Epidemiologia de bactérias Gram-negativas multirresistentes durante a pandemia de COVID-19 e avaliação de novas alternativas antimicrobianas

Abstract

Antimicrobial resistance among Multidrug-resistant Gram-Negative bacteria (MDR-GNB) represents a global health challenge, restricting therapeutic options for the treatment of infections. In Brazil, epidemiological data on the impact of MDR-GNB occurrence in patients with coronavirus disease 2019 (COVID-19) are limited. Thus, the objective was to evaluate the clinical outcome and factors associated with MDR-GNB in 280 hospitalized patients with or without COVID-19, through a case-control study, carried out between March/2020 and December/2021. The case group (COVID-19-MR-GNB) was defined as patients who were positive for COVID-19, with a clinical culture for an MDR-GNB. Control 1 (COVID-19) was defined as COVID-19 positive patients with no GNB culture. Control 2 (MDR-GNB) included patients with MDR-GNB culture and no clinical evidence of COVID-19. Control 3 (GNB) included patients cultured for a carbapenem-susceptible GNB and without clinical evidence of COVID-19. The study involved non-probabilistic controls, randomly recruited in a 1:1:1:1 ratio to cases. These groups were submitted to univariate and multivariate statistical analysis and the use of urinary catheter and central venous catheter were identified as risk factors associated with mortality; renal insufficiency; clinical sample of tracheal secretion, use of carbapenems and polymyxin. Mortality was significantly higher in patients in the COVID-19-MDR-GNB case group compared to the three COVID-19, MDR-GNB and GNB control groups (p = ≤ 0.02). The data demonstrate that the occurrence of MDR-GNB associated with COVID-19 has a significant impact on the increase in mortality. In order to contribute to the control of MDR GNB, the synergistic potential of a bioactive compound (carvacrol) associated with an antibiotic (polymyxin B) was investigated, seeking to contribute to the development of new antimicrobials against polymyxin-resistant K. pneumoniae. It was observed that it had an inhibitory effect on biofilm formation and demonstrated antimicrobial potential in vitro and in vivo, representing a therapeutic alternative to be explored in the development of new antimicrobials. Since antimicrobial peptides have stood out in the pharmaceutical market, due to their antimicrobial properties, a patent review was carried out on antimicrobial peptides developed and tested against polymyxin-resistant K. pneumoniae, in order to investigate progress in the development of new antimicrobials peptides. The results indicate that although many peptides are reported to have activity against K. pneumoniae, a minority have been tested effectively against polymyxin-resistant strains. Additionally, investments are needed in order to advance in the development stages with the aim of introducing them to the antimicrobial market. In this context, the development of this study corroborates the recommendations of the World Health Organization, for the containment of antimicrobial resistance, which encourages epidemiology studies and research in the development of new antimicrobials, in order to control the spread of multidrug-resistant microorganisms and improve the prognosis of patients.