Treatment With Liposomal Amphotericin B for All Confirmed Cases of Human Visceral Leishmaniasis in Brazil: A Budget Impact Analysis.

OBJECTIVES: To estimate the budget impact of the expansion of liposomal amphotericin B use for all confirmed cases of visceral leishmaniasis (VL) in Brazil. Currently, the first-line medicine for VL treatment is meglumine antimoniate. Liposomal amphotericin B is indicated only for patients with a greater risk of severity by the disease. METHODS: The analysis was performed from the perspective of the Brazilian public healthcare system over 3 years, considering the following 2 scenarios: the reference scenario with the current recommendations for VL treatment and the alternative scenario based on the use of liposomal amphotericin B for all patients. A diffusion rate of 60% was used in the first year, 80% in the second year, and 100% in the third year. The epidemiological parameters used in the analysis came from the Notifiable Diseases Information System and from a clinical trial that evaluated the efficacy and safety of medicines for the treatment of VL in the country. The costs were related to the treatment of VL and to hospital and outpatient care. RESULTS: In the reference scenario, the total cost for treatment of the 3453 VL confirmed cases in 2014 was $1 447 611.75. The incremental budget impact with the use of liposomal amphotericin B for all the VL confirmed cases was $299 646.43 in the third year. CONCLUSIONS: The analysis presented will support the decision process for the use and expansion of liposomal amphotericin B for all VL confirmed cases in Brazil.

Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media.

PURPOSE: To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy. DESIGN: Cost-effectiveness analysis (CEA). PARTICIPANT: Base case of a patient with Fuch's endothelial dystrophy undergoing a first eye keratoplasty. METHODS: Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs). RESULTS: In the reference case, a corneal endothelial graft stored in amphotericin B-supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs. CONCLUSIONS: Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.

Cost-effectiveness of selective digestive decontamination (SDD) versus selective oropharyngeal decontamination (SOD) in intensive care units with low levels of antimicrobial resistance: an individual patient data meta-analysis.

OBJECTIVE: To determine the cost-effectiveness of selective digestive decontamination (SDD) as compared to selective oropharyngeal decontamination (SOD) in intensive care units (ICUs) with low levels of antimicrobial resistance. DESIGN: Post-hoc analysis of a previously performed individual patient data meta-analysis of two cluster-randomised cross-over trials. SETTING: 24 ICUs in the Netherlands. PARTICIPANTS: 12 952 ICU patients who were treated with ≥1 dose of SDD (n=6720) or SOD (n=6232). INTERVENTIONS: SDD versus SOD. PRIMARY AND SECONDARY OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER; ie, costs to prevent one in-hospital death) was calculated by comparing differences in direct healthcare costs and in-hospital mortality of patients treated with SDD versus SOD. A willingness-to-pay curve was plotted to reflect the probability of cost-effectiveness of SDD for a range of different values of maximum costs per prevented in-hospital death. RESULTS: The ICER resulting from the fixed-effect meta-analysis, adjusted for clustering and differences in baseline characteristics, showed that SDD significantly reduced in-hospital mortality (adjusted absolute risk reduction 0.0195, 95% CI 0.0050 to 0.0338) with no difference in costs (adjusted cost difference €62 in favour of SDD, 95% CI -€1079 to €935). Thus, SDD yielded significantly lower in-hospital mortality and comparable costs as compared with SOD. At a willingness-to-pay value of €33 633 per one prevented in-hospital death, SDD had a probability of 90.0% to be cost-effective as compared with SOD. CONCLUSION: In Dutch ICUs, SDD has a very high probability of cost-effectiveness as compared to SOD. These data support the implementation of SDD in settings with low levels of antimicrobial resistance.

Treatment for human visceral leishmaniasis: a cost-effectiveness analysis for Brazil.

