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Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles

Hussain MA, Ahmed D, Anwar A, Perveen S, Ahmed S, Anis I, et al.

Int Microbiol, 2019 Jun;22(2):239-246.
PMID: 30810990 DOI: 10.1007/s10123-018-00043-3

Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.

Matched MeSH terms: Antifungal Agents/pharmacology*
Comparative Study of the Effects of Fluconazole and Voriconazole on Candida glabrata, Candida parapsilosis and Candida rugosa Biofilms

Madhavan P, Jamal F, Pei CP, Othman F, Karunanidhi A, Ng KP

Mycopathologia, 2018 Jun;183(3):499-511.
PMID: 29380188 DOI: 10.1007/s11046-018-0243-z

Infections by non-albicans Candida species are a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. This study was aimed to demonstrate the in vitro antibiofilm activity of fluconazole (FLU) and voriconazole (VOR) against C. glabrata, C. parapsilosis and C. rugosa with diverse antifungal susceptibilities to FLU and VOR. The antibiofilm activities of FLU and VOR in the form of suspension as well as pre-coatings were assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay. Morphological and intracellular changes exerted by the antifungal drugs on Candida cells were examined by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results of the antibiofilm activities showed that FLU drug suspension was capable of killing C. parapsilosis and C. rugosa at minimum inhibitory concentrations (MICs) of 4× MIC FLU and 256× MIC FLU, respectively. While VOR MICs ranging from 2× to 32× were capable of killing the biofilms of all Candida spp tested. The antibiofilm activities of pre-coated FLU were able to kill the biofilms at ¼× MIC FLU and ½× MIC FLU for C. parapsilosis and C. rugosa strains, respectively. While pre-coated VOR was able to kill the biofilms, all three Candida sp at ½× MIC VOR. SEM and TEM examinations showed that FLU and VOR treatments exerted significant impact on Candida cell with various degrees of morphological changes. In conclusion, a fourfold reduction in MIC50 of FLU and VOR towards ATCC strains of C. glabrata, C. rugosa and C. rugosa clinical strain was observed in this study.

Matched MeSH terms: Antifungal Agents/pharmacology*
Fulltext Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report

Abu Talib DN, Yong MH, Nasaruddin RA, Che-Hamzah J, Bastion MC

Medicine (Baltimore), 2021 Apr 09;100(14):e25459.
PMID: 33832156 DOI: 10.1097/MD.0000000000025459

RATIONALE: Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcome.
PATIENT CONCERNS: A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks' course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.
DIAGNOSIS: He was diagnosed with EFE but the condition responded poorly with the medications.
INTERVENTIONS: He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.
OUTCOMES: At 3 months' follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.
LESSONS: Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.

Matched MeSH terms: Antifungal Agents/therapeutic use
Fulltext Successful treatment of Candida albicans endocarditis in a child with leukemia--a case report and review of the literature

Ariffin H, Ariffin W, Tharam S, Omar A, de Bruyne J, Lin HP

Singapore Med J, 1999 Aug;40(8):533-6.
PMID: 10572495

Candida species is now being increasingly recognised as an important cause of endocarditis especially in immunocompromised patients. A case of Candida albicans endocarditis in a child with acute lymphoblastic leukemia (ALL) is reported. The child did not have a central venous catheter at any time. Treatment consisted of intravenous amphotericin B and fluconazole for 3 weeks followed by oral fluconazole for 2 weeks. No surgical resection was necessary. We highlight here the importance of echocardiography in the management of prolonged febrile neutropenia and discuss the dilemma of continuing chemotherapy in such patients.

Matched MeSH terms: Antifungal Agents/administration & dosage*
The inhibitory effects of aureobasidin A on Candida planktonic and biofilm cells

Tan HW, Tay ST

Mycoses, 2013 Mar;56(2):150-6.
PMID: 22882276 DOI: 10.1111/j.1439-0507.2012.02225.x

Aureobasidin A (AbA) is a cyclic depsipeptide antifungal compound that inhibits a wide range of pathogenic fungi. In this study, the in vitro susceptibility of 92 clinical isolates of various Candida species against AbA was assessed by determining the planktonic and biofilm MICs of the isolates. The MIC(50) and MIC(90) of the planktonic Candida yeast were 1 and 1 μg ml(-1), respectively, whereas the biofilm MIC(50) and MIC(90) of the isolates were 8 and ≥64 μg ml(-1) respectively. This study demonstrates AbA inhibition on filamentation and biofilm development of C. albicans. The production of short hyphae and a lack of filamentation might have impaired biofilm development of AbA-treated cells. The AbA resistance of mature Candidia biofilms (24 h adherent population) was demonstrated in this study.

