During the Covid-19 pandemic period, the indiscriminate use of macrolide-class antibiotics was frequent among the Brazilian population due to the lack of knowledge and information with a scientific basis. Thus, the class of drugs that includes azithromycin, clarithromycin, and erythromycin, which alter metabolic reactions in the body and act on the immune system, was widely used without medical prescription. Samples of bacterial strains from hospital environments were obtained during the most extensive spread of Covid-19 and studied in the present article, emphasizing the investigation for macrolide resistance genes (erm and msr) bacteria of the genus Staphylococcus isolated from urinary tract infections. In addition, the physiological, genetic, immunological, and socio-epidemiological aspects were highlighted with a focus on the One Health approach and implications on the gut-brain axis in this integrative research, revealing that the inappropriate use of antibiotics directly affects entire communities, representing a significant concern for public and environmental health.