OBJECTIVE: To estimate the cost-effectiveness of strategies for the treatment of VL in Brazil. METHODS: Cost-effectiveness study comparing three therapeutic options: meglumine antimoniate (MA), liposomal amphotericin B (LAMB) and a combination of LAMB plus MA (LAMB plus MA), from public health system and societal perspectives. An analytical decision-making model was used to compare strategies for the following outcomes: early therapeutic failure avoided at 30 days, days of hospitalisation avoided and VL cure at 180 days. The efficacy and safety parameters of the drugs came from a randomised, open-label trial and the cost data came from a cost-of-illness study, both carried out in Brazil. RESULTS: For all outcomes analysed, the LAMB strategy was more effective. The MA strategy was inferior to the LAMB plus MA strategy for the outcomes early therapeutic failure avoided and cure. When only LAMB and MA were compared from a societal perspective, a cost of US$ 278.56 was estimated for each additional early therapeutic failure avoided, a cost of US$ 26.88 for each additional day of hospitalisation avoided and a cost of US$ 89.88 for each additional case of cured VL, for the LAMB strategy vs. MA. CONCLUSION: In Brazil, the LAMB strategy proved to be cost-effective for treating VL, considering a GDP per capita as the willingness-to-pay threshold, for all of the outcomes analysed in comparison to MA.

OBJECTIF: Estimer la rentabilité des stratégies de traitement de la leishmaniose viscérale (LV) au Brésil. MÉTHODES: Etude coût-efficacité comparant trois options thérapeutiques: l'antimoniate de méglumine (AM), amphotéricine B liposomale (LAMB) et une combinaison de LAMB et MA (LAMB plus AM), du point de vue du système de santé publique et sociétal. Un modèle décisionnel analytique a été utilisé pour comparer les stratégies pour les résultats suivants: échec thérapeutique précoce évité à 30 jours, jours d'hospitalisation évités et guérison de la LV à 180 jours. Les paramètres d'efficacité et de sécurité des médicaments provenaient d'un essai randomisé ouvert et les données relatives aux coûts, d'une étude sur le coût de la maladie, toutes deux menées au Brésil. RÉSULTATS: Pour tous les résultats analysés, la stratégie LAMB était plus efficace. La stratégie AM était inférieure à la stratégie LAMB plus AM pour les résultats: échec thérapeutique précoce évité et guérison. Lorsque seules les stratégies LAMB et AM ont été comparées d'un point de vue sociétal, un coût de 278,56 USD a été estimé pour chaque échec thérapeutique précoce additionnel évité, un coût de 26,88 USD pour chaque jour d'hospitalisation additionnel évité et un coût de 89,88 USD pour chaque cas additionnel de LV guéri, pour la stratégie LAMB par rapport à AM. CONCLUSION: Au Brésil, la stratégie LAMB s'est avérée rentable pour traiter la LV, considérant un PIB par habitant comme seuil de volonté de payer, pour tous les résultats analysés par rapport à l'AM.

AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study.

INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results.

Cost-effectiveness analysis of diagnostic-therapeutic strategies for visceral leishmaniasis in Brazil.

INTRODUCTION: Visceral leishmaniasis (VL) is fatal if not diagnosed and treated. This study aimed to estimate the cost-effectiveness of diagnostic-therapeutic alternatives for VL in Brazil. METHODS: A decision model estimated the life expectancy and costs of six diagnostic-therapeutic strategies. RESULTS: IT LEISH + liposomal amphotericin B emerged the best option, presenting lower costs and higher effectiveness. DAT-LPC + liposomal amphotericin B showed an incremental cost-effectiveness ratio of US$ 326.31 per life year. CONCLUSIONS: These findings indicate the feasibility of incorporating DAT and designating liposomal amphotericin B as the first-line drug for VL in Brazil.

Burden of acute kidney injury in HIV patients under deoxycholate amphotericin B therapy for cryptococcal meningitis and cost-minimization analysis of amphotericin B lipid complex.

Deoxycholate amphotericin B (d-AMB) has a higher rate of acute kidney injury (AKI) in comparison of lipid formulations. However, lipid amphotericin B has high costs in developing countries. The aim of this study is to assemble a model of cost-minimization of amphotericin B lipid complex (ABLC) in patients with cryptococcal meningitis. This is a retrospective study done in a cohort of patients with cryptococcal meningitis to study the economic impact of its use in developing countries. Cost analysis were based on direct cost of different antifungal therapies, chronic dialysis after discharge, and survival of patients based on a retrospective cohort of 102 patients infected with human immunodeficiency virus with confirmed diagnosis of cryptococcal meningitis. From 102 patients treated with d-AMB, 60.78% developed any grade of AKI and 10.78% developed AKI demanding hemodialysis. The percentage of patients with meningeal cryptococcosis treated with d-AMB that requeired chronic HD was 2.39%. The same model was performed for patient that would be treated with ABLC, which resulted in 0.20% of patients demanding chronic HD due to its lower nephrotoxicity. When the model is applied in 100 patients, the total costs with d-AMB would be US$ 184,543 and with ABLC would be US$ 1,640,109 in 5 years. Treatment with ABLC would be cost saving in comparison to d-AMB treatment, if early switch of treatment occurred in patients presenting AKI. The change should be as soon as possible to avoid further complication, like dialysis, which is associated with a lower life expectancy.

