MedWorm: Caspofungin

Caspofungin Use in Patients with Invasive Candidiasis caused by Common Non-albicans Candida Species: Review of the Caspofungin Database.

Antimicrobial Agents and Chemotherapy — Mon, 15 Mar 2010 00:00:00 +0100

Authors: Colombo AL, Ngai AL, Bourque M, Bradshaw SK, Strohmaier KM, Taylor AF, Lupinacci RJ, Kartsonis NA Increasing rates of invasive candidiasis caused by non-albicans Candida species have been reported worldwide. Particular concerns have been raised for C. parapsilosis because of reduced in vitro susceptibility to echinocandins. We identified 212 patients with invasive candidiasis due to non-albicans Candida species (>/=5 cases per species) in 5 clinical trials of caspofungin monotherapy from the pharmaceutical Sponsor's (Merck and Co., Inc.) database: 71 C. parapsilosis, 65 C. tropicalis, 54 C. glabrata, 10 C. krusei, 9 C. guilliermondii, and 5 C. lusitaniae; 167 cases caused by C. albicans were also identified. Efficacy was assessed at the end of caspofungin therapy. Success (...

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Chapter 8 - Fungal infections in immunocompromised patients

Jornal Brasileiro de Pneumologia — Fri, 12 Mar 2010 15:34:44 +0100

As complicações pulmonares se constituem na maior causa de morbidade e mortalidade no hospedeiro imunocomprometido, devido à deficiência nos mecanismos básicos de defesa. Independente da causa da imunodepressão, infecções bacterianas, virais e fúngicas são as mais frequentes. Entre as infecções fúngicas, a aspergilose é a mais comum (incidência de 1-9% e mortalidade de 55-92%) nos diferentes tipos de transplantados. Embora a forma pneumônica seja a mais frequente, lesões do sistema nervoso central e sinusite não são raras. O sinal do halo em TC de tórax representa uma área de baixa atenuação em volta do nódulo, revelando edema ou hemorragia. O padrão ouro para o diagnóstico é a identificação do fungo por cultura de escarro, amostras de LBA ou biópsia. Na falta...

Transcriptional Regulation of Chitin Synthases by Calcineurin Controls Paradoxical Growth of Aspergillus fumigatus in Response to Caspofungin

The Aspergillus Website - articles — Thu, 11 Mar 2010 00:00:00 +0100

Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, Steinbach WJ (Source: The Aspergillus Website - articles)

Chapter 8: Fungal infections in immunocompromised patients

Jornal Brasileiro de Pneumologia — Thu, 04 Mar 2010 16:48:33 +0100

Interaction of Candida albicans biofilms with antifungals: transcriptional response and binding of antifungals to beta-glucans.

Antimicrobial Agents and Chemotherapy — Mon, 01 Mar 2010 00:00:00 +0100

Authors: Vediyappan G, Rossignol T, d'Enfert C Candida albicans can form biofilms that exhibit elevated intrinsic resistance to various antifungal agents, in particular azoles and polyenes. The molecular mechanisms that are involved in the antifungal resistance of biofilms remain poorly understood. We have used transcript profiling to explore the early transcriptional responses of mature C. albicans biofilms exposed to various antifungal agents. Mature C. albicans biofilms grown under continuous flow were exposed for up to 2h to concentrations of Fluconazole (FLU), Amphotericin B (AMB) and caspofungin (CAS) that, while lethal for planktonic cells, were not lethal for biofilms. Interestingly, FLU exposed biofilms did not show any significant changes in gene expression over the course of...

Synergistic Activities of Three Triazoles with Caspofungin against Candida glabrata isolates Determined by Time-Kill, Etest and Disk Diffusion Methods.

Antimicrobial Agents and Chemotherapy — Mon, 01 Mar 2010 00:00:00 +0100

Authors: Kiraz N, Dag I, Yamac M, Kiremitci A, Kasifoglu N, Oz Y The combination of voriconazole, fluconazole, itraconazole with caspofungin was evaluated against 50 Candida glabrata isolates by the time-kill, disk diffusion and Etest methods. The majority of antifungal combinations were indifferent. By the time kill method, synergistic activity was detected at eight (16%) of caspofungin-voriconazole and seven (14%) of caspofungin-fluconazole combinations, but synergy was not seen in caspofungin-itraconazole combination. Further comparisons of the Etest and disk diffusion synergy techniques with the time kill method are warranted. PMID: 20194697 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

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Retrospective evaluation of caspofungin therapy in invasive aspergillosis (RECAM-IA)

Mycoses — Wed, 24 Feb 2010 00:00:00 +0100

To evaluate caspofungin in high-risk invasive aspergillosis (IA) patient, a retrospective review of patient characteristics, antifungal therapies and clinical outcomes on hospitalised patients at sites in Russia, Canada, Germany, and Thailand was performed. Fifty-five patients were included, six with proven and 49 with probable aspergillosis; 76.4% had haematological diseases, 80% were on immunosuppressive drugs, 32.7% were neutropenic at caspofungin initiation. Median duration of prior antifungal therapy was 9 days (range 1[ndash]232). Reasons for initiating caspofungin included: disease refractory to first-line antifungal (49.1%) and toxicities with prior antifungals (18.2%). Median caspofungin therapy duration was 14 days (range 2[ndash]62), with a median of 13 days (range 1[ndash]62) a...

Quantitation of azoles and echinocandins in the compartments of peripheral blood by liquid chromatography tandem mass spectrometry.

Antimicrobial Agents and Chemotherapy — Mon, 22 Feb 2010 00:00:00 +0100

Authors: Farowski F, Cornely OA, Vehreschild JJ, Hartmann P, Bauer T, Steinbach A, Rüping MJ, Müller C A rapid turn-around is a pre-requisite of therapeutic drug monitoring (TDM). For antifungals this need is still unmet, since hardly any method has been established to simultaneously quantitate concentrations of different antifungal classes. A liquid chromatography tandem mass spectroscopy (LC-MS/MS) was developed allowing quantitation of anidulafungin (ANF), caspofungin (CSF), isavuconazole (ISC), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). Quantitation was successful in diluted plasma, peripheral blood mononuclear cells (PBMC), polymorphonuclear leucocytes (PMN), and erythrocytes (RBC). A triple quadrupole mass spectrometer in selected reaction monitoring ...

Intraocular caspofungin: in vitro safety profile for human ocular cells

Mycoses — Fri, 19 Feb 2010 00:00:00 +0100

This study investigates the safety profile of caspofungin for intraocular application in a cell-culture model. Endothelial toxicity of caspofungin was evaluated in cultured human corneas. Possible toxic effects of caspofungin (5[ndash]300 [mu]g ml[minus]1) in corneal endothelial cells (CEC), primary human trabecular meshwork cells (TMC) and primary human retinal pigment epithelium (RPE) cells were evaluated after 24 h and under conditions of inflammatory stress by treatment with tumour necrosis factor-alpha (TNF-[alpha]), lipopolysaccharides (LPS) or interleukin-6 (IL-6) and hydrogen peroxide (H2O2). Toxicity was evaluated by tetrazolium dye-reduction assay; cell viability was quantified by a microscopic live[ndash]dead assay. No corneal endothelial toxicity could be detected after 30 days...

Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi

The Aspergillus Website - articles — Thu, 18 Feb 2010 00:00:00 +0100

Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA (Source: The Aspergillus Website - articles)

Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study

The Aspergillus Website - articles — Thu, 11 Feb 2010 00:00:00 +0100

Herbrecht R, Maertens J, Baila L, Aoun M, Heinz W, Martino R, Schwartz S, Ullmann AJ, Meert L, Paesmans M, Marchetti O, Akan H, Ameye L, Shivaprakash M, Viscoli C (Source: The Aspergillus Website - articles)

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A retrospective nationwide case study on the use of a new antifungal agent: patients treated with caspofungin during 2001-2004 in Finland

The Aspergillus Website - articles — Thu, 11 Feb 2010 00:00:00 +0100

Anttila VJ, Salonen J, Ylipalosaari P, Koivula I, Riikonen P, Nikoskelainen J (Source: The Aspergillus Website - articles)

Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis

The Aspergillus Website - articles — Thu, 11 Feb 2010 00:00:00 +0100

Maertens J, Glasmacher A, Herbrecht R, Thiebaut A, Cordonnier C, Segal BH, Killar J, Taylor A, Kartsonis N, Patterson TF, Aoun M, Caillot D, Sable C; Caspofungin Combination Therapy Study Group (Source: The Aspergillus Website - articles)

Efficacy of amphotericin B or amphotericin B-intralipid in combination with caspofungin against experimental aspergillosis

The Aspergillus Website - articles — Thu, 11 Feb 2010 00:00:00 +0100

Sionov E, Mendlovic S, Segal E (Source: The Aspergillus Website - articles)

Comparative efficacies of conventional amphotericin b, liposomal amphotericin B (AmBisome), caspofungin, micafungin, and voriconazole alone and in combination against experimental murine central nervous system aspergillosis

The Aspergillus Website - articles — Thu, 11 Feb 2010 00:00:00 +0100

Clemons KV, Espiritu M, Parmar R, Stevens DA (Source: The Aspergillus Website - articles)

In Vitro Fungicidal Activity of Echinocandins against Candida metapsilosis, C. orthopsilosis and C. parapsilosis by Time Killing Studies.

Antimicrobial Agents and Chemotherapy — Tue, 09 Feb 2010 00:00:00 +0100

Authors: Cantón E, Espinel-Ingroff A, Pemán J, Del Castillo L Anidulafungin, micafungin and caspofungin in vitro activity was evaluated by MIC and time-kill methods against Candida metapsilosis, C. orthopsilosis and C. parapsilosis. All echinocandins showed lower MICs (mean MICs 0.05-0.71 mg/L) and the highest killing rates (-0.06 to -0.05 CFU/mL/h) for C. metapsilosis and C. orthopsilosis than for C. parapsilosis (mean MICs 0.59-1.68 mg/L). Micafungin and anidulafungin killing rates were greater than that of caspofungin. None of the echinocandins had fungicidal activity against C. parapsilosis. PMID: 20145083 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

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Changes in the Proteome of Candida albicans in Response to Azole, Polyene, and Echinocandin Antifungal Agents.

Antimicrobial Agents and Chemotherapy — Tue, 09 Feb 2010 00:00:00 +0100

Authors: Hoehamer CF, Cummings ED, Hilliard GM, Rogers PD The yeast Candida albicans is an opportunistic human fungal pathogen and cause of superficial and systemic infections in immunocompromised patients. The classes of antifungal agents most commonly used to treat Candida infections are the azoles, polyenes, and echinocandins. In the present study, we identified changes in C. albicans protein abundance using 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF MS) following exposure to representatives of azole (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of antifungal agents. We id...

Susceptibility to five antifungals of Aspergillus fumigatus strains isolated from chronically colonised cystic fibrosis patients receiving azole therapy

International Journal of Antimicrobial Agents — Mon, 08 Feb 2010 00:00:00 +0100

Abstract: Exposure of Aspergillus fumigatus to stressful antifungal therapies may result in decreased susceptibility. The aim of the present work was to evaluate the susceptibility to azole and non-azole antifungals of 159 isolates of A. fumigatus collected from cystic fibrosis (CF) patients receiving azole antifungal therapy. The genetic diversity of the fungal isolates was assessed using microsatellite genotyping, and some strains were found in patient's sputum samples more than 4 years apart. No resistant isolates [minimal inhibitory concentration (MIC)/minimal effective concentration (MEC)≥4μg/mL] were identified to the antifungals amphotericin B, caspofungin, itraconazole and voriconazole. A single A. fumigatus isolate was identified outside of the epidemiological cut-off of 0.25μ...

