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Echinocandins in the treatment of candidaemia and invasive candidiasis: clinical and economic perspectives

Neoh CF, Slavin M, Chen SC, Stewart K, Kong DC

Int J Antimicrob Agents, 2014 Mar;43(3):207-14.
PMID: 24670423 DOI: 10.1016/j.ijantimicag.2013.08.010

Candidaemia and invasive candidiasis (IC) complicate modern medical therapy, contributing to high morbidity and mortality. Managing candidiasis is costly, with an additional healthcare expenditure of nearly US$300 million annually. Recent consensus guidelines have suggested the use of newer antifungal agents, such as echinocandins, for the treatment of candidaemia and IC owing to promising clinical outcomes compared with older-generation antifungal agents, but at higher drug acquisition and administration costs. Comprehensive cost-effectiveness data for echinocandins in treating candidaemia and IC remain relatively scant, underlining the need for more studies to incorporate robust economic analyses into clinical decisions. Assessment of the cost efficiencies of these expensive antifungal agents is essential for maximising health outcomes within the constraints of healthcare resources. This review will explore the epidemiology of candidaemia and IC in the context of clinical and economic aspects of the antifungal agents used to treat IC, especially the echinocandins. Standardising the outcome measure, methodology and reporting of results used in economic studies is central to ensure validity and comparability of the findings. Future studies comparing the economic advantages of all available antifungal treatment options and in the context of new diagnostic tools for fungal infections are anticipated.

Matched MeSH terms: Echinocandins/therapeutic use*
Fulltext Population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation-an ASAP ECMO study

Abdul-Aziz MH, Diehl A, Liu X, Cheng V, Corley A, Gilder E, et al.

Antimicrob Agents Chemother, 2025 Feb 13;69(2):e0143524.
PMID: 39692515 DOI: 10.1128/aac.01435-24

This study aimed to describe the population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) and to identify dosing regimens with a high likelihood of achieving effective exposures. Serial blood samples were collected over a single-dosing interval during ECMO. Total plasma concentrations were measured by a validated chromatographic assay. A population pharmacokinetic model was built and Monte Carlo dosing simulations were performed using Monolix. The probability of target attainment (PTA) and fractional target attainment (FTA) rates were simulated for various caspofungin dosing regimens against Candida albicans, Candida glabrata, and Candida parapsilosis. In all, 64 plasma concentration-time points were obtained from 8 critically ill patients receiving ECMO. Plasma concentration-time data for caspofungin were best described by a one-compartment model with first-order elimination. Lean body weight was identified as a significant covariate of volume of distribution. The typical volume of distribution and clearance of caspofungin in this cohort were 8.13 L and 0.55 L/h, respectively. The licensed caspofungin dosing regimen (a loading dose of 70 mg on day 1 followed by a maintenance dose of either 50 mg/day or 70 mg/day) demonstrated optimal PTA rates (≥90%) against C. albicans with an MIC of ≤0.064 mg/L, C. glabrata with an MIC of ≤0.125 mg/L, and C. parapsilosis with an MIC of ≤0.064 mg/L. The FTA analysis suggested that the licensed dosing regimen is only optimal (≥95%) against Candida glabrata, regardless of lean body weight. A higher-than-standard empirical dosing regimen (e.g., a loading dose of 100 mg on day 1, followed by a maintenance dose of 100 mg daily) is likely advantageous for critically ill patients receiving ECMO.

Matched MeSH terms: Echinocandins/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: Echinocandins/therapeutic use
Clinical utility of caspofungin eye drops in fungal keratitis

Neoh CF, Daniell M, Chen SC, Stewart K, Kong DC

Int J Antimicrob Agents, 2014 Aug;44(2):96-104.
PMID: 24933448 DOI: 10.1016/j.ijantimicag.2014.04.008

Treatment of fungal keratitis remains challenging. To date, only the polyenes and azoles are commonly used topically in the management of fungal keratitis. Natamycin, a polyene, is the only antifungal eye drop that is commercially available; the remainder are prepared in-house and are used in an 'off-label' manner. Failure of medical treatment for fungal keratitis is common, hence there is a need for more effective topical antifungal therapy. To increase the antifungal eye drop armamentarium, it is important to investigate the utility of other classes of antifungal agents for topical use. Caspofungin, an echinocandin antifungal agent, could potentially be used to address the existing shortcomings. However, little is known about the usefulness of topically administered caspofungin. This review will briefly explore the incidence, epidemiology and antifungal treatment of fungal keratitis. It will focus primarily on evidence related to the efficacy, safety and practicality of using caspofungin eye drops in fungal keratitis.

Matched MeSH terms: Echinocandins/therapeutic use*
Pharmacoeconomic evaluation of micafungin versus caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in Turkey

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

Eur J Clin Microbiol Infect Dis, 2018 Mar;37(3):537-544.
PMID: 29185089 DOI: 10.1007/s10096-017-3147-9

Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.

Matched MeSH terms: Echinocandins/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: Echinocandins/therapeutic use*
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: Echinocandins/therapeutic use
Fulltext Invasive aspergillosis in paediatric oncology patients

Muda Z, Ibrahim H, Abdulrahman EJ, Menon BS, Zahari Z, Zaleha AM, et al.

Med J Malaysia, 2008 Dec;63(5):415-6.
PMID: 19803305 MyJurnal

Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

Matched MeSH terms: Echinocandins/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: Echinocandins/therapeutic use*