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Fulltext In vitro activity of fluconazole and voriconazole against clinical isolates of Candida spp. by E-test method

Madhavan P, Jamal F, Chong PP, Ng KP

Trop Biomed, 2010 Aug;27(2):200-7.
PMID: 20962716 MyJurnal

The in vitro susceptibility of clinical Candida isolates towards fluconazole and voriconazole was determined using the E-test method. A total of 41 clinical isolates recovered from patients since 2004 until 2009 from two local hospitals in Kuala Lumpur, Malaysia were used. These comprised Candida tropicalis, Candida albicans, Candida krusei, Candida parapsilosis, Candida rugosa, Candida dubliniensis and Candida glabrata. Strains from American Type Culture Collection were used as quality control. Lawn cultures of the isolates on RPMI-1640 agar medium supplemented with 2% glucose were incubated with the E-test strips at 35ºC for 48 h. Our results show that 71% were susceptible to fluconazole and 90% were susceptible to voriconazole. All strains of C. krusei were resistant to fluconazole and 50% were susceptible in a dose-dependent manner to voriconazole. There were 66% and 33% of C. glabrata that were resistant to fluconazole and voriconazole. Our study revealed that majority of the clinical Candida isolates was susceptible to fluconazole and voriconazole with a small percentage being resistant to both the drugs.

Matched MeSH terms: Fluconazole/pharmacology*
Genetic diversity, antifungal susceptibility and enzymatic characterisation of Malaysian clinical isolates of Candida glabrata

Lotfalikhani A, Khosravi Y, Sabet NS, Na SL, Ng KP, Tay ST

Trop Biomed, 2018 Dec 01;35(4):1123-1130.
PMID: 33601859

Candida glabrata has been reported as the second or third most common yeast species isolated from patients with vaginitis and invasive candidiasis. This study was aimed to determine the genetic diversity, antifungal susceptibility and enzymatic profiles of C. glabrata isolated from vaginal and blood samples in the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre. A random amplified polymorphic DNA (RAPD) analysis method, using M13 and (GTG)5 primers, was used for strain differentiation of C. glabrata isolates. Antifungal susceptibility testing of C. glabrata isolates was determined using E-test against amphotericin B, caspofungin, fluconazole and voriconazole and microbroth dilution method against clotrimazole. The enzymic profiles of C. glabrata were determined using APIZYM semi-quantitation kit and egg-yolk agar method. A total of 14 RAPD patterns were identified amongst C. glabrata isolates investigated this study. Susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole was noted. Approximately one third of the isolates demonstrated resistance to clotrimazole (MIC>=1 µg/ml). A single isolate of C. glabrata was resistant to caspofungin (MIC:1.5 µg/ml). Enzymatic activities of acid and alkaline phosphatase, aminopeptidases, esterase and lipase and phospholipase were detected in the C. glabrata isolates. The genetic diversity and antifungal susceptibility profiles of C. glabrata isolates were presented in this study. Continued surveillance and monitoring of the incidence and antifungal resistance in C. glabrata isolates is necessary.

Matched MeSH terms: Fluconazole
Cryptococcus humicolus meningitis: first case report in Malaysia

Ramli SR, Leong MC, Khaithir TM, Aziz MN, Loons LC, Rafia MH

Southeast Asian J. Trop. Med. Public Health, 2012 Sep;43(5):1212-7.
PMID: 23431829

We report a case of Cryptococcus humicolus meningitis complicated by communicating hydrocephalus in an apparently immunocompetent 49-year-old psychiatric patient from a nursing home. He presented with a history of poor oral intake, weight loss, headache, vomiting, blurred vision, frequent falls and unsteady gait for the previous three months. He had a history of chronic cough, productive of whitish sputum for the previous month but no hemoptysis. Cerebrospinal fluid culture was positive for Cryptococcus humicolus. He was treated with intravenous amphotericin B and oral fluconazole and had clinical and microbiological improvement after three weeks of treatment. Unfortunately, the patient acquired nosocomial methicillin-resistant Staphylococcus aureus infection and died due to overwhelming sepsis.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext Cryptococcal meningitis in an immunocompetent child: a case report and literature review