Fluconazole, caspofungin, voriconazole in combination with amphotericin B

Central European Journal of Medicine — Mon, 01 Feb 2010 06:47:42 +0100

Abstract Combined antifungal therapy has been suggested to enhance the efficacy and reduce the toxicity of antifungal agents. The aim of the study was to investigate the in vitro synergistic activity of caspofungin, voriconazole, and fluconazole with amphotericin B against ten isolates of Candida parapsilosis and Candida albicans strains which were resistant to azoles or amphotericin B. Three different antifungal combinations (amphotericin B [AP] — caspofungin [CS], amphotericin B — fluconazole [FL], and AP — voriconazole [VO]) were evaluated for in vitro synergistic effect by the microdilution checkerboard and E-test methods. For the majority of strains, the combination test showed indifferent activity. Via the E-test method, synergistic activity was seen in 3 strains ...

In Vitro Antifungal Activities of D11-2040, a beta-1,6-Glucan Inhibitor, with or without Currently Available Antifungal Drugs.

Biological and Pharmaceutical Bulletin — Mon, 01 Feb 2010 00:00:00 +0100

In this study, we further evaluated the antifungal profile of D11-2040. It alone strongly inhibited the vegetative growth and/or hyphal development of various Candida species, but no significant activity was observed against Cryptococcus neoformans or any of the filamentous fungi tested. Synergism was detected for C. albicans in the interaction of D11-2040 and caspofungin by the chequerboard method and in that of D11-2040 and fluconazole by the time-kill method. Slight but positive interactions were observed in several combinations for C. neoformans and Aspergillus fumigatus as well. These results suggested that beta-1,6-glucan inhibitors have promising potential as single drugs as well as concomitants. PMID: 20118539 [PubMed - in process] (Source: Biological and Pharmaceutical Bulleti...

Transcriptional Regulation of Chitin Synthases by Calcineurin Controls Paradoxical Growth of Aspergillus fumigatus in Response to Caspofungin.

Antimicrobial Agents and Chemotherapy — Mon, 01 Feb 2010 00:00:00 +0100

Authors: Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, Steinbach WJ Attenuated activity of echinocandin antifungals at high concentrations, known as the "paradoxical effect", is a well-established phenomenon in Candida albicans and Aspergillus fumigatus. In the yeast C. albicans, upregulation of chitin biosynthesis via the PKC, HOG, and Ca(2+)/calcineurin signaling pathways is an important cell wall stress response that permits growth in the presence of high concentrations of echinocandins. However, nothing is known of the molecular mechanisms regulating the mould A. fumigatus and its paradoxical response to echinocandins. Here we show that laboratory strain of A. fumigatus and five of seven clinical A. fumigatus isolates tested display varying magnitudes of paradoxical g...

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Fungicidal activity and morphological alterations of Candida albicans induced by echinocandins: study of strains with reduced caspofungin susceptibility

Mycoses — Wed, 27 Jan 2010 00:00:00 +0100

Caspofungin is a member of the echinocandin class of antifungal compounds that inhibit 1,3-[beta]-d-Glucan synthase. As patient exposure to caspofungin (CAS) broadens, the number of infecting strains with reduced susceptibility to this drug is expected to rise. In the present study, the in vitro effects of varying concentrations of CAS against Candida albicans isolates presenting reduced susceptibility to CAS were studied in comparison with a reference strain. Two C. albicans isolates presenting high minimal inhibitory concentrations (MIC = 8 [mu]g ml[minus]1) were selected: one isolate obtained in the laboratory under continuous antifungal selection pressure (CaIn-R) and one clinical isolate (CaClin-R) from a patient with a therapeutic failure. Results showed that after 24 h of CAS exposu...

Combination of caspofungin or anidulafungin with antimicrobial peptides results in potent synergistic killing of Candida albicans and Candida glabrata in vitro

International Journal of Antimicrobial Agents — Wed, 27 Jan 2010 00:00:00 +0100

Abstract: Administering synergistic combinations of antifungals could be a route to overcome problems with toxicity and the development of resistance. Combination of the echinocandins caspofungin or anidulafungin with a range of structurally diverse antimicrobial peptides resulted in potent synergistic killing of Candida spp. in vitro. Fungicidal synergy was measured by calculating fractional inhibitory concentration indices from checkerboard assays as well as loss of viability. Inhibitory combinations of the antifungals did not induce cytotoxicity in vitro. However, in a murine model of systemic candidiasis, co-administration of caspofungin with one example of the cationic peptides tested, ranalexin, did not show enhanced efficacy compared with the single treatments alone. Further study u...

Activity of aminocandin (IP960; HMR3270) compared with amphotericin B, itraconazole, caspofungin and micafungin in neutropenic murine models of disseminated infection caused by itraconazole-susceptible and -resistant strains of Aspergillus fumigatus

The Aspergillus Website - articles — Fri, 22 Jan 2010 00:00:00 +0100

Warn PA, Sharp A, Morrissey G, Denning DW (Source: The Aspergillus Website - articles)

Caspofungin Etest Endpoint for Aspergillus Shows Poor Agreement with the Reference Minimum Effective Concentration (MEC)

The Aspergillus Website - articles — Fri, 22 Jan 2010 00:00:00 +0100

Fuller J, Schofield A, Jiwa S, Sand C, Jansen B, Rennie R (Source: The Aspergillus Website - articles)

Prophylaxis of invasive aspergillosis with voriconazole or caspofungin in patients with acute leukemia during building works

The Aspergillus Website - articles — Fri, 22 Jan 2010 00:00:00 +0100

Chabrol A, Cuzin L, Huguet F, Alvarez M, Verdeil X, Linas MD, Cassaing S, Giron J, Tetu L, Attal M, Récher C (Source: The Aspergillus Website - articles)

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In vitro activity of antifungal combinations against Candida albicans biofilms

Journal of Antimicrobial Chemotherapy — Thu, 21 Jan 2010 08:07:07 +0100

Conclusions We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction. (Source: Journal of Antimicrobial Chemotherapy)

Caspofungin-non-susceptible Candida isolates in cancer patients

Journal of Antimicrobial Chemotherapy — Thu, 21 Jan 2010 08:07:07 +0100

Objectives To identify the frequency of caspofungin-non-susceptible Candida isolates in cancer patients with candidiasis. Methods We reviewed the in vitro susceptibilities (M27-A3 CLSI method) of 650 Candida spp. associated with invasive candidiasis episodes in 582 hospitalized cancer patients (2005–08). Results and conclusions We identified seven caspofungin-non-susceptible Candida strains (three Candida tropicalis, two Candida glabrata and two Candida albicans) from 650 Candida isolates (1%). C. tropicalis (three out of seven) was the most common non-susceptible species isolated. All patients responded to a change of antifungal therapy. Further surveillance should focus on the potential broader emergence of echinocandin resistance, as the clinical use of this antifungal class con...

In vitro Activities of Eight Antifungal Drugs Against 55 Clinical Isolates of Fonsecaea.

Antimicrobial Agents and Chemotherapy — Tue, 19 Jan 2010 00:00:00 +0100

Authors: Najafzadeh MJ, Badali H, Illnait-Zaragozi MT, De Hoog GS, Meis JF Clinical isolates of Fonsecaea pedrosoi (n = 21), Fonsecaea monophora (n = 25), and Fonsecaea nubica (n = 9) were tested in vitro against eight antifungal drugs. The resulting MIC90s across all strains (n=55) were in increasing order posaconazole (0.063 mug/ml), itraconazole (0.125 mug/ml), isavuconazole (0.25 mug/ml), voriconazole (0.5 mug/ml), amphotericin B (2mug/ml), caspofungin (2mug/ml), anidulafungin (2mug/ml), and fluconazole (32 mug/ml). PMID: 20086140 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

Rapid differentiation of Candida albicans from non-C. albicans directly in a variety of clinical specimens using fluorescent in situ hybridisation

Mycoses — Wed, 13 Jan 2010 00:00:00 +0100

In this study, we established a protocol for the application of a fluorescent in situ hybridisation (FISH) assay on different clinical samples, and analysed the effectiveness of this protocol for discriminating these organisms without prior cultivation. The FISH protocol for differentiating C. albicans from non-C. albicans species showed 95% sensitivity and 100% specificity. The positive predictive value was 100% and the negative predictive value was 94% compared with results obtained using traditional methods. Three clinical samples were FISH negative and culture positive, the percentage of false negatives with FISH was 4.0%. The results indicate that the FISH protocol is effective and reliable for the rapid differentiation of C. albicans from non-C. albicans species directly in clinical ...

Caspofungin for post solid organ transplant invasive fungal disease: results of a retrospective observational study

Transplant Infectious Disease — Tue, 12 Jan 2010 00:00:00 +0100

This study was designed to determine clinical outcomes with caspofungin in patients with proven or probable invasive fungal infection (IFI) after a solid organ transplant (SOT) procedure. In this retrospective observational study, data were collected for a single episode of IFI in patients with an SOT between January 2004 and June 2007. Response was determined by the investigator as favorable (complete or partial) or unfavorable (stable disease or failure) at the end of caspofungin therapy (EOCT). The primary effectiveness population was the proportion of patients who received [ge]5 doses of caspofungin (modified all-patients-treated population). Safety was assessed for patients who received [ge]1 dose of caspofungin. A total 81 of patients from 13 sites in China, Germany, Italy, and the U...

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Caspofungin: Development of caspofungin resistance in Candida glabrata infection: case report

Reactions — Mon, 11 Jan 2010 14:23:59 +0100

(Source: Reactions)

Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study

Bone Marrow Transplantation — Mon, 11 Jan 2010 00:00:00 +0100

Authors: R Herbrecht, J Maertens, L Baila, M Aoun, W Heinz, R Martino, S Schwartz, A J Ullmann, L Meert, M Paesmans, O Marchetti, H Akan, L Ameye, M Shivaprakash & C Viscoli (Source: Bone Marrow Transplantation)

Trailing or paradoxical growth of Candida albicans when exposed to caspofungin is not associated with microsatellite genotypes.

Antimicrobial Agents and Chemotherapy — Mon, 11 Jan 2010 00:00:00 +0100

Authors: Khlif M, Bogreau H, Michel-Nguyen A, Ayadi A, Ranque S Multilocus microsatellite polymorphisms in 27 clinical Candida albicans isolates were found to be clearly unrelated to in-vitro paradoxical growth or trailing effect with caspofungin. These findings suggest that such in vitro phenotypes are either gained or lost too rapidly to be predicted by more stable genomic markers. PMID: 20065050 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

Current therapeutic approaches to fungal infections in immunocompromised hematological patients

Blood Reviews — Thu, 07 Jan 2010 00:00:00 +0100

Summary: Invasive fungal infections are significant causes of morbidity and mortality in patients with hematological malignancies. Patients with acute myeloid leukemia and those who have undergone allogeneic hematopoietic stem cell transplantation are at especially high risk. Various fungal agents are responsible for this complication, but Aspergillus spp. and Candida spp. are the most frequently isolated micro-organisms; less commonly, infections could be caused by Zygomycetes or other rare molds or yeasts.Several new systemically-administered antifungal agents have been approved for clinical use since 2001; these agents include liposomal amphotericin B, voriconazole, caspofungin, and posaconazole, and they represent a major advance in antifungal therapy and have improved the prognosis of...

