ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT)

Ullmann, Andrew J.; Akova, Murat; Herbrecht, Raoul; Viscoli, Claudio; Arendrup, Maiken Cavling; Arıkan-Akdağlı, Sevtap; Bassetti, Matteo; Billé, Jacques; Calandra, Thierry; Castagnola, Elio; Cornely, Oliver A.; Donnelly, J. Peter; Garbino, Jorge; Groll, Andreas H.; Hope, William; Jensen, Henrik Elvang; Kullberg, Bart Jan; Lass‐Flörl, Cornelia; Lortholary, Olivier; Meersseman, Wouter; Petrikkos, George; Richardson, Malcolm; Roilides, Emmanuel; Verweij, Paul E.; Cuenca‐Estrella, Manuel

doi:10.1111/1469-0691.12041

Cited by 295 publications

(187 citation statements)

References 148 publications

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“…Fluconazole, itraconazole, posaconazole, voriconazole, and micafungin are recommended for prophylactic use in patients with hematologic malignancies (9,10). Although the results of randomized clinical trials support the prophylactic benefits of these agents (7,8,11), each may be limited in their use: fluconazole has no activity against molds (12); posaconazole demonstrates broad-spectrum activity against both yeasts and molds (13), but optimal absorption of the oral suspension of posaconazole is dependent on administration with a high-fat meal (however, the delayed-release tablets have improved bioavailability) (14); voriconazole is as effective as fluconazole in preventing IFIs (15) but has been associated with breakthrough mucormycosis and a high incidence of side effects (16,17); itraconazole tablets have variable bioavailability, and its oral suspension has poor tolerability (18); and micafungin is available only as an intravenous (i.v.)…”

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confidence: 99%

Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study

Cornely

Böhme²,

Schmitt‐Hoffmann

et al. 2015

Antimicrob Agents Chemother

103

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Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n ‫؍‬ 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n ‫؍‬ 12). The mean ؎ standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1 ؎ 22.3 g · h/ml and 113.1 ؎ 19.6 g · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n ‫؍‬ 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.) I nvasive fungal infections (IFIs) are associated with significant morbidity, mortality, and health care costs in patients with hematologic malignancies (1, 2). Allogeneic hematopoietic stem cell transplantation and chemotherapy-associated neutropenia place patients with acute myeloid leukemia (AML) at risk of developing an IFI (3). Aspergillus spp. and Candida spp. are the predominant IFI pathogens in patients with acute leukemia (1, 3, 4). However, other molds, such as the Mucorales, Scedosporium spp., and Fusarium spp., are emerging as pathogens in this setting and are associated with high mortality rates (1).Because IFIs are often difficult to diagnose, and delays in treatment can significantly increase the risk of mortality (5, 6), antifungal prophylaxis has become a commonly used strategy in patients at high risk of IFIs (7, 8). Fluconazole, itraconazole, posaconazole, voriconazole, and micafungin are recommended for prophylactic use in patients with hematologic malignancies (9, 10). Although the results of randomized clinical trials support the prophylactic benefits of these agents (7,8,11), each may be limited in their use: fluconazole has no activity against molds (12); posaconazole demonstrates broad-spectrum activity against both yeasts and mo...

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mentioning

confidence: 99%

Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study

Cornely

Böhme²,

Schmitt‐Hoffmann

et al. 2015

Antimicrob Agents Chemother

103

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“…he echinocandins caspofungin and micafungin are now well established as first-line agents for the treatment of candidemia and other forms of invasive candidiasis (IC) (1)(2)(3). The in vitro activities of caspofungin and micafungin against Candida spp.…”

mentioning

confidence: 99%

Use of Micafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 3,764 Clinical Isolates of Candida by Use of CLSI Methods and Interpretive Criteria