Othman N, Abdullah NA, Wahab ZA

Southeast Asian J. Trop. Med. Public Health, 2004 Dec;35(4):930-4.
PMID: 15916093

An immunocompetent 5 year-old girl presented with pyrexia of unknown origin associated with headache. Initial investigations showed leukocytosis and an increased erythrocyte sedimentation rate. A Widal-Weil Felix test, blood film for malarial parasites, mycoplasma IgM antibody, cultures from blood and urine, full blood picture, Mantoux test, and chest x-ray were all negative. A lumbar puncture was done as part of a work-up for pyrexia of unknown origin. Cryptococcus neoformans was seen on India ink examination and confirmed on culture. She was treated with 10 weeks of intravenous amphotericin B and 8 weeks of fluconazole. Further immunological tests did not reveal any defect in the cell-mediated immune system. C. neoformans meningitis may present with non-specific symptoms and should be considered in a work-up for pyrexia of unknown origin.

Matched MeSH terms: Fluconazole/therapeutic use
Emphysematous pyelonephritis caused by Candida infection

Kamaliah MD, Bhajan MA, Dzarr GA

Southeast Asian J. Trop. Med. Public Health, 2005 May;36(3):725-7.
PMID: 16124446

We present an interesting and rare case of a diabetic patient who developed extensive unilateral emphysematous pyelonephritis (EPN) which was caused by fungal infection. The diagnosis was confirmed on computed tomography (CT) scan of the abdomen. Repeated urine cultures grew Candida albicans but no other organisms were isolated. The patient remained febrile and unwell despite parenteral broad spectrum antibiotics and antifungal treatment. She underwent nephrectomy and then made a good clinical recovery.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext Candida albicans infection of a prosthetic knee replacement: a case report

Badrul B, Ruslan G

Med J Malaysia, 2000 Sep;55 Suppl C:93-6.
PMID: 11200051

We report a 64 year old man who developed Candida albicans infection following total knee arthroplasty. A two-stage exchange arthroplasty was performed after an initial swab culture grew Acinobacter sp. A scanty growth of yeast was also found from the tissue culture. Intravenous cefuroxime was instituted for six weeks followed by reimplantation four months after the removal. Three weeks after that revision, the prosthesis became infected and a culture of knee aspirate established the diagnosis of Candida albicans infection. Treatment consisted of thorough debridement of the involved joint and oral fluconazole for a year. Infection was never totally resolved and a secondary infection with methicillin resistant staphylococcus aureus then developed. Excision arthroplasty was done at two and a half years after the initial infection. At five years follow-up the infection was quiescent and he had a range of movement of 30 degrees to 70 degrees. Knee brace was used to control the valgus-varus stability.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext Disseminated histoplasmosis in a non-immunocompromised child

Hasliza M, Nur Atiqah NA, Lim CB, Hussain IH

Med J Malaysia, 1999 Mar;54(1):120-4.
PMID: 10972016

We describe a 2 year-old non-immunocompromised girl with disseminated histoplasmosis who presented with a 2-month history of fever and bloody diarrhoea. On presentation, she was severely wasted and anaemic. There were gross hepatosplenomegaly and multiple lymphadenopathy. A septic screen was negative. A subsequent stool culture isolated Salmonella enteriditis. Serial Widal-Weil Felix (WWF) titres showed serological response after 2 weeks of Ceftriaxone. However, she continued to have spiking fever, bloody diarrhoea and weight loss. She developed pancytopaenia and disseminated intravascular coagulation. A bone marrow aspirate and trephine, and lymph node biopsy showed the presence of Histoplasma capsulatum, confirmed by Gomori-Methenamine Silver staining. She responded to intravenous amphotericin B followed by fluconazole (intravenous then oral) for 6 months after discharge. Human Immunodeficiency Virus screening tests were negative. Complement and immunoglobulin levels were normal. T and B enumeration tests showed gross leucopaenia with very low T cell function with defective phagocytic function. A repeat T and B cell enumeration test and phagocytic function tests done 3 months later were normal.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext An unusual cause of haemoptysis and headache: cryptococcosis

