Synthesis and Characterization of Cassava Gum Hydrogel Associated with Chlorhexidine and Evaluation of Release and Antimicrobial Activity.

Hydrogels from natural sources are attracting increasing interest due to their ability to protect biologically active molecules. Starch extracted from cassava tubers is a promising material for synthesizing these hydrogels. Copolymerization of cassava gum and incorporation of chlorhexidine digluconate (CLX) into the hydrogels is confirmed by changes in the crystallographic profile, as observed through X-ray diffraction, and a shift in the 1000 cm-1 band in the Fourier-transform infrared spectroscopy spectrum. The differential scanning calorimetry reveals changes in the decomposition temperature of the synthesized hydrogels related to CLX volatility. Micrographs illustrate the material's porosity. Release tests indicate a constant linear release over 72 h, while antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans is satisfactory, with 100% effectiveness from 0.5% CLX and the formation of inhibition halos. Toxicity and biocompatibility studies show no cytotoxicity. The continuous release of chlorhexidine is promising for components of biomedical implants and applications as it can ensure antimicrobial action according to specific therapeutic needs.

Chemical composition of Piper gaudichaudianum Kunth essential oil and evaluation of its antimicrobial and modulatory effects on antibiotic resistance, antibiofilm, and cell dimorphism inhibitory activities.

Essential oils extracted from many plant species have different biological activities, among which microbial activity stands out. Species of the genus Piper have antimicrobial potential against different species of bacteria and fungi. In this sense, the present study aimed to determine the chemical composition of the essential oil from the leaves of Piper gaudichaudianum (EOPG), as well as to investigate their antimicrobial activity and their modulatory effect on the Norfloxacin resistance in the Staphylococcus aureus SA1199B strain overproducer of the NorA efflux pump. Furthermore, their inhibitory activities on the biofilm formation as well as on the cellular differentiation of C. albicans were evaluated. Gas chromatography analysis identified 24 compounds, such as hydrocarbon sesquiterpenes (54.8%) and oxygenated sesquiterpenes (28.5%). To investigate the antimicrobial potential of EOPG against S. aureus, E. coli, and C. albicans, a microdilution assay was performed, and no intrinsic antimicrobial activity was observed. On the other hand, the oil potentiated the activity of Norfloxacin against the SA1199B strain, indicating that EOPG could be used in association with Norfloxacin against S. aureus strains resistant to this antibiotic. EOPG also inhibited S. aureus biofilm formation, as evidenced by the crystal violet assay. In the dimorphism assay, EOPG was able to inhibit the cell differentiation process in C. albicans. Results indicate that EOPG could be used in association with Norfloxacin in the treatment of infections caused by resistant S. aureus strains overproducing the NorA efflux pump. Furthermore, its ability to inhibit the formation of hyphae by C. albicans suggests that EOPG could also be applied in the prevention and/or treatment of fungal infections.

Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii.

Acinetobacter baumannii is an important opportunistic pathogen that causes serious health-related infections, especially in intensive care units. The present study aimed to investigate the antimicrobial activity of Riparin-B (Rip-B) alone and in association with norfloxacin against multidrug-resistant clinical isolates of A. baumannii. For this, the minimum inhibitory concentrations were determined by the microdilution method. For the evaluation of resistance-modulating activity, MIC values for antibiotics were determined in the presence or absence of subinhibitory concentrations of Rip-B or chlorpromazine (CPZ). The AdeABC-AdeRS efflux system genes from these isolates were detected by PCR. Docking studies were also carried out to evaluate the interaction of Riparin-B and the AdeABC-AdeRS efflux system. The study was conducted from 2017 to 2019. The results showed that Rip-B showed weak intrinsic activity against the strains tested. On the other hand, Rip-B was able to modulate norfloxacin's response against A. baumannii strains that express efflux pump-mediated resistance. Docking studies provided projections of the interaction between Rip-B and EtBr with the AdeB protein, suggesting that Rip-B acts by competitive inhibition with the drug. Results found by in vitro and in silico assays suggest that Rip-B, in combination with norfloxacin, has the potential to treat infections caused by multidrug-resistant A. baumanni with efflux pump resistance.

Efflux Pump (QacA, QacB, and QacC) and ß-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains.

The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of ß-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of ß-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 µg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on ß-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and ß-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and ß-lactam antibiotics, suggesting that they may act by inhibiting ß-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.

