scholarly journals Techniques for the Assessment of In Vitro and In Vivo Antifungal Combinations

2021 ◽  
Vol 7 (2) ◽  
pp. 113
Author(s):  
Anne-Laure Bidaud ◽  
Patrick Schwarz ◽  
Guillaume Herbreteau ◽  
Eric Dannaoui
Keyword(s):  
Animal Models ◽  
Fungal Infections ◽  
Acquired Resistance ◽  
Adequate Treatment ◽  
Combination Treatments ◽  
Target Organs ◽  
Fungal Load ◽  
Time Kill

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs.

scholarly journals Current status of in vitro and in vivo antifungal activities of posaconazole

2013 ◽  
Vol 1 (1) ◽  
pp. 18-22
Author(s):  
He Sun ◽  
Xin Su ◽  
Yi Shi
Keyword(s):  
Animal Models ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
Current Status ◽  
Dimorphic Fungi ◽  
Antifungal Activities ◽  
Endemic Fungi ◽  
Yeasts And Molds

Abstract Posaconazole (POS) is a new triazole drug with broad-spectrum in vitro activity against most yeasts and molds such as Candida, Cryptococcus neoformans, Aspergillus, Fusarium and Zygomycetes, as well as certain species of dimorphic fungi and endemic fungi. In immunocompetent or immunocompromised animal models with invasive fungal infections, POS has demonstrated highly effective, broad-spectrum antifungal activities. In vitro and in vivo antifungal activities of POS were superior to those of other azoles against Candida glabrata, Candida krusei, Aspergillus terrus, Fusarium and Zygomycetes. In vivo susceptibility studies have shown promising efficacy of POS against life-threatening fungal infections in animal models with different immune status and infection sites.

scholarly journals Addition of Gentamicin or Rifampin Does Not Enhance the Effectiveness of Daptomycin in Treatment of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 53 (10) ◽  
pp. 4172-4177 ◽  
Author(s):  
J. M. Miró ◽  
C. García-de-la-Mària ◽  
Y. Armero ◽  
D. Soy ◽  
A. Moreno ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Statistical Difference ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Acquired Resistance ◽  
Rabbit Model ◽  
Human Pharmacokinetics ◽  
Methicillin Resistant ◽  
Time Kill

ABSTRACT This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1× and 2× the MIC yielded synergy, while the addition of rifampin at 2 to 4 μg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated ± gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 μg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.

scholarly journals Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data

2020 ◽  
Vol 6 (4) ◽  
pp. 192
Author(s):  
Yanan Zhao ◽  
David S. Perlin
Keyword(s):  
Animal Models ◽  
Fungal Pathogens ◽  
Animal Studies ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Current Status ◽  
Parent Molecule ◽  
Treatment And Prevention

Rezafungin is a novel echinocandin drug being developed as a first-line option for treatment and prevention of invasive fungal infections. As a result of a structural modification in its parent molecule anidulafungin, rezafungin has acquired unique chemical stability conferring prolonged pharmacokinetics, as well as an administration advantage in the clinical setting compared to other drugs in the same class. Rezafungin displays potent in vitro activity against a wide spectrum of fungal pathogens, which is reflected in robust in vivo efficacy and/or pharmacodynamic studies using various animal models as well as in promising clinical trials data. This review describes in vivo characterization of rezafungin using animal models, current status of clinical development and key findings from these studies.

scholarly journals Antimicrobial Effects of Minocycline, Tigecycline, Ciprofloxacin, and Levofloxacin against Elizabethkingia anophelis using In Vitro Time-Kill Assays and In Vivo Zebrafish Animal Models

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 285
Author(s):  
Jiun-Nong Lin ◽  
Chung-Hsu Lai ◽  
Yi-Han Huang ◽  
Chih-Hui Yang
Keyword(s):  
Animal Models ◽  
Antibacterial Activities ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Time Kill

