Estudos epidemiológicos de bactérias multirresistentes na cidade de Pelotas e suscetibilidade à diidropirimidinona

Abstract

Bacterial resistance to antibiotics is a global public health problem. The indiscriminate use of antibiotics has accelerated this process, causing increased morbidity and mortality of healthcare-related infections. The increasing inefficiency of existing antibiotics has led to the need for the development of new antibacterial drugs, causing researchers' interest in the medicinal properties of nitrogen-containing heterocyclic compounds, the "Bignelli compounds", especially dihydropyrimidinones. The objective of this study was to analyze the susceptibility profile of antibiotics, multiresistant bacteria with patient data, sample origin and infection site of two hospitals in Pelotas, RS-Brazil, and to test them in vitro against new compounds of dihydropyrimidinones of synthetic origin. The study was conducted between October 2018 and January 2019, with the sample calculation including 286 multiresistant bacterial isolates from at least three classes of antibiotics. The isolates were collected from the pulmonary, abdominal, superficial, blood and urine samples of patients hospitalized in an intensive care unit for adult and neonatal care, infirmaries, private beds and covenants, as well as outpatient clinics. Statistical analyzes were performed using SPSS software version 20.0. The reports were issued by the Clinical Analysis Laboratories of each hospital studied, in automated system VITEK® 2 (bio Mérieux, France) and BD PHOENIX, according to the recommendations of the Clinical and Laboratory Standards Institute, 2012. The efficacy of the three dihydropyrimidinone compounds was tested in vitro against the multiresistant bacteria of selected hospital clinical origin. These compounds were synthesized by the Laboratory of Lipidomics and Bio-organic of the Federal University of Pelotas, RS-Brazil. The analyzes were carried out by means of the Minimal Inhibitory Concentration and Minimum Bactericidal Concentration by the broth microdilution method. The cytotoxicity of the compounds was evaluated in mouse fibroblasts, a 3T3 cell line. The epidemiological profile indicated greater bacterial resistance in male patients, older than 70 years, hospitalized in infirmaries, predominantly in the urinary tract. Klebsiella pneumoniae was the most prevalent with 17.8%. Gram negative bacilli: Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa, showing increased resistance to penicillins, quinolones and cephalosporins. Among Gram-positive cocci, the most resistant were Staphylococcus aureus, Staphylococcus coagulase negative and Staphylococcus haemolyticus, compared to macrolides, lincosamines, and glycopropeptides. The synthetic compounds showed minimal inhibitory activity in Gram-positive cocci in concentration (0.16-80 μg/mL) with bactericidal action and Gram-negative bacilli (23.2-80 μg/mL) with bacteriostatic action and were not cytotoxic at the highest concentration tested (80 μg/mL). E. faecium had the best MIC of 0.16 μg / mL while Escherichia coli was the most resistant in two of the isolates tested. The study concluded that health-care-related infections are a serious public health problem in the context of their implementation. Pointing out the need for new research and the development of prevention and fighting strategies at the local level, confirming that this is an epidemic at the global level. Indicating that the three dihydropyrimidinone compounds tested showed good antibacterial activity against multiresistant bacteria, constituting promising alternatives for the development of new antibiotics.