Synergy in penicillin, cephalosporin, amphenicols, and aminoglycoside against MDR S. aureus isolated from Camel milk

Abstract This study investigated the synergy testing of penicillin, cephalosporin, amphenicols, and aminoglycoside in the camel milk (n=768 samples), subsequently used for isolation of MDR S. aureus targeting mecA gene. Antibiotic susceptibility of S. aureus showed >90% isolates were sensitive to ciprofloxacin and trimethoprim and resistant against oxacillin, ampicillin, and cefoxitin. Further, 50-85% of the S. aureus were sensitive to gentamicin, oxytetracycline, and chloramphenicol and resistant against cefotaxime, vancomycin, and cefixime. Minimum inhibitory concentration (MIC) of cefotaxime, (C) and ampicillin (A) in combination with gentamicin (G) was reduced by 99.34% and 70.46%, respectively, while with chloramphenicol (Ch), reduction was 57.49% and 60%, respectively. In addition, the Fractional Inhibitory Concentration Index (FICI) of G+A, Ch+C and Ch+G combinations showed synergy against 80%, 60%, and 30% of MDR S. aureus, respectively. Similarly, C+A and Ch+G displayed indifferent interaction against 70 % and 30% of isolates, respectively, while the later showed additive interaction against 10% of MDR S. aureus. Altogether, our results described effective combination of gentamicin and chloramphenicol with ampicillin and cefotaxime to combat MDR S. aureus

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.

Antibacterial effects of small molecule antidiabetic agent Halicin against Staphylococcus aureus / 中华检验医学杂志

Objective:To investigate the effect of small molecule antibacterial agent Halicin against Staphylococcus aureus. Methods:The minimum inhibitory concentration (MIC) and minimum bactericidal concentration of Halicin against S. aureus were detected by the microbroth dilution method. The time-kill assay of Halicin against S. aureus was detected by agar plate dilution method. Micro checkerboard dilution method was used to determine the synergistic antibacterial activity between Halicin and conventional antibiotics. Crystal violet staining method was used to assess the biofilm inhibitory and eradicating activity of Halicin. Hemolysis rate was used to detect the mammal cell toxicity of Halicin. Through the mouse skin abscess model, take the skin tissue around the abscess to grind and dilute the colony to detect the antibacterial effect of Halicin in vivo. Results:Halicin showed significant bacteriostasis effects against S. aureus with the minimum inhibitory concentration of 2-4 mg/L. Halicin could significantly reduce the average CFU counts of S. aureus about 5.5×10 6 CFU/ml in a concentration-dependent manner after 8 h treatment at the concentration of 16 mg/L. The fractional inhibitory concentration value between Halicin and ampicillin was 0.5, showing a synergistic antibacterial efficacy. Halicin effectively inhibited the formation of biofilms at the concentration of 4 × MIC, reducing the total biofilm biomass ( A570) from (2.89±0.09) to (1.35±0.17) ( t=11.12, P<0.05). However, there was no eradication effect against preformed biofilms. In addition, Halicin had almost no hemolytic activity on red blood cells even at the concentration up to 128 mg/L. It showed that 20 mg/kg Halicin reduced bacterial burden about 3.0×10 7 CFU/ml in vivo. Conclusion:Halicin had a strong antimicrobial activity against S. aureus with no hemolytic activity.

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.

Effect of clove oil combined with quinolones antibiotics on methicillin-resistant Staphylococcus aureus / 中草药

