RESUMO
Acinetobacter baumannii is a bacteria associated with nosocomial infections and outbreaks, difficult to control due to its antibiotic resistance, ability to survive in adverse conditions, and biofilm formation adhering to biotic and abiotic surfaces. Therefore, this study aimed to evaluate the antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) and polymyxin B alone and combined in biofilms formed by isolates of carbapenem-resistant A. baumannii (CR-Ab). In the biofilm formation inhibition assay, CR-Ab strains were exposed to different concentrations of the treatments before inducing biofilm formation, to determine the ability to inhibit/prevent bacterial biofilm formation. While in the biofilm rupture assay, the bacterial biofilm formation step was previously carried out and the adhered cells were exposed to different concentrations of the treatments to evaluate their ability to destroy the bacterial biofilm formed. All CR-Ab isolates and ATCC® 19606™ used in this study are strong biofilm formers. The antibiofilm activity of Bio-AgNP and polymyxin B against CR-Ab and ATCC® 19606™ demonstrated inhibitory and biofilm-disrupting activity. When used in combination, Bio-AgNP and polymyxin B inhibited 4.9-100% of biofilm formation in the CR-Ab isolates and ATCC® 19606™. Meanwhile, when Bio-AgNP and polymyxin B were combined, disruption of 6.8-77.8% of biofilm formed was observed. Thus, antibiofilm activity against CR-Ab was demonstrated when Bio-AgNP was used alone or in combination with polymyxin B, emerging as an alternative in the control of CR-Ab strains.
RESUMO
To find novel antibiotic drugs, six 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H derivatives named 1b, 1d (pyrazoles), 2a, 2b, 2c, and 2d (thiazoles) were evaluated in silico and in vitro. The in silico analyses were based on ADME pharmacokinetic parameters (absorption, distribution, metabolism, and excretion). The in vitro antibacterial activity was evaluated in Gram-positive and Gram-negative species (Staphylococcus aureus ATCC® 25904, Staphylococcus epidermidis ATCC® 35984, Klebsiella pneumoniae ATCC® 700603, and Acinetobacter baumannii ATCC® 19606), by determination of minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), kinetics curve, and antibiofilm assays. As results, the azoles have activity against the Gram-negative species K. pneumoniae ATCC® 700603 and A. baumannii ATCC® 19606. No antibacterial activity was observed for the Gram-positive bacteria evaluated. Thus, the azoles were evaluated against clinical isolates of K. pneumoniae carbapenemase (KPC) and A. baumannii multidrug-resistant (Ab-MDR). All azoles have antibacterial activity against Ab-MDR isolates (Gram-negative) with MIC values between 512 µg/mL and 1,024 µg/mL. Against KPC isolates the azoles 1b, 1d, and 2d present antibacterial activity (MIC = 1,024 µg/mL). In the kinetics curve assay, the 1b and 1d pyrazoles reduced significantly viable cells of Ab-MDR isolates and additionally inhibited 86.6 to 95.8% of the biofilm formation. The in silico results indicate high possibility to permeate the blood-brain barrier (2b) and was predict human gastrointestinal absorption (all evaluated azoles). Considering that the research and development of new antibiotics is a priority for drug-resistant pathogens, our study revealed the antibacterial and antibiofilm activity of novel azoles against K. pneumoniae and A. baumannii pathogens.