scholarly journals Pharmacodynamic Interaction ofQuercus infectoriaGalls Extract in Combination with Vancomycin against MRSA Using Microdilution Checkerboard and Time-Kill Assay

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Dayang Fredalina Basri ◽  
Radhiah Khairon
Keyword(s):  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Bactericidal Effect ◽  
Pharmacodynamic Interaction ◽  
Killing Rate ◽  
Mrsa Strains ◽  
Index Value ◽  
Time Kill ◽  
Kinetics Of ◽  
Quercus Infectoria

The galls ofQuercus infectoriaOlivier possess astringent properties which helps in the tightening of the vaginal epithelium in the post-natal period. The present study aimed to observe the time-kill kinetics of the acetone and methanol extracts of gall ofQ. infectoriain combination with vancomycin against two methicillin-resistantStaphylococcus aureus(MRSA) strains; ATCC 33591 and MU 9495 (laboratory-passaged strain). Minimum inhibitory concentration (MIC) of the extracts were determined using microdilution technique whereas the checkerboard and time-kill kinetics were employed to verify the synergistic effects of treatment with vancomycin. The FIC index value of the combinations against both MRSA strains showed that the interaction was synergistic (FIC index<0.5). Time-kill assays showed the bactericidal effect of the combination treatment at 1/8XMIC of the extract and 1/8XMIC of vancomycin, were respectively at7.2±0.28 hr against ATCC 33591 compared to complete attenuation of the growth of the same strain after 8 hr of treatment with vancomycin alone. In conclusion, the combination extracts ofQ. infectoriawith vancomycin were synergistic according to FIC index values. The time-kill curves showed that the interaction was additive with a more rapid killing rate but, which did not differ significantly with vancomycin.

scholarly journals Synergistic Interaction of Methanol Extract fromCanarium odontophyllumMiq. Leaf in Combination with Oxacillin against Methicillin-ResistantStaphylococcus aureus(MRSA) ATCC 33591

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Dayang Fredalina Basri ◽  
Vimashiinee Sandra
Keyword(s):  
Inhibitory Concentration ◽  
Methanol Extract ◽  
Bactericidal Effect ◽  
Acetone Extract ◽  
Pharmacodynamic Interaction ◽  
Antistaphylococcal Activity ◽  
Preliminary Study ◽  
Canarium Odontophyllum ◽  
Time Kill ◽  
Acetone Extracts

Canarium odontophyllum(CO) Miq. has been considered as one of the most sought-after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC) of 312.5 μg/mL and 156.25 μg/mL and Minimum Bactericidal Concentration (MBC) of 625 μg/mL and 312.5 μg/mL, respectively. Fractional Inhibitory Concentration (FIC) indices were obtained via the chequerboard dilution assay where methanol extract-oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index ≤ 0.5). The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 × MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves ofC. odontophyllumhave the potential to be developed into antistaphylococcal agents.

scholarly journals New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 709
Author(s):  
Marta Jorba ◽  
Marina Pedrola ◽  
Ouldouz Ghashghaei ◽  
Rocío Herráez ◽  
Lluis Campos-Vicens ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Efflux Pump ◽  
Synergistic Effects ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Detailed Characterization ◽  
Low Concentrations ◽  
Pump Activity ◽  
Bacteriological Evaluation ◽  
Kinetics Of

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported.

scholarly journals In VitroBactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Iveta Zadrazilova ◽  
Sarka Pospisilova ◽  
Karel Pauk ◽  
Ales Imramovsky ◽  
Jarmila Vinsova ◽  
...  
Keyword(s):  
Minimum Bactericidal Concentration ◽  
Bacterial Count ◽  
Bactericidal Effect ◽  
Final Concentration ◽  
Control Strain ◽  
Time Points ◽  
Time Kill ◽  
Kinetics Of ◽  
Bactericidal Agent ◽  
Quality Control Strain

