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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
Liquid chromatographic method for the determination of plasma itraconazole and its hydroxy metabolite in pharmacokinetic/bioavailability studies

Wong JW, Nisar UR, Yuen KH

J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Dec 25;798(2):355-60.
PMID: 14643517

A sensitive and selective high-performance liquid chromatographic method was developed for the determination of itraconazole and its active metabolite, hydroxyitraconazole, in human plasma. Prior to analysis, both compounds together with the internal standard were extracted from alkalinized plasma samples using a 3:2 (v/v) mixture of 2,2,4-trimethylpentane and dichloromethane. The mobile phase comprised 0.02 M potassium dihydrogen phosphate-acetonitrile (1:1, v/v) adjusted to pH 3.0. Analysis was run at flow-rate of 0.9 ml/min with excitation and emission wavelengths set at 260 and 365 nm, respectively. Itraconazole was found to adsorb on glass or plastic tubes, but could be circumvented by prior treating the tubes using 10% dichlorodimethylsilane in toluene. Moreover, rinsing the injector port with acetonitrile helped to overcome any carry-over effect. This problem was not encountered with hydroxyitraconazole. The method was sensitive with limit of quantification of 3 ng/ml for itraconazole and 6 ng/ml for hydroxyitraconazole. The calibration curve was linear over a concentration range of 2.8-720 ng/ml for itraconazole and 5.6-720 ng/ml for the hydroxy metabolite. Mean recovery value of the extraction procedure for both compounds was about 85%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 15%. Hence, the method is suitable for use in pharmacokinetic and bioavailability studies of itraconazole.

Matched MeSH terms: Itraconazole/blood*; Itraconazole/pharmacokinetics
Chromoblastomycosis in Sarawak, East malaysian Borneo

Yap FB

Trans R Soc Trop Med Hyg, 2010 Feb;104(2):168-9.
PMID: 19766279 DOI: 10.1016/j.trstmh.2009.05.016

A retrospective study was conducted to determine the clinical characteristics and treatment outcomes of 11 new patients with a histological diagnosis of chromoblastomycosis at Sarawak General Hospital, Malaysia, between 1996 and 2008. The majority (81.8%) were males, and the median age at presentation was 40 years. Over half the patients were farmers. All the patients had irregular verrucous lesions, mostly on the lower limbs (90.9%), and had initially been misdiagnosed. The mean duration of the lesions was 13.8 years. Oral terbinafine and itraconazole were administered to all the patients; clinical cure was seen in 54.5%, and partial response in 18.2%. Concomitant electrocautery and cryotherapy were only effective for small lesions.

Matched MeSH terms: Itraconazole/therapeutic use
Fulltext Chromoblastomycosis

Yap FB

Int J Infect Dis, 2010 Jun;14(6):e543-4.
PMID: 19889559 DOI: 10.1016/j.ijid.2009.07.005
Matched MeSH terms: Itraconazole/administration & dosage
Fulltext A Diabetic Elderly Man with Finger Ulcer

Mohamad N, Badrin S, Wan Abdullah WNH

Korean J Fam Med, 2018 Mar;39(2):126-129.
PMID: 29629046 DOI: 10.4082/kjfm.2018.39.2.126

Fixed cutaneous sporotrichosis is a differential diagnosis that can be considered in diabetic patients who present with a poorly healing ulcer. Although its prevalence is low, it can occur in patients with immunocompromised status. Here we report a case of a 70-year-old man with diabetes mellitus who presented with a 1-month history of an unhealed ulcer over the tip of his left middle finger. He experienced a cat bite over his left middle finger 1 month prior to the appearance of the lesion. A skin biopsy revealed the presence of Sporothrix schenckii. Oral itraconazole 200 mg twice daily was started empirically and the patient showed marked improvement in the skin lesion after 2 months of therapy.

Matched MeSH terms: Itraconazole
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
The potential to treat lung cancer via inhalation of repurposed drugs

Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D

Adv Drug Deliv Rev, 2018 08;133:107-130.
PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012

Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.

Matched MeSH terms: Itraconazole/administration & dosage; Itraconazole/therapeutic use*
Fulltext Scopulariopsis brevicaulis infection in a patient with acute myeloid leukemia

Ng KP, Soo-Hoo TS, Na SL, Gan GG, Sangkar JV, Teh AKH

Med J Malaysia, 2003 Oct;58(4):608-12.
PMID: 15190640

Scopulariopsis brevicaulis is a soil fungus normally associated with onychomycosis. It causes subcutaneous infection in immunocompromised patients and is rarely isolated from blood. A case of systemic Scopulariopsis brevicaulis infection was reported in a patient with acute myeloid leukemia. The patient developed persistent fever that did not respond to wide spectrum antibiotics and amphotericin B. Scopulariopsis brevicaulis was the only pathogen isolated from blood cultures. The fever subsided with itraconazole and there was no recurrence of fungal infection with prolonged maintenance of oral itraconazole.