Matched MeSH terms: Antifungal Agents/pharmacology
Fulltext Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes

Rudramurthy GR, Swamy MK, Sinniah UR, Ghasemzadeh A

Molecules, 2016 Jun 27;21(7).
PMID: 27355939 DOI: 10.3390/molecules21070836

Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered "miracle drugs" and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future.

Matched MeSH terms: Antifungal Agents/administration & dosage
Fulltext Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced β-Carotene Production in M. circinelloides CBS 277.49

Naz T, Nazir Y, Nosheen S, Ullah S, Halim H, Fazili ABA, et al.

Biomed Res Int, 2020;2020:8890269.
PMID: 33457420 DOI: 10.1155/2020/8890269

Carotenoids produced by microbial sources are of industrial and medicinal importance due to their antioxidant and anticancer properties. In the current study, optimization of β-carotene production in M. circinelloides strain 277.49 was achieved using response surface methodology (RSM). Cerulenin and ketoconazole were used to inhibit fatty acids and the sterol biosynthesis pathway, respectively, in order to enhance β-carotene production by diverting metabolic pool towards the mevalonate pathway. All three variables used in screening experiments were found to be significant for the production of β-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior β-carotene production using central composite design of RSM. Our results found that the synergistic combination of C/N ratios, cerulenin, and ketoconazole at different concentrations affected the β-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10 μg/mL cerulenin, and 150 mg/L ketoconazole, producing maximum β-carotene of 4.26 mg/L (0.43 mg/g) which was 157% greater in comparison to unoptimized medium (1.68 mg/L, 0.17 mg/g). So, it was concluded that metabolic flux had been successfully redirected towards the mevalonate pathway for enhanced β-carotene production in CBS 277.49.

Matched MeSH terms: Antifungal Agents/chemistry
Fulltext Assessment of Euphorbia hirta L. leaf, flower, stem and root extracts for their antibacterial and antifungal activity and brine shrimp lethality

Rajeh MA, Zuraini Z, Sasidharan S, Latha LY, Amutha S

Molecules, 2010 Aug 31;15(9):6008-18.
PMID: 20877206 DOI: 10.3390/molecules15096008

The antimicrobial activities of the methanolic extracts of Euphorbia hirta L leaves, flowers, stems and roots were evaluated against some medically important bacteria and yeast using the agar disc diffusion method. Four Gram positive (Staphylococcus aureus, Micrococcus sp., Bacillus subtilis and Bacillus thuringensis), four Gram negative (Escherichia coli, Klebsiella pneumonia, Salmonella typhi and P. mirabilis) and one yeast (Candida albicans) species were screened. Inhibition zones ranged between 16-29 mm. Leaves extract inhibited the growth of all tested microorganisms with large zones of inhibition, followed by that of flowers, which also inhibited all the bacteria except C. albicans. The most susceptible microbes to all extracts were S. aureus and Micrococcus sp. Root extract displayed larger inhibition zones against Gram positive bacteria than Gram negative bacteria and had larger inhibition zones compared to stem extract. The lowest MIC values were obtained with E. coli and C. albicans (3.12 mg/mL), followed by S. aureus (12.50 mg/mL) and P. mirabilis (50.00 mg/mL). All the other bacteria had MIC values of 100.00 mg/mL. Scanning Electron Microscopic (SEM) studies revealed that the cells exposed to leaf extract displayed a rough surface with multiple blends and invaginations which increased with increasing time of treatment, and cells exposed to leaf extract for 36 h showed the most damage, with abundant surface cracks which may be related to final cell collapse and loss of function. Time-kill assay of C. albicans indicated a primarily fungicidal effect at 1- and 2-fold MIC. E. hirta extracts had LC(50) values of 0.71, 0.66, 0.41 and 0.03 mg/mL for stems, leaves, roots and flowers, respectively against Artemia salina. Hence, these plants can be used to discover new bioactive natural products that may serve as leads in the development of new pharmaceuticals.