A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistantStaphylococcus aureus(MRSA) andS. aureusATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f),N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound1fexhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log10 CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log10 CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.

scholarly journals The Combination of Daptomycin and Fosfomycin Has Synergistic, Potent, and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureusin a Rabbit Model of Experimental Endocarditis

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Cristina García-de-la-Mària ◽  
Oriol Gasch ◽  
Javier García-Gonzalez ◽  
Dolors Soy ◽  
Evelyn Shaw ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Combined Therapy ◽  
Rabbit Model ◽  
Bactericidal Effect ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTWe investigated whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistantStaphylococcus aureus(MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to performin vitrotime-kill studies using standard (106) and high (108) inocula. Combined therapy was compared to daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied, and the equivalents of cloxacillin at 2 g/4 h, fosfomycin at 2 g/6 h, and daptomycin at 6 to 10 mg/kg/day were administered intravenously. A combination of daptomycin and either fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 μg/ml) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/day in terms of both the proportion of sterile vegetations (100% versus 72%,P= 0.046) and the decrease in the density of bacteria within the vegetations (P= 0.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/day (100% versus 93%,P= 1.00) and had activity similar to that of daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/day (100% versus 88%,P= 0.48). Daptomycin nonsusceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.

scholarly journals Rapid Bactericidal Activity of Daptomycin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Peritonitis in Mice as Measured with Bioluminescent Bacteria

2007 ◽  
Vol 51 (5) ◽  
pp. 1787-1794 ◽  
Author(s):  
Lawrence I. Mortin ◽  
Tongchuan Li ◽  
Andrew D. G. Van Praagh ◽  
Shuxin Zhang ◽  
Xi-Xian Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Bactericidal Effect ◽  
Methicillin Resistant ◽  
Bioluminescent Bacteria ◽  
New Antibiotics ◽  
Luminescent Signal ◽  
Mrsa Strains ◽  
Kinetics Of

ABSTRACT The rising rates of antibiotic resistance accentuate the critical need for new antibiotics. Daptomycin is a new antibiotic with a unique mode of action and a rapid in vitro bactericidal effect against gram-positive organisms. This study examined the kinetics of daptomycin's bactericidal action against peritonitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in healthy and neutropenic mice and compared this activity with those of other commonly used antibiotics. CD-1 mice were inoculated intraperitoneally with lethal doses of MSSA (Xen-29) or MRSA (Xen-1), laboratory strains transformed with a plasmid containing the lux operon, which confers bioluminescence. One hour later, the animals were given a single dose of daptomycin at 50 mg/kg of body weight subcutaneously (s.c.), nafcillin at 100 mg/kg s.c., vancomycin at 100 mg/kg s.c., linezolid at 100 mg/kg via gavage (orally), or saline (10 ml/kg s.c.). The mice were anesthetized hourly, and photon emissions from living bioluminescent bacteria were imaged and quantified. The luminescence in saline-treated control mice either increased (neutropenic mice) or remained relatively unchanged (healthy mice). In contrast, by 2 to 3 h postdosing, daptomycin effected a 90% reduction of luminescence of MSSA or MRSA in both healthy and neutropenic mice. The activity of daptomycin against both MSSA and MRSA strains was superior to those of nafcillin, vancomycin, and linezolid. Against MSSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than nafcillin or linezolid. Against MRSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than vancomycin or linezolid. The rapid decrease in the luminescent signal in the daptomycin-treated neutropenic mice underscores the potency of this antibiotic against S. aureus in the immune-suppressed host.

