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Acinetobacter baumannii, a prominent emerging pathogen, is responsible for persistent and recurrent healthcare-associated infections (HAIs). Its bacterial resistance and virulence factors, such as biofilm formation, contribute to its survival in hospital environments. Combination therapy has proven to be an effective approach for controlling these infections; however, antimicrobial resistance and compound toxicity can hinder antimicrobial efficacy. Numerous in vitro studies have demonstrated the synergistic effect of antimicrobials and natural products against multidrug-resistant (MDR) A. baumannii biofilm. Riparin III, a natural alkamide derived from Aniba riparia (Nees) Mez., possesses various biological activities, including significant antimicrobial potential. Nonetheless, no reports are available on the use of this compound in conjunction with conventional antimicrobials. Hence, this study aimed to investigate the inhibition and eradication of A. baumannii MDR biofilm by combining riparin III and colistin, along with potential ultrastructural changes observed in vitro. Clinical isolates of A. baumannii, known for their robust biofilm production, were inhibited, or eradicated in the presence of the riparin III/colistin combination. Furthermore, the combination resulted in several ultrastructural alterations within the biofilm, such as elongated cells and coccus morphology, partial or complete disruption of the biofilm's extracellular matrix, and cells exhibiting cytoplasmic material extravasation. At the synergistic concentrations, the riparin III/colistin combination exhibited a low hemolytic percentage, ranging from 5.74% to 6.19%, exerting inhibitory and eradicating effects on the A. baumannii biofilm, accompanied by notable ultrastructural changes. These findings suggest its potential as a promising alternative for therapeutic purposes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acinetobacter baumannii is an opportunistic pathogen associated with increased morbidity and mortality in Healthcare-associated infections (HAI). Combination antimicrobial therapy, meropenem, amikacin and colistin, has been used as an alternative in multidrug-resistant (MDR) A. baumannii infections due to reduced treatment options. However, these combinations are not always effective and exhibit high toxicity. Empiric therapy of intravenous immunoglobulin (IVIG) associated with antimicrobials has shown promising results in bacterial infections, considering the immunomodulatory action of IVIG. Thus, the aim of this study was to determine the combined antimicrobial action and to describe the ultrastructural changes caused in ten MDR A. baumannii isolates submitted to IVIG alone and in combination with colistin, meropenem and amikacin. Minimum Inhibitory Concentration (MIC) of antimicrobials and checkerboard were determined. Isolates were submitted to 4 mg/mL of IVIG alone and in combination with different synergistic sub-MIC of antimicrobials tested, and processed for scanning electron microscopy. Nine bacterial isolates showed meropenem-resistant, two isolates had colistin-intermediate, and four isolates were considered intermediate to amikacin. Synergism in five isolates for meropenem/amikacin and meropenem/colistin were observed. Bacterial cells submitted to IVIG and meropenem, amikacin and colistin presented several ultrastructural changes, such as cell elongation and rupture, membrane roughness, incomplete cell division, cell surface "bubbles" and "depression". A. baumannii isolates presented high resistance to meropenem and synergism among evaluated antimicrobials. In addition, it was possible to verify in vitro that IVIG associated with meropenem, amikacin and colistin is a promising alternative for MDR A. baumannii infections. Thus, these data support the continued empirical use and stimulate in vivo analyzes with IVIG to search for new therapeutic options for HAI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Natural products have been used to treat various infections; however, the development of antimicrobials has made natural products in disuse. Riparin I, II and III are natural alkamide isolated from Aniba riparia (Ness) Mez (Lauraceae), that exhibit economic importance and it is used in traditional medicine, and popularly known as "louro". This study investigated the cytotoxicity, antimicrobial and antibiofilm activity, and ultrastructural changes in vitro by riparins I, II and III in Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. We analyzed the cytotoxicity by MTT assay in Vero cells and hemolytic action verified in human erythrocytes. The antimicrobial activity was determined by microdilution in broth against ATCC strains, identifying the susceptible species. Subsequently, only the MDR isolates of sensitive bacterial species were evaluated regarding its biofilm formation and ultrastructural changes. Riparin I presented low cytotoxicity and hemolytic percentage ranging from of 9.01%-12.97%. Only the riparin III that showed antimicrobial activity against MDR clinical isolates, and significant reduction in biofilm formation in S. aureus. Moreover, the riparin III promoted ultrastructural changes in bacterial cells, such as elongated cellular without bacterial septum, cells with a rugged appearance on the cell surface and cytoplasmic material extravasation. As has been noted riparin III has an inhibitory potential against biofilm formation in S. aureus, besides having antimicrobial activity and promoting ultrastructural changes in MDR clinical isolates. Thus, riparin III is an interesting alternative for further studies aiming to develop new therapeutic options., (Copyright © 2020 Elsevier Ltd. All rights reserved.)