Matched MeSH terms: Antifungal Agents/isolation & purification*
Fulltext Case report of a rare fungal infection Kodamaea ohmeri in COVID-19 patient in North Malaysian hospital

Farooq H, Sabesan GS, Monowar T, Chinni SV, Zainol NH

Indian J Pathol Microbiol, 2024 Jul 01;67(3):654-657.
PMID: 38391359 DOI: 10.4103/ijpm.ijpm_972_22

Kodamaea ohmeri is a rare opportunistic pathogen belonging to Saccharomycetes family. This yeast was also formerly known as Yamadazyma ohmeri or Pichia ohmeri . This opportunistic pathogen causes illness that typically affects people with impaired immune system. In this report, we discuss a fatal case involving a woman in her late 30s who was admitted to the hospital on the sixth day of her sickness after being given a COVID-19 Category 5A diagnosis. For COVID-19, she received subcutaneous heparin, cefuroxime, and intravenous corticosteroids. She was diagnosed with secondary bacterial and fungal infections in the ICU. Multiple antibiotics and antifungal were given to treat bacterial and fungal infections. An unusual fungus, Kodamaea ohmeri , was isolated from the clinical sample. On day 36, she succumbed to her infection in the ICU. The cause of death was multidrug-resistant sepsis with multiple organ failures due to COVID-19 infection, worsened by an embolism and trachea damage during a tracheostomy. To effectively manage K. ohmeri , clinicians and microbiologists must identify and be aware of this emerging human opportunistic pathogen, which can co-infect debilitated patients such as COVID-19 patients, for effective management.

Matched MeSH terms: Antifungal Agents/therapeutic use
Fulltext Antimicrobial and antioxidant activities of new metal complexes derived from 3-aminocoumarin

Kadhum AA, Mohamad AB, Al-Amiery AA, Takriff MS

Molecules, 2011 Aug 15;16(8):6969-84.
PMID: 21844844 DOI: 10.3390/molecules16086969

3-Aminocoumarin (L) has been synthesized and used as a ligand for the formation of Cr(III), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different spectroscopic methods. The elemental analyses revealed that the complexes where M=Ni(II) and Cu(II) have the general formulae [ML(2)Cl(2)], while the Cr(III) complex has the formula [CrL(2)Cl(2)]Cl. The molar conductance data reveal that all the metal chelates, except the Cr(III) one, are non-electrolytes. From the magnetic and UV-Visible spectra, it is found that these complexes have octahedral structures. The stability for the prepared complexes was studied theoretically using Density Function Theory. The total energy for the complexes was calculated and it was shown that the copper complex is the most stable one. Complexes were tested against selected types of microbial organisms and showed significant activities. The free radical scavenging activity of metal complexes have been determined by measuring their interaction with the stable free radical DPPH and all the compounds have shown encouraging antioxidant activities.

Matched MeSH terms: Antifungal Agents/chemical synthesis*; Antifungal Agents/pharmacology
Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study

Somchit N, Norshahida AR, Hasiah AH, Zuraini A, Sulaiman MR, Noordin MM

Hum Exp Toxicol, 2004 Nov;23(11):519-25.
PMID: 15625777

Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.

Matched MeSH terms: Antifungal Agents/administration & dosage; Antifungal Agents/toxicity*
Fulltext Rare Kodamaea ohmeri keratitis following a trivial vegetative trauma

Saud Al-Abbas AH, Ling JL, Muhammed J, Hussein A

BMJ Case Rep, 2019 Jun 22;12(6).
PMID: 31229985 DOI: 10.1136/bcr-2019-229660

Kodamaea ohmeri keratitis is an opportunistic pathogen seen in patients who have undergone invasive procedures and immunocompromised state. It has been identified in septicemia patients, resulting in mortality. To the best of our knowledge, we identified the first case of K. ohmeri keratitis following an injury with vegetative material. A 57-year-old woman with underlying, poorly controlled diabetes mellitus was gardening when a tree leaf accidentally poked her in the eye. Two weeks later, the patient presented with right eye pain, redness and progressive blurring of vision due to a traumatised right cornea. Slit-lamp examination showed a small inferior paracentral corneal stromal infiltrate with overlying epithelial defect. A corneal scraping sample yielded K. ohmeri from Analytical Profile Index (API) 20C yeast identification system. She was treated with intensive topical amphotericin B and fluconazole. After 6 weeks of treatment, the keratitis resolved with faint scar tissue, and her visual acuity improved.

