Dose Optimization of Antibiotic Combinations Using Fractional Inhibitory Concentration Kinetics in Resistant Bacteria

Author(s):  
Vishnu Sharma
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Olufunmiso Olusola Olajuyigbe ◽  
Anthony Jide Afolayan

A pragmatic approach to the treatment of infectious diseases with multicausal agents and prevention of the development of resistant isolates is the combination of herbal remedies with the first-line antimicrobial agents to which most of them have become resistant. This study evaluated the interactions between the ethanolic bark extract ofZiziphus mucronatawith known antimicrobial agentsin vitro. In this study, the results showed that varied zones of inhibitions (ZME—chloramphenicol (17–42 mm), ZME—amoxicillin (17–35 mm), ZME—tetracycline (17–36 mm), ZME—ciprofloxacin (20–41 mm), ZME—nalidixic acid (17–34 mm), and ZME—kanamycin (17–38 mm)) were produced by the antibacterial combinations. At the highest combined concentrations, 12 isolates (ZME—ciprofloxacin) > 10 isolates (ZME—chloramphenicol) = (ZME—kanamycin) > 6 isolates (ZME—amoxicillin) = (ZME—nalidixic acid) and 5 isolates (ZME—tetracycline) were inhibited with zones of inhibition greater than20±1.0 mm. Although the agar diffusion assay suggested that the interactions between the ethanolic extract ofZ. mucronataand the antibiotics were both synergistic and additive in nature, the fractional inhibitory concentration indices (FICI) showed that the interactions were synergistic (54.17%), additive (27.78%), indifferent (16.67%), and antagonistic (1.39%). While the fractional inhibitory concentration indices (FICIs) for synergism ranged between 0.00391 and 0.5, that of additivity ranged between 0.516 and 1.0, indifferences ranged between 1.062 and 3.0 and antagonistic interaction was 5.0. The synergistic effects implied that the antibacterial combinations would be more effective and useful in the treatment of multicausal and multidrug-resistant bacteria than a single monotherapy of either antibacterial agent.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 321
Author(s):  
Shekh Sabir ◽  
Tsz Tin Yu ◽  
Rajesh Kuppusamy ◽  
Basmah Almohaywi ◽  
George Iskander ◽  
...  

The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick Schwarz ◽  
Anne-Laure Bidaud ◽  
Eric Dannaoui

AbstractThe in vitro interactions of isavuconazole with colistin were evaluated against 15 clinical Candida auris isolates by a microdilution checkerboard technique based on the EUCAST reference method for antifungal susceptibility testing and by agar diffusion using isavuconazole gradient concentration strips with or without colistin incorporated RPMI agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index and by response surface analysis based on the Bliss model. By checkerboard, combination was synergistic for 93% of the isolates when interpretation of the data was done by fractional inhibitory concentration index, and for 80% of the isolates by response surface analysis interpretation. By agar diffusion test, although all MICs in combination decreased compared to isavuconazole alone, only 13% of the isolates met the definition of synergy. Essential agreement of EUCAST and gradient concentration strip MICs at +/− 2 log2 dilutions was 93.3%. Antagonistic interactions were never observed for any technique or interpretation model used.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Johana Rondevaldova ◽  
Olga Leuner ◽  
Alemtshay Teka ◽  
Ermias Lulekal ◽  
Jaroslav Havlik ◽  
...  

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.


2021 ◽  
Vol 16 (2) ◽  
pp. 049-061
Author(s):  
Joy Ogugua Igwe ◽  
Ugochukwu Moses Okezie ◽  
Moses Nkechukwu Ikegbunam ◽  
Charles Okechukwu Esimone

Resistant strains of bacteria has over the years rendered conventional antibiotics ineffective. Consequently, this has resulted to severe infection, prolonged treatment, high cost of treatment and often times death. This study aimed to identify reliable alternative sources of bioactive agents with activity against resistant Staphylococcus aureus, Escherichia coli and Salmonella typhi. Methanol extracts of Acalypha wilkesiana (MEAW), Senna alata (MESA) and Psidium guajava (MEPG) were tested alone and in combination against three clinical isolates. Ciprofloxacin was used as the positive control drug. A combination of Microscopic, macroscopic and molecular protocols was used to identify the test isolates. The antibiotic profiles of the isolates E. coli (E1), S. aureus (S4) and S. typhi (St2) indicated MultiDrug-Resisitant status (MDR). All the extracts demonstrated antibacterial activity against the resistant isolates with zones of inhibition that ranged between 3.1 – 25 mm and minimum inhibitory concentration of 12.5 – 200 mg/ml. Amongst the extracts tested, MESA was found to be the most active extract while MEPG was the least active extract. The combination of the different methanol extracts demonstrated synergistic effects against the test organisms with a fractional inhibitory concentration that ranged between 0.06 – 0.8 mg/ml. The observed antibacterial activity may be linked to the presence of some bioactive components such as phenolic compounds and flavonoids present in the extracts. The results of this study suggest A. wilkesiana, S. alata and P. guajava may represent reliable sources of important bioactive compounds for new drug development.


2009 ◽  
Vol 6 (4) ◽  
pp. 683-692
Author(s):  
Baghdad Science Journal

Atotal of 75 different clinical samples were collected from different hospitals in Baghdad Biochemical and morphological characterization tests showed that forty isolates were identified as Staphylococcus aureus Antibiotic susceptibility tests of all isolates towards ten antibiotics were carried out and results showed that many isolates (97.5 %) were resistant to ?-lactam antibiotic , 70 % were resistant to Tetracyclinee , 62.5% were resistant to co-trimoxazole , 60 % were resistant to ciprofloxacin , 55% were resistant both of chloramphenicol and erythromycin , 52.5% were resistant to gentamicin , 35% were resistant to rifampicin , 10% were resistant to vancomycin . According to the above results the S.aureus I1 which is isolated from patients with osteomyelitis showed resistant to all ten antibiotics therefore was used in the followed experiments. The minimum inhibitory concentration (MIC) of S.aureus I1 vancomycin, cefotaxim , penicillin G, amoxicillin , ciprofloxacin , co-trimoxazole ,gentamicin, rifampicin was checked.The results showed that isolates had MIC between (390-12500) ?g/ml. The combination of different antibiotics with vancomycin showed synergistic effect based on the Fractional inhibitory concentration index (FIC).


Author(s):  
Micah Dettweiler ◽  
Lewis Marquez ◽  
Max Bao ◽  
Cassandra L. Quave

AbstractMixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions between drugs. Natural substances can be fruitful sources of useful drug mixtures because secondary metabolites produced by living organisms do not often act in isolation in vivo. In order to facilitate the study of interactions within natural substances, a new analytical method to quantify interactions using data generated in the process of bioassay-guided fractionation is presented here: the extract fractional inhibitory concentration index (EFICI). The EFICI method uses the framework of Loewe additivity to calculate fractional inhibitory concentration values by which interactions can be determined for any combination of fractions that make up a parent extract. The EFICI method was applied to data on the bioassay-guided fractionation of Lechea mucronata and Schinus terebinthifolia for growth inhibition of the pathogenic bacterium Acinetobacter baumannii. The L. mucronata extract contained synergistic interactions (EFICI = 0.4181) and the S. terebinthifolia extract was non-interactive overall (EFICI = 0.9129). Quantifying interactions in the bioassay-guided fractionation of natural substances does not require additional experiments and can be useful to guide the experimental process and to support the development of standardized extracts as botanical drugs.


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