Combination Therapy of Sophoraflavanone B against MRSA:In VitroSynergy Testing

Sophoraflavanone B (SPF-B), a known prenylated flavonoid, was isolated from the roots ofDesmodium caudatum. The aim of this study was to determine the antimicrobial synergism of SPF-B combined with antibiotics against methicillin-resistantStaphylococcus aureus(MRSA). MRSA, a multidrug-resistant pathogen, causes both hospital- and community-acquired infections worldwide. The antimicrobial activity of SPF-B was assessed by the broth microdilution method, checkerboard dilution test, and time-kill curve assay. The MIC of SPF-B for 7 strains ofS. aureusranges from 15.6 to 31.25 μg/mL determined. In the checkerboard method, the combinations of SPF-B with antibiotics had a synergistic effect; SPF-B markedly reduced the MICs of theβ-lactam antibiotics: ampicillin (AMP) and oxacillin (OXI); aminoglycosides gentamicin (GET); quinolones ciprofloxacin (CIP) and norfloxacin (NOR) against MRSA. The time-kill curves assay showed that a combined SPF-B and selected antibiotics treatment reduced the bacterial counts below the lowest detectable limit after 24 h. These data suggest that the antibacterial activity of SPF-B against MRSA can be effectively increased through its combination with three groups of antibiotics (β-lactams, aminoglycosides, and quinolones). Our research can be a valuable and significant source for the development of a new antibacterial drug with low MRSA resistance.

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Synergy between Essential Oils of Calamintha Species (Lamiaceae) and Antibiotics

Natural Product Communications ◽

10.1177/1934578x1801300325 ◽

2018 ◽

Vol 13 (3) ◽

pp. 1934578X1801300 ◽

Cited By ~ 2

Author(s):

Marina Milenković ◽

Jelena Stošović ◽

Violeta Slavkovska

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Antibacterial Activity ◽

Essential Oil ◽

Essential Oils ◽

Broth Microdilution ◽

Bacterial Strains ◽

Microdilution Method ◽

Broth Microdilution Method ◽

The Subject

The subject of the study was the investigation of the chemical composition and antimicrobial activity of the essential oils (EOs) isolated from Calamintha sylvatica, C. vardarensis, C. nepeta and C. glandulosa, as well as their antibacterial activity in combination with antibiotics. The quantitative and qualitative analysis of EOs was performed using the GC/FID and GC/MS methods. The antimicrobial activity of EOs against six standard bacterial strains and one strain of yeast was tested using the broth microdilution method, while the antimicrobial activity of a combination of essential oils and gentamicin/ciprofloxacin was tested by the checkerboard method. The dominant components (> 10%) of the essential oils were: cis-piperitone epoxide and menthone ( C. sylvatica), pulegone and menthone ( C. vardarensis), pulegone and piperitenone ( C. nepeta), pulegone, piperitenone, menthone and piperitone ( C. glandulosa). EOs did not exhibit significant antimicrobial activity except the essential oil of C. vardarensis which was selectively active against Staphylococcus aureus (MIC - 21.25 μg/mL). The overall effect of essential oil-antibiotic combinations varied from synergistic (FICI ≤ 0.5) to antagonistic (FICI ≥ 2) depending on the bacterial strain tested.

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Antibacterial Triterpenoids from the Bark of Sonneratia alba (Lythraceae)

Natural Product Communications ◽

10.1177/1934578x1501000215 ◽

2015 ◽

Vol 10 (2) ◽

pp. 1934578X1501000

Author(s):

Harizon ◽

Betry Pujiastuti ◽

Dikdik Kurnia ◽

Dadan Sumiarsa ◽

Yoshihito Shiono ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Mass Spectrometric ◽

Broth Microdilution ◽

Mass Spectrometric Data ◽

Spectrometric Data ◽

Gram Positive Bacteria ◽

Microdilution Method ◽

Sonneratia Alba ◽

Broth Microdilution Method

The new lupane-type triterpenoid, 3β-hydroxy-lup-9(11), 12-diene, 28-oic acid (1), along with two known lupane-type triterpenoids, lupeol (2) and lupan-3p-ol (3), were isolated from the bark of Sonnetaria alba. The structure of the new compound was elucidated on the basis of spectroscopic and mass spectrometric data analysis. Using the broth microdilution method, all compounds exhibited antibacterial activity against the Gram-positive bacteria Staphylococcus aureus ATCC 6538 and Streptococcus mutans ATCC 25175, with minimum inhibitory concentrations ranging from 15-33 to 35-55 ng/mL, respectively.