Cost-effectiveness analysis of diagnostic-therapeutic strategies for visceral leishmaniasis in Brazil

Abstract INTRODUCTION: Visceral leishmaniasis (VL) is fatal if not diagnosed and treated. This study aimed to estimate the cost-effectiveness of diagnostic-therapeutic alternatives for VL in Brazil. METHODS: A decision model estimated the life expectancy and costs of six diagnostic-therapeutic strategies. RESULTS: IT LEISH + liposomal amphotericin B emerged the best option, presenting lower costs and higher effectiveness. DAT-LPC + liposomal amphotericin B showed an incremental cost-effectiveness ratio of US$ 326.31 per life year. CONCLUSIONS: These findings indicate the feasibility of incorporating DAT and designating liposomal amphotericin B as the first-line drug for VL in Brazil.

AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen). METHODS: An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance. DISCUSSION: A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN72509687 . Registered on 13 July 2017.

In-vitro and in-vivo antileishmanial activity of inexpensive Amphotericin B formulations: Heated Amphotericin B and Amphotericin B-loaded microemulsion.

Amphotericin B (AmB) is effective against visceral leishmaniasis (VL), but the renal toxicity of the conventional form, mixed micelles with deoxycholate (M-AmB), is often dose-limiting, while the less toxic lipid-based formulations such as AmBisome® are very expensive. Two different strategies to improve the therapeutic index of AmB with inexpensive ingredients were evaluated on this work: (i) the heat treatment of the commercial formulation (H-AmB) and (ii) the preparation of an AmB-loaded microemulsion (ME-AmB). M-AmB was heated to 70 °C for 20 min. The resulting product was characterized by UV spectrophotometry and circular dichroism, showing super-aggregates formation. ME-AmB was prepared from phosphate buffer pH 7.4, Tween 80®, Lipoid S100® and Mygliol 812® with AmB at 5 mg/mL. The droplet size, measured by dynamic light scattering, was about 40 nm and transmission electron microscopy confirmed a spherical shape. Rheological analysis showed low viscosity and Newtonian behavior. All the formulations were active in vitro and in vivo against Leishmania donovani (LV9). A selectivity index (CC50 on RAW/IC50 on LV9) higher than 10 was observed for ME-AmB, H-AmB and AmBisome®. Furthermore, no important in vivo toxicity was observed for all the samples. The in-vivo efficacy of the formulations after IV administration was evaluated in Balb/C mice infected with LV9 (three doses of 1 mg/kg AmB) and no significant difference was observed between H-AmB, M-AmB, ME-AmB and AmBisome®. In conclusion, these two inexpensive alternative formulations for AmB showing good efficacy and selectivity for Leishmania donovani merit further investigation.

Economic evaluation of micafungin versus liposomal amphotericin B (LAmB) for treating patients with candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Cost-effectiveness of amphotericin B formulations in the treatment of systemic fungal infections.

Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost-effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high-risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One-way and probabilistic-sensitivity analyses were conducted. The conventional formulation was the most cost-effective. No dominance was observed; however, high incremental cost-effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil.

Economic impact of treating invasive mold disease with isavuconazole compared with liposomal amphotericin B in the UK.

AIM: Invasive mold diseases (IMDs) are associated with significant morbidity and mortality. Approved treatments include voriconazole (VORI), liposomal amphotericin B (L-AMB), posaconazole (POSA) and isavuconazole (ISAV). A UK-based economic model was developed to explore the cost of treating IMDs with ISAV versus L-AMB followed by POSA. MATERIALS & METHODS: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration & monitoring, and hospitalization costs were evaluated from the healthcare system perspective. RESULTS: Per-patient costs were UK£14,842 with ISAV versus UK£18,612 with L-AMB followed by POSA. Savings were driven by drug acquisition, and administration & monitoring costs. CONCLUSION: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.