Objective: To investigate the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of clove oil combined with quinolones antibiotics in vitro, and provide scientific evidences for the treatment of MRSA infection by clove oil combined with quinolones antibiotics. Methods: Minimal inhibitory concentrations (MICs) of clove oil and four quinolones antibiotics (moxifloxacin, levofloxacin, ciprofloxacin and norfloxacin) were determined by microdilution method; Fractional inhibitory concentration (FIC) indexes of clove oil combined with four quinolones antibiotics were determined by chessboard dilution method; Inhibition effect of MRSA by clove oil combined with four quinolones antibiotics was analyzed by growth curve method. MIC changes were analyzed when MRSA standard strain ATCC33591 was induced 30 generations with clove oil. Results: A total of 35 strains of MRSA isolated from clinical patients showed that the highest resistance rate was moxifloxacin (88.57%), followed by ciprofloxacin and levofloxacin (77.14%), and the lowest resistance rate was norfloxacin (74.29%). The results of FIC index analysis showed that the different thesynergistic action effects of clove oil with moxifloxacin, levofloxacin, ciprofloxacin and ornorfloxacin, were 42.86%, 37.15%, 34.28% and 34.28%, respectively; The additive effects of which were 28.57%, 25.71%, 22.86% and 42.86%, respectively; The unrelated effects of that were 28.57%, 20.00%, 42.86% and 22.86%, respectively. Among them, there was partial antagonism in experimental strains when combined with levofloxacin, accounting for 17.14%. The growth curve showed that the combination of clove oil and quinolone antibiotics had a significant synergistic inhibition on MRSA. The results of induced drug resistance test showed that MIC did not change after 30 generations of continuous induction with the clove oil, but increased to 16 times of that of ciprofloxacin under the same condition, which indicated that the clove oil was not easy to make MRSA resistant. Conclusion: Clove oil is not easy to produce drug resistance. They showed different interactions on each other when clove oil combined with quinolones antibiotics, and most strains of MRSA isolated from clinical patients had obvious synergistic and additive inhibition effect. The dosage of quinolones antibiotics could be cut when clove oil combined with quinolones antibiotics for treating MRSA infection.

Effects Of Alpha-Mangostin And Citronella Oil Against Acne Causing Bacteria

Objective: This study assessed the effects of alpha-mangostin (AM) and citronella oil (CO) working alone or in combination against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). Methods: The screening for antibacterial activity of AM and CO against P. acnes and S. aureus was carried out using the disk diffusion method. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these two substances were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICI) of a combination of AM and CO were obtained by checkerboard dilution assay. Results: The results showed that alpha-mangostin and citronella oil do indeed fight against P. acnes and S. aureus. The MICs and MBCs of AM against P. acnes and S. aureus were the same at 6.25 and 50 µg/ml, respectively. Both the MIC and the MBC of CO against P. acnes were 27.81µg/ml. The MIC and the MBC of CO against S. aureus were 112.13 and 224.25 µg/ml, respectively. The FICI of a combination of AM and CO against P. acnes and S. aureus were 2.00, indicating indifferent interaction with no additional inhibitory effect. Conclusion: AM and CO are very effective against P. acnes and S. aureus, nevertheless their effect when used together was indifferent from using alone. Further research may find that either or both of these substances combined with yet a different natural agent could provide synergy againstP. acnes and S. aureus.

In vitro antibacterial study of Shuanghuanglian combined with piperacillin/tazobactam or cefoperazone/sulbactam for extensively drug resistant Acinetobacter baumannii / 国际检验医学杂志

Objective To investigate the bacteriostasis effect of combination of Shuanghuanglian powder with piperacillin/tazobactam or cefoperazone/sulbactam for extensively drug-resistant Acinetobacter bauman-nii in vitro.Methods The minimum inhibitory concentration(MIC)and partial inhibitory concentration(FIC) index of 30 clinical isolates of Acinetobacter baumannii were measured with different concentrations of Shuan-ghuanglian,piperacillin/tazobactam,cefoperazone/sulbactam or combination.The effect of combined medica-tion was determined by FIC index.Results After shuanghuanglian combined with piperacillin/tazobactam,no strain showd synergistic effect;16.7% of the strains showed additive effect;83.3% of the strains showed ir-relevant effect;no strain showed antagonistic effect.After Shuanghuanglian combined with cefoperazone/sul-bactam,23.3% of the strains showed synergistic effect;73.3% of the strains showed additive effect;3.3% of the strains showed irrelevant effect,no antagonistic effect was shown.Conclusion The antibacterial effects of Shuanghuanglian and piperacillin/tazobactam were mostly irrelevant,while the antibacterial effect of Shuang-huanglian and cefoperazone/sulbactam are mostly synergistic and additive effect,w hich had better antibacterial effect to Acinetobacter baumannii in vitro.

