Displaying publications 21 - 35 of 35 in total

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  1. Fulltext A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica
    James JE, Lamping E, Santhanam J, Milne TJ, Abd Razak MF, Zakaria L, et al.
    Front Microbiol, 2020;11:272.
    PMID: 32296397 DOI: 10.3389/fmicb.2020.00272
    In the fungal pathogen Aspergillus fumigatus, resistance to azole antifungals is often linked to mutations in CYP51A, a gene that encodes the azole antifungal drug target lanosterol 14α-demethylase. The aim of this study was to investigate whether similar changes could be associated with azole resistance in a Malaysian Fusarium solani species complex (FSSC) isolate collection. Most (11 of 15) clinical FSSC isolates were Neocosmospora keratoplastica and the majority (6 of 10) of environmental isolates were Neocosmospora suttoniana strains. All 25 FSSC isolates had high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole, low MICs for amphotericin B, and various (1 to >32 mg/l) voriconazole susceptibilities. There was a tight association between a 23 bp CYP51A promoter deletion and high (>32 mg/l) voriconazole MICs; of 19 FSSC strains sequenced, nine isolates had voriconazole MICs > 32 mg/l, and they all contained the 23 bp CYP51A promoter deletion, although it was absent in the ten remaining isolates with low (≤12 mg/l) voriconazole MICs. Surprisingly, this association between voriconazole resistance and the 23 bp CYP51A promoter deletion held true across species boundaries. It was randomly distributed within and across species boundaries and both types of FSSC isolates were found among environmental and clinical isolates. Three randomly selected N. keratoplastica isolates with low (≤8 mg/l) voriconazole MICs had significantly lower (1.3-7.5 times) CYP51A mRNA expression levels than three randomly selected N. keratoplastica isolates with high (>32 mg/l) voriconazole MICs. CYP51A expression levels, however, were equally strongly induced (~6,500-fold) by voriconazole in two representative strains reaching levels, after 80 min of induction, that were comparable to those of CYP51B. Our results suggest that FSSC isolates with high voriconazole MICs have a 23 bp CYP51A promoter deletion that provides a potentially useful marker for voriconazole resistance in FSSC isolates. Early detection of possible voriconazole resistance is critical for choosing the correct treatment option for patients with invasive fusariosis.
    Matched MeSH terms: Itraconazole
  2. Meningitis Caused by Rhodotorula mucilaginosa in HIV-Infected Patient: A Case Report and Review of the Literature
    Mohd Nor F, Tan LH, Na SL, Ng KP
    Mycopathologia, 2015 Aug;180(1-2):95-8.
    PMID: 25739670 DOI: 10.1007/s11046-015-9879-0
    Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient's cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/µl in two previously published reports, while another report documented CD4 count as 56/µl. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.
    Matched MeSH terms: Itraconazole/therapeutic use
  3. Mycetoma or synovial sarcoma? A case report with review of the literature
    Jimenez AL, Salvo NL
    J Foot Ankle Surg, 2011 Sep-Oct;50(5):569-76.
    PMID: 21616683 DOI: 10.1053/j.jfas.2011.04.014
    Mycetoma, also commonly referred to as Madura foot, is statistically rare in the United States. However, it is endemic to other parts of the world. It is a pseudotumor characterized by a triad of tumefaction, draining sinuses, and grains. Two types exist, with each caused by different groups of organisms that require different treatment approaches. Therefore, the exact diagnosis and culture of the organism is vital to successful treatment outcomes. Synovial sarcoma, in contrast, is a malignancy much more commonly seen in the United States. It is characterized by a well-circumscribed, often palpable, mass that is usually well delineated on magnetic resonance imaging. It has characteristic histologic and genetic features that help distinguish it from other soft tissue masses. We present a case of a soft tissue mass diagnosed in the United States. The patient had several clinical and radiographic features of synovial sarcoma but the histologic outcome was mycetoma. The case is followed by a review of the published data.
    Matched MeSH terms: Itraconazole/therapeutic use
  4. Disseminated invasive aspergillosis in an apparently immunocompetent host
    Raja NS, Singh NN
    J Microbiol Immunol Infect, 2006 Feb;39(1):73-7.
    PMID: 16440127