Seasonal variation of the composition of essential oils from Piper cernuum Vell and Piper rivinoides Kunth, ADMET study, DFT calculations, molecular docking and dynamics studies of major components as potent inhibitors of the heterodimer methyltransferase complex NSP16-NSP10 SARS COV-2 protein.

Coronavirus disease (COVID-19) has the virus that causes the SARS-CoV-2 severe acute respiratory syndrome, which has reached a pandemic proportion, with thousands of deaths worldwide already registered. It has no standardized effective clinical treatment, arousing the urgent need for the discovery of bioactive compounds for the treatment of symptoms of COVID-19. In this context, the present study aimed to evaluate the influence of seasonality on the yield and chemical composition of the essential oils of Piper cernuum and Piper rivinoides as well as to evaluate the anti-SARS-CoV-2 potential of the major components of each oil by molecular docking and quantum chemical calculation (Density Functional Theory method), being possible indicate that the winter and autumn periods, the seasons of the year where it is possible to obtain the highest percentage of Piper cernuum and Piper rivinoides oils, respectively. Regarding the anti-SARS-Cov-2 potential, the present work showed that the dihydroagarofuran present in Piper cernuum, presented a strong interaction with amino acid residues from Mpro, presenting a potential similar to Remdesivir, a drug for clinical use. Regarding methyltransferase, dihydroagarofuran (Piper cernuum) and myristicin (Piper rivinoids) showed better affinity, with important interactions at the active site of the inhibitor Sinefugin, suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2. Molecular docking and molecular dynamics studies represent an initial step, being indicative for future in vitro studies of dihydroagarofuran and myristicin, as possible pharmacological tools for COVID-19.Communicated by Ramaswamy H. Sarma.

Antiulcerogenic and Antibacterial Effects of Chitosan Derivatives on Experimental Gastric Ulcers in Rats.

Gastric ulcer is an injury that develops on the lining of the stomach due to an imbalance between aggressive and defensive agents. Chitosan derivatives demonstrate promising biological activities in accelerating the healing activity of gastric lesions. Thus, this study aimed at investigating the healing activity of gastric lesion, induced by acetic acid (80%), of the chitosan derivative with acetylacetone (Cac) modified with ethylenediamine (Cacen) or diethylenetriamine (Cacdien). The biological activity was determined based on cytotoxicity, antibacterial activity, and gastroprotective activities. The results showed no significant difference in the cytotoxicity, a better antibacterial activity against S. aureus and E. coli, and a positive result on the healing of gastric lesions of the materials (Cac 18.4%, Cacen 55.2%, and Cacdien 68.1%) compared to pure chitosan (50.7%). Therefore, the results indicate that derivatives of chitosan are promising biomaterials for application in the control of lesions on the gastric mucosa.

Mechanism of the lethal effect of Riparin E against bacterial and yeast strains.

Riparins are alkamides naturally found in the fruits of Aniba riparia (Nees) Mez, but currently synthetic molecules as Riparin E (Rip-E) can be obtained. Potential biological of Rip-E as schistosomicidal agent against Schistosoma mansoni worms, as well as against Staphylococcus aureus strains has already been described. However, the mechanism of action related to antimicrobial activity of Rip-E against bacterial or fungi species has not yet been reported. This study had as objective to evaluate the Rip-E antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as against yeast species of clinical importance. Minimal inhibitory concentrations of the compound against bacterial and yeast strains were determined by microdilution method. To verify if a possible lethal effect caused by Rip-E were related to plasma membrane damage, microbial cells treated with Rip-E were stained with 7-aminoactinomycin D (7-AAD) and analyzed by flow cytometry. Rip-E showed a bactericide effect against Gram-positive species S. aureus and S. epidermidis, as well as, against Gram-negative species Escherichia coli and Salmonella enterica Typhimurium, but was inactive against Pseudomonas aeruginosa. Moreover, Rip-E showed activity against fungi species Candida albicans and C. tropicalis. S. aureus, E. coli and C. albicans cells treated with Rip-E were marked with 7-aminoactinomycin D (7-AAD) indicating that Rip-E can cause plasma membrane damage, acting as a potential microbicide agent for prevention or treatment of infectious diseases.

Chemical composition and potentiating action of Norfloxacin mediated by the essential oil of Piper caldense C.D.C. against Staphylococcus aureus strains overexpressing efflux pump genes.