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Etomidate inhibits the growth of MRSA and exhibits synergism with oxacillin

Future Microbiology ◽

10.2217/fmb-2020-0078 ◽

2020 ◽

Vol 15 (17) ◽

pp. 1611-1619

Author(s):

Lívia G do AV Sá ◽

Cecília R da Silva ◽

João B de A Neto ◽

Thiago M Cândido ◽

Leilson C de Oliveira ◽

...

Keyword(s):

Flow Cytometry ◽

Antimicrobial Activity ◽

Cell Death ◽

Antibacterial Activity ◽

Antibacterial Effect ◽

Broth Microdilution ◽

Action Mechanism ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Mrsa Strains

Aim: The purpose of this study was to evaluate the antimicrobial activity of the anesthetic etomidate against strains of MRSA and biofilms. Materials & methods: The antibacterial effect of etomidate was assessed by the broth microdilution method. To investigate the probable action mechanism of the compound flow cytometry techniques were used. Results: MRSA strains showed MIC equal to 500 and 1000 μg/ml of etomidate. Four-fifths (80%) of the tested MRSA strains demonstrated synergistic effect with oxacillin. Etomidate also showed activity against MRSA biofilm at concentration of 250 μg/ml. Cytometric analysis revealed that the cells treated with etomidate leading to cell death, probably by apoptosis. Conclusion: Etomidate showed antibacterial activity against MRSA.

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In Vitro Activity of Dalbavancin against Refractory Multidrug-Resistant (MDR) Staphylococcus aureus Isolates

Antibiotics ◽

10.3390/antibiotics9120865 ◽

2020 ◽

Vol 9 (12) ◽

pp. 865

Author(s):

Dafne Bongiorno ◽

Lorenzo Mattia Lazzaro ◽

Stefania Stefani ◽

Floriana Campanile

Keyword(s):

Staphylococcus Aureus ◽

Bactericidal Activity ◽

Reference Strain ◽

Multidrug Resistant ◽

Microdilution Method ◽

Broth Microdilution Method ◽

High Prevalence ◽

Time Kill ◽

Reference Strains

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections, always treated with vancomycin and daptomycin, has led to the emergence of vancomycin-intermediate (VISA), heteroresistant vancomycin-intermediate (hVISA) and daptomycin non-susceptible (DNS) S. aureus. Even if glycopeptides and daptomycin remain the keystone for treatment of resistant S. aureus, the need for alternative therapies that target MRSA has now become imperative. The in vitro antibacterial and bactericidal activity of dalbavancin was evaluated against clinically relevant S. aureus showing raised antibiotic resistance levels, from methicillin-susceptible to Multidrug-Resistant (MDR) MRSA, including hVISA, DNS and rifampicin-resistant (RIF-R) strains. A total of 124 S. aureus strains were tested for dalbavancin susceptibility, by the broth microdilution method. Two VISA and 2 hVISA reference strains, as well as a vancomycin-resistant (VRSA) reference strain and a methicillin-susceptible Staphylococcus aureus (MSSA) reference strain, were included as controls. Time–kill curves were assayed to assess bactericidal activity. Dalbavancin demonstrated excellent in vitro antibacterial and bactericidal activity against all S. aureus resistance classes, including hVISA and DNS isolates. The RIF-R strains showed the highest percentage of isolates with non-susceptibility, reflecting the correlation between rpoB mutations and VISA/hVISA emergence. Our observations suggest that dalbavancin can be considered as an effective alternative for the management of severe MRSA infections also sustained by refractory phenotypes.

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Cannabidiol (CBD) repurposing as antibacterial: promising therapy of CBD plus polymyxin B against superbugs

10.1101/2021.04.12.439341 ◽

2021 ◽

Author(s):

Nathalia Abichabki ◽

Luisa Vieira Zacharias ◽

Natalia Columbaro Moreira ◽

Fernando Bellissimo-Rodrigues ◽

Fernanda de Lima Moreira ◽

...

Keyword(s):