How SH, Kuan YC, Ng TH, Ramachandram K, Fauzi AR

Malays J Pathol, 2008 Dec;30(2):129-32.
PMID: 19291924 MyJurnal

Pulmonary cryptococcosis can be clinically silent in non-HIV infected patients but can also present as nodules and masses on the chest radiograph, which can be mistaken for tuberculosis or lung cancer. Common symptoms include fever and cough, and uncommonly haemoptysis. This report illustrates a non-HIV infected patient whose main complaint was haemoptysis and headache. He was diagnosed with pulmonary cryptococcosis from biopsy of an endobronchial mass found on flexible bronchoscopy. Disseminated cryptoccoccal infection should be considered as a differential diagnosis in non-HIV infected patients presenting with haemoptysis and headache. Early recognition and administration of appropriate therapy will improve clinical outcome in these patients.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext Large Solitary Pulmonary Cryptococcoma Mimicking Lung Carcinoma in an Immunocompetent Patient

Anandpara KM, Aswani Y, Hira P

Malays J Med Sci, 2018 Feb;25(1):114-118.
PMID: 29599641 DOI: 10.21315/mjms2018.25.1.13

Cryptococcosis is a life-threatening mycosis typically seen in immunocompromised patients. Pulmonary cryptococcosis generally presents as multiple or solitary nodular opacities. Cryptococcal infection presenting as a destructing cavernoma (cryptococcoma) without diffuse infiltration of the lung is an extremely rare presentation, even in immunocompromised patients. This report presents a healthy, HIV negative, immunocompetent patient who presented with a large solitary lung mass provisionally diagnosed as a lung malignancy on radiological imaging that proved to be a large cryptococcoma after biopsy. The patient was treated with liposomal Amphotericin B and fluconazole, and the lesion showed regression on serial imaging. This case report thus highlights an unconventional presentation of pulmonary cryptococcosis in an immunocompetent individual.

Matched MeSH terms: Fluconazole
MRI and CT findings of cryptococcal vaginitis

Ranganathan S, Moosa F, Kamarulzaman A, Looi LM

Br J Radiol, 2005 Apr;78(928):353-4.
PMID: 15774599

Cryptococcus neoformans is a yeast like fungus, which is commonly found in bird droppings, especially pigeons. Most cases of cryptococcal infections occur in immunocompromised patients or in those who are on long term immunosuppressant therapies. Cryptococcal infection usually presents as a meningoencephalitis or a pulmonary infection. Skin, bone and genital infections are very rare. We report the second case of vaginal cryptococcossis to be reported in English literature and the first to be imaged with CT and MRI.

Matched MeSH terms: Fluconazole/administration & dosage
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: Fluconazole/administration & dosage*
Fulltext Bruton's agammaglobulinaemia in a child presenting with cryptococcal empyema thoracis and periauricular pyogenic abscess

Wahab JA, Hanifah MJ, Choo KE

Singapore Med J, 1995 Dec;36(6):686-9.
PMID: 8781652

We describe here a case of cryptococcal empyema thoracis and periauricular pyogenic abscess in a child with Bruton's agammaglobulinaemia. The cryptococcal empyema thoracis was treated with intravenous amphotericin B and intravenous fluconazole for six weeks followed by oral fluconazole. The pyogenic periauricular abscess was surgically drained and treated with intravenous ceftazidime and cloxacillin for two weeks. He also received monthly intravenous immunoglobulin.

Matched MeSH terms: Fluconazole/administration & dosage
Fulltext Efficacy and safety of posaconazole for the prevention of invasive fungal infections in immunocompromised patients: a systematic review with meta-analysis and trial sequential analysis

Wong TY, Loo YS, Veettil SK, Wong PS, Divya G, Ching SM, et al.