Invasive aspergillosis caused by Aspergillus terreus in a living donor liver transplant recipient successfully treated by caspofungin

Mycoses — Thu, 31 Dec 2009 00:00:00 +0100

We report a high risk liver transplant recipient with multiple co-morbidities including renal failure and allograft dysfunction in whom pulmonary aspergillosis due to A. terreus was successfully treated by the echinocandin antifungal agent caspofungin. (Source: Mycoses)

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Rhodotorula mucilaginosa catheter-related fungaemia in a patient with multiple myeloma

Mycoses — Wed, 23 Dec 2009 00:00:00 +0100

We describe a 54-year-old man with MM receiving prophylaxis with fluconazole who was using a subclavian Port-A-Cath and presented two episodes of fungaemia caused by Rhodotorula mucilaginosa. The first episode was resolved with oral itraconazole and neutropenia recovery. During the second episode, caspofungin was administered without success; however, liposomal amphotericin B and catheter withdrawal resolved the fungaemia. As far as we know, this is the first case reported of R. mucilaginosa fungaemia in a patient with MM. (Source: Mycoses)

Activity of aminocandin (IP960; HMR3270) compared with amphotericin B, itraconazole, caspofungin and micafungin in neutropenic murine models of disseminated infection caused by itraconazole-susceptible and -resistant strains of Aspergillus fumigatus

International Journal of Antimicrobial Agents — Wed, 16 Dec 2009 00:00:00 +0100

Abstract: Aminocandin (IP960; HMR3270; NXL201) is a new echinocandin with broad-spectrum in vitro activity against Aspergillus and Candida spp. We compared the activity of aminocandin with that of amphotericin B (AmB), itraconazole (ITC) and caspofungin (CAS) in murine models of disseminated aspergillosis against three strains of A. fumigatus, two of which were fully susceptible (AF293 and A1163) and one was resistant to ITC (AF91). Mice were rendered temporarily neutropenic or persistently neutropenic with cyclophosphamide and were infected intravenously 3 days later. Temporarily neutropenic mice were treated with either intraperitoneal (i.p.) AmB (5mg/kg/dose), oral (p.o.) ITC (25mg/kg/dose), intravenous (i.v.) aminocandin (0.25–10mg/kg/dose), i.p. aminocandin (1mg/kg/dose) or solvent ...

Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials

European Journal of Clinical Microbiology & Infectious Diseases — Tue, 15 Dec 2009 06:49:24 +0100

Abstract Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment suc...

A Clinical Review of Echinocandins in Pediatric Patients (January) (CE).

The Annals of Pharmacotherapy — Tue, 15 Dec 2009 00:00:00 +0100

CONCLUSIONS: Further comparative trials are needed to more clearly define the role of echinocandins, either as monotherapy or in combination for difficult-to-treat infections, in the pediatric population. PMID: 20009006 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Phaeohyphomycosis due to Alternaria species in transplant recipients

Transplant Infectious Disease — Thu, 10 Dec 2009 00:00:00 +0100

In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens. (Source: Transplant Infectious Disease)

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Invasive zygomycosis in patients with graft-versus-host disease after allogeneic stem cell transplantation

Transplant Infectious Disease — Tue, 08 Dec 2009 00:00:00 +0100

M. Leithauser, C. Kahl, C. Aepinus, F. Prall, M. Maruschke, H. Riemer, D. Wolff, K. Jost, I. Hilgendorf, M. Freund, C. Junghanss. Invasive zygomycosis in patients with graft-versus-host disease after allogeneic stem cell transplantationTranspl Infect Dis 2009. All rights reservedAbstract: Invasive mold infections are a threat to immunosuppressed patients such as patients with graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Up to 10% of SCT recipients develop invasive aspergillosis (IA). Invasive zygomycosis (IZ) may occur during treatment against IA. Here we report 4 SCT patients with GVHD diagnosed with IZ. All patients had received myeloablative hematopoietic SCT and developed chronic GVHD requiring systemic immunosuppression. Underlying diseases were a...

Prophylaxis of invasive aspergillosis with voriconazole or caspofungin in patients with acute leukemia during building works.

Haematologica — Tue, 08 Dec 2009 00:00:00 +0100

Conclusions This study suggests that antifungal prophylaxis voriconazole could be useful in acute leukemia patients undergoing first remission-induction chemotherapy where there is a high-risk of invasive aspergillosis. PMID: 20007135 [PubMed - as supplied by publisher] (Source: Haematologica)

FDA staff suggests addition of paediatric liver warning to US label of caspofungin (Cancidas®)

NeLM - News — Mon, 07 Dec 2009 00:00:00 +0100

Source: Reuters Health News Area: News According to a Reuters report, FDA staff will recommend that changes be made to the US label for caspofungin (Cancidas®) to warn of possible liver problems in children. This recommendation is contained in briefing materials to be considered by the FDA's Pediatric Advisory Committee this week. The FDA staff said their review of reported adverse events showed that in seriously ill children (under age 17) there were some cases of abnormal liver function tests and of liver injury. These cases were mostly in children with 'many competing causes for their hepatotoxicity'. The FDA staff noted that caspofungin is frequently used in children with other serious illness who are taking multiple drugs, which makes it hard to establish caus...

Systemic fungal infections

Medicine — Mon, 30 Nov 2009 16:03:40 +0100

Abstract: The incidence of systemic fungal infections has increased over the last two decades. An expanded range of antifungal agents are now available. Voriconazole is a broad spectrum triazole. In treatment of invasive aspergillosis, voriconazole was associated with higher survival at 12 weeks compared to starting therapy with amphotericin B deoxycholate. Posaconazole is similar but with a different side effect profile and is a useful alternative. Caspofungin is the first of a new class of intravenous antifungals, the echinocandins. It is active against Candida and Aspergillus, and is as effective with fewer adverse events than amphotericin B in treatment of invasive candidiasis. Anidulafungin and micafungin are similar. The management of invasive candidiasis and aspergillosis is discuss...

The echinocandins: three useful choices or three too many?

International Journal of Antimicrobial Agents — Fri, 27 Nov 2009 00:00:00 +0100

Abstract: Echinocandins act by inhibiting 1,3-β-d-glucan synthesis in the fungal cell wall. The three licensed agents in this class, namely anidulafungin, caspofungin and micafungin, have a favourable pharmacological profile. These agents are narrow spectrum with clinically relevant activity against Candida and Aspergillus spp. Several trials have established the non-inferiority of these agents over existing agents in the treatment of invasive fungal infections. Caspofungin is also licensed for empirical antifungal therapy of presumed fungal infections in patients with febrile neutropenia. This paper reviews the literature on echinocandins. (Source: International Journal of Antimicrobial Agents)

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Caspofungin/micafungin: Various toxicities in an elderly patient: case report

Reactions — Sun, 22 Nov 2009 14:04:51 +0100

(Source: Reactions)

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients

Journal of Antimicrobial Chemotherapy — Tue, 10 Nov 2009 17:10:20 +0100

Conclusions Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of ≤35%. Underlying disease-related factors had a major impact on results. (Source: Journal of Antimicrobial Chemotherapy)

A rescue therapy with a combination of caspofungin and liposomal amphotericin B or voriconazole in children with haematological malignancy and refractory invasive fungal infections

Mycoses — Tue, 10 Nov 2009 00:00:00 +0100

Combination treatment of paediatric invasive fungal infections (IFIs) has rarely been reported. A total of 17 children with 19 IFI episodes were enrolled in the study. The median age of the patients was 5.3 (range 0.5[ndash]17) years. IFI was classified as proven in 4, probable in 12 and possible in 3 episodes. These patients received empiric antifungal treatment, which consisted of liposomal amphotericin B (LAmB) monotherapy for a median duration of 12 days (range 3[ndash]69 days). All patients were refractory to LAmB; therefore, caspofungin was added to the therapy in 11 patients. In the remaining six patients, LAmB was ceased and a combination of caspofungin and voriconazole was started. Among the patients who received caspofungin + LAmB, four did not show favourable response and the co...

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients.

The Aspergillus Website - articles — Fri, 06 Nov 2009 00:00:00 +0100

Viscoli C, Herbrecht R, Akan H, Baila L, Sonet A, Gallamini A, Giagounidis A, Marchetti O, Martino R, Meert L, Paesmans M, Ameye L, Shivaprakash M, Ullmann AJ, Maertens J; on behalf of the Infectious Disease Group of the EORTC. (Source: The Aspergillus Website - articles)

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients.

The Aspergillus Website - articles — Fri, 06 Nov 2009 00:00:00 +0100

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Kodamaea ohmeri fungaemia successfully treated with caspofungin

International Journal of Antimicrobial Agents — Fri, 06 Nov 2009 00:00:00 +0100

We present the first patient with K. ohmeri fungaemia successfully treated with caspofungin. (Source: International Journal of Antimicrobial Agents)

Susceptibility testing of Candida species to echinocandins: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion and agar-dilution using RPMI and IsoSensitest medium.

Antimicrobial Agents and Chemotherapy — Mon, 02 Nov 2009 00:00:00 +0100

In conclusion, no test was perfect but anidulafungin susceptibility testing using WT-UL to define susceptibility reliably identified fks hot spot mutants. PMID: 19884370 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment

Mycoses — Wed, 28 Oct 2009 00:00:00 +0100

The combination of amphotericin B and sodium deoxycholate is the formulation most used in clinical practice. The development of new agents such as amphotericin with lipid formulations, caspofungin, voriconazole and other azolic derivatives, promoted alternatives to amphotericin B deoxycholate. However, because of the high cost of these new drugs, their use is difficult in a scenario of limited resources. A few strategies have been devised to make the use of amphotericin B deoxycholate less toxic. In this review, we seek to describe the accumulated knowledge about this molecule, with focus on its use in continuous infusion, which appears to be an alternative to reduce toxicity, while maintaining its clinical efficacy. (Source: Mycoses)

invasive aspergillosis in patients with acute myeloid leukemia: SEIFEM-2008 registry study.

Haematologica — Thu, 22 Oct 2009 00:00:00 +0100

Conclusions Our series confirms the downward trend in mortality rates reported in previous series, with all new drugs providing similar survival and response rates. Recovery from neutropenia and disease stage are crucial prognostic factors. Efficacious antifungal drugs bridge the gap due to poor hematological and immunological reconstitution. PMID: 19850903 [PubMed - as supplied by publisher] (Source: Haematologica)

Micafungin appears to be cost saving versus caspofungin when used to treat candidaemia and invasive candidiasis

PharmacoEconomics and Outcomes News — Mon, 19 Oct 2009 14:44:06 +0100

(Source: PharmacoEconomics and Outcomes News)

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Assessment of the In-vitro Kinetic Activity of Caspofungin against Candida glabrata.

