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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: Candidiasis/diagnosis*; Candidiasis/therapy*
In vitro antifungal susceptibilities of Candida isolates from patients with invasive candidiasis in Kuala Lumpur Hospital, Malaysia

Amran F, Aziz MN, Ibrahim HM, Atiqah NH, Parameswari S, Hafiza MR, et al.

J Med Microbiol, 2011 Sep;60(Pt 9):1312-1316.
PMID: 21459913 DOI: 10.1099/jmm.0.027631-0

The in vitro antifungal susceptibilities of 159 clinical isolates of Candida species from patients with invasive candidiasis in Kuala Lumpur Hospital, Malaysia, were determined against amphotericin B, fluconazole, voriconazole, itraconazole and caspofungin. The most common species were Candida albicans (71 isolates), Candida parapsilosis (42 isolates), Candida tropicalis (27 isolates) and Candida glabrata (12 isolates). The susceptibility tests were carried out using an E-test. The MIC breakpoints were based on Clinical Laboratory Standards Institute criteria. Amphotericin B and voriconazole showed the best activities against all the isolates tested, with MIC(90) values of ≤1 µg ml(-1) for all major species. Only one Candida lusitaniae isolate was resistant to amphotericin B, and all the isolates were susceptible to voriconazole. In total, six isolates were resistant to fluconazole, comprising two isolates of C. albicans, two of C. parapsilosis, one C. tropicalis and one C. glabrata, and all of these isolates showed cross-resistance to itraconazole. The MIC(90) of itraconazole was highest for C. glabrata and C. parapsilosis. Caspofungin was active against most of the isolates except for five isolates of C. parapsilosis. The MIC(90) of caspofungin against C. parapsilosis was 3 µg ml(-1). In conclusion, amphotericin B remains the most active antifungal agent against most Candida species except for C. lusitaniae. Voriconazole is the best alternative for fluconazole- or itraconizole-resistant isolates. Although five of the C. parapsilosis isolates showed in vitro resistance to caspofungin, more clinical correlation studies need to be carried out to confirm the significance of these findings. Currently, despite the increase in usage of antifungals in our hospitals, especially in the management of febrile neutropenia patients, the antifungal-resistance problem among clinically important Candida isolates in Kuala Lumpur Hospital is not yet worrying. However, continued antifungal-susceptibility surveillance needs to be conducted to monitor the antifungal-susceptibility trends of Candida species and other opportunistic fungal pathogens.

Matched MeSH terms: Candidiasis, Invasive/microbiology*
Purification and comparison of intracellular proteinase A in Candida spp. isolates from Malaysian and Iranian patients and infected mice

Amri Saroukolaei S, Pei Pei C, Shokri H, Asadi F

J Mycol Med, 2012 Jun;22(2):149-59.
PMID: 23518017 DOI: 10.1016/j.mycmed.2012.01.002

To compare the specific intracellular proteinase A activity in clinical isolates of Candida species isolated from Iranian and Malaysian patients, the blood and kidneys of mice infected by Candida cells isolated from these human patients.

Matched MeSH terms: Candidiasis/microbiology*; Candidiasis/epidemiology
Lactobacillus probiotics restore vaginal and gut microbiota of pregnant women with vaginal candidiasis

Ang XY, Roslan NS, Ahmad N, Yusof SM, Abdullah N, Nik Ab Rahman NN, et al.

Benef Microbes, 2023 Nov 23;14(5):421-431.
PMID: 38350486 DOI: 10.1163/18762891-20220103

The development of probiotics has now included the areas along the gut-vaginal axis. We thus aimed to investigate the effects of lactobacilli probiotic to modulate and restore vaginal and gut microbiota of pregnant women with vaginal candidiasis (VC). A randomised, double-blind and placebo-controlled study was performed in 78 pregnant women with VC. Patients were randomised to either the probiotic (SynForU-HerCare) or placebo which were administered at baseline and continued for 8-weeks (two capsules/day of 9.5 log cfu/capsule). Microbiota profiles were assessed at time points of weeks-0, 4 and 8 for high vaginal swab and faecal samples. Shannon diversity index showed that after 8-weeks amid VC, a shift in microbial community compositional changes occurred in the high vaginal region at both genus (P=0.025) and species (P=0.044) levels, where the administration of probiotic prevented such a shift. These changes were mainly attributed to a decreased in abundance of Lactobacillus (P=0.042) accompanied by increased abundance of Prevotella (P=0.002) and Atopobium (P=0.002) in the placebo group while the probiotic group remained unchanged over time. The administration of probiotics also prevented a reduced abundance of faecal phylum Firmicutes after 8-weeks as seen in the placebo group (P<0.0001), which also showed reduction at subsequent taxonomic levels of class, family, genera and species. VC has not only altered the microbiota of vagina regions but also gut microbiota profiles, causing lessening of gut microbiota that are crucial for gut nutrient availability, protection and immunity. The administration of lactobacilli probiotics has prevented such a shift, leading to better modulated gut and vaginal microenvironment amid VC. The study was registered at ClinicalTrials.gov: identifier number NCT03940612.

