scholarly journals In vitro activity of allicin combined with two antibiotics on intestinal Shigella

2017 ◽  
Vol 6 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Yuchi Jia ◽  
Xiaomei Wu

Abstract Objective We aimed to evaluate the combined antibacterial effects of allicin in combination with levofloxacin and ceftriaxone on Shigella isolated from the intestinal tract in vitro. Materials and Methods Using a checkerboard design, broth microdilution assay was used to test the effects of the compounds on the organism. We also determined the MIC of the two groups of antibacterial drugs against 30 strains of Shigella and calculated the fractional inhibitory concentration (FIC) index, to judge the combination effect. Result After the combined application of allicin and ceftriaxone the MIC decreased significantly. Distribution of the FIC index was as follows: FIC ≤0.5, accounting for 10%; 0.5< FIC ≤1.0, accounting for 60%; 1 < FIC ≤2, accounting for 30%; FIC >2, percentage is zero. After combined application of allicin and levofloxacin, distribution of FIC index was as follows: FIC≤0.5, ratio is zero; 0.5< FIC ≤1, accounting for 56.7%; 1 < FIC ≤2, accounting for 43.3%; FIC >2, ratio is zero. Conclusion After the combined use of ceftriaxone, levofloxacin, and allicin, most of the tests showed synergistic effects and additive effects on Shigella, while some of them showed no correlation and no antagonistic effect.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 123-123
Author(s):  
Gunhild Von Amsberg ◽  
Mirjam Zilles ◽  
Philipp Gild ◽  
Winfried Alsdorf ◽  
Lukas Boeckelmann ◽  
...  

123 Background: Recent developments in the treatment of metastatic castration resistant prostate cancer (mCRPC) lead to a revival of platinum-based chemotherapy demonstrating increased activity in patients with aggressive variants of disease. Here, we report on the results of a combinational salvage therapy with cisplatin, ifosfamide and paclitaxel (TIP) in mCRPC. Methods: We retrospectively analyzed patients with mCRPC treated with TIP at the University Hospital Hamburg-Eppendorf between November 2013 and September 2020. Accompanying in vitro analyses were performed using human prostate carcinoma cell lines harboring different levels of drug resistance including the docetaxel-resistant sublines PC3-DR and DU45-DR. Results: In total, 17 mCRPC patients treated with TIP were eligible for efficacy analyses with a median age of 65 yrs. At baseline, liver metastases were present in 88%, metastases of other visceral sides (lung, adrenal gland, brain) in 47% and bone metastases in 76% of the patients. Median hemoglobin was 9.8mg/dl, LDH 903 U/l and AP 205 U/l. Median PSA value was 77 ng/ml covering a wide range including three patients with a PSA-value below 1ng/ml. NSE was evaluated in 83% of the patients (median 38,5 U/l). Patients were extensively pretreated with a median of three treatment lines before TIP (100% docetaxel, 82% abirateron and/or enzalutamide, 47% cabazitaxel, 41% others). A median of 3,5 cycles of TIP were applied with 29% of the patients receiving the maximum of 6 cycles. Four patients discontinued treatment due to side effects (PNP, infection, ifosfamide induced psychosis). At interim analyses, 59 % of the patients showed a radiological response or stable disease with only one patient progressing till the end of treatment. Median PFS was 2.5 months, median OS 6 months. A decrease of PSA > 30% and LDH > 50% was observed in 41% and 35% of the patients, respectively. In vitro experiments revealed additive effects of TIP in 22Rv1, LNCaP and DU45 cells and synergistic effects in neuroendocrine LASCPC-01 cells. In PC3 cells, TIP induced antagonistic effects at lower doses, whereas dose-independent additive effects were observed in docetaxel-resistant PC3-DR. Surprisingly, preliminary data of combined therapies with different drug pairs suggest an antagonistic effect of paclitaxel in the combination with both, cisplatin and ifosfamide. Conclusions: Combinational therapy with cisplatin, ifosfamide and paclitaxel showed promising activity in some patients with aggressive mCRPC. Preclinical data suggest that the drug combination of cisplatin and ifosfamide rule the efficacy of TIP in mCRPC.


Author(s):  
Pinheiro L. S. ◽  
Sousa J. P. ◽  
Sousa J. P. ◽  
Barreto N. A. ◽  
Dantas T B ◽  
...  