Matched MeSH terms: Antifungal Agents/administration & dosage; Antifungal Agents/therapeutic use
Fulltext The Antimicrobial efficacy of Elaeis guineensis: characterization, in vitro and in vivo studies

Vijayarathna S, Zakaria Z, Chen Y, Latha LY, Kanwar JR, Sasidharan S

Molecules, 2012 Apr 26;17(5):4860-77.
PMID: 22538489 DOI: 10.3390/molecules17054860

The urgent need to treat multi-drug resistant pathogenic microorganisms in chronically infected patients has given rise to the development of new antimicrobials from natural resources. We have tested Elaeis guineensis Jacq (Arecaceae) methanol extract against a variety of bacterial, fungal and yeast strains associated with infections. Our studies have demonstrated that E. guineensis exhibits excellent antimicrobial activity in vitro and in vivo against the bacterial and fungal strains tested. A marked inhibitory effect of the E. guineensis extracts was observed against C. albicans whereby E. guineensis extract at ½, 1, or 2 times the MIC significantly inhibited C. albicans growth with a noticeable drop in optical density (OD) of the bacterial culture. This finding confirmed the anticandidal activity of the extract on C. albicans. Imaging using scanning (SEM) and transmission (TEM) electron microscopy was done to determine the major alterations in the microstructure of the extract-treated C. albicans. The main abnormalities noted via SEM and TEM studies were the alteration in morphology of the yeast cells. In vivo antimicrobial activity was studies in mice that had been inoculated with C. albicans and exhibited good anticandidal activity. The authors conclude that the extract may be used as a candidate for the development of anticandidal agent.

Matched MeSH terms: Antifungal Agents/pharmacology*; Antifungal Agents/chemistry
Fulltext "Nature cures:" An alternative herbal formulation as a denture cleanser

Sushma R, Sathe TT, Farias A, Sanyal PK, Kiran S

Ann Afr Med, 2017;16(1):6-12.
PMID: 28300045 DOI: 10.4103/aam.aam_43_16

BACKGROUND: Candida albicans is one of the microorganisms which harbor the oral cavity, especially in elderly. However, the incidence of existence of this increases in patients using removable dental prosthesis. There is therefore a need to test the anticandidal efficacy of these cost-effective, easily available products to be used as routine denture cleansers.
AIM AND OBJECTIVES: (1) To evaluate antifungal properties of triphala churna on the heat cure denture base material. (2) To evaluate the antifungal effect of chlorhexidine gluconate on the heat cure denture base material. (3) To compare the antifungal effect of triphala churna and chlorhexidine gluconate with a control. (4) To evaluate which among triphala churna and chlorhexidine gluconate has a better antifungal property on the heat cure denture base material.
MATERIALS AND METHODS: Study population consisted of sixty dentures wearers from those attending the Outpatient Department of Prosthodontics of the School of Dentistry, Krishna Institute of Medical Sciences Deemed University, Karad. Swabs were collected from the dentures before and after the use of triphala and chlorhexidine. The swabs were cultured on Sabouraud dextrose agar and the total Candida counts were determined.
CONCLUSION: Triphala as an antifungal is shown to have more efficacy than the conventional chlorhexidine mouthwash. Résumé Arrière-plan: Candida albicans est l'un des micro-organismes qui abritent la cavité buccale surtout chez les personnes âgées. Cependant, l'incidence de l'existence de cette augmentation chez les patients utilisant des prothèses dentaires amovibles. Il est donc nécessaire de tester l'efficacité anticancédique de ces produits rentables et faciles à utiliser pour être utilisés comme nettoyants de routine pour prothèses dentaires. Buts et Objectifs: (1) Évaluer les propriétés antifongiques de Triphala churna sur le matériau de base de la prothèse thermo-durcissable. (2) Évaluer l'effet antifongique du gluconate de chlorhexidine sur le matériau de base de la prothèse thermo-durcissable. (3) Comparer l'effet antifongique de Triphala churna et du gluconate de chlorhexidine avec un témoin. (4) Évaluer lequel parmi Triphala churna et le gluconate de chlorhexidine a une meilleure propriété antifongique sur le matériel de base de la prothèse de durcissement à chaud. Matériaux et Méthode: La population de l'étude était constituée de soixante porteurs de prothèses dentaires de ceux qui fréquentaient le Département de Prosthodontie de l'École des Sciences Dentaires de l'Institut Krishna des Sciences Médicales de l'Université de Karad. Des prélèvements ont été effectués sur les prothèses avant et après l'utilisation de Triphala et de chlorhexidine. On a cultivé les écouvillons sur de l'agar Sabouraud dextrose et on a déterminé le nombre total de candida.
CONCLUSION: Triphala comme un anti fongique est démontré pour avoir plus d'efficacité que le lavage de la bouche classique chlorhexidine.

