scholarly journals Evaluation of Amebicidal and Cysticidal Activities of Antifungal Drug Isavuconazonium Sulfate against Acanthamoeba T4 Strains

2021 ◽  
Vol 14 (12) ◽  
pp. 1294
Author(s):  
Brian Shing ◽  
Mina Balen ◽  
Anjan Debnath
Keyword(s):  
Invasive Aspergillosis ◽  
Acanthamoeba Keratitis ◽  
Antagonistic Effect ◽  
Antifungal Drug ◽  
Corneal Infection ◽  
Human Eye ◽  
Polyhexamethylene Biguanide ◽  
Amebicidal Activity ◽  
Acanthamoeba Species

Acanthamoeba species of amebae are often associated with Acanthamoeba keratitis, a severe corneal infection. Isavuconazonium sulfate is an FDA-approved drug for the treatment of invasive aspergillosis and mucormycosis. This prodrug is metabolized into the active isavuconazole moiety. Isavuconazole was previously identified to have amebicidal and cysticidal activity against Acanthamoeba T4 strains, but the activity of its prodrug, isavuconazonium sulfate, against trophozoites and cysts remains unknown. Since it is not known if isavuconazonium can be metabolized into isavuconazole in the human eye, we evaluated the activities of isavuconazonium sulfate against trophozoites and cysts of three T4 genotype strains of Acanthamoeba. Isavuconazonium displayed amebicidal activity at nanomolar concentrations as low as 1.4 nM and prevented excystation of cysts at concentrations as low as 136 μM. We also investigated the cysticidal activity of isavuconazonium sulfate in combination with a currently used amebicidal drug polyhexamethylene biguanide (PHMB). Although combination of isavuconazonium with PHMB did not elicit an obvious synergistic cysticidal activity, the combination did not cause an antagonistic effect on the cysts of Acanthamoeba T4 strains. Collectively, these findings suggest isavuconazonium retains potency against Acanthamoeba T4 strains and could be adapted for Acanthamoeba keratitis treatment.

scholarly journals Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 276
Author(s):  
Kawish Iqbal ◽  
Sumayah Abdelnasir Osman Abdalla ◽  
Ayaz Anwar ◽  
Kanwal Muhammad Iqbal ◽  
Muhammad Raza Shah ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Amphotericin B ◽  
Central Nervous System Infection ◽  
Acanthamoeba Castellanii ◽  
Acanthamoeba Keratitis ◽  
Free Living ◽  
Granulomatous Amoebic Encephalitis ◽  
Nano Drug Delivery ◽  
Free Living Amoeba ◽  
Acanthamoeba Species

The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.

scholarly journals Toll‐DeficientDrosophilaFlies as a Fast, High‐Throughput Model for the Study of Antifungal Drug Efficacy against Invasive Aspergillosis andAspergillusVirulence

2005 ◽  
Vol 191 (7) ◽  
pp. 1188-1195 ◽  
Author(s):  
Michail S. Lionakis ◽  
Russell E. Lewis ◽  
Gregory S. May ◽  
Nathan P. Wiederhold ◽  
Nathaniel D. Albert ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
High Throughput ◽  
Drug Efficacy ◽  
Antifungal Drug ◽  
Throughput Model

Genotyping of Acanthamoeba Species Isolated from Keratitis Patients by PCR Sequencing Methods in Tehran, Iran

2019 ◽  
Author(s):  
Tooran Nayeri Chegeni ◽  
Fatemeh Ghaffarifar ◽  
Majid Pirestani ◽  
Fariba Khoshzaban ◽  
Abdolhosein Dalimi Asl ◽  
...  
Keyword(s):  
Contact Lenses ◽  
Pcr Amplification ◽  
Acanthamoeba Keratitis ◽  
Local Alignment ◽  
Sequencing Analysis ◽  
Search Tool ◽  
Skin Nodules ◽  
Acanthamoeba Species ◽  
Eye Clinic

  Background and Aims: Amoebae of the genus Acanthamoeba are unicellular amphizoic opportunistic pathogens that may cause fatal granulomatous encephalitis, eye keratitis, amebic pneumonitis and skin nodules as well as abscesses in humans and animals. Acanthamoeba keratitis is caused by trauma to the eye, contaminated cleaning solutions and the use of contact lenses. The aim of the present study was to identify the genotypes of Acanthamoeba in all patients with a clinical diagnosis of Acanthamoeba keratitis referring to eye clinic in Tehran using polymerase chain reaction (PCR).  Materials and Methods: In this study, samples were collected from 35 patients who had referred to the eye clinic and were cultured on 1.5% non-nutrient agar. DNA was extracted, and then PCR amplification was performed using genus specific primers. Sequencing analysis and basic local alignment search tool search were conducted to determine the genotypes. Phylogenetic tree was generated using maximum likely algorithm in phylogenetic program MEGA version 6.  Results: Eight cases were positive for Acanthamoeba using genus specific primer pairs. All specimens were reported as genotype T4. Conclusions: Determination of genotypes showed all isolates belonging to genotype T4; this abundance may be due to its higher prevalence in the environment or its greater virulence. However, further analysis of clinical and environmental samples is necessary to clarify this property.   