In Vitro Activities of Tigecycline in Combination with Imipenem Against Multi-drug Resistant and Pan-drug Resistant Acinetobacter Baumannii Isolates / 医药导报

Objective To evaluate the in vitro antimicrobial activity of tigecycline in combination with imipenem against multi-drug resistant and pan-drug resistant Acinetobacter baumannii isolates,so as to discuss the feasibility of drug combination and provide the basis for chnical rational use of antimicrobial agents.Methods Sixteen multi-drug resistant and pan-drug resistant Acinetobacter baumannii isolates were collected between January and April in 2015 from all kinds of infected specimens of Nanjing Drun Tower Hospital.The protocol was designed by checkerboard method,and the minimum inhibitory concentration (MIC) of antibiotics was determined by microdilution broth method,and the fractional inhibitory concentration (FIC) index was calculated according to MIC results.Results The average value of MIC (MICG),MIC50,MIC90 of tigecycline and imipenem single were 1.73,1,4 μg·mL-1and 31.00,32,64 μg·mL-1.When tigecycline was combined with imipenem,MICG,MIC50,MIC90 of tigecycline and imipenem were 0.24,0.25,0.50 μg·mL-1 and 8.16,8.00,16.00 μg·mL-1,respectively.Compared with the drug single use groups,MIC was significandy decreased in the drug combination group.In 6 strains (37.50％),synergy effect (FIC≤0.5) was observed,and in 10 strains (62.50％),additive effect (0.5 ＜ FIC ≤ 1) was found.No negative and independent effects were shown.Conclusion Both additive and synergistic action is observed when tigecyclineis combined with imipenem against multi-drug resistant and pan-drug resistant Acinetobacter baumannii isolates.No negative and independent effects are shown.This combination use against multi-drug resistant and pan-drug resistant Acinetobacter baumannii may be an effective therapy for clinical treatment.

Synergistic Antimicrobial Activity of Berberine Hydrochloride, Baicalein and Borneol against Candida albicans / 中草药·英文版

Objective To determine the synergistic effects of berberine hydrochloride, baicalein, and borneol in different combinations on Candida albicans. Methods The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the three agents, and the checkerboard method was simultaneously used to determine the MIC and fractional inhibitory concentration index (FICI) of the combination of three antimicrobial agents to study their extracorporeal effects. Results Berberine hydrochloride was the most potent inhibitor of C. albicans (MIC and MBC of 0.160 and 0.640 mg/mL), followed by borneol (MIC and MBC of 0.320 and 0.640 mg/mL) and baicalein (MIC and MBC of 1.28 and 20.48 mg/mL). Moreover, the antifungal effect of the combination was significantly stronger than that tested alone. Further in vivo study showed that the mortality rate of tainted mice reduced over 50% compared with the control group. Conclusion The results of experiments in vitro and in vivo indicate the synergistic effect of the combination of three antimicrobial agents on C. albicans, which can make reference for the future clinical treatment.

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)

Study on the anti-bacteria effects of polymyxin B combined with meropenem against pan-drug-resistant pseudomonas aeruginosa / 中国生化药物杂志

Objective To evaluate the anti-bacteria effects of polymyxin B combined with meropenem against 30 strains pan-drug resistant pseudomonas aeruginosa that separated in clinic. Methods The minimal inhibitory concentration (MICs) of 30 strains pan-drug resistant pseudomonas aeruginosa after treated with polymyxin B and meropenem as single-use or combination use were determined by both microdilution method and checkerboard method. The FIC index was calculated, then the type of combination effect was determined according to FIC index, which was used to determine whether there was synergistic or antagonistic effects. Results The MICs of pan-drug resistant pseudomonas aeruginosa were reduced significantly after polymyxin B combined with meropenem when compared with single-use. The percentages of the FIC index that less than 0.5 and the index between 0.5 and 1 were 60%and 30%respectively. Conclusion The results indicate that the combinations of polymyxin B with meropenem have good synergistic and additive effects against pan-drug resistant pseudomonas aeruginosa, there is no antagonism.