Sci Rep, 2020 09 03;10(1):14575.
PMID: 32884060 DOI: 10.1038/s41598-020-71571-0

Invasive fungal infections are a potentially life-threatening complication in immunocompromised patients. The aim of this study was to assess the efficacy and safety of posaconazole as compared with other antifungal agents for preventing invasive fungal infections in immunocompromised patients. Embase, CENTRAL, and MEDLINE were searched for randomized conweekmonthtrolled trials (RCTs) up to June 2020. A systematic review with meta-analysis of RCTs was performed using random-effects model. Trial sequential analysis (TSA) was conducted for the primary outcome to assess random errors. A total of five RCTs with 1,617 participants were included. Posaconazole prophylaxis was associated with a significantly lower risk of IFIs (RR, 0.43 [95% CI 0.28 to 0.66, p = 0.0001]) as compared to other antifungal agents. No heterogeneity was identified between studies (I2 = 0%). No significant associations were observed for the secondary outcomes measured, including risk reduction of invasive aspergillosis and candidiasis, clinical failure, all-cause mortality, and treatment-related adverse events, except for infection-related mortality (RR, 0.31 [95% CI 0.15 to 0.64, p = 0.0001]). Subgroup analysis favoured posaconazole over fluconazole for the prevention of IFIs (RR, 0.44 [95% CI 0.28 to 0.70, p = 0.0004]). TSA confirmed the prophylactic benefit of posaconazole against IFIs. Posaconazole is effective in preventing IFIs among immunocompromised patients, particularly those with hematologic malignancies and recipients of allogenic hematopoietic stem cell transplantation.

Matched MeSH terms: Fluconazole/therapeutic use*
Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole

Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA

Parasitol Res, 2018 Jan;117(1):265-271.
PMID: 29218442 DOI: 10.1007/s00436-017-5701-x

Infectious diseases are the leading cause of morbidity and mortality, killing more than 15 million people worldwide. This is despite our advances in antimicrobial chemotherapy and supportive care. Nanoparticles offer a promising technology to enhance drug efficacy and formation of effective vehicles for drug delivery. Here, we conjugated amphotericin B, nystatin (macrocyclic polyenes), and fluconazole (azole) with silver nanoparticles. Silver-conjugated drugs were synthesized successfully and characterized by ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Conjugated and unconjugated drugs were tested against Acanthamoeba castellanii belonging to the T4 genotype using amoebicidal assay and host cell cytotoxicity assay. Viability assays revealed that silver nanoparticles conjugated with amphotericin B (Amp-AgNPs) and nystatin (Nys-AgNPs) exhibited significant antiamoebic properties compared with drugs alone or AgNPs alone (P

Matched MeSH terms: Fluconazole/pharmacology*; Fluconazole/chemistry
Antifungal agents in preventing oral candidiasis in clinical oncology: A network meta-analysis

Shen Loo Y, Yee Wong T, Veettil SK, Se Wong P, Gopinath D, Mooi Ching S, et al.

Oral Dis, 2021 Oct;27(7):1631-1643.
PMID: 32762108 DOI: 10.1111/odi.13588

OBJECTIVE: This review examined the comparative efficacy and safety of antifungal agents in preventing oral candidiasis among patients on cancer treatment.
METHODS: We performed a systematic review and network meta-analysis based on randomised controlled trials that compared antifungal agents to placebo or other antifungal agents used in patients undergoing cancer treatment. Relative ranking of antifungal agents was evaluated with surface under the cumulative ranking (SUCRA) probability score. A total of 20 randomised controlled trials (3,215 participants) comparing 11 interventions were included.
RESULTS: Compared with placebo, clotrimazole was ranked the best agent for preventing the incidence of oral candidiasis (risk ratio (RR), 0.21 [95% CI 0.08 to 0.55]; SUCRA = 0.89). Fluconazole was ranked the safest among other antifungal agents (SUCRA = 0.80), whereas clotrimazole (SUCRA = 0.36) and amphotericin B (SUCRA = 0.18) were ranked low for safety. Amphotericin B was associated with highest risk of adverse events (RR, 3.52 [95% CI 1.27 to 9.75]).
CONCLUSION: Clotrimazole is the most effective in preventing oral candidiasis, whereas fluconazole has the most favourable risk-benefit profile in patients undergoing cancer treatment. However, we are unable to recommend clotrimazole as the best choice to prevent oral candidiasis due to unavailability of studies comparing clotrimazole with other antifungal agents.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext The Current Status of Feline Sporotrichosis in Malaysia

Siew HH

Nihon Ishinkin Gakkai Zasshi, 2017;58(3):E107-E113.
PMID: 28855477 DOI: 10.3314/mmj.17.014

Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.