    Aspergillosis is a spectrum of diseases caused by members of the genus Aspergillus that continues to pose a significant threat to immunocompromised, organ transplant, neutropenic and cancer patients. In view of increasing risk factors leading to invasive aspergillosis, it is imperative for clinicians to be familiar with the clinical presentation, diagnostic methods and management of the disease. We describe a 34-year-old immunocompetent male patient receiving chemotherapy for Aspergillus fumigatus infection that had disseminated to lung, liver and spleen. A computed tomogram of thorax and abdomen showed thick-walled cavities of different sizes with air fluid levels, consolidation in both lungs and involvement of liver and spleen. His broncheoalveolar lavage and sputum specimens yielded A. fumigatus. Successful treatment of this infection was achieved with amphotericin B and itraconazole.
    Matched MeSH terms: Itraconazole/therapeutic use
  5. 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: Itraconazole/administration & dosage; Itraconazole/toxicity*
  6. 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: Itraconazole/therapeutic use
  7. Penicillium marneffei infection in an African man
    Yap FB, Thevarajah S, Asmah J
    Dermatol. Online J., 2010;16(7):2.
    PMID: 20673530
    Penicilliosis is a systemic fungal infection caused by Penicillium marneffei. The infection is most commonly seen in Southeast Asia, Southern China, Hong Kong, and Taiwan. It is rarely seen among individuals of African descent. Here, we report a case of penicilliosis in an African man from Namibia who was studying in Malaysia. He presented with multiple umbilicated papules associated with cough, fever, loss of appetite, and weight. He also had urethral discharge and admitted to unprotected sexual intercourse with multiple partners. Histopathological examination of a skin papule showed the presence of multiple 2 to 4 microm intracellular yeast cells. Culture of the papule revealed Penicillium marneffei. The serology for human immunodeficiency virus (HIV) was positive. This case illustrates the need to recognize penicilliosis in any individuals staying or travelling to Southeast Asia and the need to look for underlying HIV infection in adults with umbilicated papules.
    Matched MeSH terms: Itraconazole/therapeutic use
  8. Chronic nonhealing ulcer of the right thumb with multiple subcutaneous nodules
    Manohar A, Nizlan MN
    Orthopedics, 2008 Jul;31(7):710.
    PMID: 19292371
    A 60-year-old man presented with a 3-month history of nonhealing ulcer over the tip of his right thumb. The ulcer started as a blister over the tip of the thumb that later ruptured and spread proximally to cover the whole pulp area of the thumb. There was no history of trauma, fever, weight loss, or loss of appetite. He is a pensioner and an avid gardener. He has a few cats as pets. The patient initially presented to a private orthopedic surgeon with a nonhealing ulcer of the right thumb. Multiple debridements were unsuccessful in ameliorating the ulcer. Three months after the onset of the initial lesion, multiple painless erythematous nodules had developed on his right arm, and one on the right thigh. All routine blood investigations were nondiagnostic. Swab culture from the ulcer failed to grow any organism and a course of antibiotics did not resolve the problem. Cultures of the biopsy specimen using Sabouraud's dextrose agar and potato carrot medium grew dark brown plaques that microscopically appeared to be branching hyphae. A diagnosis of sporotrichosis of the right upper limb was made and the patient was started on antifungal treatment immediately (T. Itraconazole [Sporanox] 200 mg BD). One month after commencement of antifungal treatment, the ulcer began to dry up and at 3 months all the lesions including the one on the right thigh had healed.
    Matched MeSH terms: Itraconazole/therapeutic use*
  9. Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats
    Somchit N, Wong CW, Zuraini A, Ahmad Bustamam A, Hasiah AH, Khairi HM, et al.
    Drug Chem Toxicol, 2006;29(3):237-53.
    PMID: 16777703
    Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.
    Matched MeSH terms: Itraconazole/toxicity*
  10. Itraconazole- and fluconazole-induced toxicity in rat hepatocytes: a comparative in vitro study
    Somchit N, Hassim SM, Samsudin SH
    Hum Exp Toxicol, 2002 Jan;21(1):43-8.
    PMID: 12046723
    This current study was to investigate the in vitro cytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose- and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.
    Matched MeSH terms: Itraconazole/toxicity*
  11. Comparison of two in vitro antifungal sensitivity tests and monitoring during therapy of Sporothrix schenckii sensu stricto in Malaysian cats
    Han HS, Kano R, Chen C, Noli C
    Vet Dermatol, 2017 Feb;28(1):156-e32.
    PMID: 28133872 DOI: 10.1111/vde.12417
    BACKGROUND: Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown.

