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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 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
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 Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units-the SAFE-ICU study

Roberts JA, Sime FB, Lipman J, Hernández-Mitre MP, Baptista JP, Brüggemann RJ, et al.

Intensive Care Med, 2025 Feb;51(2):302-317.
PMID: 39899034 DOI: 10.1007/s00134-025-07793-5

PURPOSE: Appropriate antifungal therapy is a major determinant of survival in critically ill patients with invasive fungal disease. We sought to describe whether contemporary dosing of antifungals achieves therapeutic exposures in critically ill patients.
METHODS: In a prospective, open-label, multicenter pharmacokinetic study, intensive care unit (ICU) patients prescribed azoles, echinocandins, or polyene antifungals for treatment or prophylaxis of invasive fungal disease were enrolled. Blood samples were collected on two occasions, with three samples taken during a single dosing interval on each occasion. Total concentrations were centrally measured using validated chromatographic methods. Pharmacokinetic parameters were estimated using noncompartmental methods. Antifungal dosing adequacy was assessed using predefined PK/PD targets.
RESULTS: We included 339 patients from 30 ICUs across 12 countries. Median age 62 (interquartile range [IQR], 51-70) years, median APACHE II score 22 (IQR, 17-28), and 61% males. Antifungal therapy was primarily prescribed for treatment (80.8%). Fluconazole was the most frequently prescribed antifungal (40.7%). The most common indication for treatment was intra-abdominal infection (30.7%). Fungi were identified in 45% of patients, of which only 26% had a minimum inhibitory concentration available. Target attainment was higher for patients receiving prophylaxis (> 80% for most drugs). For patients receiving treatment, low target attainment was noted for voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%) and amphotericin B (41.7%).
CONCLUSION: This study highlights the varying degrees of target attainment across antifungal agents in critically ill patients. While a significant proportion of patients achieved the predefined PK/PD targets, wide variability and subtherapeutic exposures persist.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03136926, 2017-04-21.

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
Prevalence of albicans and non-albicans candiduria in a Malaysian medical centre

Ding CH, Wahab AA, Muttaqillah NA, Tzar MN

J Pak Med Assoc, 2014 Dec;64(12):1375-9.
PMID: 25842581

To determine the proportion of albicans and non-albicans candiduria in a hospital setting and to ascertain if fluconazole is still suitable as empirical antifungal therapy based on antifungal susceptibility patterns of Candida species.

Matched MeSH terms: Fluconazole/therapeutic use
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*
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
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/therapeutic use*
Fulltext Comparison between efficacy of allicin and fluconazole against Candida albicans in vitro and in a systemic candidiasis mouse model

Khodavandi A, Alizadeh F, Harmal NS, Sidik SM, Othman F, Sekawi Z, et al.

FEMS Microbiol Lett, 2011 Feb;315(2):87-93.
PMID: 21204918 DOI: 10.1111/j.1574-6968.2010.02170.x

The efficacy of allicin compared with fluconazole in alleviating systemic Candida albicans infections was evaluated both in vitro and in vivo through a systemic candidiasis mouse model. Determination of in vitro minimum inhibitory concentrations (MICs) for different C. albicans isolates revealed that both allicin and fluconazole showed different MICs that ranged from 0.05 to 12.5 μg mL(-1) and 0.25 to 16 μg mL(-1) , respectively. A time-kill study showed a significant effect of allicin (P<0.01) against C. albicans, comparable to that of fluconazole. Scanning electron microscopy observation revealed that, similar to fluconazole, allicin produced structural destruction of C. albicans cell surface at low MIC and lysis or puncture at high MIC concentrations. Treatment of BALB/c mice systemically infected with C. albicans showed that although the allicin treatment (at 5 mg kg(-1) day(-1) ) was slightly less efficacious than fluconazole treatment in terms of the fungal load reduction and host survival time, it was still effective against C. albicans in terms of mean survival time, which increased from 8.4 to 15.8 days. These results demonstrate the efficacy of anticandidal effects of allicin both in vitro and in an animal model of candidiasis and affirm the potential of allicin as an adjuvant therapy to fluconazole.

Matched MeSH terms: Fluconazole/therapeutic use*
Subcutaneous Infection Associated with Trichosporon ovoides: A Case Report and Review of Literature

Mohd Tap R, Sabaratnam P, Ramli NY, Hashim R, Mohd Fuat AR, Ng PP, et al.

Mycopathologia, 2016 Apr;181(3-4):285-90.
PMID: 26493614 DOI: 10.1007/s11046-015-9958-2

Trichosporon species are opportunistic yeasts which can cause infections, especially in immunocompromised patients. This is a report of Trichosporon ovoides that caused subcutaneous infection in a patient with underlying ischemic heart disease. The identification of fungal isolate was confirmed by PCR sequencing of ITS and large subunit regions in rRNA gene. In vitro susceptibility study showed that the isolate was susceptible to amphotericin B, fluconazole and voriconazole, and resistant to caspofungin, anidulafungin and itraconazole. The lesion improved after treatment with oral fluconazole and topical miconazole.

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
Idiopathic CD4+ T-lymphocytopenia in a child with disseminated cryptococcosis

Menon BS, Shuaib IL, Zamari M, Haq JA, Aiyar S, Noh LM

Ann Trop Paediatr, 1998 Mar;18(1):45-8.
PMID: 9692001

We describe a Malay girl with disseminated cryptococcosis affecting the lungs, liver, lymph nodes and bones. The diagnosis was made by culture of the bone marrow. Tests of immune function showed that she was HIV-negative but the CD4 percentage was persistently low. Idiopathic CD4+ T-lymphocytopenia was diagnosed. The child died despite two courses of anti-fungal therapy.

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 Rare Kodamaea ohmeri keratitis following a trivial vegetative trauma

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

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

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

Matched MeSH terms: Fluconazole/therapeutic use
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: Fluconazole/therapeutic use

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