Structural elucidation, mechanism of action, antibacterial proficiency and synergistic forte of purified Euphorbia hirta whole plant extract against multi-drug resistant otitis media infection / Elucidación estructural, mecanismo de acción, competencia antibacteriana y fuerza sinérgica del extracto de planta entera de Euphorbia hirta purificado contra la infección por otitis media resistente a múltiples fármacos

This study investigated the antibacterial potential of Euphorbia hirtawhole plant extracts, honey and conventional antibiotics and their synergistic effects against selected multidrug resistant and typed bacterial strains associated with otitis media. E. hirtawhole plant extract was purified using column chromatography technique. The antibacterial assays of extracts were done using standard microbiological procedures. Protein, sodium and potassium ion leakage of the synergistic mixtures was determined using flame-photometry. At 100 mg/ml, acetone extracts presented highest inhibition against S. aureus (NCTC 6571) with 32 ± 0.83 mm zone of inhibition. The fractional inhibitory concentration indices displayed higher synergism in combination of plant extract, honey and ciprofloxacin against P. mirabilisat 0.02 compared to drug combination synergy standard (≤ 0.5). This work revealed augmentation of ciprofloxacin potency when combined with purified E. hirta acetone extract and honey and implies their high potential in the treatment of multidrug resistant infectionof otitis media.

Este estudio investigó el potencial antibacteriano de extractos de plantas enteras de Euphorbia hirta, miel y antibióticos convencionales y sus efectos sinérgicos contra cepas bacterianas seleccionadas multirresistentes y tipificadas asociadas con la otitis media. El extracto de la planta entera de E. hirtase purificó usando la técnica de cromatografía en columna. Los ensayos antibacterianos de extractos se realizaron utilizando procedimientos microbiológicos estándar. La fuga de iones de proteínas, sodio y potasio de las mezclas sinérgicas se determinó mediante fotometría de llama. A 100 mg/ml, los extractos de acetona presentaron la mayor inhibición contra S. aureus (NCTC 6571) con una zona de inhibición de 32 ± 0,83 mm. Los índices de concentración inhibitoria fraccional mostraron un mayor sinergismo en combinación de extracto de planta, miel y ciprofloxacina contra P. mirabilisa 0,02 en comparación con el estándar de sinergia de combinación de fármacos (≤ 0,5). Este trabajo reveló un aumento de la potencia de la ciprofloxacina cuando se combina con extracto de acetona purificado de E. hirtay miel e implica sualto potencial en el tratamiento de infecciones de otitis media resistentes a múltiples fármacos.

Synergic effect of simvastatin in combination with amphotericin B against environmental strains of Cryptococcus neoformans from northeastern Brazil: a prospective experimental study

BACKGROUND: Statins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects. OBJECTIVE: To evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings. DESIGNAND SETTING: Experimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil. METHODS: Statin susceptibility tests of Cryptococcus neoformans samples were performed as prescribed in standards. Interactions of simvastatin with amphotericin and fluconazole were evaluated using the checkerboard microdilution method. Presence of these interactions was quantitatively detected through determining the fractional inhibitory concentration index (FICI). RESULTS: Isolates of Cryptococcus neoformans were obtained from 30 of the 206 samples of dry bird excreta (14.5%) that were collected from pet shops and houses. Ten isolates were selected for susceptibility tests. All of them were susceptible to amphotericin and fluconazole. All presented minimum inhibitory concentration (MIC) > 128 µg/ml and, thus, were resistant in vitro to simvastatin. An in vitro synergic effect was shown through combined testing of amphotericin B and simvastatin, such that six isolates (60%) presented FICI < 0.500. Two isolates showed considerable reductions in MIC, from 1 µg/ml to 0.250 µg/ml. No synergic effect was observed through combining fluconazole and simvastatin. CONCLUSION: These results demonstrate that simvastatin should be considered to be a therapeutic alternative, capable of potentiating the action of amphotericin B. However, further studies are necessary to clarify the real effect of simvastatin as an antifungal agent.