scholarly journals Stability of an ophthalmic formulation of polyhexamethylene biguanide in gamma-sterilized and ethylene oxide sterilized low density polyethylene multidose eyedroppers

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4549 ◽  
Author(s):  
Yassine Bouattour ◽  
Philip Chennell ◽  
Mathieu Wasiak ◽  
Mireille Jouannet ◽  
Valérie Sautou
Keyword(s):  
Ethylene Oxide ◽  
Acanthamoeba Keratitis ◽  
Low Density Polyethylene ◽  
Array Detector ◽  
Eye Drops ◽  
Low Density ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Polyhexamethylene Biguanide ◽  
Initial Ph

Background Polyhexamethylene biguanide (PHMB) eye drops are a frequently used medication to treat Acanthamoeba keratitis. In the absence of marketed PHMB eye drops, pharmacy-compounding units are needed to prepare this much needed treatment, but the lack of validated PHMB stability data severely limits their conservation by imposing short expiration dates after preparation. In this study we aim to assess the physicochemical and microbiological stability of a 0.2 mg/mL PHMB eye drop formulation stored in two kinds of polyethylene bottles at two different temperatures. Methods A liquid chromatography coupled with diode array detector stability-indicating method was validated to quantify PHMB, using a cyanopropyl bonded phase (Agilent Zorbax Eclipse XDB-CN column 4.6 × 75 mm with particle size of 3.5 μm) and isocratic elution consisting of acetonitrile/deionized water (3/97 v/v) at a flow rate of 1.3 mL/min. PHMB eye drops stability was assessed for 90 days of storage at 5 and 25 °C in ethylene oxide sterilized low density polyethylene (EOS-LDPE) and gamma sterilized low density polyethylene (GS-LDPE) bottles. The following analyses were performed: visual inspection, PHMB quantification and breakdown products (BPs) screening, osmolality and pH measurements, and sterility assessment. PHMB quantification and BP screening was also performed on the drops emitted from the multidose eyedroppers to simulate in-use condition. Results The analytical method developed meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity, and is stability indicating. During 90 days of storage, no significant decrease of PHMB concentration was found compared to initial concentration in all stored PHMB eye drops. However, BP were found at day 30 and at day 90 of monitoring in both kind of bottles, stored at 5 and 25 °C, respectively. Although no significant variation of osmolality was found and sterility was maintained during 90 days of monitoring, a significant decrease of pH in GS-LDPE PHMB eye drops was noticed reaching 4 and 4.6 at 25 °C and 5 °C respectively, compared to initial pH of 6.16. Discussion Although no significant decrease in PHMB concentration was found during 90 days of monitoring in all conditions, the appearance of BPs and their unknown toxicities let us believe that 0.2 mg/mL PHMB solution should be conserved for no longer than 60 days in EOS-LDPE bottles at 25 °C.

Chemical Constituents and Antiamoebic of Methanolic Fraction from Peperomia pellucida (Linn.)Kunth

2014 ◽  
Vol 709 ◽  
pp. 417-421
Author(s):  
Chanyapat Sangsuwon ◽  
Weena Jirujchariyakul ◽  
Kosol Roongruangchai
Keyword(s):  
Chemical Constituents ◽  
Acanthamoeba Keratitis ◽  
Spectroscopic Methods ◽  
Opportunistic Pathogens ◽  
Free Living ◽  
Methanol Fraction ◽  
Polyhexamethylene Biguanide ◽  
Causative Agents ◽  
Dye Staining ◽  
Good Hygiene

Acanthamoeba spp. is the free living protozoain the environment which are opportunistic pathogens of human [1]. Acanthamoeba spp. is the causative agents of Acanthamoeba keratitis (AK)[2]. The risks of AK increased by using contact lens are not good hygiene. Antiamoebic therapy were biguanides chlorhexidine (BCH) or polyhexamethylene biguanide (PHMB) which were not effective enough to kill Acanthamoeba cysts [3]. Reported, plant for protected glaucoma, anti-inflammatory and analgesic properties are Peperomiapellucida in Piperaceae family. This interesting of studied P. pellucida for antiamoebic. Dried plant of P. pellucida was chromatographic by Diaion HP20 and fractionated into methanol : water (1:1, FrI), methanol (FrII) and ethyl acetate (FrIII). The methanol fraction (FrII) was damaged morphological and changed structural of Acanthamoeba cysts, detected by toluidine dye staining are shown under the light microscope, in IC50 29.28±3.64%.The active methanol fraction was studied by chromatography, gave four fractionated fraction A1-A4. A1 led to the isolation of compounds 1, A2 and A3 isolated compounds 2-5. They were identified using spectroscopic methods.

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