Antibacterial and synergic effects of gallic acid-grafted-chitosan with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA)

2014 ◽  
Vol 60 (10) ◽  
pp. 629-638 ◽  
Author(s):  
Dae-Sung Lee ◽  
Sung-Hwan Eom ◽  
Young-Mog Kim ◽  
Hye Seon Kim ◽  
Mi-Jin Yim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gallic Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Cell Envelope ◽  
Bactericidal Effect ◽  
Clinical Isolates ◽  
Methicillin Resistant ◽  
New Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is spreading worldwide, emphasizing the need to search for new antibiotics. The anti-MRSA activities of gallic acid-grafted-chitosans (GA-g-chitosans) were investigated against 2 MRSA standards and 10 MRSA clinical isolates by determining the minimum inhibitory concentrations (MICs). GA-g-chitosan (I), which has the highest gallic acid content, exhibited the strongest anti-MRSA activities, with MICs of 32–64 μg/mL. A time-kill investigation revealed that GA-g-chitosan (I) exhibited a bactericidal effect at twice the MIC, also demonstrating good thermal and pH stability. Investigation of cell envelope integrity showed the release of intracellular components with an increasing absorbance value at 260 nm, indicating cell envelope damage caused by the GA-g-chitosan (I), which was further confirmed by transmission electron microscopy. When GA-g-chitosans were combined with β-lactams, including ampicillin and penicillin, synergistic effects were observed on the 2 standard MRSA strains and on the 10 clinical isolates, with fractional inhibitory indices ranging from 0.125 to 0.625. In the time-kill dynamic confirmation test, synergistic bactericidal effects were observed for the combinations of GA-g-chitosans with β-lactams, and over 4.0 log CFU/mL reductions were observed after 24 h when combination treatment was used. These results may prove GA-g-chitosans to be a potent agent when combined with ampicillin and penicillin for the elimination of MRSA.

scholarly journals Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance of Staphylococcus aureus

2021 ◽  
Vol 22 (7) ◽  
pp. 3778
Author(s):  
Qian-Qian Li ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Synergistic Effects ◽  
Penicillin Binding Protein ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Mrsa Strains ◽  
Phytochemical Components ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) has always been a threatening pathogen. Research on phytochemical components that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigate the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and explore its possible mechanism for eliminating MRSA. The minimum inhibitory concentrations (MICs) of DMC against MRSA strains was determined by the broth microdilution method, and the results showed that the MIC of DMC was 62.5 μg/mL. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time–kill assay. The ATP synthase inhibitors were employed to block the metabolic ability of bacteria to explore their synergistic effect on the antibacterial ability of DMC. In addition, western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. As results, DMC hindered the translation of penicillin-binding protein 2a (PBP2a) and staphylococcal enterotoxin and reduced the transcription of related genes. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

scholarly journals In Vitro Synergy of Pongamia pinnata Extract in Combination with Antibiotics for Inhibiting and Killing Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 103 ◽  
Author(s):  
Po-An Su ◽  
Shun-Lai Li ◽  
Hung-Jen Tang ◽  
Chi-Chung Chen ◽  
Ying-Chen Lu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Seed Coat ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Pongamia Pinnata ◽  
Multiple Drug ◽  
Methicillin Resistant ◽  
Time Kill

Aims: Currently, we face the serious problem of multiple drug-resistant pathogens. The development of new antimicrobial agents is very costly and time-consuming. Therefore, the use of medicinal plants as a source of alternative antibiotics or for enhancing antibiotic effectiveness is important. Methods: The antibacterial effects of aqueous extracts of the seed coat of Pongamia pinnata (Linn.) Pierre in combination with several antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) were tested by broth dilution, checkerboard, and time-kill methods. Results: For the combinations of P. pinnata with ampicillin, meropenem, cefazolin, cefotaxime, cefpirome, and cefuroxime, 70% to 100% were synergistic, with a fractional inhibitory concentration (FIC) index of < 0.5. For the time-kill method with 0.5× minimum inhibitory concentration (MIC) of P. pinnata in combination with 8, 4, 2, and 1 µg mL−1 of the various antibiotics, almost all of the combinations showed synergistic effects, even with the lowest concentrations of P. pinnata, except for aztreonam. No antagonistic effect was observed for these combinations. Conclusions: Based on these findings, aqueous seed coat extracts of P. pinnata have good potential for the design of new antimicrobial agents.