Matched MeSH terms: Antifungal Agents/pharmacology; Antifungal Agents/therapeutic use*
Fulltext Size dependent effects of antifungal phytogenic silver nanoparticles on germination, growth and biochemical parameters of rice (Oryza sativa L), maize (Zea mays L) and peanut (Arachis hypogaea L)

Prasad TNVKV, Adam S, Visweswara Rao P, Ravindra Reddy B, Giridhara Krishna T

IET Nanobiotechnol, 2017 Apr;11(3):277-285.
PMID: 28476985 DOI: 10.1049/iet-nbt.2015.0122

Advancement in materials synthesis largely depends up on their diverse applications and commercialisation. Antifungal effects of phytogenic silver nanoparticles (AgNPs) were evident, but the reports on the effects of the same on agricultural crops are scant. Herein, we report for the first time, size dependent effects of phytogenic AgNPs (synthesised using Stevia rebaudiana leaf extract) on the germination, growth and biochemical parameters of three important agricultural crops viz., rice (Oryza sativa L), maize (Zea mays L) and peanut (Arachis hypogaea L). AgNPs with varied sizes were prepared by changing the concentration and quantity of the Stevia rebaudiana leaf extract. As prepared AgNPs were characterized using the techniques, such as high-resolution transmission electron microscopy, particle size and zeta potential analyser. The measured (dynamic light scattering technique) average sizes of particles are ranging from 68.5 to 116 nm. Fourier transform infrared studies confirmed the participation of alcohols, aldehydes and amides in the reduction and stabilisation of the AgNPs. Application of these AgNPs to three agricultural crop seeds (rice, maize and peanut) resulted in size dependent effects on their germination, growth and biochemical parameters such as, chlorophyll content, carotenoid and protein content. Further, antifungal activity of AgNPs also evaluated against fungi, Aspergillus niger.

Matched MeSH terms: Antifungal Agents/administration & dosage*; Antifungal Agents/chemistry
Fulltext Isolation and Characterization of an Atypical Metschnikowia sp. Strain from the Skin Scraping of a Dermatitis Patient

Kuan CS, Ismail R, Kwan Z, Yew SM, Yeo SK, Chan CL, et al.

PLoS One, 2016;11(6):e0156119.
PMID: 27280438 DOI: 10.1371/journal.pone.0156119

A yeast-like organism was isolated from the skin scraping sample of a stasis dermatitis patient in the Mycology Unit Department of Medical Microbiology, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The isolate produced no pigment and was not identifiable using chromogenic agar and API 20C AUX. The fungus was identified as Metschnikowia sp. strain UM 1034, which is close to that of Metschnikowia drosophilae based on ITS- and D1/D2 domain-based phylogenetic analysis. However, the physiology of the strain was not associated to M. drosophilae. This pathogen exhibited low sensitivity to all tested azoles, echinocandins, 5-flucytosine and amphotericin B. This study provided insight into Metschnikowia sp. strain UM 1034 phenotype profiles using a Biolog phenotypic microarray (PM). The isolate utilized 373 nutrients of 760 nutrient sources and could adapt to a broad range of osmotic and pH environments. To our knowledge, this is the first report of the isolation of Metschnikowia non-pulcherrima sp. from skin scraping, revealing this rare yeast species as a potential human pathogen that may be misidentified as Candida sp. using conventional methods. Metschnikowia sp. strain UM 1034 can survive in flexible and diverse environments with a generalist lifestyle.

Matched MeSH terms: Antifungal Agents/pharmacology
Occurrence and characterization of Candida nivariensis from a culture collection of Candida glabrata clinical isolates in Malaysia

Tay ST, Lotfalikhani A, Sabet NS, Ponnampalavanar S, Sulaiman S, Na SL, et al.

