scholarly journals The synergistic effect of minocycline and azole antifungal drugs against Scedosporium and Lomentospora species

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Fang Yang ◽  
Yi Sun ◽  
Qiaoyun Lu
Keyword(s):  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Azole Resistance ◽  
Antifungal Effect ◽  
Combined Use ◽  
Antagonistic Interactions

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.

scholarly journals Reversal of Azole Resistance inCandida albicansby Sulfa Antibacterial Drugs

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Hassan E. Eldesouky ◽  
Abdelrahman Mayhoub ◽  
Tony R. Hazbun ◽  
Mohamed N. Seleem
Keyword(s):  
Treatment Options ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Azole Resistance ◽  
Global Public Health ◽  
Sulfa Drugs ◽  
Antibacterial Drugs ◽  
Content Type

ABSTRACTInvasive candidiasis presents an emerging global public health challenge due to the emergence of resistance to the frontline treatment options, such as fluconazole. Hence, the identification of other compounds capable of pairing with fluconazole and averting azole resistance would potentially prolong the clinical utility of this important group. In an effort to repurpose drugs in the field of antifungal drug discovery, we explored sulfa antibacterial drugs for the purpose of reversing azole resistance inCandida. In this study, we assembled and investigated a library of 21 sulfa antibacterial drugs for their ability to restore fluconazole sensitivity inCandida albicans. Surprisingly, the majority of assayed sulfa drugs (15 of 21) were found to exhibit synergistic relationships with fluconazole by checkerboard assay with fractional inhibitory concentration index (ΣFIC) values ranging from <0.0312 to 0.25. Remarkably, five sulfa drugs were able to reverse azole resistance in a clinically achievable range. The structure-activity relationships (SARs) of the amino benzene sulfonamide scaffold as antifungal agents were studied. We also identified the possible mechanism of the synergistic interaction of sulfa antibacterial drugs with azole antifungal drugs. Furthermore, the ability of sulfa antibacterial drugs to inhibitCandidabiofilm by 40%in vitrowas confirmed. In addition, the effects of sulfa-fluconazole combinations onCandidagrowth kinetics and efflux machinery were explored. Finally, using aCaenorhabditis elegansinfection model, we demonstrated that the sulfa-fluconazole combination does possess potent antifungal activityin vivo, reducingCandidain infected worms by ∼50% compared to the control.

scholarly journals Eugenol and Isoeugenol In Association with Antifungal Against Cryptococcus neoformans

2017 ◽  
Vol 9 (4) ◽  
Author(s):  
Pinheiro L. S. ◽  
Sousa J. P. ◽  
Sousa J. P. ◽  
Barreto N. A. ◽  
Dantas T B ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Antagonistic Effect ◽  
Antifungal Drugs ◽  
Antifungal Effect ◽  
Beneficial Effects ◽  
Combined Use ◽  
Antifungal Effects

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.

scholarly journals Activities of Moxifloxacin in Combination with Macrolides against Clinical Isolates of Mycobacterium abscessus and Mycobacterium massiliense

2012 ◽  
Vol 56 (7) ◽  
pp. 3549-3555 ◽  
Author(s):  
Go-Eun Choi ◽  
Ki-Nam Min ◽  
Choul-Jae Won ◽  
Kyeongman Jeon ◽  
Sung Jae Shin ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Ex Vivo ◽  
Synergistic Effects ◽  
Mycobacterium Abscessus ◽  
Infection Model ◽  
Content Type ◽  
Treatment Regimens ◽  
Mycobacterium Massiliense

ABSTRACTInfections caused byMycobacterium abscessusandMycobacterium massilienseare on the rise among humans. Although macrolides, including clarithromycin (CLR) and azithromycin (AZM), are key antibiotics for the treatment ofM. abscessusandM. massilienseinfections, treatment regimens for these infections are still largely undefined. In this study, we evaluated thein vitro,ex vivo, andin vivoactivities of moxifloxacin (MXF) in combination with macrolides against clinically isolatedM. abscessusandM. massiliensestrains. Overall, CLR, AZM, and MXF alone showed activity against both speciesin vitro,ex vivo, andin vivo. When MXF was combined with a macrolide againstM. abscessusisolates, antagonism was observed in 65.4% (17/26) of the strains with CLR and 46.2% (12/26) of the strains with AZMin vitroas well as in 66.7% (10/15) of the strains with CLR and 40.0% (6/15) of the strains with AZM in macrophages as determined by the fractional inhibitory concentration index. In contrast, either indifferent or synergistic effects of the MXF-macrolide combinations were observed against onlyM. massiliensestrains. Moreover, a murine infection model showed similar results. Antagonism between the MXF and macrolide combinations was observed in five out of sevenM. abscessusstrains, while indifferent and synergistic effects for these combinations were observed for three of the sixM. massiliensestrains tested, respectively. In conclusion, the activity of MXF in combination with a macrolide differed forM. abscessusandM. massilienseinfections and the addition of MXF to macrolide therapy had no benefit for the treatment ofM. abscessusinfections.