Infectious diseases caused by multidrug-resistant microorganisms has increased in the last years. Piper species have been reported as a natural source of phytochemicals that can help in combating fungal and bacterial infections. This study had as objectives characterize the chemical composition of the essential oil from Piper caldense (EOPC), evaluate its potential antimicrobial activity, and investigate the synergistic effect with Norfloxacin against multidrug-resistant S. aureus overproducing efflux pumps, as well as, verify the EOPC ability to inhibit the Candida albicans filamentation. EOPC was extracted by hydrodistillation, and the chemical constituents were identified by gas chromatography, allowing the identification of 24 compounds (91.9%) classified as hydrocarbon sesquiterpenes (49.6%) and oxygenated sesquiterpenes (39.5%). Antimicrobial tests were performed using a 96-well plate microdilution method against C. albicans ATCC 10231, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 standard strains, as well as against multidrug-resistant strains S. aureus SA1199B (overexpressing norA gene), S. aureus K2068 (overexpressing mepA gene) and S. aureus K4100 (overexpressing qacC gene). The oil showed activity against C. albicans ATCC 10231 (≥ 512 µg/mL) and was able to inhibit hyphae formation, an important mechanism of virulence of C. albicans. On the other hand, EOPC was inactive against all bacterial strains tested (≤ 1,024 µg mL). However, when combined with Norfloxacin at subinhibitory concentration EOPC reduced the Norfloxacin and Ethidium bromide MIC values against S. aureus strains SA1199B, K2068 and K4100. These results indicate that EOPC is a source of phytochemicals acting as NorA, MepA and QacC inhibitors.

Potentiating activity of Norfloxacin by synthetic chalcones against NorA overproducing Staphylococcus aureus.

Staphylococcus aureus is responsible for a series of infections occurring in both human and animal hosts. S. aureus SA1199B is a strain resistant to hydrophilic fluoroquinolone due to overproduction of the NorA efflux pump that has been used as a microbial model to evaluate if a compound act as efflux pump inhibitor. Finding substances from natural or synthetic origin able to reverse resistance mechanisms like those of efflux pumps is a challenge. The use of Chalcones and their derivatives is of great chemical and pharmacological interest, as they present a simple structure and several pharmacological activities. This study aims to evaluate the antibacterial potential of 4 synthetic chalcones, as well as to evaluate their action in the modulation of Norfloxacin resistance against the strain SA1199B strain. Microdilution assays were performed for evaluation of the antimicrobial activity. For evaluation of the modulating effect on resistance to Norfloxacin or EtBr, MIC values of these compounds were determined in the absence or presence of subinhibitory concentrations used of each chalcone. MICs values of both Norfloxacin and EtBr were significantly reduced in the presence of all tested chalcones, indicating that inhibition of the active efflux of these compounds by NorA could be a possible mechanism of action of the chalcones. These results show that the compounds studied have a high potential as a NorA inhibitor, with the best modulating effect verified for the compound 3. Pharmacokinetic and toxicity predictive studies indicated a high intestinal absorption and good volume of distribution for chalcones by oral administration, activity in the central nervous system and ease to be transported between biological membranes. Emphasizing that analogs 1 and 4 were easily metabolized by CYP3A4 enzyme, constituting a pharmacological active ingredient without toxic risk due to metabolic activation. These chalcones combined with Norfloxacin could be a promise technological strategy to be applied in the treatment of infections caused by S. aureus overproducing NorA.

Chemical synthesis, molecular docking and MepA efflux pump inhibitory effect by 1,8-naphthyridines sulfonamides.

This study aimed to evaluate the antibacterial activity and to verify, in silico and in vitro, the inhibition of efflux mechanisms using a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The chemical synthesis occurred through the thermolysis of the Meldrum's acid adduct. The sulfonamide derivatives were obtained by the sulfonylation of 2-amino-5­chloro-1,8-naphthyridine with commercial benzenesulfonyl chloride. Antibacterial activity was assessed by the broth microdilution test. Efflux pump inhibitory capacity was evaluated in silico by molecular docking and in vitro by analyzing synergistic effects on ciprofloxacin and ethidium bromide (EtBr) and by EtBr fluorescence emission assays. The following 1,8-naphthyridines were synthesized: 4-methyl-N-(5­chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10a); 2,5-dichloro-N-(5­chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10b); 4-fluoro-N-(5­chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10c); 2,3,4-trifluoro-N-(5­chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10d); 3-trifluoromethyl-N-(5­chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10e); 4­bromo-2,5-difluoro-N-(5­chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10f). The 1,8-naphthyridines derivatives associated with sulfonamides did not show antibacterial activity. However, they showed a favorable pharmacokinetic profile with possible MepA efflux pump inhibitory action, demonstrated in molecular docking. In addition to the promising results in reducing the concentration of intracellular EtBr. 1,8-naphthyridines act as putative agents in the inhibitory action of the MepA efflux pump.