Mycopathologia, 2014 Oct;178(3-4):307-14.
PMID: 25022264 DOI: 10.1007/s11046-014-9778-9

BACKGROUND: Candida nivariensis and C. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from C. glabrata. However, there is little data on the prevalence and antifungal susceptibilities of these species.
OBJECTIVE: This study investigated the occurrence of C. nivariensis and C. bracarensis in a culture collection of 185 C. glabrata isolates at a Malaysian teaching hospital.
METHODS: C. nivariensis was discriminated from C. glabrata using a PCR assay as described by Enache-Angoulvant et al. (J Clin Microbiol 49:3375-9, 2011). The identity of the isolates was confirmed by sequence analysis of the D1D2 domain and internal transcribed spacer region of the yeasts. The isolates were cultured on Chromogenic CHROMagar Candida (®) agar (Difco, USA), and their biochemical and enzymic profiles were determined. Antifungal susceptibilities of the isolates against amphotericin B, fluconazole, voriconazole and caspofungin were determined using E tests. Clotrimazole MICs were determined using a microbroth dilution method.
RESULTS: There was a low prevalence (1.1 %) of C. nivariensis in our culture collection of C. glabrata. C. nivariensis was isolated from a blood culture and vaginal swab of two patients. C. nivariensis grew as white colonies on Chromogenic agar and demonstrated few positive reactions using biochemical tests. Enzymatic profiles of the C. nivariensis isolates were similar to that of C. glabrata. The isolates were susceptible to amphotericin B, fluconazole, voriconazole and caspofungin. Clotrimazole resistance is suspected in one isolate.
CONCLUSION: This study reports for the first time the emergence of C. nivariensis in our clinical setting.

Matched MeSH terms: Antifungal Agents/pharmacology
Fulltext Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

Lim WM, Rajinikanth PS, Mallikarjun C, Kang YB

Int J Nanomedicine, 2014;9:2117-26.
PMID: 24833900 DOI: 10.2147/IJN.S57565

The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.

Matched MeSH terms: Antifungal Agents/administration & dosage
Cutaneous sporotrichosis: a six-year review of 19 cases in a tertiary referral center in Malaysia

Tang MM, Tang JJ, Gill P, Chang CC, Baba R

Int J Dermatol, 2012 Jun;51(6):702-8.
PMID: 22607289 DOI: 10.1111/j.1365-4632.2011.05229.x

Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics.

Matched MeSH terms: Antifungal Agents/therapeutic use
Locally isolated yeasts from Malaysia: identification, phylogenetic study and characterization

Oslan SN, Salleh AB, Rahman RN, Basri M, Chor AL

Acta Biochim. Pol., 2012;59(2):225-9.
PMID: 22577620

Yeasts are a convenient platform for many applications. They have been widely used as the expression hosts. There is a need to have a new yeast expression system to contribute the molecular cloning demands. Eight yeast isolates were screened from various environment sources and identified through ribosomal DNA (rDNA) Internal Transcribed Spacer (ITS). Full sequence of the rDNA ITS region for each isolate was BLASTed and phylogenetic study was constructed by using MEGA4. Among the isolates, isolate WB from 'ragi' (used to ferment carbohydrates) could be identified as a new species in order Saccharomycetales according to rDNA ITS region, morphology and biochemical tests. Isolate SO (from spoiled orange), RT (rotten tomato) and RG (different type of 'ragi') were identified as Pichia sp. Isolates R1 and R2, S4 and S5 (from the surrounding of a guava tree) were identified as Issatchenkia sp. and Hanseniaspora sp., respectively. Geneticin, 50 µg/mL, was determined to be the antibiotic marker for all isolates excepted for isolates RT and SO which used 500 µg/mL and 100 µg/mL Zeocin, respectively. Intra-extracellular proteins were screened for lipolytic activity at 30°C and 70°C. Thermostable lipase activity was detected in isolates RT and R1 with 0.6 U/mg and 0.1 U/mg, respectively. In conclusion, a new yeast-vector system for isolate WB can be developed by using phleomycin or geneticin as the drugs resistance marker. Moreover, strains RT and R1 can be investigated as a novel source of a thermostable lipase.

Matched MeSH terms: Antifungal Agents/pharmacology

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