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
Keyword(s):  
Intestinal Tract ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Antagonistic Effect ◽  
Additive Effects ◽  
In Vitro Activity ◽  
Antibacterial Effects ◽  
Combined Application ◽  
Combined Use

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.

scholarly journals Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Combined Use

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.

scholarly journals In Vitro and In Vivo Experimental Activities of Antifungal Agents against Fusarium solani

1999 ◽  
Vol 43 (5) ◽  
pp. 1256-1257 ◽  
Author(s):  
J. Guarro ◽  
I. Pujol ◽  
E. Mayayo
Keyword(s):  
Drug Therapy ◽  
Amphotericin B ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Disseminated Infection

ABSTRACT In the treatment of disseminated Fusarium infections, amphotericin B either alone or in combination with flucytosine and rifampin is the drug therapy most frequently used. The efficacy of these antifungal drugs was evaluated in a murine disseminated-infection model, with five strains of Fusarium solani. All the treatments were clearly ineffective.

scholarly journals Azole Resistance by Loss of Function of the Sterol Δ5,6-Desaturase Gene (ERG3) in Candida albicans Does Not Necessarily Decrease Virulence

2012 ◽  
Vol 56 (4) ◽  
pp. 1960-1968 ◽  
Author(s):  
L. A. Vale-Silva ◽  
A. T. Coste ◽  
F. Ischer ◽  
J. E. Parker ◽  
S. L. Kelly ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Premature Stop Codon ◽  
Antifungal Drugs ◽  
Ergosterol Biosynthesis ◽  
Azole Resistance ◽  
Wild Type ◽  
Disseminated Candidiasis ◽  
Double Base

ABSTRACTThe inactivation ofERG3, a gene encoding sterol Δ5,6-desaturase (essential for ergosterol biosynthesis), is a known mechanism ofin vitroresistance to azole antifungal drugs in the human pathogenCandida albicans. ERG3inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified aC. albicansclinical isolate (VSY2) with high-level resistance to azole drugsin vitroand an absence of ergosterol but normal filamentation. Sequencing ofERG3in VSY2 revealed a double base deletion leading to a premature stop codon and thus a nonfunctional enzyme. The reversion of the double base deletion in the mutant allele (erg3-1) restored ergosterol biosynthesis and full fluconazole susceptibility in VSY2, confirming thatERG3inactivation was the mechanism of azole resistance. Additionally, the replacement of bothERG3alleles byerg3-1in the wild-type strain SC5314 led to the absence of ergosterol and to fluconazole resistance without affecting filamentation. In a mouse model of disseminated candidiasis, the clinicalERG3mutant VSY2 produced kidney fungal burdens and mouse survival comparable to those obtained with the wild-type control. Interestingly, while VSY2 was resistant to fluconazole bothin vitroandin vivo, theERG3-derived mutant of SC5314 was resistant onlyin vitroand was less virulent than the wild type. This suggests that VSY2 compensated for thein vivofitness defect ofERG3inactivation by a still unknown mechanism(s). Taken together, our results provide evidence that contrary to previous reports inactivation ofERG3does not necessarily affect filamentation and virulence.

scholarly journals Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans

2021 ◽  
Vol 12 ◽  
Author(s):  
Liu-Yan Su ◽  
Guang-Hui Ni ◽  
Yi-Chuan Liao ◽  
Liu-Qing Su ◽  
Jun Li ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Signaling Pathway ◽  
Treatment Method ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Drug Resistant ◽  
Mycelium Growth

The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4′-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo. TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro, with a partial inhibitory concentration index (FICI) of 0.0188–0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans. The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans. Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections.

scholarly journals A preliminary study of in vitro and in vivo synergistic effects of ciprofloxacin and D-tyrosine against Pseudomonas aeruginosa isolates

2020 ◽  
Vol 19 (8) ◽  
pp. 1731-1736
Author(s):  
Huirong Li ◽  
Wei Jiang ◽  
Xiaoshuang He ◽  
Mengting Chen
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effects ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Infection Model ◽  
Antimicrobial Effects ◽  
Kill Curve ◽  
Zebrafish Infection

Purpose: To investigate the synergistic antimicrobial effects of ciprofloxacin and D-tyrosine against drug-resistant bacteria.Method: The antimicrobial effects of ciprofloxacin and D-tyrosine on clinical isolates of multidrugresistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) no. 3556 were determined in vitro based on time-kill curve, and in vivo in P. aeruginosa-zebrafish infection model. Furthermore, 30 clinical isolates of multidrug-resistant P. aeruginosa were used in vitro to ascertain the synergistic effect of the two agents.Results: Combined use of ciprofloxacin and D-tyrosine produced synergistic effects against the clinical isolate of P. aeruginosa no. 3556 in vitro and in vivo. Synergism occurred in 96.67 % (95 % CI, range 83.33 - 99.41 %) of the clinical isolates, and ciprofloxacin dose was reduced in 90 % (95 % CI, range 74.38 - 96.54 %) of the clinical isolates in vitro.Conclusion: These preliminary results suggest that the combination of ciprofloxacin and D-tyrosine is a promising therapeutic strategy against MDR P. aeruginosa infections. Keywords: Ciprofloxacin, D-tyrosine, Synergistic, P. aeruginosa, Zebrafish infection model, Time-killing curve

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