Esin Senol

Fulminating fungal sinusitis caused by Valsa sordida, a plant pathogen, in a patient immunocompromised by acute myeloid leukemia

We describe a case in which a patient immunocompromised by acute myeloid leukemia experienced acute fulminating invasive fungal sinusitis followed by pneumonia and then death. Though the microbiology of the pneumonia could not be directly investigated, nasal lesions revealed fungal mycelium. Valsa sordida was consistently cultured from a biopsied sample. The fungus was identified to the genus level based on morphology in culture and DNA sequence homology, and then was placed at species level by means of phylogenetic analysis of the nuclear ribosomal internal transcribed spacer region. The fungus is in the order Diaporthales, family Valsaceae in the Ascomycota and is distributed worldwide as a pathogen of trees in the genera Populus and Salix. Kochs postulates were demonstrated to apply in a neutropenic rat model. The fungus was susceptible to antifungals with MIC-0 scores of 0.0313 microg/ml for amphotericin B, 0.25 microg/ml for voriconazole, 0.0313 microg/ml for caspofungin, and MIC-2 of 16 microg/ml for fluconazole. This is the first substantiated report of an isolate in the genus Valsa (anamorph Cytospora) being identified in human disease.

Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey

Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB.

Candida dubliniensis puede producir bola fúngica pulmonar

We describe a case of cavitary pneumonia due to Candida dubliniensis along with fungemia due to Candida kefyr in a leukemic patient. This is the first case of C. dubliniensis isolated in our laboratory. The identification was performed by phenotypic and molecular methods such as thermotolerance test, carbohydrate fermentation and polymerase chain reaction.

Isolated Severe Immune Thrombocytopenia due to Acute Brucellosis

Mild anemia and leukopenia are the most common hematologic findings in the course of acute brucellosis. However severe form of thrombocytopenia is less frequently reported. The patient was admitted to the hospital with fever, gingival bleeding, and petechial skin lesions related to severe thrombocytopenia. He was investigated for the causes of thrombocytopenia. Test results showed that Wright agglutination test was positive at 1/5120 titer, and blood culture was positive for Brucella melitensis. Finally, he was diagnosed as acute brucellosis. Rifampicin and doxycycline treatment was started on he third day of admission. A bone marrow aspiration was performed on the seventh day of admission because of severe thrombocytopenia did not response to brucellosis treatment. The result of bone marrow aspiration was consistent with idiopathic thrombocytopenic purpura. With the addition of corticosteroid treatment, his complaints resolved immediately, and thrombocyte count rose to normal range. He was discharged on the 12th day of rifampicin and doxycycline therapy, and he was successfully completed 6-week therapy. In cases of brucella induced immune thrombocytopenia, corticosteroid treatment might be useful for the prevention of bleeding complications.

Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey

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.

Pharmacoeconomic evaluation of micafungin versus caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in Turkey

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.

Cost effectiveness of caspofungin vs. voriconazole for empiric therapy in Turkey

Invasive fungal infections from febrile neutropenia are associated with significant cost and mortality. The mainstay of treatment has been liposomal amphotericin B, however, echinocandins and azoles have shown promise as alternative treatments. Data on clinical efficacy exist, however, data incorporating pharmacoeconomic considerations are required in Turkey. The aim of this study was to investigate the cost effectiveness of caspofungin vs. voriconazole in empiric treatment of febrile neutropenia in Turkey. A decision analytic model was utilised, built upon two randomised‐controlled trials and supplemented with expert panel input from clinicians in Turkey. A five‐point composite outcome measure was utilised and sensitivity analyses were performed to demonstrate the robustness of the model. The base case scenario resulted in caspofungin being preferred by TL2,533, TL29,256 and TL2,536 per patient treated, successfully treated patient and patient survival, respectively (approx. USD1414, 16 328 and 1415); sensitivity analyses did not change the outcome. Monte Carlo simulation highlighted a 78.8% chance of favouring caspofungin. The result was moderately sensitive to treatment duration and acquisition cost of the antifungal agents compared. This is the first pharmacoeconomic study comparing caspofungin to voriconazole within Turkey, resulting in an advantage towards caspofungin. The study will aid in formulary decision‐making based on the clinical and economic consequences of each agent in the Turkish health care setting.

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.