterobacter/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosAssuntos
Antidepressivos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Reposicionamento de Medicamentos , Micoses/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antidepressivos/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Ensaios Clínicos como Assunto , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Humanos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
The repositioning of approved drugs is atopic of interest for the academy and the pharmaceutical industry. The synergistic combination of these drugs can be successful in the treatment of infections caused by resistant bacteria. This study aimed to assess the in vitro synergistic antibacterial activity of sertraline and disulfiram and their interaction with ciprofloxacin and sulfamethoxazole/trimethoprim. We determined the minimum inhibitory concentration, the minimum bactericidal concentration and the fractional inhibitory concentration index. Eighteen bacterial strains were used, being nine American Type Culture Collection reference strains and nine multidrug resistant clinical isolates. Synergy was detected between sertraline and disulfiram against a strain of Staphylococcus aureusATCC 25923 and a clinical isolate of S. aureus. When associated to sulfamethoxazole/trimethoprim and ciprofloxacin, sertraline and disulfiram showed eight synergistic events, which occurred against three different standard strains and two multidrug resistant clinical isolates. When the minimum bactericidal concentration was determined, the bactericidal activity of sertraline was enhanced with disulfiram. Our results suggest that these drugs, widely used to treat depression and chronic alcoholism, have antibacterial potential individually, in association, and combined with antimicrobials, what makes their repositioning a promising therapeutic alternative for the effective treatment of infections caused by multidrug resistant bacteria.
RESUMO
Abstract The treatment of infections caused by resistant microorganisms represents a big challenge in healthcare due to limited treatment options. For this reason, the discovery of new active substances which are able to perform innovative and selective actions is of great impact nowadays. Statins and triazenes (TZC) have consolidated as a promising class of compounds, characterized by the expressive biological activity, especially antimicrobial activities. The aim of this study was to assess the in vitro synergistic antibacterial effect of the association of statins and a new TZC complex {[1-(4-bromophenyl)-3-phenyltriazene N 3-oxide-κ 2 N 1,O 4](dimethylbenzylamine-κ 2 C 1,N 4)palladium(II)} (Pd(DMBA)LBr) against American Type Culture Collection (ATCC) strains and clinical isolates. The complex and the statins showed bacterial activity of all tested strains and clinical isolates, evidencing that TZC complexion with metals can be promising. Simvastatin showed synergy when associated to the complex (FICI≤0.5), being the minimum inhibitory concentration (MIC) of 16 µg mL-1 found in 6 samples. Thus, it is possible to infer that the association between Pd(DMBA)LBr and simvastatin consists of an alternative to increase the pontential of these compounds, since statins have low toxicity.