Antibacterial Activity ◽

Bacterial Species ◽

Public Health Problem ◽

Polymyxin B ◽

Multidrug Resistant ◽

Broth Microdilution ◽

Microdilution Method ◽

Rescue Treatment ◽

Broth Microdilution Method

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria are a major worldwide public health problem. In the last decades, resistance to last-resort antibiotics such as polymyxin B (PB) have been increasingly observed among these superbugs, compromising the effectiveness of antimicrobial therapy. The present study aimed (i) to assess the ultrapure Cannabidiol (CBD) antibacterial activity against a broad diversity of Gram-negative (GN) and Gram-positive (GP) bacteria (44 different species, 95 strains), comprising standard strains and clinical isolates, and (ii) to investigate the antibacterial activity of the combination CBD + PB against GN bacteria, including chromosomal- and plasmid-acquired PB-resistant and intrinsically PB-resistant GNB. We evaluated CBD in vitro antibacterial activity using the standard broth microdilution method, and the antibacterial activity of the combination CBD + PB was screened using the standard broth microdilution and confirmed by checkerboard assay. CBD exhibited antibacterial activity against different GP bacterial species, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, and Moraxella catarrhalis), and Mycobacterium tuberculosis. The combination CBD + PB exhibited antibacterial activity against PB-resistant GNB (e.g., Klebsiella pneumoniae) as well as additive and/or synergistic effect against LOS-expressing GND. The antibacterial activity of the combination CBD + PB against Pseudomonas aeruginosa and plasmid-mediated colistin-resistant (MCR-1) E. coli strains could be only demonstrated in the presence of phenylalanine-arginine-beta-naphthylamide (PA-beta-N). In conclusion, our results show promising translational potential of the combination CBD + PB against MDR and XDR GNB, including PB-resistant K. pneumoniae, highlighting its potential as a rescue treatment for life-threatening infections caused by these superbugs.

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Study on Demethoxycurcumin as a promising approach to reverse methicillin-resistance of Staphylococcus aureus

10.21203/rs.3.rs-200260/v1 ◽

2021 ◽

Author(s):

Qian-Qian Li ◽

Ok-Hwa Kang ◽

Dong-Yeul Kwon

Keyword(s):

Staphylococcus Aureus ◽

Atp Synthase ◽

Methicillin Resistance ◽

Synergistic Effects ◽

Inhibitory Effect ◽

Current Treatment ◽

Broth Microdilution ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Time Kill

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) has always been a thorny pathogen, posing serious threat to public health. Current treatment resort for MRSA infections is still scarce. Research on phytochemical component that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigating the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and exploring its possible mechanism for eliminating MRSA resistance. Methods The present study determined minimum inhibitory concentrations (MICs) of DMC, oxacillin, ampicillin and gentamicin against MRSA strains by the broth microdilution method. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time-kill assay. The membrane-permeabilizing agents and ATP synthase inhibitors were employed to explore their impact on the antibacterial ability of DMC. Western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. Results The MIC of DMC against MRSA is 62.5 µg/ml by broth microdilution method. The synergy between DMC and gentamicin was confirmed by checkerboard method and time-kill assay. When ATP synthase inhibitors blocked the metabolic ability of bacteria, the antibacterial effect of DMC was enhanced. The production of penicillin-binding protein 2a (PBP2a) protein and related genes were reduced by DMC at sub-inhibitory concentrations. In addition, DMC hindered the translation of staphylococcal enterotoxin and the transcription of related gene. Conclusions Based on our results, DMC has a significant inhibitory effect on the vitality of MRSA, and it can be inferred that the mechanism by which DMC reverses MRSA resistance is related to the ability of DMC to block resistance determinants (PBP2a and β-lactamase) and S. aureus exotoxin. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

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Evaluation of the Antibacterial Activity and Efflux Pump Reversal of Thymol and Carvacrol against Staphylococcus aureus and Their Toxicity in Drosophila melanogaster

Molecules ◽

10.3390/molecules25092103 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2103 ◽

Cited By ~ 2

Author(s):

Zildene de Sousa Silveira ◽

Nair Silva Macêdo ◽

Joycy Francely Sampaio dos Santos ◽

Thiago Sampaio de Freitas ◽

Cristina Rodrigues dos Santos Barbosa ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Drosophila Melanogaster ◽

Inhibitory Concentration ◽

Efflux Pump ◽

Antibacterial Activities ◽

Broth Microdilution ◽

Microdilution Method ◽

Efflux Pump Inhibition ◽

Broth Microdilution Method

The antibacterial activity and efflux pump reversal of thymol and carvacrol were investigated against the Staphylococcus aureus IS-58 strain in this study, as well as their toxicity against Drosophila melanogaster. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, while efflux pump inhibition was assessed by reduction of the antibiotic and ethidium bromide (EtBr) MICs. D. melanogaster toxicity was tested using the fumigation method. Both thymol and carvacrol presented antibacterial activities with MICs of 72 and 256 µg/mL, respectively. The association between thymol and tetracycline demonstrated synergism, while the association between carvacrol and tetracycline presented antagonism. The compound and EtBr combinations did not differ from controls. Thymol and carvacrol toxicity against D. melanogaster were evidenced with EC50 values of 17.96 and 16.97 µg/mL, respectively, with 48 h of exposure. In conclusion, the compounds presented promising antibacterial activity against the tested strain, although no efficacy was observed in terms of efflux pump inhibition.