In vitro antileishmanial and immunomodulatory activities of the synthetic analogue riparin E.

Leishmaniases are infectious diseases caused by protozoa of the genus Leishmania, that may have different clinical manifestations. First line drugs used in the treatment of leishmaniosis are high costly, and are very aggressive requiring medical monitoring. Thus new therapeutic alternatives are needed and, in this context, natural products have been considered as a source of new antileishmania agents. Riparins are alkamides found in the unripe fruits of Aniba riparia. Several biological activities are described for this group of compounds, such as antimicrobial and antiparasitic potential. The objective of this work was to evaluate the anti-leishmania activity riparin E (Rip-E) in vitro, against promastigotes and internalized amastigotes of Leishmania amazonensis. Rip-E was able to inhibit promastigote cell growth (IC50 4.7 µg/ml) and to reduce the percentage of macrophages infected with amastigotes, reducing its infectivity (survival index) (IC50 1.3 µg/ml). The cytotoxicity against BALB/c murine macrophages was also assessed (CC50 50.6 µg/ml) and the selectivity index was 38.9. Rip-E also demonstrated immunomodulatory activity, evidenced by the increase of the phagocytic capacity and lysosomal activity. However, Rip-E did not affect directly the production of nitric oxide. These results suggest that Rip-E has antileishmania potential, by both its direct inhibitory effect and its ability to activate macrophages.

Phthalic anhydride esterified chicha gum: characterization and antibacterial activity.

The objective of this research was to modify chicha gum with phthalic anhydride to obtain a new biologically active material. The chemical modification of the gum structure was proven through FTIR, elemental analysis, XRD, TG, and DSC. The derived materials demonstrated excellent inhibitory effect against P. aeruginosa and K. pneumoniae species (rating 100% inhibition) and could also inhibit Escherichia coli growth. The best antimicrobial activity observed for the derivatives suggests that chicha gum hydrophobization due to the addition of phthalic groups improved the interaction of these derivatives with bacterial cell wall components. On the other hand, the derivatives increased CC50 in macrophages but did not present acute toxicity or hemolytic activity, indicating that they are promising for use in prophylaxis or treatment of infections caused by Gram-negative bacteria.

Cashew-gum-based silver nanoparticles and palygorskite as green nanocomposites for antibacterial applications.

Nanocomposite materials have been proposed to enhance the properties of different materials. In this study, palygorskite (Pal) clay is proposed as a support matrix for silver nanoparticles stabilised with cashew gum (Anacardium occidentale L.) (AgNPs-CG), producing the Pal/AgNPs-CG nanocomposite, whose bactericidal activity was studied. AgNPs-CG was synthesised using a green method in which CG acted as a reducing and stabilising agent for these nanostructures. AgNPs-CGs were subsequently characterised then adsorbed to the Pal surface, which was previously treated to remove impurities such as quartz. Pal and Pal/AgNPs-CG were characterised by X-ray diffraction, specific surface area, thermal analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, and transmission electron microscopy. The antibacterial activity assay by the direct contact method showed that the synergistic effect of the combination of AgNPs-CG and Pal increased the bactericidal effect of the nanomaterial compared with the AgNPs-CG activity, reaching a percentage inhibition of up to 70.2% against E. coli and 85.3% against S. aureus. Nanocomposite atoxicity was demonstrated by the Artemia Salina model. Thus, the Pal/AgNPs-CG nanocomposite emerges as a nanomaterial with potential antibacterial applications.

Antibacterial and cytotoxic properties from esterified Sterculia gum.