Elizabethkingia anophelis is a multidrug-resistant pathogen. This study evaluated the antimicrobial activity of minocycline, tigecycline, ciprofloxacin, and levofloxacin using in vitro time-kill assays and in vivo zebrafish animal models. The E. anophelis strain ED853-49 was arbitrarily selected from a bacterial collection which was concomitantly susceptible to minocycline, tigecycline, ciprofloxacin, and levofloxacin. The antibacterial activities of single agents at 0.5–4 × minimum inhibitory concentration (MIC) and dual-agent combinations at 2 × MIC using time-kill assays were investigated. The therapeutic effects of antibiotics in E. anophelis-infected zebrafish were examined. Both minocycline and tigecycline demonstrated bacteriostatic effects but no bactericidal effect. Minocycline at concentrations ≥2 × MIC and tigecycline at concentrations ≥3 × MIC exhibited a long-standing inhibitory effect for 48 h. Bactericidal effects were observed at ciprofloxacin and levofloxacin concentrations of ≥3 × MIC within 24 h of initial inoculation. Rapid regrowth of E. anophelis occurred after the initial killing phase when ciprofloxacin was used, regardless of the concentration. Levofloxacin treatment at the concentration of ≥2 × MIC consistently resulted in the long-lasting and sustainable inhibition of bacterial growth for 48 h. The addition of minocycline or tigecycline weakened the killing effect of fluoroquinolones during the first 10 h. The minocycline-ciprofloxacin or minocycline–levofloxacin combinations achieved the lowest colony-forming unit counts at 48 h. Zebrafish treated with minocycline or a combination of minocycline and levofloxacin had the highest survival rate (70%). The results of these in vitro and in vivo studies suggest that the combination of minocycline and levofloxacin is the most effective therapy approach for E. anophelis infection.

scholarly journals Activity of Oritavancin and Its Synergy with Other Antibiotics against Mycobacterium abscessus Infection In Vitro and In Vivo

2021 ◽  
Vol 22 (12) ◽  
pp. 6346
Author(s):  
Gaoyan Wang ◽  
Jia Tanga ◽  
Jiajia Feng ◽  
Wenqi Dong ◽  
Xinyu Huo ◽  
...  
Keyword(s):  
Bacterial Load ◽  
Acquired Resistance ◽  
Bactericidal Effect ◽  
Mycobacterium Abscessus ◽  
Drug Resistant ◽  
Cell Growth Inhibition ◽  
Time Kill ◽  
Viable Treatment

Background: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. Methods: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time–kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. Results: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. Conclusions: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.

Transplantation of Adipose-derived Cells for Periodontal Regeneration: A Systematic Review

2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Platelet Rich Plasma ◽  
Periodontal Regeneration ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Cell Sources ◽  
Study Designs

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.

68Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with 68Ga-NODAGA-AE105

2019 ◽  
Vol 18 (9) ◽  
pp. 1289-1294 ◽  
Author(s):  
Kusum Vats ◽  
Rohit Sharma ◽  
Haladhar D. Sarma ◽  
Drishty Satpati ◽  
Ashutosh Dash
Keyword(s):  
Solid Phase ◽  
Evaluation Studies ◽  
Radiochemical Yield ◽  
In Vivo Evaluation ◽  
Peptide Conjugates ◽  
Biodistribution Studies ◽  
Target Organs ◽  
U87mg Tumor

Aims: The urokinase Plasminogen Activator Receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPARexpressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes. Method: The peptide conjugates, HBED-CC-AE105-NH2 and NODAGA-AE105-NH2 were manually synthesized by standard Fmoc solid phase strategy and subsequently radiolabeled with 68Ga eluted from a commercial 68Ge/68Ga generator. In vitro cell studies for the two radiotracers were performed with uPAR positive U87MG cells. Biodistribution studies were carried out in mouse xenografts with the subcutaneously induced U87MG tumor. Results: The two radiotracers, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 that were prepared in >95% radiochemical yield and >96% radiochemical purity, exhibited excellent in vitro stability. In vivo evaluation studies revealed higher uptake of 68Ga-HBED-CC-AE105 in U87MG tumor as compared to 68Ga-NODAGAAE105; however, increased lipophilicity of 68Ga-HBED-CC-AE105 resulted in slower clearance from blood and other non-target organs. The uPAR specificity of the two radiotracers was ascertained by significant (p<0.05) reduction in the tumor uptake with a co-injected blocking dose of unlabeled AE-105 peptide. Conclusion: Amongst the two radiotracers studied, the neutral 68Ga-NODAGA-AE105 with more hydrophilic chelator exhibited faster clearance from non-target organs. The conjugation of HBED-CC chelator (less hydrophilic) resulted in negatively charged 68Ga-HBED-CC-AE105 which was observed to have high retention in blood that decreased target to non-target ratios.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models

mAbs ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1954136
Author(s):  
Sujatha Kumar ◽  
Srimoyee Ghosh ◽  
Geeta Sharma ◽  
Zebin Wang ◽  
Marilyn R. Kehry ◽  
...  
Keyword(s):  
Animal Models ◽  
Immune Function ◽  
Cellular Assays ◽  
In Vivo Animal Models

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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