Matched MeSH terms: Fluconazole/pharmacology
In vitro susceptibilities of Malaysian clinical isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii to five antifungal drugs

Tay ST, Tanty Haryanty T, Ng KP, Rohani MY, Hamimah H

Mycoses, 2006 Jul;49(4):324-30.
PMID: 16784448

The in vitro susceptibilities of Malaysian clinical isolates of Cryptococcus neoformans var. grubii and C . gattii to five antifungal drugs (amphotericin B, flucytosine, fluconazole, itraconazole and ketoconazole) were determined using the Etest method. None of the Malaysian isolates was resistant to amphotericin B and ketoconazole. Isolates resistant to flucytosine, fluconazole and itraconazole were observed in this study. Minimum inhibition concentrations (MICs) of > or = 32 microg ml(-1) against flucytosine, > or = 64 microg ml(-1) against fluconazole and > or = 1 microg ml(-1) against itraconazole were noted in four (8.3%), two (4.2%) and one (2.1%) isolates respectively. There was no significant difference in the MICs for both Cryptococcus species (P > 0.05), indicating that C. gattii was as susceptible as var. grubii to all the antifungal drugs tested. No significant difference in the MICs for both Cryptococcus species collected from 1980 to 1990 and 2002 to 2004 were observed (P > 0.05).

Matched MeSH terms: Fluconazole/pharmacology
First isolation of Candida wangnamkhiaoensis from the blood of immunocompromised paediatric patient

Tap RM, Ho Betty LS, Ramli NY, Suppiah J, Hashim R, Sabaratnam P, et al.

Mycoses, 2016 Nov;59(11):734-741.
PMID: 27427490 DOI: 10.1111/myc.12509

Candida wangnamkhiaoensis is a species clustered under the Hyphopichia clade has not ever been isolated from any clinical specimens. To the best of our knowledge, this is the first report of C. wangnamkhiaoensis associated with fungaemia in immunocompromised paediatric patient. The isolate was assigned a strain name as UZ1679/14, in which the identification was confirmed by a polymerase chain reaction-sequencing of the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rRNA gene. Antifungal susceptibility pattern showed that the isolate was sensitive to anidulafungin, caspofungin, fluconazole and voriconazole. The patient clinically improved after the antifungal treatment with caspofungin.

Matched MeSH terms: Fluconazole/pharmacology
Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey

Neoh CF, Senol E, Kara A, Dinleyici EC, Turner SJ, Kong DCM

Mycoses, 2017 Nov;60(11):714-722.
PMID: 28699297 DOI: 10.1111/myc.12651

Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Matched MeSH terms: Fluconazole/economics; Fluconazole/therapeutic use*
In vitro investigation of antifungal activity of allicin alone and in combination with azoles against Candida species

Khodavandi A, Alizadeh F, Aala F, Sekawi Z, Chong PP

Mycopathologia, 2010 Apr;169(4):287-95.
PMID: 19924565 DOI: 10.1007/s11046-009-9251-3

Candidiasis is a term describing infections by yeasts from the genus Candida, and the type of infection encompassed by candidiasis ranges from superficial to systemic. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. In this study, we used allicin, an allyl sulfur derivative of garlic, to demonstrate both its intrinsic antifungal activity and its synergy with the azoles, in the treatment of these yeasts in vitro. In this study, the MIC(50) and MIC(90) of allicin alone against six Candida spp. ranged from 0.05 to 25 microg/ml. However, when allicin was used in combination with fluconazole or ketoconazole, the MICs were decreased in some isolates. Our results demonstrated the existing synergistic effect between allicin and azoles in some of the Candida spp. such as C. albicans, C. glabrata and C. tropicalis, but synergy was not demonstrated in the majority of Candida spp. tested. Nonetheless, In vivo testing needs to be performed to support these findings.

Matched MeSH terms: Fluconazole/pharmacology

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