Matched MeSH terms: Candidiasis, Vulvovaginal*
Intravenous fluconazole for bilateral endogenous Candida endophthalmitis

Annamalai T, Fong KC, Choo MM

J Ocul Pharmacol Ther, 2011 Feb;27(1):105-7.
PMID: 21235384 DOI: 10.1089/jop.2010.0117

To report a case of bilateral endogenous candida endophthalmitis treated with intravenous fluconazole.

Matched MeSH terms: Candidiasis/drug therapy*
Fulltext Candida sake--a rare cause of fungal endocarditis

Anuradha S, Agarwal SK, Prakash A, Singh NP, Kaur R

Med J Malaysia, 2008 Mar;63(1):75-6.
PMID: 18935744
Matched MeSH terms: Candidiasis/microbiology*
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: Candidiasis/diagnosis; Candidiasis/drug therapy*; Candidiasis/immunology
Detection of Candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy samples

Bakri MM, Cannon RD, Holmes AR, Rich AM

J Oral Pathol Med, 2014 Oct;43(9):704-10.
PMID: 24931506 DOI: 10.1111/jop.12193

The aim of this study was to investigate the relationship between expression of Candida albicans alcohol dehydrogenases (ADH) genes in archival formalin-fixed paraffin-embedded (FFPE) samples from biopsies of leukoplakia.

Matched MeSH terms: Candidiasis, Oral/microbiology
Isolates of the emerging pathogen Candida auris present in the UK have several geographic origins

Borman AM, Szekely A, Johnson EM

Med Mycol, 2017 Jul 01;55(5):563-567.
PMID: 28204557 DOI: 10.1093/mmy/myw147

Candida auris has recently emerged as a serious nosocomial health risk, with widespread outbreaks in numerous hospitals worldwide and the existence of geographic region-specific discrete clonal lineages. Here we have compared the rDNA sequences of 24 isolates of Candida auris from 14 different hospital centers in the United Kingdom with those of strains from different international origins present in the public sequence databases. Here we show that UK isolates of C. auris fall into three well-supported clades corresponding to lineages that have previously been reported from India, Malaysia and Kuwait, Japan and Korea, and South Africa, respectively.

Matched MeSH terms: Candidiasis/microbiology*
Oral Thrush

Chaubal T, Bapat R

Am J Med, 2018 09;131(9):e371-e372.
PMID: 29730363 DOI: 10.1016/j.amjmed.2018.04.020
Matched MeSH terms: Candidiasis, Oral/diagnosis*
Early-Stage Multifocal Candida chorioretinitis in an Immunocompromised Woman

Chen KJ, Chou HD, Teh WM

Ophthalmol Retina, 2019 10;3(10):887.
PMID: 31585711 DOI: 10.1016/j.oret.2019.05.023
Matched MeSH terms: Candidiasis/diagnosis*; Candidiasis/microbiology
A serological survey to determine the prevalence of fungal infection in cancer patients at the Hospital Kuala Lumpur

Cheong I, Tan SC, Wong WH, Zainuddin RH, Yassin MS

Family Physician, 1994;6:9-11.

A study was conducted to determine the prevalence of fungal infection in cancer patients warded at the Hospital Kuala Lumpur. There were 138 patients included in the study: 74 with haematological malignancies and 64 with solid tumours. Serological results showed that for candidiasis 16/138 (11.5%) and 10/134 (7.5%) were greater than 1:8 reactive for antigen and antibodies respectively. For aspergillosis, 29/122 (23.8%) sera were antigen reactive. Only 1/133 each (O.SO/o) was reactive for cryptococcal antigen and antibody. The types of malignancies, the age of the patient, a history of neutropenia, the duration of the cancer, the number of courses of chemotherapy or radiotherapy were not predictive of fungal infections. In view of the high serological evidence of fungal infection and the lack of a reliable diagnostic test, empirical antifungal treatment must be considered in all febrile neutropenic cancer patients.