Sterculia gums, as karaya and chicha gum, are complex branched and polydisperse heteropolysaccharides which can have their applications extended by improving their characteristics through chemical modifications. The objective of this work was to increase the antimicrobial activity of karaya and chicha gum through chemical modification with maleic anhydride. The incorporation of anhydride in the gum structure was confirmed by the characterization techniques. The derived biopolymers were synthesized and characterized by FTIR, X-ray diffraction, Thermogravimetric analysis and elemental analysis. Antimicrobial activity was evaluated against the Staphylococcus aureus strain (ATCC 25923). Mammalian cytotoxicity assays were also performed by MTT and hemolysis tests. The derivatives showed excellent antibacterial action inhibiting almost 100% of bacterial growth and did not present significant cytotoxicity in mammalian cells. The results showed that the derivatives are promising for biomedical applications aiming the control of infectious diseases caused by S. aureus.

Chalcones Isolated from Arrabidaea brachypoda Flowers as Inhibitors of NorA and MepA Multidrug Efflux Pumps of Staphylococcus aureus.

Bacterial resistance to antibiotics has become a public health issue around the world. The present study aimed to evaluate the antibacterial activity of chalcones isolated from flowers of Arrabidaea brachypoda, and their potential as efflux pump inhibitors of Staphylococcus aureus efflux pumps. Microdilution assays were performed with natural products from A. brachypoda. Chalcones 1, 3, 4, and 5 did not show intrinsic antimicrobial activity against all S. aureus strains tested, but they were able to potentiate the Norfloxacin action against the SA1199-B (norA) strain, with a better modulating action for the 4 trimethoxylated chalcone. All chalcones were also able to potentiate the action of EtBr against SA1199-B strain, suggesting a potential NorA inhibition. Moreover, chalcone 4 was able to interfere in the activity of MepA, and interfered weakly in the QacA/B activity. Molecular docking analyzes showed that tested chalcones are capable of binding in the hydrophobic cavity of NorA and MepA, in the same Norfloxacin binding site, indicating that chalcone 4 compete with the antibiotic for the same NorA and MepA binding sites. Association of chalcone 4 with Norfloxacin could be an alternative against multidrug resistant S. aureus over-productive of NorA or MepA.

Modified chicha gum by acetylation for antimicrobial and antiparasitic applications: Characterization and biological properties.

It was developed a material to act as an antimicrobial and antiparasitic agent through a modification reaction in the gum structure extracted from the plant Sterculia striata. This material was characterized, the oxidant activity was evaluated and the antimicrobial activity against Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhimurium and Klebsiella pneumoniae was investigated, in addition to the effect against Leishmania amazonensis, testing its acute toxicity and its cytotoxicity in human cells. Characterization techniques proved the success of chemical modification. The modification led to an increase in antioxidant activity, with excellent antibacterial activity, reaching almost 100% inhibition for P. aeruginosa and S. Typhimurium, and inhibitory effect above 70% against L. amazonensis, with an affinity far superior to the parasite than macrophages. The derivative showed no acute toxicity, it was non-hemolytic, increased cell viability in macrophages and fibroblasts, and stimulated cell proliferation of keratinocytes, thus being a strong candidate to be used as an antimicrobial and antiparasitic agent in biomedical applications.

Antimicrobial activity and inhibition of the NorA efflux pump of Staphylococcus aureus by extract and isolated compounds from Arrabidaea brachypoda.

Arrabidaea brachypoda is a native shrub of the Brazilian Cerrado widely used in the folk medicine for treatment of renal diseases and articular pains. This study aimed to, first, evaluate the antimicrobial activity of both extracts and isolated molecules Brachydins BR-A and BR-B obtained from the flowers of A. brachypoda against Staphylococcus aureus, Escherchia coli and Candida albicans species. A second objective was to investigate if these natural products were able to potentiate the Norfloxacin activity against the strain Staphylococcus aureus SA1199-B that overexpress the norA gene encoding the NorA efflux pump. Extracts and isolated compounds were analyzed by HPLC-PDA and LC-ESI-MS respectively. Minimal inhibitory concentrations of Norfloxacin or Ethidium Bromide (EtBr) were determined in the presence or absence of ethanolic extract, dichloromethane fraction, as well as BR-A or BR-B by microdilution method. Only BR-B showed activity against Candida albicans. Addition of ethanolic extract, dichloromethane fraction or BR-B to the growth media at sub-inhibitory concentrations enhanced the activity of both Norfloxacin and EtBr against S. aureus SA1199-B, indicating that these natural products and its isolated compound BR-B were able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. Moreover, BR-B inhibited the EtBr efflux in the SA1199-B strain confirming that it is a NorA inhibitor. Isolated BR-B was able to inhibit an important mechanism of multidrug-resistance very prevalent in S. aureus strains, thus its use in combination with Norfloxacin could be considered as an alternative for the treatment of infections caused by S. aureus strains overexpressing norA.