    OBJECTIVES: To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy.

    METHODS: Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months.

    RESULTS: Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy.

    CONCLUSION: The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility.

    Matched MeSH terms: Itraconazole/therapeutic use
  12. Fulltext Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced cytotoxicity in hepatocytes
    Somchit N, Ngee CS, Yaakob A, Ahmad Z, Zakaria ZA
    J Toxicol, 2009;2009:912320.
    PMID: 20130764 DOI: 10.1155/2009/912320
    Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetized 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.
    Matched MeSH terms: Itraconazole
  13. Fulltext Epidemiological and clinical features of Talaromycosis (Penicilliosis) Marneffei among human immunodeficiency virus-infected patients in Malaysia
    Syaziah, I., Azura, S.S., Tzar, M.N.
    Medicine & Health, 2018;13(2):103-113.
    MyJurnal
    The AIDS epidemic in Southeast Asia has led to a marked rise in the incidence of talaromycosis (penicilliosis) marneffei. The aim of this cross-sectional study was to determine the clinico-epidemiological features and outcome predictors of talaromycosis in Malaysia. We identified Talaromycosis marneffei cases from cultures of sterile specimens from 191 human immunodeficiency virus (HIV)- infected patients. Talaromycosis increased from 20-25 (2010-2011) to 45-50 cases per year (2012-2014). Talaromycosis was the HIV-presenting illness in 117 (61.3%) patients. The incidence of talaromycosis as HIV-presenting illness showed an increasing trend from 10.7 (2010) to 26.4 (2014) cases per 1000 new HIV patients. The patients were between 19 and 74 of age (mean 37.2+9.4 years) and the male to female ratio was 7.7:1. Malay (73, 38.2%) and Chinese (70, 36.3%) were the most prevalent ethnic groups. Common clinical manifestations included loss of weight (85.9%), fever (84.8%) and cough (67%), while skin lesions were only present in 42.9% cases. Common concurrent infections were oral candidiasis (79.6%), tuberculosis (36.1%) and hepatitis C infection (20.9%). Most patients (93.7%) were anaemic with mean haemoglobin level of 9.9+2.3 g/dL, 39% had impaired liver function, and 18.8% were neutropaenic. Median CD4 cell count was 16 cells/L. Most patients (70.4%) received intravenous amphotericin B followed by itraconazole. At 8-month follow up, 148 (81.8%) patients were alive while 33 (18.2%) had died. Intravenous drug abuse, concurrent toxoplasma encephalitis and concurrent Pneumocystis jiroveci pneumonia independently predicted death outcome in both univariate and multivariate logistic regression analyses.
    Matched MeSH terms: Itraconazole
  14. Talaromyces (Penicillium) species infection in the central nervous system
    Chuah CH, Ong YC, Kong BH, Woo YY, Wong PS, Leong KN, et al.
    J R Coll Physicians Edinb, 2020 Jun;50(2):138-140.
    PMID: 32568283 DOI: 10.4997/JRCPE.2020.211
    Talaromycosis typically occurs as an opportunistic infection among immunocompromised individuals. Infection caused by species other than T. marneffei is uncommon. While most reported cases describe infection in the lungs, we report an extremely rare intracranial Talaromyces species infection. This 61-year-old with end-stage renal disease who was unwell for the previous two months, presented with fever and worsening confusion lasting for three days. Lumbar puncture was suggestive of meningitis. Cerebrospinal fluid (CSF) culture was later confirmed to be Penicillium chrysogenum. The patient was co-infected with Group B Streptococcus sepsis. He improved with amphotericin B and ceftriaxone and was discharged with oral itraconazole for four weeks. However, he died of unknown causes two weeks later at home. Talaromyces species infection in the central nervous system is uncommon. This case highlighted a rare but life-threatening fungal meningitis. Among the four reported cases worldwide, none of the patients survived.
    Matched MeSH terms: Itraconazole
  15. Epidemiology of candidemia and antifungal susceptibility in invasive Candida species in the Asia-Pacific region
    Wang H, Xu YC, Hsueh PR
    Future Microbiol, 2016 10;11:1461-1477.
    PMID: 27750452
    In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3.9-10%) and voriconazole (5-17.8%), and echinocandin resistance (2.1-2.2% in anidulafungin and 2.2% in micafungin) among invasive C. glabrata complex isolates are increasing in prevalence. Moreover, not all isolates of C. tropicalis have been shown to be susceptible to fluconazole (nonsusceptible rate, 5.7-11.6% in China) or voriconazole (nonsusceptible rate, 5.7-9.6% in China).
    Matched MeSH terms: Itraconazole/therapeutic use
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