Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology.

Huijgens, P.C.; Simoons-Smit, A. M.; Loenen, A. C. Van; Prooy, E.; Tinteren, Harm van; Ossenkoppele, Gert J.; Jonkhoff, A. R.

doi:10.1136/jcp.52.5.376

Cited by 69 publications

(47 citation statements)

References 26 publications

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“…22,23 Doses lower than 400 mg/d failed to show a marked benefit and have not been carried out in a placebo controlled fashion. 17,[24][25][26][27] Since moulds and Candida krusei, harbor intrinsic resistance to fluconazole and only dose dependent activity against Candida glabrata, breakthrough infections with these fungi have occurred. 16,21,23,28,29 The clinical relevance of the development of resistance during fluconazole prophylaxis is still a matter of debate, 30,31 while a general shift towards higher rates of strains exhibiting primary resistance have been clearly shown in the intensive care setting.…”

Section: Azolesmentioning

confidence: 99%

“…Itraconazole capsules lead to adequate plasma levels with delay, if at all, and thus are not recommended as a start-up for prophylaxis of invasive fungal infection. 27,33,34 A superior bioavailability is achieved with itraconazole oral suspension. A double-blind, double dummy, placebo controlled trial comparing the suspension at a dose of 2.5 mg/kg bid plus nystatin 500.000 IU qid to nystatin alone found a more effective reduction in the rate of fatal candidemia from 2% to zero.…”

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confidence: 99%

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Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Cornely¹,

Böhme²,

Buchheidt³

et al. 2009

Haematologica

155

102

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© F e r r a t a S t o r t i F o u n d a t i o nO IntroductionThe rising incidence of invasive fungal infections, especially invasive aspergillosis, compromises therapeutic outcomes in hematologic cancer patients and in transplant recipients. [1][2][3][4][5] The utilization of newly introduced antifungal agents clearly improved the tolerability of patients combating severe underlying diseases. 6,7 Despite better outcome in primary treatment of invasive aspergillosis in comparison to conventional amphotericin B, response and survival require further improvement. 8,9 Additionally, early diagnosis of invasive fungal infections is critical.10 But usually diagnosis is delayed and thus hampers further treatment outcome. 11Therefore, the prevention of invasive fungal infections upfront has become the major goal in patient care in high-risk patient populations. Since the first edition of these recommendations regarding antifungal prophylaxis, close to 20 relevant publications have been added to the field, necessitating an updated review of their impact on clinical decision making. 12 On the other hand new meta-analyses on prophylaxis of invasive fungal infections have also been published, but do not differentiate between specific patient populations and risk factors. 13,14 To maintain comparability with the previous recommendation, the EBM criteria proposed by the Infectious Diseases Society of America (IDSA) are again employed throughout this document (Table 1). 15 Several newly introduced antifungal agents have been utilized in prophylaxis for the first time. These and other new studies have been incorporated into this updated guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Oncology. The aim of this review is to provide the treating physician an up-to-date tool for the daily bedside decisions on primary antifungal prophylaxis. Objectives of antifungal prophylaxisIt is evident that the most relevant endpoint of antifungal prophylaxis is the reduction of mortality. However, death attributable to invasive fungal infection is difficult to prove and a reduction in overall mortality as a desirable endpoint of any clinical decision is difficult to achieve in the context of multiple competing illnesses in a severely immunocompromised host. Thus usually the reduction of the incidence rate of breakthrough invasive fungal infection is chosen as the primary endpoint of clinical trials. Improving rates of mucosal or other superficial infection and reducing colonization are no proper endpoints for antifungal prophylaxis with systemically active compounds. Design and MethodsThe guideline was prepared by a group of German clinicians. Systematic literature search comprised Medline, CancerLit, Embase, Cochrane Library and conference proceedings of Advances Against Aspergillosis, ASH, EBMT, ECCMID, ESMO, Focus on Fungal Infections, and ICAAC/IDSA, yielding a total of 86 clinical trials comprising 16,922 patients. Data extracted by OAC and MSi from each clinical study identifie...