Chemical identification and antimicrobial potential of essential oil of Piper rivinoides kunth (BETIS-WHITE).

The family Piperaceae is known for presenting in its species flavoring, healing and antimicrobial properties among others. The objective of the present study was: to study the chemical profile of the essential oil of Piper rivinoides (EOPR); to analyze its anti-bacterial and antifungal potential, as well as to evaluate the antifungal and antibiotic-modifying capacity. The chemical constituents were identified by gas chromatography with flame ionization detector (GC-FID), allowing the identification of 7 constituents of a total of 86.99%. E-Isoelemicin was identified as the main constituent of petroleum (40.81%). Clinically relevant MIC results were obtained against fungi in which the inhibitory concentration remained <256 µg/mL, as for Candida albicans 4127 (217.6 µg/mL). The association of EOPR with an antifungal showed a high synergistic affinity against the strains of C. tropicalis 40042 and 4262. We concluded that no intrinsic EOPR activity was observed at any concentrations tested against bacteria. However, EOPR associated with Gentamicin acted synergistically against S. aureus 10 and Escherichia coli 06, but with Erythromycin there was a synergistic effect against Escherichia coli 06, and antagonism with norfloxacin.

Antimicrobial activity of Phyllanthus amarus Schumach. & Thonn and inhibition of the NorA efflux pump of Staphylococcus aureus by Phyllanthin.

The aim of this study was to evaluate the antimicrobial activity of ethanoic extract of P. amarus (PAEE) and its compound Phyllanthin, as well as, investigate if these natural products could modulate the fluoroquinolone-resistance in S. aureus SA1199-B by way of overexpression of the NorA efflux pump. Microdilution tests were carried out to determine the minimal inhibitory concentration (MIC) of the PAEE or Phyllanthin against several bacterial and yeast strains. To evaluate if PAEE or Phyllanthin were able to act as modulators of the fluoroquinolone-resistance, MICs for Norfloxacin and ethidium bromide were determined in the presence or absence of PAEE or Phyllanthin against S. aureus SA1199-B. PAEE showed antimicrobial activity against Gram-negative strains, meanwhile Phyllanthin was inactive against all strains tested. Addition of PAEE or Phyllanthin, to the growth media at sub-inhibitory concentrations enhanced the activity of the Norfloxacin as well as, Ethidium Bromide, against S. aureus SA1199-B. These results indicate that Phyllanthin is able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. This hypothesis was supported by in silico docking analysis which confirmed that Phyllantin is a NorA ligand. Thus, this compound could be used as a potentiating agent of the Norfloxacin activity in the treatment of infections caused by fluoroquinolone-resistant S. aureus.

High rates of methicillin-resistant Staphylococcus aureus colonisation in a Brazilian Intensive Care Unit.

OBJECTIVE: To evaluate the colonisation rate of Staphylococcus aureus in the oropharynx and the insertion site of central venous catheters in intensive care unit patients. DESIGN: Cross-sectional study. SETTING: Brazilian intensive care unit. MEASUREMENTS: Samples were collected from October to December 2015 from the oropharyngeal cavity and central venous catheter insertion site of 110 patients. Samples that presented growth of Staphylococcus aureus were isolated and their sensitivity profiles were tested for several antimicrobials. FINDINGS: The study participants (110) were mostly females older than 60 years (53.6%). The mean length of hospitalisation was 15.5 days (±31.3). A total of 188 biological samples were collected: 110 collected from the oropharynx and 78 from the central venous catheter insertion site. A 35% (n = 38/110) S. aureus colonisation rate of the patients was observed in at least one collection site. In the oropharynx alone, a 31% rate (n = 34/110) was found, and a 12.8% rate (n = 10/78) at central venous catheter insertion sites only. MRSA colonisation in the oropharynx or at the central venous catheter occurred in 29 (26.4%) patients and vancomycin resistant Staphylococcus aureus was present in 24 (22.4%) of the patients studied. Patients hospitalised for seven days or more were 4.8 times more likely to be colonised compared to patients hospitalised less than seven days (95% CI = 1.2-28.5). CONCLUSION: The oropharynx and the central venous catheter are important reservoirs of this bacterium that in critical conditions may become pathogenic. The data showed a high degree of resistance of the bacterial populations isolated to different drugs, which may hinder the control of these organisms.