The antifungal therapy combined is used in clinical practice of several mycoses as it may increase the efficacy of the treatment. The use of natural products (phytochemicals) in combination with conventional antifungal drugs has been related to beneficial effects, mainly synergistic effects. The aim of this study was to evaluate the effect of the combined use of eugenol / isoeugenol, compounds with recognized antimicrobial activity, in association with antifungal amphotericin B against strains of Cryptococcus neoformans. The combined antifungal effect were be determined from the Fraction Inhibitory Concentration index - checkerboard technique. The results obtained in this study showed that eugenol in combination with amphotericin B had antagonistic effect against the strains of C. neoformans, LM 615 and INCQS 40221 (FIC index 6.0 and 4.0), respectively. The combination of the isoeugenol and amphotericin B also showed antagonistic effects for both the LM 615 strain and INCQS 40221 (FIC index 6.0 and 5.0), respectively. This study contributed to the understanding of the antifungal effects of the association of phenylpropanoids (eugenol / isoeugenol) with amphotericin B. Further studies are needed to evaluate and compare the effects of the association of these phytochemicals with other conventional antifungal drugs used against C. neoformans.


2017 ◽  
Vol 242 (7) ◽  
pp. 731-743 ◽  
Author(s):  
Chiu-Fai Kuok ◽  
Sai-On Hoi ◽  
Chi-Fai Hoi ◽  
Chi-Hong Chan ◽  
Io-Hong Fong ◽  
...  

Antibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA. Impact statement Antibiotic resistant is a well-known threat to global health and methicillin-resistant Staphylococcus aureus is one of the most significant ones. These resistant bacteria kill thousands of people every year and therefore a new effective antimicrobial treatment is necessary. This study identified the herbs and their associated bioactive ingredients that can potential the effects of current antibiotics. These herbs have long history of human usage in China and have well-defined monograph in the Chinese Pharmacopeia. These indicate their relatively high clinical safety and may have a quicker drug development process than that of a new novel antibiotic. Based on the results of this study, the authors will perform further in vitro and animal studies, aiming to accumulate significant data for the application of clinical trial.


1997 ◽  
Vol 41 (4) ◽  
pp. 850-852 ◽  
Author(s):  
N X Chin ◽  
I Weitzman ◽  
P Della-Latta

Fluvastatin, a cholesterol-lowering drug, exhibited minimal activity (MICs of 64 to >128 microg/ml) against Candida species and Cryptococcus neoformans. When fluvastatin was combined with fluconazole or itraconazole, both synergistic and additive effects were noted (fractional inhibitory concentration indices of < or = 0.156 to 0.625; fractional lethal concentration indices of < or = 0.156 to 0.75). This combined fungicidal activity was confirmed by time-versus-killing studies.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Fang Yang ◽  
Yi Sun ◽  
Qiaoyun Lu

Abstract Background This study was aimed to determine the potency of Minocycline (MIN) and azoles, including itraconazole (ITR), voriconazole (VOR) and posaconazole (POS) against Scedosporium and Lomentospora species. Results This study revealed that MIN exhibited no significant antifungal activity against any of the tested strains, whereas in vitro combination of MIN with ITR, VOR or POS showed satisfactory synergistic effects against 8 (80%), 1 (10%), and 9 (90%) strains, respectively. Moreover, combined use of MIN with azoles decreased the minimum inhibitory concentration (MIC) range from 5.33–16 μg/ml to 1–16 μg/ml for ITR, from 0.42–16 μg/ml to 0.21–16 μg/ml for VOR, and from 1.33–16 μg/ml to 0.33–16 μg/ml for POS. Meanwhile, no antagonistic interactions were observed between the above combinations. The G. mellonella infection model demonstrated the in vivo synergistic antifungal effect of MIN and azoles. Conclusions The present study demonstrated that combinations between MIN and azoles lead to synergistic antimicrobial effects on Scedosporium and Lomentospora species, while showing a potential for overcoming and preventing azole resistance.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Nursenem Karaca ◽  
Görkem Şener ◽  
Betül Demirci ◽  
Fatih Demirci

AbstractCombination of various compounds and essential oils for pharmaceutical formulations withdraw attention. In this present study, it was aimed to evaluate the in vitro potential synergistic antibacterial effect of Lavandula latifolia (spike lavender) essential oil with camphor by using the checkerboard method against the human pathogens; Staphylococcus aureus and Listeria monocytogenes. Pharmacopoeia quality L. latifolia essential oil and racemic camphor were analyzed and verified by GC-FID and GC/MS, simultaneously. In vitro antibacterial activity of essential oil and camphor (MIC range: 0.16–20 mg/mL) and standard antimicrobial clarithromycin (MIC range: 0.125–16 μg/mL) were carried out by broth microdilution against S. aureus and L. monocytogenes standard strains, respectively. Resulting antibacterial effects were evaluated for their fractional inhibitory concentrations (FICs) as antagonistic, additive and synergistic effects. The analytical results showed that the major component of essential oil was linalool (45.2%) and 1,8-cineole (25.6%). Antibacterial effects of essential oil were determined as MIC 1.25–5 mg/mL. As a result of the experiments, L. latifolia essential oil–camphor combinations were identified as “synergistic (FIC ≤ 0.5), and additive (0.5 < FIC ≤ 1)” in the respective combinations, suggesting further evaluation for formulations for potential antimicrobial applications in food and pharmaceuticals.


PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.


1988 ◽  
Vol 8 (4) ◽  
pp. 277-279
Author(s):  
Wendy L. Vaudry ◽  
Claudia Gratton ◽  
Kinga Kowalewska ◽  
Wanda M. Wenman

The minimum inhibitory concentration (MIC) of daptomycin was compared with that of four other antimicrobial agents against clinically relevant staphylococci. Sixtyfive isolates were obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) who contracted peritonitis. These isolates comprised 29 S. Sureus strains (all sensitive to oxacillin); 25 S. epidermidis strains (14 sensitive and 9 resistant to oxacillin); and 11 unspeciated coagulase-negative staphylococci (2 sensitive and 11 resistant to oxacillin). All of the oxacillin susceptible strains were inhibited by ≤2 mg/L of the five antibiotics tested. The oxacillin resistant staphylococci were also resistant to cefuroxime and variably resistant to cefamandole, but were uniformly susceptible to both vancomycin and daptomycin. Daptomycin possesses equivalent in vitro activity to vancomycin against strains of S. Sureus and coagulase negative staphylococci associated with CAPD peritonitis. If vancomycin resistance becomes a significant problem in these patients, and daptomycin is shown to be active against vancomycin resistant organisms, then it would have potential usefulness as an alternative to vancomycin in the treatment of peritonitis caused by multiply -resistant staphylococci.


Author(s):  
Negar Fallah ◽  
Sanaz Namazi ◽  
Negar Balmeh ◽  
Samira Mahmoudi ◽  
Fereshteh Mirzaei Poor

Introduction: So far, a lot of attempts have been carried out to find antimicrobial compounds. In this study, it was also tried to investigate the antibacterial effects of Achillea millefolium on standard Klebsiella, S. pyogenes, and oral bacterias strain. Material and Methods: The aerial parts of Achillea millefolium were used and the aqueous, ethanolic, methanolic, acetone and hydroethanolic extracts were prepared. After the preparation of standard strains of Klebsiella, S. pyogenes, and oral bacterias and sterilization of extracts by the Millipore filter, the antibacterial effects of these extracts on the mentioned microorganisms were assessed by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and well diffusion at the concentration 50 mg/ml. The test was repeated three times for each bacterium. Results: It was exposed that aqueous extract of Achillea millefolium had the most distinguished antimicrobial effects against all studied strains and methanolic extract had antimicrobial effects only on S. pyogenes. MIC and MBC of effective extracts were the basic concentration (50mg/ml), and non-growth zone was not observed in other serial dilution in case of all bacteria. Conclusion: The Achillea millefolium can be admitted as an antibacterial medicinal herb. Thus, it can be concluded that after evaluating their effects in vitro, Achillea millefolium can be utilized as an alternative to the routine chemical drugs.


2020 ◽  
Vol 6 (2) ◽  
pp. 128-133
Author(s):  
Asih Rahayu ◽  
Chylen Setiyo Rini ◽  
Yos Adi Prakoso ◽  
Bagus Uda Palgunadi ◽  
Muhammad Aris Munandar

Background and Aim: The massive utilization of antibiotics has increased resistant genes produced by bacteria. Many bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), have become resistant against ampicillin (AMP). The combination of an herbal extract with AMP is expected to generate synergistic effects and may restore the susceptibility of MRSA against AMP. This study aimed to analyze the potency of Sauropus androgynous extract (SAE) as a single extract and combination with AMP against MRSA. Materials and Methods: Sauropus androgynous was extracted using 60% ethanol. SAE biochemical compounds were analyzed qualitatively and quantitatively. SAE, AMP, and SAE+AMP were tested against MRSA isolates to determine the minimum inhibitory concentration and fractional inhibitory concentration. The inhibition of penicillin-binding proteins 2a (PBP2a) was analyzed using a latex agglutination test. Further, the disruptive membrane effects of SAE, AMP, and SAE+AMP were analyzed using a scanning electron microscope. The analysis of data was conducted using SPSS version 16 with p=0.01. Results: SAE contained bioactive compounds such as phenolics and flavonoids. Further, 2 mg/mL of SAE could be used as the potential concentration against MRSA isolates in vitro. In addition, the utilization of SAE+AMP generated synergistic effects, restored the susceptibility of isolates against AMP, decreased the synthesis of PBP2a by the MRSA, and induced ultrastructural changes in the bacterial membrane. Conclusion: This study indicated that the utilization of SAE potentially inhibits the growth of MRSA through decreasing of PBP2a expression, disruption of the MRSA membrane, while the combination of SAE+AMP showed synergistic effects against MRSA.


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