scholarly journals Time-Kill Kinetics of Rezafungin (CD101) in Vagina-Simulative Medium for Fluconazole-Susceptible and Fluconazole-ResistantCandida albicansand Non-albicans CandidaSpecies

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jeffrey B. Locke ◽  
Amanda L. Almaguer ◽  
Joanna L. Donatelli ◽  
Ken F. Bartizal
Keyword(s):  
Antifungal Activity ◽  
Fungicidal Activity ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
The Novel ◽  
Testing Conditions ◽  
Fluconazole Resistant ◽  
Time Kill ◽  
Kinetics Of

Background.While echinocandins demonstrate excellent efficacy againstCandidaspecies in disseminated infections and demonstrate potent minimal inhibitory concentration (MIC) values under standard susceptibility testing conditions, investigation under conditions relevant to the vaginal environment was needed. We assessed the antifungal activity and time-kill kinetics of the novel echinocandin rezafungin (formerly CD101) under such conditions, againstCandidaspecies relevant to vulvovaginal candidiasis (VVC).Methods. Susceptibility testing of fluconazole-susceptible and fluconazole-resistantC. albicans,C. glabrata,C. tropicalis,C. parapsilosis, andC. kruseiwas performed in RPMI at pH 7.0 and in vagina-simulative medium (VSM) at pH 4.2 for topical rezafungin, terconazole, fluconazole, and amphotericin B. Time-kill kinetics were evaluated for rezafungin and terconazole at 2, 8, 32, and 128 μg/ml over 72 hours.Results.Rezafungin MIC values were the same or 2-fold higher in VSM/pH 4.2 versus RPMI/pH 7.0. SomeC. albicansterconazole MIC values were lower, but most were significantly higher in VSM than in RPMI. Rezafungin was fungicidal against 11/14 strains and near-fungicidal against the others. Terconazole (128 μg/ml) was fungicidal againstC. kruseiand near-fungicidal against susceptibleC. parapsilosisbut fungistatic versus all other strains evaluated.Conclusion.Rezafungin retained anti-Candidaactivity and fungicidal activity under in vitro conditions relevant to VVC.

scholarly journals Lack of Bactericidal Antagonism or Synergism In Vitro between Oxacillin and Vancomycin against Methicillin-Susceptible Strains of Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 773-777 ◽  
Author(s):  
Christian Joukhadar ◽  
Satish Pillai ◽  
Christine Wennersten ◽  
Robert C. Moellering ◽  
George M. Eliopoulos
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Effect ◽  
Separate Experiment ◽  
General Belief ◽  
Bacterial Killing ◽  
Fixed Concentration ◽  
Mrsa Strains ◽  
Time Kill ◽  
Year 2000

ABSTRACT With the current high prevalence of infection caused by methicillin-resistant Staphylococcus aureus (MRSA) strains but in light of the general belief that β-lactam antibiotics are more effective than vancomycin against infections caused by methicillin-susceptible S. aureus (MSSA) isolates, clinicians may utilize antistaphylococcal penicillins in combination with vancomycin for the empirical treatment of S. aureus infections. Vancomycin is considered to kill MSSA more slowly than oxacillin. Thus, we sought to evaluate the interaction of the combination of oxacillin and vancomycin on bacterial killing in vitro. Ten clinical isolates of MSSA isolated in the year 2000 were investigated. The killing observed at 24 h by vancomycin at 20 μg/ml, oxacillin at 16 μg/ml, or the combination did not differ (approximately 2.5 to 3.5 log10 CFU/ml). In a separate experiment, we assessed bacterial killing in a dynamic model simulating the free plasma concentration profiles expected following the administration of a combination of vancomycin at 1 g every 12 h and oxacillin at 1 g every 6 h. The time-kill profiles of these regimens against S. aureus ATCC 29213 were comparable to those observed in the fixed-concentration experiments. Using these methods, we found no evidence that vancomycin antagonized the bactericidal effect of oxacillin or that there was any benefit from use of the combination.

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