Antimicrobial Agents and Chemotherapy — Sun, 18 Oct 2009 23:00:00 +0100

The objective was to evaluate the in vitro activity of caspofungin alone and in combination against C. glabrata. In vitro assays demonstrated that caspofungin alone showed excellent fungicidal activity against C. glabrata, including fluconazole-resistant strains. The combination of caspofungin/azoles showed potential synergy against C. glabrata. Overall, caspofungin demonstrated excellent in vitro activity alone and in combination against strains of C. glabrata. PMID: 19841143 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

The Aspergillus Website - articles — Mon, 05 Oct 2009 00:00:00 +0100

Lafaurie M, Lapalu J, Raffoux E, Breton B, Lacroix C, Socié G, Porcher R, Ribaud P, Touratier S, Molina JM (Source: The Aspergillus Website - articles)

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

The Aspergillus Website - articles — Sun, 04 Oct 2009 23:00:00 +0100

Lafaurie M, Lapalu J, Raffoux E, Breton B, Lacroix C, Socié G, Porcher R, Ribaud P, Touratier S, Molina JM (Source: The Aspergillus Website - articles)

Comparison of antifungal MICs for yeasts obtained using the EUCAST method in a reference laboratory and the Etest in nine different hospital laboratories

Clinical Microbiology and Infection — Wed, 23 Sep 2009 23:00:00 +0100

Clin Microbiol Infect In routine laboratory practice, the determination of MICs of antifungals for yeasts often relies on the Etest, because of a good correlation with reference methods. However, this correlation was established through predesigned studies, rather than prospective testing. The surveillance programme of fungaemia (YEASTS programme), implemented since 2003, facilitated our comparison of the Etest and the EUCAST results, obtained on a routine basis in nine different hospitals and in a reference laboratory, respectively. The analysis included 690 isolates recovered from blood culture (362 Candida albicans, 113 Candida glabrata, 69 Candida parapsilosis, 55 Candida tropicalis, 31 Cryptococcus neoformans, and 60 other yeast species) that were tested for their susceptibility to am...

In vitro interactions between amphotericin B and other antifungal agents and rifampin against Fusarium spp.

Mycoses — Mon, 21 Sep 2009 23:00:00 +0100

In this study, we evaluated the in vitro interactions of amphotericin B with caspofungin, ketoconazole, 5-flucytosine, itraconazole, miconazole, rifampin, fluconazole, terbinafine and voriconazole against isolates of Fusarium spp. using the chequerboard method with interactions evaluated by fractional inhibitory concentration indices. The highest percentages of synergistic interactions were observed for the combinations of amphotericin B and caspofungin (68.7%), amphotericin B and rifampin (68.7%), amphotericin B plus 5-flucytosine (59.3%) and amphotericin B with voriconazole (37.5%). The pattern of susceptibility to antifungal agents among Fusarium species and their consequence on the effects of drug combinations are also discussed. (Source: Mycoses)

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Efungumab: A Novel Agent in the Treatment of Invasive Candidiasis (November).

The Annals of Pharmacotherapy — Mon, 21 Sep 2009 23:00:00 +0100

CONCLUSIONS: Efungumab is a new antifungal agent with a novel mechanism of action. Available clinical data and synergy studies support the use of efungumab in combination with other antifungal agents for the treatment of IC. Further safety data are needed before formulary recommendations can be made. PMID: 19773528 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

The Aspergillus Website - articles — Mon, 14 Sep 2009 23:00:00 +0100

Vehreschild JJ, Sieniawski M, Reuter S, Arenz D, Reichert D, Maertens J, Böhme A, Silling G, Martino R, Maschmeyer G, Rüping MJ, Ullmann AJ, Cornely OA (Source: The Aspergillus Website - articles)

Identification of novel cell wall destabilizing antifungal compounds using a conditional Aspergillus nidulans protein kinase C mutant

Journal of Antimicrobial Chemotherapy — Tue, 08 Sep 2009 23:00:00 +0100

Conclusions This work demonstrates the feasibility of using a conditional Aspergillus mutant to conduct a small-molecule library screen to identify novel ‘hit’ compounds affecting cell wall integrity. (Source: Journal of Antimicrobial Chemotherapy)

Intraocular penetration of voriconazole and caspofungin in a patient with fungal endophthalmitis

Journal of Antimicrobial Chemotherapy — Tue, 08 Sep 2009 23:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

In Candida albicans, resistance to flucytosine and terbinafine is linked to MAT locus homozygosity and multilocus sequence typing clade 1

FEMS Yeast Research — Sun, 06 Sep 2009 23:00:00 +0100

A panel of 637 isolates of Candida albicans that had been typed by multilocus sequence typing (MLST) and tested for susceptibility to amphotericin B, caspofungin, fluconazole, flucytosine, itraconazole, ketoconazole, miconazole, terbinafine and voriconazole was the material for a statistical analysis of possible associations between antifungal susceptibility and other properties. For terbinafine and flucytosine, the greatest proportion of low-susceptibility isolates, judged by two resistance breakpoints, was found in MLST clade 1 and among isolates homozygous at the MAT locus, although only three isolates showed cross-resistance to the two agents. Most instances of low susceptibility to azoles, flucytosine and terbinafine were among oropharyngeal isolates from HIV-positive individuals. Sta...

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Case report: H1N1 pneumonitis treated with intravenous zanamivir

NeLM - News — Thu, 03 Sep 2009 23:00:00 +0100

Source: Lancet Area: News This case report describes a 22-year old woman with neutropenia following chemotherapy for Hodgkin's disease, who developed pandemic H1N1 2009 influenza virus infection not responding to oseltamivir 75 mg twice daily and broad-spectrum antimicrobials (meropenem, teicoplanin, and caspofungin). Her condition deteriorated and she was admitted to ITU, requiring ventilation. Despite 6 days of nasogastric oseltamivir, high level H1N1 RNA was detected in bronchoalveolar lavage (BAL) on day 10. As there were high volume gastric aspirates, this was replaced by nebulised zanamivir on days 6 to 13 but there was no clinical or virological response. The authors note that intravenous zanamivir (600mg BD; unlicensed therapy provided by GlaxoSm...

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

Clinical Microbiology and Infection — Thu, 03 Sep 2009 00:00:00 +0100

Clin Microbiol Infect A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutrope...

Updated national IV monograph on caspofungin (Cancidas®)

NeLM - News — Tue, 01 Sep 2009 23:00:00 +0100

Source: Medusa Area: News An updated IV monograph on caspofungin (Cancidas®) is now available from the NHS injectable medicines guide website (Medusa) at the link below (registration required for access). (Source: NeLM - News)

Echinocandins: The Newest Class of Antifungals (October) (CE).

The Annals of Pharmacotherapy — Mon, 31 Aug 2009 23:00:00 +0100

CONCLUSIONS: Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary. PMID: 19724014 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

International Journal of Antimicrobial Agents — Mon, 24 Aug 2009 23:00:00 +0100

Abstract: Patients surviving invasive fungal disease (IFD) and needing further antineoplastic chemotherapy are at high risk of recurrent fungal infection. In the absence of randomised controlled trials in this area, secondary prophylactic regimens are diverse. From 448 patients registered with the Multinational Case Registry of Secondary Antifungal Prophylaxis, we performed an analysis of patients receiving caspofungin (CAS) or itraconazole (ITC). All patients had an underlying haematological malignancy and had been diagnosed with an episode of IFD earlier in their course of treatment. Data collected comprised demographics, underlying disease, first episode of IFD, antifungal prophylaxis, incidence and outcome of breakthrough IFD and survival. A total of 75 patients were evaluated, compris...

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Caspofungin: Acute liver failure in an infant: case report

Reactions — Mon, 24 Aug 2009 12:02:41 +0100

(Source: Reactions)

Prevalence rates and antifungal susceptibility profiles of the Candida parapsilosis species complex: results from a nationwide surveillance of candidaemia in Brazil

Clinical Microbiology and Infection — Mon, 17 Aug 2009 00:00:00 +0100

Clin Microbiol Infect The genetically heterogeneous taxon Candida parapsilosis was recently reclassified into three species: Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis. The prevalences of these species among 141 bloodstream isolates tested in Brazil were 88% for C. parapsilosis, 9% for C. orthopsilosis, and 3% for C. metapsilosis. Except for three C. orthopsilosis isolates that were considered resistant to 5-flucytosine, all isolates representing the different species of this complex were susceptible to polyenes, triazoles and caspofungin. (Source: Clinical Microbiology and Infection)

In vitro analysis of the occurrence of a paradoxical effect with different echinocandins and Candida albicans biofilms

International Journal of Antimicrobial Agents — Tue, 11 Aug 2009 23:00:00 +0100

The echinocandins have excellent in vitro activity against Candida albicans biofilms . The in vitro activities of caspofungin (CAS), micafungin (MFG) and anidulafungin (AFG) against Candida biofilms have been compared with other antifungal agents including the azoles and polyenes . Although each echinocandin exhibits certain unique pharmacological characteristics, all three echinocandins are believed to be clinically equivalent for the treatment of invasive candidiasis. We sought to compare directly the in vitro antifungal effects of AFG, CAS and MFG against mature C. albicans biofilms. (Source: International Journal of Antimicrobial Agents)

Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis

Journal of Antimicrobial Chemotherapy — Mon, 10 Aug 2009 23:00:00 +0100

Conclusions We have developed a novel model of CVC-associated candidiasis in mice. Using this model we demonstrate the efficacy of caspofungin for the treatment and prevention of C. albicans biofilms in vivo. (Source: Journal of Antimicrobial Chemotherapy)

[Pilot Drug Utilization Study of systemic antifungal agents in the Hospital Clínico San Carlos. Proposal of a study method.]

Revista Espanola de Quimioterapia — Sun, 09 Aug 2009 11:48:18 +0100

Conclusions. The method is considered satisfactory for the evaluation of antifungal treatments and is proposed for being used in larger studies. For all the antifungal agents evaluated, a high degree of appropriateness of use was found, though some conditions are considered improvable. Key words: Antifungal agents. Drug utilization study. Study method. Prescription. Appropriateness. Indication. Selection of drugs. Rev Esp Quimioter 2009;22(3):127-134. PMID: 19662545 [PubMed - in process] (Source: Revista Espanola de Quimioterapia)

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Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case‐Control Study to Assess Risks for Disease and Outcome

The Journal of Infectious Diseases Latest Issue — Thu, 06 Aug 2009 19:50:44 +0100

Conclusions. The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis (Source: The Journal of Infectious Diseases Latest Issue)

Caspofungin: in pediatric patients with fungal infections.

Paediatric Drugs — Tue, 04 Aug 2009 09:22:02 +0100

Authors: Garnock-Jones KP, Keam SJ black triangle Caspofungin is the first echinocandin to be approved for the treatment of fungal infections in pediatric patients. The antifungal properties of caspofungin result from interference with fungal cell-wall integrity. black triangle In vitro, caspofungin is fungicidal against Candida spp. and fungistatic against Aspergillus spp., but has little or no fungicidal or fungistatic activity against Cryptococcus neoformans, the Zygomycetes, Fusarium spp., or Trichosporon beigelii. black triangle Caspofungin was effective as empirical antifungal therapy in pediatric patients with persistent fever and neutropenia. Almost half (46%) of caspofungin recipients and one-third (32%) of liposomal amphotericin B recipients achieved an overall favorable resp...

Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001-2007)

Cancer — Thu, 23 Jul 2009 23:00:00 +0100

The incidence, epidemiology, Candida species distribution, resistance patterns, and outcome of candidemia in high-risk hematologic malignancy and/or stem cell transplantation patients have not been extensively described since the introduction of new antifungal agents.In this retrospective study, the authors reviewed the medical records and microbiologic data of hematologic malignancy patients with candidemia at The University of Texas M. D. Anderson Cancer Center from March 2001 to February 2007.The authors analyzed 173 episodes of candidemia (170 patients), 125 (72%) of which were breakthrough cases after prior antifungal agents, mainly fluconazole (28 [22%]), caspofungin (25 [20%]), and voriconazole (18 [14%]). The incidence of candidemia (per 100,000 inpatient days) remained relatively ...

Invasive Aspergillus fumigatus infection after Plasmodium falciparum malaria in an immuno-competent host: case report and review of literature

Malaria Journal — Sun, 19 Jul 2009 23:00:00 +0100

Conclusions: The patient was successfully treated with voriconazol and caspofungin. This is the first survival of malaria-associated invasive aspergillosis. (Source: Malaria Journal)

Cancidas (Caspofungin Acetate) - updated on RxList

RxList - New and Updated Drug Monographs — Mon, 13 Jul 2009 07:00:00 +0100

Cancidas (Caspofungin Acetate) drug description - FDA approved labeling for prescription drugs and medications at RxList (Source: RxList - New and Updated Drug Monographs)

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Caspofungin: In Pediatric Patients with Fungal Infections

Pediatric Drugs — Sun, 05 Jul 2009 11:23:25 +0100

(Source: Pediatric Drugs)

Caspofungin: In Pediatric Patients with Fungal Infections.

Pediatric Drugs — Sun, 05 Jul 2009 11:23:23 +0100

Page: 259DOI: 10.2165/00148581-200911040-00005Authors: Garnock-Jones, Karly P.; Keam, Susan J. (Source: Pediatric Drugs)

Lost in translation: differences in antimicrobial indication approval policies between the United States and Europe.

Clinical Therapeutics — Tue, 30 Jun 2009 23:00:00 +0100

CONCLUSIONS: Differences in the indications for most antimicrobial agents were found between the United States and Europe. Because any approved indication can be viewed as scientific evidence, these differences may raise legal issues regarding the treatment of specific entities. To minimize these differences, coordination is needed between the FDA and EMEA regarding the procedures for approving indications. PMID: 19695409 [PubMed - in process] (Source: Clinical Therapeutics)

Successful management of postpneumonectomy Aspergillus pleural empyema by combined surgical and anti-fungal treatment with voriconazole and caspofungin

The Aspergillus Website - articles — Thu, 25 Jun 2009 00:00:00 +0100

Bonatti H, Lass-Floerl C, Angerer K, Singh N, Lechner M, Stelzmueller I, Singh R, Schmid T, Geltner C (Source: The Aspergillus Website - articles)

Successful management of postpneumonectomy Aspergillus pleural empyema by combined surgical and anti-fungal treatment with voriconazole and caspofungin

The Aspergillus Website - articles — Wed, 24 Jun 2009 23:00:00 +0100

Bonatti H, Lass-Floerl C, Angerer K, Singh N, Lechner M, Stelzmueller I, Singh R, Schmid T, Geltner C (Source: The Aspergillus Website - articles)

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Caspofungin for the treatment of candidaemia in patients with haematological malignancies

Clinical Microbiology and Infection — Sun, 21 Jun 2009 23:00:00 +0100

This study was prospectively conducted in 11 haematology divisions over a 2-year period to evaluate the efficacy of caspofungin in 24 neutropenic patients with haematological malignancies (HM) and candidaemia. These patients had received chemotherapy for HM and were neutropenic (PNN < 0.5 × 109/L) for a median of 12 days (2[ndash]41) before candidaemia. The patients received caspofungin for a median duration of 12 days (range 6[ndash]26), obtaining a favourable overall response of 58%. At 30 days, 11 patients had died (46%); candidaemia was responsible for mortality in six patients (25%). These results suggest that treatment of candidaemia with caspofungin in neutropenic HM was efficacious, as it is in non-haematological subgroups. (Source: Clinical Microbiology and Infection)

Biofilm formation and the effect of caspofungin on the biofilm structure of Candida spp. bloodstream isolates.

Antimicrobial Agents and Chemotherapy — Sun, 21 Jun 2009 23:00:00 +0100

In this study, biofilm formation by different Candida species, particularly C. albicans, C. tropicalis, and C. parapsilosis, was evaluated, and the effect of caspofungin (CAS) was assessed using a clinically relevant in vitro model system. CAS displayed in vitro activity against C. albicans and C. tropicalis cells within biofilms. Biofilm formation was evaluated after 48h of antifungal drug exposure and the effects of CAS on preformed Candida species biofilms were visualized using scanning electron microscopy (SEM). Several species-specific differences of the cellular morphologies associated with biofilms were observed. Our results confirmed the presence of paradoxical growth (PG) in C. albicans and C. tropicalis biofilms in the presence of high CAS concentrations. These findings were also...

Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-{beta}-D-glucan synthase: implication for the existing susceptibility breakpoint.

Antimicrobial Agents and Chemotherapy — Sun, 21 Jun 2009 23:00:00 +0100

Authors: Garcia-Effron G, Lee S, Park S, Cleary JD, Perlin DS Thirteen Candida glabrata strains harboring a range of mutations in hot spot regions of FKS1 and FKS2 were studied. The mutations were linked to an echinocandin reduced susceptibility phenotype. Sequence alignments showed that 11 out of the 13 mutants harbored a mutation in FKS1 or FKS2 not previously implicated in echinocandin reduced susceptibility in C. glabrata. A detailed kinetic characterization demonstrated that amino acid substitutions in Fks1p and Fks2p reduced drug sensitivity in mutant 1,3-beta-D-glucan synthase by 2-3 log orders relative to wild type enzyme. These mutations were also found to reduce the catalytic efficiency of the enzyme (Vmax) and to influence the relative expression of FKS genes. In view of the...

Oral candidiasis caused by Kodamaea ohmeri in a HIV patient in Chennai, India

Mycoses — Mon, 15 Jun 2009 04:00:00 +0100

Kodamaea ohmeri was isolated from a 38-year-old HIV seropositive woman with pseudomembranous oral candidiasis. The isolate was identified by the API 20 C yeast identification system and confirmed by sequence analysis. Antifungal susceptibility testing done by E-test showed that the isolate was susceptible to voriconazole, amphotericin B and caspofungin. (Source: Mycoses)

Antifungal activity of miconazole against recent Candida strains

Mycoses — Mon, 15 Jun 2009 04:00:00 +0100

The objective of this study was to determine the antifungal activity of MICON and comparators against recent clinical isolates of Candida spp. using standard Clinical and Laboratory Standards Institute methodology. One hundred and fifty isolates, consisting of 25 strains each of Candida albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis and C. dubliniensis, were tested. Of these, twenty-two strains were known to be FLU-resistant. Minimum inhibitory concentrations (MICs) were determined for MICON, amphotericin B (AM), caspofungin (CAS), clotrimazole (CLOT), FLU, itraconazole (ITRA), nystatin (NYS) and voriconazole (VOR). MICON demonstrated potent inhibitory activity against all of the strains tested. The MIC90 for MICON was 0.12 [mu]g ml[minus]1 against FLU-susceptible strains...

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In vitro synergistic effects of antituberculous drugs plus antifungals against Coccidioides posadasii

International Journal of Antimicrobial Agents — Wed, 10 Jun 2009 23:00:00 +0100

Abstract: The aim of the present study was to evaluate the in vitro interactions of antituberculous drugs (ATDs) with antifungals against Coccidioides posadasii. Eighteen drug combinations, formed by an ATD (isoniazid, pyrazinamide or ethambutol) plus an antifungal (amphotericin B, ketoconazole, itraconazole, fluconazole, voriconazole or caspofungin), were tested using the checkerboard method. All the antimicrobial combinations inhibited C. posadasii strains and synergistic interactions were observed for 10 combinations. Antagonism between the tested drugs was not observed. Stronger synergistic interactions were seen in the combinations formed by triazoles plus ethambutol as well as itraconazole plus pyrazinamide. Further studies in animal models are needed to confirm the usefulness of the...

In vitro analyses of the combination of high-dose doxycycline and antifungal agents against Candida albicans biofilms

International Journal of Antimicrobial Agents — Tue, 09 Jun 2009 23:00:00 +0100

Abstract: The potential of antifungal agents used as antimicrobial lock therapy (ALT) for the conservative management of catheter-related candidemia has not been fully defined. We sought to determine the antifungal effect of high-dose doxycycline (DOX), alone or in combination with standard concentrations of amphotericin B (AMB), caspofungin (CAS) or fluconazole (FLC), against biofilms formed by Candida albicans in vitro. DOX alone (at 2048μg/mL and 1024μg/mL) demonstrated up to an 85% reduction of the metabolic activity of the C. albicans biofilm. Regardless of the concentration tested, FLC alone showed minimal activity (mean 22.9% reduction) against the C. albicans biofilm. When DOX 2048μg/mL was used in combination with FLC, antifungal activity also increased up to 85%, suggesting an...

Clinical outcomes of lung-transplant recipients treated by voriconazole and caspofungin combination in aspergillosis

Journal of Clinical Pharmacy and Therapeutics — Tue, 02 Jun 2009 04:00:00 +0100

Background and objective: Invasive pulmonary aspergillosis (IPA) is a serious cause of death among immune-compromised patients such as organ-transplant recipients. Recently, voriconazole has been approved for first-line therapy in IPA. Theoretically, optimal voriconazole blood level (superior to 1 mg/L according to recent studies) should be reached within 24 h. In practice, a significantly longer time seems to be needed in lung-transplant recipients. Therefore, caspofungin is now used in combination with voriconazole to provide cover against Aspergillus spp. infection during this gap. The first aim of this study was to investigate Aspergillus spp. infection treated with this combination and the atter's tolerability. The median time for attainment of apparently active blood levels in lung t...

Breakthrough Rhinocerebral Mucormycosis in a Liver Transplant Patient Receiving Caspofungin

Transplantation Proceedings — Sun, 31 May 2009 23:00:00 +0100

Abstract: Zygomycetes are among the most frequent causes of non-Aspergillus mycelial fungal infections in transplant recipients. We have described a single case of breakthrough zygomycosis. A young Japanese woman presented because of idiopathic fulminant hepatitis and renal failure. On the third day of admission, she underwent orthotopic liver transplantation. A considerable amount of red blood cells and fresh frozen plasma were transfused during surgery. On posttransplant day 2, Candida albicans was isolated from respiratory secretions; prophylactic caspofungin was prescribed. During the next 6 days, C albicans was isolated from tracheal secretions, surgical wound, and exudates and stools. Ventilator-associated pneumonia was diagnosed day 4. Her renal function did not improve during the p...

Microbial Spectrum in Surgical Infections Based on a Microbiological Routine Monitoring over the10-Year Period from 1995 to 2004.