Antibacterial effect of crude methanol Carica papaya L. (papaya) extract and amoxicillin combination

Background: the emergence of multi-drug resistant bacteria and the diseases caused by them are a serious threat to global health necessitating an urgent need for new approaches to combat them. Synergy studies of conventional antimicrobial drugs and medicinal plants with antibacterial effects are important to establish whether it is prudent to recommend their concurrent administration to get successful treatments. Objective: evaluate the antibacterial effect resulting from the combination of Carica papaya (papaya) and amoxicillin. Methods: the papaya methanol extract was obtained from seeds and phytochemical screening was done. Checkerboard assay was used to determine the Minimum Inhibitory Concentration. Combined effect of both Carica papaya methanol extract and amoxicillin was determined by calculating the Fractional Inhibitory Concentration index. Strains of Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 were used in the tests. Results: phenols and tannins were found in the Carica papaya seed methanol extract. The minimum inhibitory concentration of Carica papaya extract was 100 µg/mL for both microorganisms studied which was higher than the Minimum Inhibitory Concentration of amoxicillin being 3.12 µg/mL for Escherichia coli and 0.2 µg/mL for Staphylococcus aureus. The Fractional Inhibitory Concentration of the combination of drugs was 0.99 for Escherichia coli and 2.51 for Staphylococcus aureus. Conclusions: the antibacterial effect of Carica papaya extract may be attributed to the presence of phenolic compounds. There was no interaction between amoxicillin and Carica papaya extract on Staphylococcus aureus, but the antimicrobial activity against Escherichia coli of both drugs can be potentiated by their additive interaction(AU)

Introducción: la creciente multi-resistencia bacteriana y emergencia de enfermedades causadas por estas bacterias, constituyen un serio problema global, por lo que es importante y urgente el desarrollo de nuevas propuestas terapéuticas para combatirlas. Estudios sinérgicos sobre la combinación de antimicrobianos convencionales y plantas con efectos antibacterianos son importantes para determinar si es aconsejable la administración concomitante de los mismos. Objetivo: evaluar el efecto antibacteriano de la combinación de Carica papaya (papaya) y amoxicilina. Método: fueron usadas semillas de papaya para obtener el extracto alcohólico de papaya y realizado el estudio fitoquímico. La Concentración Mínima Inhibitoria fue determinada por el método del tablero de ajedrez. La Concentración Inhibitoria Fraccionada se calculó para medir el posible efecto sinérgico de la combinación entre el extracto alcohólico de Carica papaya y la amoxicilina. Cepas de Staphylococcus aureus ATCC 25923 y Escherichia coli ATCC 25922 fueron usadas. Resultados: en el extracto alcohólico de papaya fueron encontrados fenoles y taninos. La Concentración Mínima Inhibitoria del extracto de papaya coincidió para ambos microorganismos (100 µg/mL), la cual fue mayor que la Concentración Mínima Inhibitoria de la amoxicilina, siendo 3.125 µg/mL para Escherichia coli y 0.2 µg/mL para Staphylococcus aureus. La Concentración Inhibitoria Fraccionada de la combinación de drogas, fue 0.99 para Escherichia coli y 2.51 para Staphylococcus aureus. Conclusiones: los compuestos fenólicos presentes en el extracto de papaya pueden ser responsables de su efecto antimicrobiano. No existe interacción entre la amoxicilina y el extracto metanólico de papaya contra Staphylococcus aureus. Sin embargo, la actividad antomicrobiana contra Escherichia coli puede ser potenciada por su interacción aditiva(AU)

ß-Lapachone activity in synergy with conventional antimicrobials against methicillin resistant Staphylococcus aureus strains.

The aim of this study was to evaluate the antimicrobial activity of lapachol, α-lapachone, ß-lapachone and six antimicrobials (ampicillin, amoxicillin/clavulanic acid, cefoxitin, gentamicin, ciprofloxacin and meropenem) against twelve strains of Staphylococcus aureus from which resistance phenotypes were previously determined by the disk diffusion method. Five S. aureus strains (LFBM 01, LFBM 26, LFBM 28, LFBM 31 and LFBM 33) showed resistance to all antimicrobial agents tested and were selected for the study of the interaction between ß-lapachone and antimicrobial agents, busing checkerboard method. The criteria used to evaluate the synergistic activity were defined by the Fractional Inhibitory Concentration Index (FICI). Among the naphthoquinones, ß-lapachone was the most effective against S. aureus strains. FICI values ranged from 0.07 to 0.5, suggesting a synergistic interaction against multidrug resistant S. aureus (MRSA) strains. An additive effect was observed with the combination ß-lapachone/ciprofloxacin against the LFBM 33 strain. The combination of ß-lapachone with cefoxitin showed no added benefit against LFBM 31 and LFBM 33 strains. This study demonstrated that, in general, ß-lapachone combined with beta lactams antimicrobials, fluoroquinolones and carbapenems acts synergistically inhibiting MRSA strains.