Cost-effectiveness of liposomal amphotericin B in hospitalised patients with mucocutaneous leishmaniasis.

OBJECTIVE: To compare the cost-effectiveness of L-AmB with that of SbV and AmB-D, for the treatment of mucocutaneous leishmaniasis in a hospital in north-east Brazil. METHODS: We developed an economic model based on retrospective data of 73 hospitalised patients in 2006-2012, from hospital and public health system perspectives. RESULTS: In the economic model, 82.2% of patients who started treatment with L-AmB had completed it after 2 months, vs. 22.0% for the SbV and 19.9% for the AmB-D groups. After 12 months of follow-up, these proportions were 100% in the L-AmB, 77.4% in the AmB-D and 72.2% in the SbV group. Markov chain analyses showed that the group that started therapy with SbV had the lowest mean total cost (US$ 3782.38), followed by AmB-D (US$ 5211.27) and L-AmB (US$ 11 337.44). The incremental cost-effectiveness ratio for L-AmB was US$ 18 816.23 against SbV and US$ 24 504.65 against AmB-D. In the sensitivity analysis, the drug acquisition cost of L-AmB significantly influenced the results. CONCLUSIONS: In the treatment of mucocutaneous leishmaniasis, L-AmB is a cost-effective alternative to SbV and AmB-D owing to its higher effectiveness, safety and shorter course.

The direct costs of treating human visceral leishmaniasis in Brazil.

INTRODUCTION:: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS:: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS:: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS:: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

The direct costs of treating human visceral leishmaniasis in Brazil

Abstract INTRODUCTION: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

A Cheap and Convenient Method of Liposome Preparation Using Glass Beads as a Source of Shear Force.

Liposomes, the biocompatible lipid bilayer vesicles, have attracted immense attention due to their distinctive features such as efficient vehicle for the delivery of a wide range of therapeutic agents, adjustable formulation properties, and high drug entrapment efficiency. In this contribution, we present a simple method for the preparation of liposomes using glass beads and compared the potential of this method with conventional methods of liposome preparation. The prepared liposomes were characterized by different analytical techniques (HPLC, DLS, TEM, differential scanning calorimetry, and in vitro drug release). Our findings revealed that the particle size of liposomes is mainly dependent on the size of the glass beads and the glass bead shearing time. An average liposome size of 67.7 ± 25.5 nm was obtained using 2-mm glass beads after 24-h incubation at 200 rpm. The liposomes prepared under the optimized conditions exhibited a high encapsulation efficiency of 92.1 ± 1.7% with 31.08% drug release after 360 min at 37°C. In conclusion, the developed method is a simple and convenient process of liposome preparation of different sizes with desirable entrapment efficiency capacity.

Assessment of high-priced systemic antifungal prescriptions.

OBJECTIVES: To assess compliance with international guidelines for costly antifungal prescriptions and to compare these results with a first study performed in 2007. METHODS: Retrospective study including all costly antifungal prescriptions made in surgical and medical intensive care units and in a hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were assessed in terms of indication, dosage, and antifungal de-escalation. RESULTS: Seventy-four treatments were analyzed. Treatments were prescribed for prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%). Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%) and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%, and inappropriate in 23%. Prescriptions were inappropriate for the following reasons: lack of dosage adjustment in light of the hepatic function (10 cases), underdosage or excessive dosage by>25% of the recommended dose in seven cases. De-escalation to fluconazole was implemented in 40% of patients presenting with a fluconazole-susceptible candidiasis. CONCLUSION: The overall incidence of appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively, P=0.004). Nevertheless, costly antifungal prescriptions need to be optimized in particular for empirical therapy, dosage adjustment, and potential de-escalation to fluconazole.

The cost of treating mucormycosis with isavuconazole compared with standard therapy in the UK.

AIM: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole. MATERIALS & METHODS: As a matched case-control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs - drug acquisition, monitoring and administration, and hospitalization costs - were estimated from the National Health Service perspective. RESULTS: Per-patient costs for ISAV and liposomal AMB + posaconazole were UK£26,810 and UK£41,855, respectively, with savings primarily driven by drug acquisition and hospitalization costs. CONCLUSION: ISAV may reduce costs compared with standard mucormycosis therapy.