Zentralblatt fur Chirurgie — Sun, 31 May 2009 23:00:00 +0100

CONCLUSION: A systematic, microbiological, long-term monitoring is indispensable since i) microbial detection plays a growing role to include the various types of infections in the spectrum of diagnosis for DRG, ii) alterations of the microbial spectrum can only be detected through a long-term observation period (MRSA, fungi) and iii) simultaneously developing antibiotic resistances can be determined (MRSA, ESBL strains in Enterobacteriae, fluconazol-resistant fungi). This can have an infectious, biological, hygienic and cost-determining as well as a health policy relevance among others, with considerable additional costs (e. g., isolation of patients, cost-intensive substitutional medication) with necessary reimbursement. PMID: 19536716 [PubMed - as supplied by publisher] (Source: Zen...

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Successful management of postpneumonectomy Aspergillus pleural empyema by combined surgical and anti-fungal treatment with voriconazole and caspofungin

Mycoses — Sat, 30 May 2009 04:00:00 +0100

Aspergillus pleural empyema is a rare but often fatal infection complicating thoracic surgery. Three men and one woman aged 23[ndash]47 years were diagnosed with Aspergillus pleural empyema after lung resection. Underlying diseases were lung cancer (n = 2), Hodgkin's disease (n = 1) and thoracic trauma (n = 1). The treatment protocol consisted of systemic anti-fungal treatment with caspofungin and voriconazole, intrapleural application of amphotericin B and surgical debridement with secondary closure of the leaking bronchial stump. Two patients with chronic Aspergillus pleural empyema had been pretreated with itraconazole and/or amphotericin B. Two patients were treated with a thoracostoma. Two patients had undergone pneumonectomy for previously diagnosed pulmonary aspergillosis. Caspofung...

Prosthetic valve endocarditis caused by Candida lusitaniae, an uncommon pathogen: a case report

Journal of Medical Case Reports — Mon, 18 May 2009 23:00:00 +0100

Conclusion: The infection was lethal despite aggressive medical and surgical management and sterilization of blood cultures. The outcome of our case illustrates the need to recognize Candida lusitaniae fungemia as a life-threatening infection in a patient with a prosthetic aortic valve. (Source: Journal of Medical Case Reports)

High caspofungin levels in alveolar cells of a lung transplant patient with suspected pulmonary aspergillosis

International Journal of Antimicrobial Agents — Thu, 14 May 2009 23:00:00 +0100

Opportunistic invasive fungal infections are a major cause of morbidity and mortality in immunocompromised patients, for example following transplantation of stem cells or solid body organs such as lung, liver, kidney or heart. Caspofungin acetate, the first echinocandin approved by the US Food and Drug Administration (FDA) in 2001, has a wide spectrum of activity against many clinically important fungi, including Aspergillus and Candida spp. . It has been studied extensively in numerous randomised clinical trials. The substance has been shown to be efficacious in the treatment of oesophageal and oropharyngeal candidiasis and became the therapy of choice of invasive aspergillosis and candidiasis . Caspofungin is also approved for the treatment of pulmonary aspergillosis, however its in viv...

Economic impact of caspofungin as compared with liposomal amphotericin B for empirical therapy in febrile neutropenia in Australia

Journal of Antimicrobial Chemotherapy — Mon, 11 May 2009 04:00:00 +0100

Conclusions This is the first economic study to evaluate the place of caspofungin as empirical therapy in Australia. Caspofungin is more cost-beneficial than LAmB, which contradicts the current Australian guidelines of recommending LAmB as the first choice for empirical therapy. (Source: Journal of Antimicrobial Chemotherapy)

A prospective, multicenter study of caspofungin for the treatment of documented Candida or Aspergillus infections in pediatric patients

The Aspergillus Website - articles — Fri, 08 May 2009 18:23:11 +0100

Zaoutis TE, Jafri HS, Huang LM, Locatelli F, Barzilai A, Ebell W, Steinbach WJ, Bradley J, Lieberman JM, Hsiao CC, Seibel N, Laws HJ, Gamba M, Petrecz M, Taylor AF, Strohmaier KM, Chow JW, Kartsonis NA, Ngai AL (Source: The Aspergillus Website - articles)

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[Keratomycosis: diagnosis and therapy.]

Der Ophthalmologe — Thu, 30 Apr 2009 23:00:00 +0100

Authors: Behrens-Baumann W Diagnosis of fungal keratitis is only straightforward if it presents in its typical form with pyramidal-shaped hypopyon, prominent geographical corneal infiltration and satellites. However, in contact-lens wearers clinical presentation is untypical at early infection. Corneal debridement is therefore necessary, which simultaneously facilitates penetration of the antimycotic into the corneal stroma. At present, voriconazole is the medication of choice, if not changed after microbiological diagnosis to a specifically more potent substance - e.g. posaconazole or caspofungin. Amphotericin B may be used for repeated intracameral or intravitreal injection. Simultaneous application of steroids is useful. PMID: 19424703 [PubMed - in process] (Source: Der Ophthalm...

Sensitivity of Candida albicans isolates to caspofungin – comparison of microdilution method and E-test procedure

Articles of Archives of Medical Science - TERMEDIA publishing house — Wed, 22 Apr 2009 13:53:23 +0100

Conclusions: Caspofungin demonstrated an excellent potency against C. albicans isolates and the E-test method appears to be useful for determination of in vitro caspofungin activity against these pathogens. (Source: Articles of Archives of Medical Science - TERMEDIA publishing house)

Overview of Antifungal Agents

Clinics in Chest Medicine — Mon, 20 Apr 2009 19:12:59 +0100

This article is a comprehensive clinically focused review of currently available antifungals administered by way of the intravenous or inhalational route: amphotericin B and its lipid formulations, fluconazole, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, anidulafungin, and flucytosine. Emphasis is placed on pharmacodynamics and kinetics, drug interactions, adverse events, and evidence for their use. Selected clinical trials demonstrating the efficacy of these agents are also reviewed. (Source: Clinics in Chest Medicine)

In vitro activity of caspofungin and voriconazole against uncommon Candida spp.

International Journal of Antimicrobial Agents — Mon, 20 Apr 2009 14:26:34 +0100

Candida spp. remain the leading cause of invasive fungal infections, and ca. 90–95% of Candida bloodstream infections are due to five species, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei . (Source: International Journal of Antimicrobial Agents)

Effect of filamentation and mode of growth on antifungal susceptibility of Candida albicans

International Journal of Antimicrobial Agents — Sun, 19 Apr 2009 23:00:00 +0100

Abstract: Biofilm formation involving profuse hyphal growth is a major characteristic of Candida spp. and confers higher antifungal resistance than its planktonic mode of growth. We investigated the antifungal susceptibility of Candida albicans and its hyphal mutants (Δefg1/efg1, Δcph1/cph1 and ΔΔcph1/cph1 efg1/efg1) to commonly used antifungals during planktonic, adhesion and biofilm modes of growth. The minimum inhibitory concentration (MIC) of each antifungal agent was determined for a lower inoculum (1×103cells/mL) and higher inoculum (1×107cells/mL) of planktonic Candida. Furthermore, MICs of C. albicans biofilms and adhesion modes of growth were determined with a standard XTT assay. Candida albicans in adhesion and biofilm modes of growth, but not in planktonic mode, were resis...

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Candida glabrata fungaemia in a tertiary centre in Taiwan: antifungal susceptibility and outcomes

International Journal of Antimicrobial Agents — Thu, 09 Apr 2009 23:00:00 +0100

Abstract: The proportion of non-albicans candidaemia has increased during recent decades, especially Candida glabrata. We evaluated the antifungal susceptibility, clinical features and outcome of C. glabrata fungaemia treated in a tertiary centre in Taiwan. All episodes of C. glabrata fungaemia during 1999–2005 were identified from microbiology laboratory records and all C. glabrata isolates were subjected to antifungal susceptibility testing by the broth microdilution method. A total of 177 episodes of C. glabrata fungaemia were documented, accounting for 30% of the 598 episodes of candidaemia. A dramatic decline of C. glabrata causing candidaemia from 2003 (46.8%) to 2005 (15.8%) was noted, accompanied by decreased fluconazole consumption. The most common underlying diseases in these p...

Increased Virulence of Zygomycetes Organisms Following Exposure to Voriconazole: A Study Involving Fly and Murine Models of Zygomycosis

The Journal of Infectious Diseases Latest Issue — Thu, 09 Apr 2009 19:44:23 +0100

Conclusions. Exposure of Zygomycetes organisms to voriconazole selectively enhanced their virulence. The mechanisms underlying these phenotypic changes should be studied further. (Source: The Journal of Infectious Diseases Latest Issue)

The effects of caspofungin and voriconazole in an experimental fungal infection of the ear due to Aspergillus

European Archives of Oto-Rhino-Laryngology — Thu, 02 Apr 2009 05:51:14 +0100

Abstract The purpose of the study was to evaluate the effectiveness of caspofungin and voriconazole in the treatment of experimental Aspergillus otits media in an experimental rabbit model. A total of 30 New Zealand white rabbits were divided into four treatment groups and one control group. The rabbits were immunosuppressed by cyclophosphamide and triamcinolone acetonide. The right ear of each rabbit was infected by an injection of the inoculum of 0.1 ml (8.6 × 103 CFU/0.1 ml) of Aspergillus fumigatus into the middle ear cavity. At 72 h after the inoculation, amphotericin B 1 mg/kg per day (n = 6), itraconazole 10 mg/kg per day (n = 6), voriconazole 10 mg/kg per day (n = 6) and caspofungin 5 mg/...

[Micafungin in invasive candidiasis among oncohematological patients]

Revista Iberoamericana de Micologia — Mon, 30 Mar 2009 23:00:00 +0100

CONCLUSIONS: Comparative phase III studies have demonstrated non-inferiority of micafungin compared to standard antifungal agents for invasive candidiasis. Micafungin is safe and effective in the treatment of children and adults with invasive candidiasis. Effectivity in invasive infections caused by non-albicans Candida spp is especially relevant in onco-hematological patients receiving fluconazole prophylaxis. PMID: 19463282 [PubMed - in process] (Source: Revista Iberoamericana de Micologia)

[Micafungin: experimental therapy of fungal infections in animal models]

Revista Iberoamericana de Micologia — Mon, 30 Mar 2009 23:00:00 +0100

CONCLUSIONS: Seven, of a total of 18 articles reviewed, were done in animal models of candidiasis and six in animal models of pulmonary or SNC aspergillosis. Similarly to the other echinocandins, caspofungin and anidulafungin, micafungin seems to exert a fungicidal activity against Candida albicans and Candida glabrata and a fungistatic activity against Aspergillus fumigatus. The paradoxical effect observed in lung tissue the experimental caspofungin treatment of aspergillosis has not been seen in the case of micafungin. The available data demonstrate a higher efficacy of micafungin versus fluconazole in the experimental treatment of C. albicans infections caused by strains susceptible in vitro to both drugs. To improve the efficacy of micafungin in the treatment of C. glabrata and A. fumi...

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[Pharmacodynamics and pharmacokinetcis of micafungin in adults, children and neonate]

Revista Iberoamericana de Micologia — Mon, 30 Mar 2009 23:00:00 +0100

CONCLUSIONS: The pharmacodynamic and pharmacokinetic profiles of micafungin imply that this drug is a safe alternative for the treatment of fungal infections. Micafungin can be safely co-administered with most drugs without the need for dosage adaptation even in patients with renal o liver function impairment. PMID: 19463274 [PubMed - in process] (Source: Revista Iberoamericana de Micologia)

In Vitro Activity of Terbinafine Combined with Caspofungin and Azoles Against Pythium insidiosum.

