The synergic and addictive activity of biogenic silver nanoparticle associated with meropenem against carbapenem-resistant Acinetobacter baumannii.

AIMS: Antibiotic management of infections caused by Acinetobacter baumannii often fails due to antibiotic resistance (especially to carbapenems) and biofilm-forming strains. Thus, the objective here was to evaluate in vitro the antibacterial and antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) combined with meropenem, against multidrug-resistant isolates of A. baumannii. METHODS AND RESULTS: In this study, A. baumannii ATCC® 19606™ and four carbapenem-resistant A. baumannii (Ab) strains were used. The antibacterial activity of Bio-AgNP and meropenem was evaluated through broth microdilution. The effect of the Bio-AgNP association with meropenem was determined by the checkboard method. Also, the time-kill assay and the integrity of the bacterial cell membrane were evaluated. Furthermore, the antibiofilm activity of Bio-AgNP and meropenem alone and in combination was determined. Bio-AgNP has antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 0.46 to 1.87 µg ml-1. The combination of Bio-AgNP and meropenem showed a synergistic and additive effect against Ab strains, and Bio-AgNP was able to reduce the MIC of meropenem from 4- to 8-fold. Considering the time-kill of the cell, meropenem and Bio-AgNP when used in combination reduced bacterial load to undetectable levels within 10 min to 24 h after treatment. Protein leakage was observed in all treatments evaluated. When combined, meropenem/Bio-AgNP presents biofilm inhibition for Ab2 isolate and ATCC® 19606™, with 21% and 19%, and disrupts the biofilm from 22% to 50%, respectively. The increase in nonviable cells in the biofilm can be observed after treatment with Bio-AgNP and meropenem in carbapenem-resistant A. baumannii strains. CONCLUSIONS: The combination of Bio-AgNP with meropenem can be a therapeutic option in the treatment of infections caused by carbapenem-resistant A. baumannii.

Biogenic silver nanoparticle (Bio-AgNP) has an antibacterial effect against carbapenem-resistant Acinetobacter baumannii with synergism and additivity when combined with polymyxin B.

AIMS: Carbapenem-resistant Acinetobacter baumannii represents a public health problem, and the search for new antibacterial drugs has become a priority. Here, we investigate the antibacterial activity of biogenic silver nanoparticles (Bio-AgNPs) synthesized by Fusarium oxysporum, used alone or in combination with polymyxin B against carbapenem-resistant A. baumannii. METHODS AND RESULTS: In this study, ATCC® 19606™ strain and four carbapenem-resistant A. baumannii strains were used. The antibacterial activity of Bio-AgNPs and its synergism with polymyxin B were determined using broth microdilution, checkboard methods and time-kill assays. The integrity of the bacterial cell membrane was monitored by protein leakage assay. In addition, the cytotoxicity in the VERO mammalian cell line was also evaluated, and the selectivity index was calculated. Bio-AgNPs have an antibacterial activity with MIC and MBC ranging from 0.460 to 1.870 µg/ml. The combination of polymyxin B and Bio-AgNPs presents synergy against four of the five strains tested and additivity against one strain in the checkerboard assay. Considering the time of cell death, Bio-AgNPs killed all carbapenem-resistant isolates and ATCC® 19606™ within 1 h. When combined, Bio-AgNPs presented 16-fold reduction of the polymyxin B MIC and showed a decrease in terms of viable A. baumannii cells in 4 h of treatment, with synergic and additive effects. Protein leakage was observed with increasing concentrations for Bio-AgNPs treatments. Additionally, Bio-AgNP and polymyxin B showed dose-dependent cytotoxicity against mammalian VERO cells and combined the cytotoxicity which was significantly reduced and presented a greater pharmacological safety. CONCLUSIONS: The results presented here indicate that Bio-AgNPs in combination with polymyxin B could represent a good alternative in the treatment of carbapenem-resistant A. baumannii. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrates the synergic effect between Bio-AgNPs and polymyxin B on carbapenem-resistant A. baumannii strains.