Matched MeSH terms: Candidiasis
Fulltext Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 exhibit strong antifungal effects against vulvovaginal candidiasis-causing Candida glabrata isolates

Chew SY, Cheah YK, Seow HF, Sandai D, Than LT

J Appl Microbiol, 2015 May;118(5):1180-90.
PMID: 25688886 DOI: 10.1111/jam.12772

This study investigates the antagonistic effects of the probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 against vulvovaginal candidiasis (VVC)-causing Candida glabrata.

Matched MeSH terms: Candidiasis, Vulvovaginal/microbiology*
Fulltext The glyoxylate cycle and alternative carbon metabolism as metabolic adaptation strategies of Candida glabrata: perspectives from Candida albicans and Saccharomyces cerevisiae

Chew SY, Chee WJY, Than LTL

J Biomed Sci, 2019 Jul 13;26(1):52.
PMID: 31301737 DOI: 10.1186/s12929-019-0546-5

BACKGROUND: Carbon utilization and metabolism are fundamental to every living organism for cellular growth. For intracellular human fungal pathogens such as Candida glabrata, an effective metabolic adaptation strategy is often required for survival and pathogenesis. As one of the host defence strategies to combat invading pathogens, phagocytes such as macrophages constantly impose restrictions on pathogens' access to their preferred carbon source, glucose. Surprisingly, it has been reported that engulfed C. glabrata are able to survive in this harsh microenvironment, further suggesting alternative carbon metabolism as a potential strategy for this opportunistic fungal pathogen to persist in the host.
MAIN TEXT: In this review, we discuss alternative carbon metabolism as a metabolic adaptation strategy for the pathogenesis of C. glabrata. As the glyoxylate cycle is an important pathway in the utilization of alternative carbon sources, we also highlight the key metabolic enzymes in the glyoxylate cycle and its necessity for the pathogenesis of C. glabrata. Finally, we explore the transcriptional regulatory network of the glyoxylate cycle.
CONCLUSION: Considering evidence from Candida albicans and Saccharomyces cerevisiae, this review summarizes the current knowledge of the glyoxylate cycle as an alternative carbon metabolic pathway of C. glabrata.

Matched MeSH terms: Candidiasis/metabolism*
Vulvovaginal candidosis: contemporary challenges and the future of prophylactic and therapeutic approaches

Chew SY, Than LT

Mycoses, 2016 May;59(5):262-73.
PMID: 26765516 DOI: 10.1111/myc.12455

Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal pathogen Candida species. In fact, three out of every four women will experience at least one occasion of VVC during some point in their lives. Although uncomplicated VVC is relatively harmless, the complicated VVC such as recurrent attack often creates restlessness and depression in the patients, thus greatly affects their quality of life. Managements of VVC are usually associated with the use of antimycotic suppositories, topical cream or oral agents. These antimycotic agents are either available over-the-counter or prescribed by the clinicians. In recent decades, the rise of clinical challenges such as the increased prevalence of resistant Candida strains, recurrent VVC infection and adverse effects of multidrug interactions have necessitated the development of novel therapeutic or prophylactic options to combat the complicated VVC in the future. In this review, we discuss the current antimycotic treatments available for Candida vaginitis and the problems that exist in these seemingly effective treatments. Besides, we attempt to contemplate some of the future and prospective strategies surrounding the development of alternative therapeutic and prophylactic options in treating and preventing complicated VVC respectively.

Matched MeSH terms: Candidiasis, Vulvovaginal
Fulltext Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata

Chew SY, Ho KL, Cheah YK, Ng TS, Sandai D, Brown AJP, et al.

Sci Rep, 2019 02 26;9(1):2843.
PMID: 30808979 DOI: 10.1038/s41598-019-39117-1

The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1∆ cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention.

Matched MeSH terms: Candidiasis/immunology; Candidiasis/microbiology*
Fulltext Torulopsis glabrata in vaginitis

Chin CS, Cheong YM

Med J Malaysia, 1988 Sep;43(3):250-1.
PMID: 3241585
Matched MeSH terms: Candidiasis, Vulvovaginal/microbiology*
Fulltext Multi-step pathogenesis and induction of local immune response by systemic Candida albicans infection in an intravenous challenge mouse model