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Section: Azolesmentioning

confidence: 99%

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confidence: 99%

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Cornely¹,

Böhme²,

Buchheidt³

et al. 2009

Haematologica

155

102

View full text Add to dashboard Cite

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“…Nonetheless, these fungal infection-related mortality rates are comparable to those reported from other clinical studies evaluating fluconazole and itraconazole (fluconazole, 1.2-3.0%; itraconazole, Ͻ 1.0 -15.2%). 8,9,12,[15][16][17] In addition, no prophylaxis-related deaths occurred with either lipid-based amphotericin B product.…”

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confidence: 96%

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

Mattiuzzi

Kantarjian

Lim

et al. 2004

Cancer

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Ab initio quantum chemical computations have been done to determine the energetics and reaction pathways of hydroformylation of higher alkenes using a rhodium complex homogeneous catalyst. Calculation of fragments of the potential energy surfaces of the HRh(CO)(PPh3)3‐catalyzed hydroformylation of 1‐decene, 1‐dodecene, and styrene were performed by the restricted Hartree‐Fock method at the second‐order MØller‐Plesset (MP2) level of perturbation theory and basis set of 6‐31++G(d,p). Geometrically optimized structures of the intermediates and transition states were identified. Three generalized rate models were developed on the basis of above reaction path analysis as well as experimental findings reported in the literature. The kinetic and equilibrium parameters of the models were estimated by nonlinear least square regression of available literature data. The model based on H2‐oxidative addition fitted the data best; it predicts the conversion of all the alkenes quite satisfactorily with an average deviation of 7.6% and a maximum deviation of 13%. © 2009 American Institute of Chemical Engineers AIChE J, 2009

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“…[1][2][3] In view of the poor prognosis of disseminated fungal disease, many centres administer antimycotic agents prophylactically. Fluconazole has emerged as the most widely used prophylactic agent in neutropenic patients and has been used in doses varying from 50 to 400 mg. [4][5][6][7][8][9][10] Its optimal dose in antifungal prophylaxis remains to be determined. 5,6 Not only has fluconazole been found to be highly effective in eliminating colonisation and infection by Candida spp.…”

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confidence: 99%

“…In a recent randomised trial we reported a 100% mortality in patients with proven fungal infections due to Aspergillus or Mucor spp., the overall incidence of such infections in our population being 5%. 10 In an attempt to reduce both incidence of, and mortality from these infections, an open-label, randomised clinical trial was initiated, to compare the safety and efficacy of intravenous ABCD with oral fluconazole in the prevention of fungal disease in neutropenic patients with haematological malignancies. For the prophylactic use of ABCD we decided to administer half of the daily dose that is generally recommended for antifungal therapy.…”

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Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial

Timmers

Zweegman

Simoons-Smit

et al. 2000

Bone Marrow Transplant

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Summary:We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of unresolved fever after 4 days of empirical antibacterial therapy, patients in both treatment groups were to receive ABCD, 4 mg/kg/day. However, the study had to be stopped in an early phase, due to severe side-effects of ABCD. A total of 24 patients were enrolled, 12 patients were randomly assigned to receive prophylactic ABCD, which was administered for a mean of 13.9 days. Fluconazole prophylaxis was given to 12 patients for a mean of 21.2 days. Therapeutic ABCD, 4 mg/kg, was initiated in four patients because of suspected fungal infection, all of whom had initially received fluconazole. A high rate of infusion-related toxicity of ABCD was observed. Chills occurred in 15/16 ABCD recipients (94%), accompanied by a temperature rise of у2؇C in 4/16 patients and of у1؇C but Ͻ2؇C in 10/16 patients. Other ABCD-related adverse events were hypotension (4/16), nausea with vomiting (5/16), tachycardia (7/16), headache (3/16) and dyspnoea (3/16). For premedication patients received: antihistamines (12/16), hydrocortisone (9/16) and/or morphine (6/16). ABCD was discontinued in 8/16 patients (50%) due to side-effects, which ultimately dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe infusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy. Bone Marrow Transplantation (2000) 25, 879-884.

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Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology.

Cited by 69 publications

References 26 publications

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial

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