Cost-effectiveness of micafungin as an alternative to fluconazole empiric treatment of suspected ICU-acquired candidemia among patients with sepsis: A model simulation

School of Public Health and Health Sciences, University of Massachusetts, Arnold House, Amherst, MA 01003, USA.
Critical care (London, England) (Impact Factor: 4.48). 07/2009; 13(3):R94. DOI: 10.1186/cc7924
Source: PubMed


Recent epidemiologic literature indicates that candidal species resistant to azoles are becoming more prevalent in the face of increasing incidence of hospitalizations with candidemia. Echinocandins, a new class of antifungal agents, are effective against resistant candidal species. As delaying appropriate antifungal coverage leads to increased mortality, we evaluated the cost-effectiveness of 100 mg daily empiric micafungin (MIC) vs. 400 mg daily fluconazole (FLU) for suspected intensive care unit-acquired candidemia (ICU-AC) among septic patients.
We designed a decision model with inputs from the literature in a hypothetical 1000-patient cohort with suspected ICU-AC treated empirically with either MIC or FLU or no treatment accompanied by a watchful waiting strategy. We examined the differences in the number of survivors, acquisition costs of antifungals, and lifetime costs among survivors in the cohort under each scenario, and calculated cost per quality adjusted life year (QALY). We conducted Monte Carlo simulations and sensitivity analyses to determine the stability of our estimates.
In the base case analysis, assuming ICU-AC attributable mortality of 0.40 and a 52% relative risk reduction in mortality with appropriate timely therapy, compared with FLU (total deaths 31), treatment with MIC (total deaths 27) would result in four fewer deaths at an incremental cost/death averted of $61,446. Similarly, in reference case, incremental cost-effectiveness of MIC over FLU was $34,734 (95% confidence interval $26,312 to $49,209) per QALY. The estimates were most sensitive to the QALY adjustment factor and the risk of candidemia among septic patients.
Given the increasing likelihood of azole resistance among candidal isolates, empiric treatment of ICU-AC with 100 mg daily MIC is a cost-effective alternative to FLU.

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    • "One article reported on the use of micafungin for suspected ICU-acquired candidemia among patients with sepsis [16]. In this study, a hypothetical cohort of 1,000 patients with suspected ICU-acquired candidemia (ICU-AC) was designed. "
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    ABSTRACT: Invasive fungal infections are on the rise. Echinocandins are a relatively new class of antifungal drugs that act by inhibition of a key enzyme necessary for integrity of the fungal cell wall. Currently there are three available agents: caspofungin, micafungin and anidulafungin. While the individual echinocandin antifungals have a different spectrum of licensed indications, basically all of them are available for the treatment of candidemia and invasive candidiasis. Antifungal treatment modalities basically include in therapy for suspected or proven infection and prophylaxis. All three drugs are comparatively expensive. Therefore a systematic review of the literature was performed to investigate the following aspects: • General aspects of cost-effectiveness in the treatment of invasive fungal infections • Cost-effectiveness of the treatment with the above-mentioned antifungals • Cost-effectiveness in two settings: therapy and prophylaxis Early initiation of antifungal therapy, adjustment after availability of microbiological results, duration of therapy, success and occurrence of severe complications (e.g renal failure) are the most important cost drivers in antifungal therapy. Considering the specific antifungals, for caspofungin the best evidence for cost-effectiveness is found in treatment of invasive candidiasis and in empiric therapy of suspected infections. Favourable economic data are available for micafungin as a cost-effective alternative to LAmB for prophylaxis in patients with hematopoietic stem cell transplantation (HSCT). For anidulafungin, cost-effectiveness was demostrated in a pharmacoeconomic model. Net savings - yet not significant - were observed in a retrospective chart review of 234 patients. Generally, however, most analyses are still based on pharmacoeconomic modelling rather than direct analysis of trial data or real-life clinical populations. As an overall conclusion, using caspofungin, micafungin, or anidulafungin is not more expensive than using other established therapies. Micafungin has proven to be cost-effective in prophylaxis if the local fungal epidemiology indicates a high level of resistance to fluconazole. Switch strategies involving early initiation of broadly active therapy with switch to cheaper alternatives according to microbiology results and clinical status and early initiation of an appropriate therapy have been proven to be cost-efficient independent of the antifungal agent.
    European journal of medical research 04/2011; 16(4):180-6. DOI:10.1186/2047-783X-16-4-180 · 1.50 Impact Factor
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    • "Whether anidulafungin is cost-effective more than fluconazole needs to be further analyzed. In a model with inputs from the literature in a hypothetical 1000-patient cohort with suspected ICU-acquired invasive candidosis (ICU-AC) treated empirically with either micafungin or fluconazole or no treatment accompanied by a watchful waiting strategy, treatment of suspected ICU-AC (for fluconazole-resistant Candida spp.) with the echinocandin at a dose of 100 mg daily was a cost-effective alternative compared with 400 mg daily FLU or observation alone [80]. "
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    ABSTRACT: Echinocandins represent the newest class of antifungal agents. Currently, three echinocandins, anidulafungin, caspofungin and micafungin are licensed for clinical use in various indications. They act as inhibitors of β-(1,3)-glucan synthesis in the fungal cell wall and have a favorable pharmacological profile. They have a broad spectrum of activity against all Candida species. Higher MIC's have been observed against C. parapsilosis and C. guilliermondii. Data from clinical trials for invasive Candida infections / candidaemia suggest that the clinical outcome of patients treated with either drug may be very similar. A comparison has been done between caspofungin and micafungin but for anidulafungin a comparative trial with another echinocandin is still lacking. All three drugs are highly effective if not superior to treatment with either fluconazole or Amphotericin B, particularly in well-defined clinical settings such as invasive Candida infections, Candida oesophagitis and candidaemia. Differences between the three echinocandins with regard to the route of metabolism, requirement for a loading dose, dose adjustment in patients with moderate to severe hepatic disease and different dosing schedules for different types of Candida infections have to be considered. Relevant drug-drug interactions of Caspofungin and Micafungin are minimal. Anidulafungin has no significant drug interactions at all. However, echinocandins are available only for intravenous use. All three agents have an excellent safety profile.
    European journal of medical research 04/2011; 16(4):159-66. DOI:10.1186/2047-783X-16-4-159 · 1.50 Impact Factor
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    • "Zilberberg and colleagues investigated the cost-effectiveness of a new echinocandin antifungal agent (micafungin) as an alternative to fluconazole in the empirical treatment of suspected ICU-acquired candidaemia among septic patients in a simulation model [33]. In the base case analysis, the authors assumed a high attributable mortality of ICU-acquired candidaemia (40%) and an overly optimistic risk reduction (52%) in mortality with appropriate timely therapy. "
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    ABSTRACT: In 2009 Critical Care provided important and clinically relevant research data for management and prevention of infections in critically ill patients. The present review summarises the results of these observational studies and clinical trials and discusses them in the context of the current relevant scientific and clinical background. In particular, we discuss recent epidemiologic data on nosocomial infections in intensive care units, present new approaches to prevention of ventilator-associated pneumonia, describe recent advances in biomarker-guided antibiotic stewardship and attempt to briefly summarise specific challenges related to the management of infections caused by multidrug-resistant microorganisms and influenza A (H1N1).
    Critical care (London, England) 11/2010; 14(6):240. DOI:10.1186/cc9268 · 4.48 Impact Factor
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