Matched MeSH terms: Itraconazole/therapeutic use*
Fulltext In silico identification of novel tuberculosis drug targets in mycobacterium tuberculosis P450 enzymes by interaction study with azole drugs

Suresh Kumar

Malaysian Journal of Medicine and Health Sciences, 2020;16(101):24-30.
MyJurnal

Introduction: Tuberculosis (TB) is one of the utmost serious infectious diseases worldwide. The emergence of multi- drug resistance demands the development of better or new putative drug targets for tuberculosis. Recent studies sug- gest Mycobacterium tuberculosis cytochrome P450 enzymes as promising drug targets and azole drugs as potential inhibitors. Methods: Various computational tools, like Expasy Protparam, Swiss model, RaptorX and Phyre2 were used to analyze 12 Mycobacterium tuberculosis P450 enzymes and determine their three-dimensional structure. The structural validation was done through a Ramachandran plot using RAMPAGE server. The docking of P450 enzymes with azole drugs was done with autodock ver 4.2.6. Results: Based on sub-cellular localization prediction using CEL- LO tool, P450 enzymes CYP123A1, CYP132A1, CYP135A1, CYP136A1, CYP140A1, and CYP143A1 were predicted to be in the cytoplasm. Through structure assessment by Ramachandran plot, the best homology modelled proteins were docked with azole drugs like clotrimazole, croconazole, econazole, fluconazole, itraconazole, itraconazole, ketaconazole and micronazole by using autodock. By docking method it is identified that ketaconazole drug has a high affinity towards most of the mycobacterium P450 enzymes followed by the itrconazole drug. CYP123A1 enzyme is preferable as a drug target due to high binding affinity towards ketoconazole followed by CYP135A1, CYP140A1 enzymes. Conclusion: This study would help in identifying putative novel drug targets in Mycobacterium tuberculosis, which can lead to promising candidates for the optimization and development of novel anti-mycobac- terial agents.

Matched MeSH terms: Itraconazole
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
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: Itraconazole/administration & dosage; Itraconazole/pharmacology
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*
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
Disseminated histoplasmosis mimicking an acute appendicitis

Marsilla MM, Khairunisa AA, Azyani Y, Petrick P

Malays J Pathol, 2019 Aug;41(2):223-227.
PMID: 31427560

INTRODUCTION: Histoplasmosis can present in a myriad of clinical manifestations, which often makes its diagnosis difficult and occasionally, deceptive.
CASE REPORT: We describe a case of a 33 years old gentleman who was clinically diagnosed as acute appendicitis at initial presentation in view of a one-week history of fever, right lower quadrant abdominal pain- and guarding at right iliac fossa. He had thrombocytopenia and lymphopenia on presentation. Mesenteric lymphadenitis and small bowel lesion were found intraoperatively, which was respectively biopsied and resected. Histopathological result confirms disseminated histoplasmosis. Retroviral screen was positive. He was treated with amphotericin B for one week, subsequently switched to oral itraconazole, followed by initiation of highly active antiretroviral therapy (HAART).
DISCUSSION: This case illustrates the various nature of histoplasmosis presentation. A high index of suspicion is needed to clinch the diagnosis and subsequently institute prompt treatment as disseminated disease can be fatal if left untreated in an immunosuppressed host.

Matched MeSH terms: Itraconazole
Paecilomyces lilacinus fungaemia in an AIDS patient: the importance of mycological diagnosis

Ding CH, Tzar MN, Rahman MM, Muttaqillah NA, Redzuan SR, Periyasamy P

Pak J Med Sci, 2014 Jul;30(4):914-6.
PMID: 25097544

Fungaemia due to Paecilomyces lilacinus is generally not considered in AIDS patients because this condition is not categorised as an AIDS-indicator illness. We report a case of a 25-year-old lady who presented to our hospital with Guillain-Barré Syndrome, with the subsequent development of refractory fungaemia, multi-organ failure and disseminated intravascular coagulopathy. Amphotericin B was given as empirical antifungal therapy. HIV screening was reactive and Paecilomyces lilacinus was isolated from her blood. The fungaemia did not resolve after one week of amphotericin B treatment. The addition of itraconazole was also unsuccessful in clearing the fungaemia. Accurate mycological diagnosis is important in the care of AIDS patients with fungaemia because of the risk of treatment failure with empirical therapy.

Matched MeSH terms: Itraconazole
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*
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
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*
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
Itraconazole-induced torsade de pointes in a patient receiving methadone substitution therapy

NoorZurani MH, Vicknasingam B, Narayanan S

Drug Alcohol Rev, 2009 Nov;28(6):688-90.
PMID: 19930027 DOI: 10.1111/j.1465-3362.2009.00128.x

Methadone, a pharmacological agent used to treat heroin dependence is relatively safe, but may cause cardiac arrhythmias in the concurrent presence of other risk factors. APPROACH AND KEY FINDINGS: This case report highlights the risk of torsade de pointes, a life-threatening cardiac arrhythmia, in a heroin-dependent patient receiving methadone substitution therapy who was prescribed itraconazole for vaginal thrush. The patient presented to the accident and emergency department for chest discomfort and an episode of syncope following two doses of itraconazole (200 mg). Electrocardiogram monitoring at the accident and emergency department showed prolonged rate-corrected QT interval leading to torsade de pointes. The patient was admitted for cardiac monitoring, and electrocardiogram returned to normal upon discontinuation of methadone.

Matched MeSH terms: Itraconazole/adverse effects*

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