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Antimicrobial Activity of Ceftaroline-Avibactam Tested against Clinical Isolates Collected from U.S. Medical Centers in 2010-2011

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02436-12 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1982-1988 ◽

Cited By ~ 32

Author(s):

Helio S. Sader ◽

Robert K. Flamm ◽

Ronald N. Jones

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Streptococcus Pneumoniae ◽

Enterobacter Cloacae ◽

Broth Microdilution ◽

Methicillin Resistant ◽

Content Type ◽

Microdilution Method ◽

Medical Centers ◽

Broth Microdilution Method

ABSTRACTCeftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active againstEnterobacteriaceae(4,908 strains; MIC90, 0.25 μg/ml; highest MIC, 4 μg/ml), including meropenem-nonsusceptibleKlebsiellaspp. and ceftazidime-nonsusceptibleEnterobacter cloacaestrains (MIC90, 1 μg/ml for both). Ceftaroline-avibactam was also active against ceftriaxone-nonsusceptibleStreptococcus pneumoniae(MIC90, 0.25 μg/ml) and methicillin-resistantStaphylococcus aureus(MIC90, 1 μg/ml).

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Antimicrobial Essential Oil Combinations to Combat Foot Odour

Planta Medica ◽

10.1055/a-0592-8022 ◽

2018 ◽

Vol 84 (09/10) ◽

pp. 662-673 ◽

Cited By ~ 4

Author(s):

Ané Orchard ◽

Alvaro Viljoen ◽

Sandy van Vuuren

Keyword(s):

Antimicrobial Activity ◽

Essential Oil ◽

Essential Oils ◽

Antimicrobial Efficacy ◽

Juniperus Virginiana ◽

Broth Microdilution ◽

Synergistic Interactions ◽

Microdilution Method ◽

Broth Microdilution Method

AbstractFoot odour (bromodosis) is an embarrassing and perplexing condition mostly caused by bacteria of the Brevibacterium species. Essential oils are a credible option as an affordable treatment of odour and contribute towards antimicrobial efficacy. Therefore, this study sets out to investigate the antimicrobial activity of essential oil combinations against odour-causing bacteria. The broth microdilution method was used to investigate the antimicrobial activity of 119 essential oil combinations, and the fractional inhibitory index was calculated to determine the interactive profile. Combinations that resulted in synergy in 1 : 1 ratios were further evaluated in different concentrations, and isobolograms were plotted to determine the influence of the ratio on overall activity. Numerous combinations could be identified as having synergistic interactions against the Brevibacterium spp. and no antagonism was observed. The combination of Juniperus virginiana (juniper) and Styrax benzoin (benzoin) demonstrated synergy against all three Brevibacterium spp. tested and J. virginiana was the essential oil responsible for the majority of the synergistic interactions. The results reported here confirm the promising potential of the majority of these oils and selected combinations in treating and controlling bromodosis.

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In VitroAntistaphylococcal Effects ofEmbelia schimperiExtracts and Their Component Embelin with Oxacillin and Tetracycline

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/175983 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Johana Rondevaldova ◽

Olga Leuner ◽

Alemtshay Teka ◽

Ermias Lulekal ◽

Jaroslav Havlik ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Medicinal Plants ◽

Bacterial Infections ◽

Inhibitory Concentration ◽

Developed Countries ◽

Positive Interactions ◽

Fractional Inhibitory Concentration ◽

Broth Microdilution ◽

Microdilution Method ◽

Broth Microdilution Method

Bacterial infections are in less-developed countries traditionally treated by remedies prepared from medicinal plants.Embelia schimperi(Vatke) is a plant used as a taenicide or disinfectant in Ethiopia, very often taken mixed with another plant species. In the present study, we examined two extracts prepared from seeds and twigs with leaves ofE. schimperiand its main present secondary metabolite embelin for their antibacterial combinatory effect with oxacillin and tetracycline against sensitive and resistantStaphylococcus aureusstrains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated through fractional inhibitory concentration sum (ΣFIC) indices. Results show many positive interactions and synergy occurring in embelin and oxacillin combinations against 4 out of 9 strains (ΣFIC 0.203–0.477) and for embelin and tetracycline combination against 3 out of 9 strains (ΣFIC 0.400–0.496). Moreover, the resistance to oxacillin has been overcome in 2 strains and to tetracycline in 3 strains. According to our knowledge, this is the first study showing antimicrobial combinatory effect ofE. schimperias well as of embelin. These findings can be used for the further research targeted on the development of new antistaphylococcal agents.

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