et al. 2014

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bDue to unacceptably high interlaboratory variation in caspofungin MIC values, we evaluated the use of micafungin as a surrogate marker to predict the susceptibility of Candida spp. to caspofungin using reference methods and species-specific interpretive criteria. The MIC results for 3,764 strains of Candida (eight species), including 73 strains with fks mutations, were used. Caspofungin MIC values and species-specific interpretive criteria were compared with those of micafungin to determine the percent categorical agreement (%CA) and very major error (VME), major error (ME), and minor error rates as well as their ability to detect fks mutant strains of Candida albicans (11 mutants), Candida tropicalis (4 mutants), Candida krusei (3 mutants), and Candida glabrata (55 mutants). Overall, the %CA was 98.8% (0.2% VMEs and MEs, 0.8% minor errors) using micafungin as the surrogate marker. Among the 60 isolates of C. albicans (9 isolates), C. tropicalis (5 isolates), C. krusei (2 isolates), and C. glabrata (44 isolates) that were nonsusceptible (either intermediate or resistant) to both caspofungin and micafungin, 54 (90.0%) contained a mutation in fks1 or fks2. An additional 10 C. glabrata mutants, two C. albicans mutants, and one mutant each of C. tropicalis and C. krusei were classified as susceptible to both antifungal agents. Using the epidemiological cutoff values (ECVs) of 0.12 g/ml for caspofungin and 0.03 g/ml for micafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 80% of the C. glabrata mutants were non-WT for both agents (96% concordance). Micafungin may serve as an acceptable surrogate marker for the prediction of susceptibility and resistance of Candida to caspofungin.

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“…he echinocandins (anidulafungin, caspofungin, and micafungin) are all considered first-line agents for the treatment of invasive candidiasis, including candidemia (1)(2)(3). Numerous in vitro studies document comparable activities of these agents against a broad range of Candida species when tested using the broth microdilution methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (4)(5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Use of Anidulafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 4,290 Clinical Isolates of Candida by Using CLSI Methods and Interpretive Criteria

et al. 2014

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bThis study addressed the application of anidulafungin as a surrogate marker to predict the susceptibility of Candida to caspofungin due to unacceptably high interlaboratory variation of caspofungin MIC values. CLSI reference broth microdilution methods and species-specific interpretive criteria were used to test 4,290 strains of Candida (eight species), including 71 strains with documented fks mutations. Caspofungin MIC values were compared with those of anidulafungin to determine the percentage of categorical agreement (CA) and very major (VME), major (ME), and minor error rates, as well as the ability to detect fks mutants. For all 4,290 isolates the CA was 97.1% (0.2% VME and ME, 2.5% minor errors) using anidulafungin as the surrogate. Among the 62 isolates of Candida albicans (4 isolates), C. tropicalis (5 isolates), C. krusei (4 isolates), C. kefyr (2 isolates), and C. glabrata (47 isolates) that were nonsusceptible (NS; either intermediate [I] or resistant [R]) to both caspofungin and anidulafungin, 52 (83.8%) contained a mutation in fks1 or fks2. Eight mutants of C. glabrata, two of C. albicans, and one each of C. tropicalis and C. krusei were classified as susceptible (S) to both antifungal agents. The remaining 7 mutants (2 C. albicans and 5 C. glabrata) were susceptible to one of the agents and either intermediate or resistant to the other. Using the epidemiological cutoff value (ECV) of 0.12 g/ml for both caspofungin and anidulafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 42 of the 55 (76.4%) C. glabrata mutants were non-WT and 8 of the 55 (14.5%) were WT for both agents (90.9% concordance). Anidulafungin can accurately serve as a surrogate marker to predict S and R of Candida to caspofungin.

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ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT)

Cited by 295 publications

References 148 publications

Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study

Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study

Use of Micafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 3,764 Clinical Isolates of Candida by Use of CLSI Methods and Interpretive Criteria

Use of Anidulafungin as a Surrogate Marker To Predict Susceptibility and Resistance to Caspofungin among 4,290 Clinical Isolates of Candida by Using CLSI Methods and Interpretive Criteria

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