Antimicrobial Agents and Chemotherapy — Mon, 16 Mar 2009 04:00:00 +0100

Authors: Cavalheiro AS, Maboni G, de Azevedo MI, Argenta JS, Pereira DI, Spader TB, Alves SH, Santurio JM In this text we evaluated the in vitro antifungal activities of terbinafine combined with caspofungin, miconazole, ketoconazole, and fluconazole against 17 P. insidiosum strains using the microdilution checkerboard method. Synergistic interactions were observed with terbinafine combined with caspofungin (41.2% of the strains), fluconazole (41.2%), ketoconazole (29.4%), and miconazole (11.8%). No antagonistic effects were observed. The combinations of terbinafine plus caspofungin or terbinafine plus fluconazole may have significant therapeutic potential for treatment of pythiosis. PMID: 19289531 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)

Pharmacokinetics of caspofungin and voriconazole in critically ill patients during extracorporeal membrane oxygenation

Journal of Antimicrobial Chemotherapy — Tue, 10 Mar 2009 04:00:00 +0100

Conclusions Our results suggest that adequate caspofungin plasma levels are maintained during ECMO. In the case of voriconazole, it is recommended to monitor plasma levels to ensure efficacy and avoid toxicity. (Source: Journal of Antimicrobial Chemotherapy)

Comparative pharmacodynamic interaction analysis of triple combinations of caspofungin and voriconazole or ravuconazole with subinhibitory concentrations of amphotericin B against Aspergillus spp.

Mycoses — Sun, 08 Mar 2009 05:00:00 +0100

The objective of this study was to investigate the effect of subinhibitory concentrations of AmB on the double combinations of caspofungin (CAS) + voriconazole (VOR) or ravuconazole (RAV) against Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus. Isolates were studied in triplicate against CAS/VOR and CAS/RAV combinations by chequerboard broth microdilution. AmB was added to each double combination at concentrations of 0, 0.1 and 0.2 [mu]g ml[minus]1. The fractional inhibitory concentration (FIC) index was calculated for the double and triple combinations. Comparative analysis was performed by repeated measures analysis followed by Dunnett's post-test. The double combinations of CAS/RAV and CAS/VOR were synergistic or additive in most conditions. Addition of AmB to the doub...

The changing face of epidemiology of invasive fungal disease in Europe

Mycoses — Sun, 08 Mar 2009 05:00:00 +0100

Invasive fungal diseases (IFDs) are an increasingly common complication in critically ill patients in Europe and are frequently fatal. Because of changes in treatment strategies and the increased use of antifungal prophylaxis, the epidemiology of IFDs has changed substantially in recent years and infections due to Candida species are no longer the majority in many institutions. In contrast, the emergence of non-Candida IFDs such as aspergillosis, zygomycosis and fusariosis has increased. European surveys indicate that Candida albicans is responsible for more than half the cases of invasive candidaemia; however, the occurrence of non-albicans-related IFDs appears to be increasing. Rates of IFD-related mortality in Europe depend on the pathogen, geographical location and underlying patient c...

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Antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in intermediate and mature development phases

Mycoses — Wed, 04 Mar 2009 05:00:00 +0100

The aim of this study was to examine the antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in the intermediate and mature development phases. Candida albicans biofilms, previously grown for either 24, 48 or 72 h in 96-well microtitre plates, were treated for 48 h with amphotericin B, caspofungin or posaconazole in increasing concentrations according to the respective minimal inhibitory concentration (MIC) determined for planktonic cells (1[ndash]128 × MIC). The biofilms were quantified using the mean optical density (OD) determined by XTT assay. Antifungal activities were expressed as percentage of reduction in OD of drug-treated biofilms compared to untreated biofilms. To test the fungicidal activity of antifungal agents, the unfixed biofilm...

A Prospective, Multicenter Study of Caspofungin for the Treatment of Documented Candida or Aspergillus Infections in Pediatric Patients

PEDIATRICS — Mon, 02 Mar 2009 05:00:00 +0100

CONCLUSIONS. Caspofungin was generally well tolerated in pediatric patients aged 6 months through 17 years. Efficacy outcomes in patients with invasive aspergillosis or invasive candidiasis were consistent with previous adult studies in these indications. (Source: PEDIATRICS)

Role for Fks1 in the intrinsic echinocandin resistance of Fusarium solani as evidenced by hybrid expression in yeast.

Antimicrobial Agents and Chemotherapy — Mon, 02 Mar 2009 05:00:00 +0100

Authors: Katiyar SK, Edlind TD The opportunistic mold Fusarium solani is intrinsically resistant to cell wall synthesis-inhibiting echinocandins (ECs) including caspofungin and micafungin. Mutations that confer acquired EC resistance in Saccharomyces cerevisiae and other normally susceptible yeast species have been mapped to the Fks1 gene; among these is the mutation of residue 639 from Phe to Tyr (F639Y) within a region designated hotspot 1. Fks1 sequence analysis identified the equivalent of Y639 in F. solani, as well as in Scedosporium prolificans, another intrinsically EC-resistant mold. To test its role in intrinsic EC resistance, we constructed Fks1 hybrids in S. cerevisiae that incorporate F. solani hotspot 1 and flanking residues. Hybrid construction was accomplished by a PCR-b...

[Invasive pulmonary aspergillosis : Occurrence in a non-neutropenic female patient with abdominal sepsis.]

Der Anaesthesist — Sat, 28 Feb 2009 05:00:00 +0100

Authors: Knüttgen D, Kamp M, Ströhlein M, Matten J, Chemaissani A, Ernestus K, Sakka SG, Wappler F Invasive pulmonary aspergillosis (IPA) is a life-threatening infection predominantly affecting immunocompromised patients, e.g. with acute leukemia. This case report demonstrates that IPA can also occur in non-neutropenic critically ill surgical patients. The case of a 63-year-old woman is reported, who developed IPA of the respiratory tract in the course of diffuse purulent peritonitis. First-line therapy with voriconazol failed to be effective. However, application of caspofungin, intensive kinetic therapy (including prone position) and airway management by interventional bronchoscopy enabled successful treatment of this severe complication. PMID: 19247622 [PubMed - as sup...

Monotherapy with caspofungin for candidaemia in adult patients with cancer: a retrospective, single institution study.

International Journal of Antimicrobial Agents — Fri, 27 Feb 2009 05:00:00 +0100

This study was performed to evaluate retrospectively the efficacy and safety of caspofungin monotherapy for candidaemia in patients with cancer. The medical records were reviewed of 63 consecutive adult patients with cancer who had candidaemia treated with caspofungin alone for at least 3 consecutive days at The University of Texas M.D. Anderson Cancer Center (March 2001-February 2007). Twenty patients (32%) had haematological malignancies. Most of the candidaemia cases (54%) were caused by non-albicans Candida spp. The most frequent isolates were C. albicans (38%) followed by Candidaparapsilosis (21%), Candidatropicalis (16%) and Candidaglabrata (10%). In vitro susceptibility studies showed that of 30 Candida isolates tested, only one C. parapsilosis isolate had a caspofungin minimum inhi...

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Successful intensive chemotherapy followed by autologous hematopoietic cell transplantation in a patient with acute myeloid leukemia and hepatosplenic candidiasis: case report and review of literature

Transplant Infectious Disease — Wed, 18 Feb 2009 05:00:00 +0100

We report a patient with acute myeloid leukemia who developed HSC during post-remission consolidation chemotherapy and was treated with a prolonged course of caspofungin followed by fluconazole. The stabilization of infection permitted further chemotherapy and autologous hematopoietic cell transplant (HCT) without breakthrough fungemia and further dissemination of candidiasis. The favorable outcome provides further evidence that with optimal treatment, the presence of stable or non-progressive HSC is not an absolute contraindication for HCT. The use of caspofungin in the primary treatment of HSC appears to be a promising approach. The favorable outcome seen in this case is encouraging, although further study on its efficacy is warranted. (Source: Transplant Infectious Disease)

Caspofungin: Breakthrough Candida spp. encephalitis in an elderly patient, treated with voriconazole and amphotericin B liposomal: case report.

Reactions Weekly — Sun, 15 Feb 2009 12:38:35 +0100

Page: 8 (Source: Reactions Weekly)

Caspofungin: Breakthrough Candida spp. encephalitis in an elderly patient, treated with voriconazole and amphotericin B liposomal: case report

Reactions — Sun, 15 Feb 2009 12:14:34 +0100

(Source: Reactions)

Clinical indications for newer antifungal agents

Journal of Hospital Medicine — Fri, 13 Feb 2009 05:00:00 +0100

Recent years have seen the release of multiple new systemic antifungal agents, significantly increasing options for the treatment of most serious fungal infections. Newly available drugs include those in the echinocandin class, including caspofungin, micafungin, and anidulafungin, as well as the newer generation triazoles, voriconazole and posaconazole. Ordering of these agents is variably restricted, depending on a given institution's policies, and all are costly. In this review we examine the available evidence and outline the role of newer antifungal medications in several common and/or important situations, including invasive and mucocutaneous Candida infection, febrile neutropenia, invasive aspergillosis, zygomycosis, and endemic mycoses. Journal of Hospital Medicine 2008;4:102-111. �...

Prophylaxis With Caspofungin for Invasive Fungal Infections in High-Risk Liver Transplant Recipients.

Transplantation — Sun, 08 Feb 2009 14:41:52 +0100

Page: 424DOI: 10.1097/TP.0b013e3181932e76Authors: Fortun, Jesus 1,11; Martin-Davila, Pilar 1; Montejo, Miguel 2; Munoz, Patricia 3; Cisneros, Jose M. 4; Ramos, Antonio 5; Aragon, Cesar 6; Blanes, Marino 7; San Juan, Rafael 8; Gavalda, Joan 9; Llinares, Pedro 10; GESITRA Study Group (Source: Transplantation)

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Differential in vitro activity of anidulafungin, caspofungin and micafungin against Candida parapsilosis isolates recovered from a burn unit

Clinical Microbiology and Infection — Thu, 05 Feb 2009 05:00:00 +0100

In this study, the activities of three echinocandins (anidulafungin, caspofungin, and micafungin) against Candida parapsilosis isolates from burn unit patients, healthcare workers and the hospital environment were determined. Additionally, the effect of these echinocandins on the cell morphology of caspofungin-susceptible and caspofungin-non-susceptible isolates was assessed using scanning electron microscopy (SEM). The C. parapsilosis isolates obtained from patients were susceptible to anidulafungin, but were less so to caspofungin and micafungin. Isolates obtained from healthcare workers or environmental sources were susceptible to all antifungals. SEM data demonstrated that although anidulafungin and caspofungin were equally active against a caspofungin-susceptible C. parapsilosis strai...

Neonatal liver abscesses due to Candida infection effectively treated with caspofungin

Acta Paediatrica — Tue, 03 Feb 2009 05:00:00 +0100

Conclusion: Our observations confirm the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal drugs. More extensive data are recommended in order to asses a specific neonatal schedule. (Source: Acta Paediatrica)

Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients

Intensive Care Medicine — Tue, 27 Jan 2009 07:56:54 +0100

Conclusion Caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in high-risk surgical patients. This needs to be further investigated in randomized trials. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s00134-009-1405-8Authors Laurence Senn, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL) Infectious Diseases Service, Department of Medicine Rue du Bugnon 46 1011 Lausanne SwitzerlandPhilippe Eggimann, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL) Adult Intensive Care Service Lausanne SwitzerlandRiadh Ksontini, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL) Visceral Surgery Service Lausanne SwitzerlandAndres Pascual, Cent...

