Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Anthelmintic resistance in Creole horses in the South of Rio Grande do Sul, Brazil / [Resistência anti-helmíntica em equinos da raça Crioula no sul do Rio Grande do Sul, Brasil]

The objective of the study was to evaluate the antiparasitic resistance against horse nematodes in the South of Rio Grande do Sul, Brazil. The results concerning the tests of anthelmintic efficacy on horses, stored in the database of the Parasitic Diseases Study Group (GEEP) - Veterinary Faculty, at the Federal University of Pelotas (UFPel), were carried out in the laboratory from 2018 to 2019. Stool samples were received from farms with breeding of adult female and male Criollo horses naturally infected, located in municipalities in the country's southern region. The antiparasitic agents tested were Triclorfon + Fenbendazole, Closantel + Albendazole, Ivermectin + Praziquantel, Fenbendazole, Ivermectin, Doramectin, Mebendazole and Moxidectin. Techniques such as Gordon and Whitlock, Coproculture and Fecal Egg Count Reduction Test were performed. Of all the antiparasitic drugs tested, it was observed that only treatments with Ivermectin 2% showed desired values. The observed results indicate that resistance to macrocyclic lactones is usual in equine parasites in this Brazilian region, despite the results with isolated Ivermectin.(AU)

O objetivo deste estudo é avaliar a resistência antiparasitária contra nematodeos de equinos no sul do Rio Grande do Sul, Brasil. Os resultados referentes aos testes de eficácia anti-helmíntica em cavalos, armazenados no banco de dados do Grupo de Estudos de Doenças Parasitárias (GEEP) - Faculdade de Veterinária, da Universidade Federal de Pelotas (UFPel), foram realizados em laboratório, no período de 2018 a 2019. Amostras de fezes foram recebidas de fazendas com criação de cavalos Crioulos adultos fêmeas e machos naturalmente infectados, localizadas em municípios da região Sul do país. Os agentes antiparasitários testados foram triclorfon + fenbendazol, closantel + ivermectina + praziquantel, fenbendazol, ivermectina, doramectina, mebendazol e moxidectina. Técnicas como Gordon e Whitlock, coprocultura e teste de redução da contagem de ovos fecais foram realizadas. De todos os antiparasitários testados, observou-se que apenas os tratamentos com ivermectina 2% apresentaram os valores desejados. Os resultados indicam que a resistência às lactonas macrocíclicas é comum em parasitas equinos nessa região brasileira, apesar dos resultados com ivermectina isolada.(AU)

Sistema microbiológico de cinco bioensayos para la detección de residuos de antibióticos / Five-assay microbiological system for the screeningf antibiotic residues

Abstract A novel microbiological system in microtiter plates consisting of five bioassays is presented for the detection and classification of antibiotic residues in milk. The bioassays were optimized for the detection of beta-lactams (Bioassay B: Geobacillus stearothermophilus), macrolides (Bioassay M: Bacillus megaterium with fusidic acid), tetracyclines (Bioassay T: B. megaterium with chloramphenicol), quinolones (Bioassay Q: Bacillus licheniformis) and sulfamides (Bioassay QS: B. licheniformis with trimethoprim) at levels near the maximum residue limits (MRL). The response of each bioassay was interpreted visually (positive or negative) after 4-5.5h of incubation. The system detects and classifies beta-lactams (5 pg/l of amoxicillin, 4 pg/l of ampicillin, 36 pg/l of cloxacillin, 22 pg/l of amoxicillin, 3 pg/l of penicillin, 114 pg/l of cephalexin, 89pg/l of cefoperazone and 116 pg/l of ceftiofur), tetracyclines (98 pg/l of chlortetracycline, 92 pg/l of oxytetracycline and 88 pg/l of tetracycline), macrolides (33 pg/l of erythromycin, 44 pg/l of tilmicosin and 50 pg/l of tylosin), sulfonamides (76 pg/l of sulfadiazine, 85 pg/l of sulfadimethoxine, 77 pg/l of sulfamethoxazole and 87pg/l of sulfathiazole) and quinolones (94 pg/l of ciprofloxacin, 98 pg/l of enrofloxacin and 79 pg/l marbofloxacin). In addition, the specificity values were high for B, T, Q (99.4%), M (98.8%) and QS (98.1%) bioassays. The control of antibiotics through this system can contribute to improving the quality and safety of dairy products.

Resumen Se presenta un novedoso sistema microbiológico en placas de microtitulación compuesto por 5 bioensayos para la detección y clasificación de residuos de antibióticos en leche. Los bioensayos fueron optimizados para la detección de betalactámicos (bioensayo B: Geobacillus stearothermophilus), macrólidos (bioensayo M: Bacillus megaterium con ácido fusídico), tetraciclinas (bioensayo T: Bacillus megaterium con cloranfenicol), quinolonas (bioensayo Q: Bacillus licheniformis) y sulfamidas (bioensayo QS: Bacillus licheniformis con trimetoprima), a niveles cercanos a los límites máximos de residuos (LMR). La respuesta de cada bioensayo se interpretó visualmente (positiva o negativa) después de 4 a 5,5 h de incubación. El sistema detecta y clasifica betalactámicos (5 pg/l de amoxicilina, 4 pg/l de ampicilina, 36 pg/l de cloxacilina, 22 pg/l de amoxicilina, 3 pg/l de penicilina, 114 pg/l de cefalexina, 89 pg/l de cefoperazona y 116 pg/l de ceftiofur), tetraciclinas (98 pg/l de clortetraciclina, 92 pg/l de oxitetraciclina y 88 pg/l de tetraciclina), macrólidos (33 pg/l de eritromicina, 44 pg/l de tilmi-cosina y 50 pg/l de tilosina), sulfamidas (76 pg/l de sulfadiacina, 85 pg/l de sulfadimetoxina, 77 pg/l de sulfametoxazol y 87 pg/l de sulfatiazol) y quinolonas (94 pg/l de ciprofloxacina, 98 pg/l de enrofloxacina y 79pg/l de marbofloxacina). Además, los valores de especificidad fueron altos para los bioensayos B, T, Q (99,4%), M (98,8%) y QS (98,1%). El control de residuos de antibióticos mediante este sistema puede contribuir a mejorar la calidad e inocuidad de los productos lácteos.

Importancia clínica del metabolismo de medicamentos (Segunda Parte) / Clinical importance and drugs metabolism (Second Part)

Parte número dos de la segunda emisión. Esta es la segunda emisión de un trabajo científico sobre metabolismo de los medicamentos su importancia clínica. En esta segunda parte tratamos sobre las interacciones de interés más sobresalientes. Además de los mecanismos de interacción, nuestro objetivo es hacer conciencia, sobre la importancia del metabolismo de ciertos medicamentos.