Chin VK, Foong KJ, Maha A, Rusliza B, Norhafizah M, Chong PP

Int J Mol Sci, 2014;15(8):14848-67.
PMID: 25153636 DOI: 10.3390/ijms150814848

Different murine species differ in their susceptibility to systemic infection with Candida albicans, giving rise to varied host immune responses, and this is compounded by variations in virulence of the different yeast strains used. Hence, this study was aimed at elucidating the pathogenesis of a clinical C. albicans isolate (HVS6360) in a murine intravenous challenge model by examining the different parameters which included the counts of red blood cells and associated components as well as the organ-specific expression profiles of cytokines and chemokines. Kidneys and brains of infected mice have higher fungal recovery rates as compared to other organs and there were extensive yeast infiltration with moderate to severe inflammation seen in kidney and brain tissues. Red blood cells (RBCs) and haemoglobin (Hb) counts were reduced throughout the infection period. Pattern recognition receptors (PRRs), chemokines and cytokine transcription profiles were varied among the different organs (kidney, spleen and brain) over 72 h post infections. Transcription of most of the PRRs, cytokines and chemokines were suppressed at 72 h post infection in spleen while continuous expression of PRRs, cytokines and chemokines genes were seen in brain and kidney. Reduction in red blood cells and haemoglobin counts might be associated with the action of extracellular haemolysin enzyme and haeme oxygenase of C. albicans in conjunction with iron scavenging for the fungal growth. Renal cells responsible for erythropoietin production may be injured by the infection and hence the combined effect of haemolysis plus lack of erythropoietin-induced RBC replenishment leads to aggravated reduction in RBC numbers. The varied local host immune profiles among target organs during systemic C. albicans infection could be of importance for future work in designing targeted immunotherapy through immunomodulatory approaches.

Matched MeSH terms: Candidiasis/immunology*; Candidiasis/metabolism
Early expression of local cytokines during systemic Candida albicans infection in a murine intravenous challenge model

Chin VK, Foong KJ, Maha A, Rusliza B, Norhafizah M, Chong PP

Biomed Rep, 2014 Nov;2(6):869-874.
PMID: 25279161

Local cytokine production is a significant indicator for disease pathogenesis or progression. Previous studies on cytokine production during systemic Candida albicans (C. albicans) infection were solely on kidney or single cell type interaction with C. albicans. Therefore, the present study aimed to assess the early cytokine expression of various target organs (kidney, spleen and brain) over a 72-h time course during systemic C. albicans infection. The local cytokine profiles of the target organs during systemic C. albicans infection were measured by cytometric bead array and ELISA analysis. The results demonstrated that interleukin-6 (IL-6) and IL-2 were statistically significant (P<0.05) in the spleen at 24 and 72 h post-infection, whereas in the kidney, IL-6 and tumor necrosis factor-α (TNF-α) were statistically significant (P<0.05) at 24 and 72 h post-infection and CXCL-1 and transforming growth factor-β (TGF-β) were statistically significant (P<0.05) at 72 h post-infection. In the brain, IL-6 and TNF-α were statistically significant (P<0.05) at 24 and 72 h post-infection, whereas TGF-β was statistically significant (P<0.05) at 72 h post-infection. These findings demonstrate that host immune responses were varied among target organs during systemic C. albicans infection. This could be important for designing targeted immunotherapy against this pathogen through immunomodulatory approaches in future exploratory research.

Matched MeSH terms: Candidiasis
Fulltext Candida albicans isolates from a Malaysian hospital exhibit more potent phospholipase and haemolysin activities than non-albicans Candida isolates

Chin VK, Foong KJ, Maha A, Rusliza B, Norhafizah M, Ng KP, et al.

Trop Biomed, 2013 Dec;30(4):654-62.
PMID: 24522136 MyJurnal

This study was aimed at determining the phospholipase and haemolysin activity of Candida isolates in Malaysia. A total of 37 Candida clinical isolates representing seven species, Candida albicans (12), Candida tropicalis (8), Candida glabrata (4), Candida parapsilosis (1), Candida krusei (4), Candida orthopsilosis (1) and Candida rugosa (7) were tested. In vitro phospholipase activity was determined by using egg yolk plate assay whereas in vitro haemolysin activity was tested by using blood plate assay on sheep blood Sabouraud's dextrose agar (SDA) enriched with glucose. Phospholipase activity was detected in 75% (9 out of 12) of the C. albicans isolates. Among the 25 non- C. albicans Candida isolates, phospholipase activity was detected in only 24% of these isolates. The phospholipase activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.002). Haemolysin activity was detected in 100% of the C. albicans, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, and C. orthopsilosis isolates while 75% of the C. krusei isolates and 12.3% of the C. rugosa isolates showed haemolysin activity. The haemolytic activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.0001).The findings in this study indicate that C. albicans isolates in Malaysia may possess greater virulence potential than the non-albicans species.

Matched MeSH terms: Candidiasis/microbiology*

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