In vitro activity of caspofungin and voriconazole against uncommon Candida spp.

International Journal of Antimicrobial Agents — Tue, 20 Jan 2009 05:00:00 +0100

Authors: Enache-Angoulvant A, Girard A, Poirot JL, Hennequin C PMID: 19162450 [PubMed - as supplied by publisher] (Source: International Journal of Antimicrobial Agents)

Myocardial and aortal involvement in a case of disseminated infection with Fusarium solani after allogeneic stem cell transplantation: report of a case

Mycoses — Wed, 14 Jan 2009 05:00:00 +0100

We describe a 57-year-old woman suffering from acute erythroblastic leukaemia. After the first course of high-dose Ara-C containing consolidation therapy, the patient developed multiple skin lesions on the left foot. A skin biopsy revealed a Fusarium infection. The lesions regressed under therapy with caspofungin and voriconazole. Leukaemia relapsed after 1 year and an allogeneic stem cell transplantation was performed for consolidation of leukaemia in second remission. Again, the patient developed macular skin lesions located on the trunk and the extremities with central pallor. Clinical examination showed fever, tachyarrhythmia and a systolic murmur. Fusarium spp. was cultured from blood samples. An antimycotic therapy with amphotericin B, voriconazole and posaconazole failed completely....

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Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus

Journal of Antimicrobial Chemotherapy — Tue, 13 Jan 2009 05:00:00 +0100

Conclusions The knowledge of the pharmacodynamic interactions between fluoroquinolones and antifungal agents may guide selection and potentially improve the outcome of immunosuppressed patients with concurrent bacterial and fungal infections. (Source: Journal of Antimicrobial Chemotherapy)

An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality

Bone Marrow Transplantation — Mon, 12 Jan 2009 05:00:00 +0100

Authors: F L Dignan, S O Evans, M E Ethell, B E Shaw, F E Davies, C E Dearden, J G Treleaven, U B G Riley, G J Morgan & M N Potter (Source: Bone Marrow Transplantation)

Frequency of paradoxical effect with caspofungin in Candida albicans

European Journal of Clinical Microbiology & Infectious Diseases — Thu, 08 Jan 2009 09:22:28 +0100

Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s10096-008-0688-yAuthors D. A. Stevens, Santa Clara Valley Medical Center Department of Medicine 751 S. Bascom Av. San Jose CA 95128-2699 USA Journal European Journal of Clinical Microbiology & Infectious DiseasesOnline ISSN 1435-4373Print ISSN 0934-9723 (Source: European Journal of Clinical Microbiology & Infectious Diseases)

Modern antifungal therapy for neutropenic fever

Current Infectious Disease Reports — Wed, 24 Dec 2008 07:41:10 +0100

Abstract Empirical antifungal therapy has been shown to decrease the number of documented fungal infections in the setting of persistent fever during neutropenia. For decades, amphotericin B deoxycholate has been considered the agent of choice for first-line therapy in this setting. New antifungal agents associated with less toxicity, including the lipid formulations of amphotericin, voriconazole, and caspofungin, are now available and are considered to be suitable alternative first-line agents. In order to ensure appropriate therapy, however, the clinician must consider not only the differences between these antifungals but also patient-specific factors before initiating treatment. Content Type Journal ArticleDOI 10.1007/s11908-009-0005-7Authors Melissa Corey, Florida...

Antifungal Therapy of Aspergillus Invasive Otitis Externa: Efficacy of Voriconazole and Review.

Antimicrobial Agents and Chemotherapy — Mon, 22 Dec 2008 05:00:00 +0100

We report two cases of Aspergillus invasive otitis externa (IOE) treated with voriconazole alone and a literature review of antifungal therapy of Aspergillus IOE. A total of 25 patients, including the two present reports, was analysed. Eighteen patients were treated with amphotericin B and nine of them received itraconazole as an additional agent. Three patients received initial therapy with itraconazole and one patient was treated with both voriconazole and caspofungin therapy. The two present patients received voriconazole therapy alone with good clinical and biological tolerance despite prolonged treatment. The last patient did not receive antifungal therapy, as the diagnosis was made post-mortem. Eighteen patients underwent an initial extensive surgical debridement. The majority of pat...

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Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment: laboratory characteristics and implication for susceptibility testing.

Antimicrobial Agents and Chemotherapy — Mon, 22 Dec 2008 05:00:00 +0100

We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery and evaluate the capability of susceptibility methods to identify candin resistance. Susceptibility to caspofungin and anidulafungin of the C. albicans was investigated by Etest, microdilution (EUCAST and CLSI), disk diffusion, agar dilution, FKS1 sequencing and in a mouse model. Tissue was examined by immunohistochemistry, PCR and sequencing for presence of A. fumigatus and resistance mutations. The MICs for the C. albicans isolate were as follows: Etest: caspofungin >32 microg/ml, anidulafungin 0.5 microg/ml; EUCAST: caspofungin 2 microg/ml, anidulafungin 0.125 microg/ml; CLSI: caspofungin 1 microg/ml, anidul...

Aqueous Humor Concentrations of Topically Administered Caspofungin in Rabbits

Karger Publishers — Fri, 19 Dec 2008 14:06:29 +0100

Ophthalmic Res 2009;41:102-105 (DOI:10.1159/000187627) (Source: Karger Publishers)

Alternaria Keratitis: Clinical Presentation and Resolution With Topical Fluconazole or Intrastromal Voriconazole and Topical Caspofungin.

Cornea — Thu, 18 Dec 2008 08:50:04 +0100

Page: 116DOI: 10.1097/ICO.0b013e31818225f8Authors: Tu, Elmer Y MD (Source: Cornea)

Caspofungin cost effective in neutropenic fever.

PharmacoEconomics & Outcomes News — Wed, 17 Dec 2008 08:24:28 +0100

Page: 6 (Source: PharmacoEconomics & Outcomes News)

Pharmacokinetics and Safety of Caspofungin in Neonates and Infants Less than 3 Months of Age.

Antimicrobial Agents and Chemotherapy — Mon, 15 Dec 2008 05:00:00 +0100

Authors: Sáez-Llorens X, Macias M, Maiya P, Pineros J, Jafri HS, Chatterjee A, Ruiz G, Raghavan J, Bradshaw SK, Kartsonis NA, Sun P, Strohmaier KM, Fallon M, Bi S, Stone JA, Chow JW Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data in neonates and very young infants. Patients <3 months old receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n=6) or subsequent multiple-dose (n=12) panel; all received caspofungin 25 mg/m(2) once daily as a 1-hour infusion. Caspofungin plasma levels were measured by HPLC and compared to historical data from adults. Patients' chronological age ranged from 1 to 11 weeks; w...

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Caspofungin cost effective in neutropenic fever

PharmacoEconomics and Outcomes News — Mon, 15 Dec 2008 03:20:04 +0100

(Source: PharmacoEconomics and Outcomes News)

Caspofungin in pediatric patients

Future Medicine: Pediatric Health — Thu, 11 Dec 2008 17:37:30 +0100

Pediatric Health , December 2008, Vol. 2, No. 6, Pages 677-685. Invasive fungal infections have emerged as one of the most significant complications in severely immunocompromised pediatric patients, such as children suffering from hematological malignancies or children undergoing hematopoietic stem cell ... (Source: Future Medicine: Pediatric Health)

Resolution of persistent Pediococcus bacteremia with daptomycin treatment: case report and review of the literature

Diagnostic Microbiology and Infectious Disease — Thu, 11 Dec 2008 00:00:00 +0100

Abstract: A case of bacteremia caused by Pediococcus acidilactici occurring in a patient with metastatic adenocarcinoma of the gallbladder is described. The bacteremia persisted despite an antimicrobial regimen of vancomycin, ciprofloxacin, metronidazole, and caspofungin. Within 36 h of switching the vancomycin to daptomycin (6 mg/kg per day), the bacteremia resolved and the patient improved clinically. Previous reports of human pediococcal infection are also reviewed. (Source: Diagnostic Microbiology and Infectious Disease)

Treatment of invasive candidiasis with echinocandins

Mycoses — Tue, 09 Dec 2008 05:00:00 +0100

Blood stream infections by Candida spp. represent the majority of invasive fungal infections in intensive care patients. The high crude mortality of invasive candidiasis remained essentially unchanged during the last two decades despite new treatment options that became available. The echinocandins, the latest class of antifungals introduced since 2001, exhibit potent activity against clinically relevant fungi including most Candida spp. In several randomised multicentre phase III trials, anidulafungin, caspofungin and micafungin showed convincing efficacy when compared with standard treatment regimens. In all trials, echinocandins were at least non-inferior to standard treatments. Anidulafungin was shown to be superior to fluconazole. Echinocandins have a favourable tolerability profile a...

Resolution of persistent Pediococcus bacteremia with daptomycin treatment: case report and review of the literature.

Diagnostic Microbiology and Infectious Disease — Tue, 09 Dec 2008 05:00:00 +0100

Authors: Suh B A case of bacteremia caused by Pediococcus acidilactici occurring in a patient with metastatic adenocarcinoma of the gallbladder is described. The bacteremia persisted despite an antimicrobial regimen of vancomycin, ciprofloxacin, metronidazole, and caspofungin. Within 36 h of switching the vancomycin to daptomycin (6 mg/kg per day), the bacteremia resolved and the patient improved clinically. Previous reports of human pediococcal infection are also reviewed. PMID: 19081696 [PubMed - as supplied by publisher] (Source: Diagnostic Microbiology and Infectious Disease)

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Caspofungin cost effective in neutropenic fever.

Inpharma Weekly — Wed, 03 Dec 2008 09:06:33 +0100

Page: 8 (Source: Inpharma Weekly)

Caspofungin cost effective in neutropenic fever

Inpharma — Wed, 03 Dec 2008 03:48:08 +0100

(Source: Inpharma)

Diagnosis and therapy of fungal infection in patients with leukemia-new drugs and immunotherapy.

Best Practice & Research. Clinical Haematology — Mon, 01 Dec 2008 05:00:00 +0100

Authors: Anaissie EJ Invasive fungal infections (IFIs) are a common problem in immunocompromised patients. Patients with leukemia, especially those undergoing stem cell transplantation, are at increased risk for IFIs, particularly invasive aspergillosis (IA). Serial monitoring with the recently approved Aspergillus galactomannan antigen test has helped to improve the diagnosis and the monitoring of treatment of IA in cancer patients. There are several new options to treat cancer patients with fungal infections. These include new antifungal agents, such as the mould-active triazoles (itraconazole, voriconazole, and posaconazole), the echinocandins (anidulafungin, caspofungin and micafungin), and the lipid formulations of amphotericin B. Immunotherapy with hematopoietic growth factors an...

Diagnosis and therapy of fungal infection in patients with leukemia--new drugs and immunotherapy.

Best Practice & Research. Clinical Haematology — Mon, 01 Dec 2008 05:00:00 +0100