In Vitro Antibacterial Activitey of Moxifloxacin Combined with Cefoperazone/Sulbactam Against Multidrug Resistant Bacteria / 中国药房

OBJECTIVE:To evaluate the antibiotic activity of Moxifloxacin (MFX) combined with Cefoperazone/Sulbactam (CPZ/SBT) against clinical common resistant bacteria for clinical reference of rational use of antibacterials.METHODS: The MIC of two antibiotics used alone or in combination on staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginosas(50 strains,respectively)and Escherichia coli,enterobacter cloacae(20 strains,respectively)were detected respectively by Vitek-32 Model (Full Automated bacterium Detection Device) and the fractional inhibitory concentration(FIC) index was calculated. RESULTS: The combination of two antibiotics significantly reduced MIC on 190 common resistant pathogenic strains and enhanced antibiotic action. Their antibacterial action in vitro was characterized by synergism and additive action. CONCLUSION: The study can present reference for hospital treatment of infection induced by common drug-resistant bacteria.

Combination Antimicrobial Susceptibility Test on 43 Multi-drug-resistant Isolates of Pseudomonas aeruginosa / 中华医院感染学杂志

OBJECTIVE To investigate the combined effect of cefoperazone/sulbactam with levofloxacin(group 1) and polymyxin B with rifampin(group 2) on 43 isolates of multi-drug-resistant Pseudomonas aeruginosa. METHODS The minimal inhibitory concentration(MIC) of all the antibiotics mentioned above was determined by agar dilution method.Fractional inhibitory concentration(FIC) index was calculated for all the selected isolates with all combinations,and the activities of antibiotics alone and in combination against the selected strains were evaluated. RESULTS The MIC of all the combined antimicrobials was reduced significantly(P

Antibacterial Activity of Water Soluble Components of Elfvingia applanata Alone and in Combinations with Quinolones

A preparation of water soluble components(EA) was made from carpophores of Elfvingia applanata(Pers.) Karst and its in vitro antibacterial activity on a number of bacterial species was examined by macrobroth dilution assay. Among 16 species of bacteria tested, the most potent antibacterial activity was observed against Staphylococcus epiderrnidis and Proteus vulgaris, of which MICs were 1.25 mg/ml. To investigate the antibacterial effects in combinations of EA with quinolone antibiotics, such as ciprofloxacin, enoxacin, lomefloxacin, norfloxacin, and ofloxacin, the fractional inhibitory concentrations(FICs) and the fractional inhibitory concentration indices(FICIs) for four bacterial strains were determined by macrobroth dilution checkerboard assay. Combinations of EA and quinolones exhibited either additive or indifferent effects of antibacterial activity in most instances. However, both synergistic and antagonistic effects were not observed in any cases.

Antibacterial Activity of Water Soluble Components of Elfvingia applanata Alone and in Combinations with Third Generation Cephalosporins

Antibacterial activity of EA, a preparation of water soluble components made from carpophores of Elfvingia applanata (Pers.) Karst, was examined by macrobroth diltution method against a number of bacterial species. Antibacterial effects of EA were expressed as minimal inhibitory concentration (MIC) for growth. Among twelve species of bacteria tested, six strains of each gram positive bacteria and gram negative bacteria, EA showed the most potent antibacterial activity against Staphylococcus epidermidis and Proteus vulgaris, of which MICs were 1.25 mg/ml of EA. To investigate the antibacterial effects of combinations of EA with third generation cepholosporins, such as cefotaxime, ceftriaxone, ceftazidime, and cefixime, the fractional inhibitory concentration (FIC) and fractional inhibitory concentration index (FICI) were determined by macrodilution checkerboard assay for twelve bacterial strains. Combinations of EA and third generation cephalosporins exhibited either additive or indifferent effects in most instances. However, synergistic effects were observed in six instances. No antagonistic effect was observed in any cases.