Oral itraconazole plus nasal amphotericin B for prophylaxis of invasive aspergillosis in patients with hematological malignancies

Todeschini, Giuseppe; Murari, C.; Bonesi, R.; Pizzolo, Giovanni; Amaddi, G.; Ambrosetti, A.; Ceru, S.; Piacentini, Igor; Martini, Nael; Montresor, P.; Perona, G.

doi:10.1007/bf01973640

Cited by 46 publications

(28 citation statements)

References 22 publications

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“…Both trials clearly showed a marked reduction of invasive fungal infections. The largest study until now was reported by Todeschini et al, 18 who compared 164 patients with 200 mg/day itraconazole and nasal amphotericin B to a historical group of 290 patients with no antifungal prophylaxis. The rate of proven invasive aspergillosis fell from 4 to 0% (P = 0.004).…”

Section: Discussionmentioning

confidence: 99%

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia

et al. 1998

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The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (Ͼ500 ng/ml) with itraconazole capsules.

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Section: Discussionmentioning

confidence: 99%

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia

et al. 1998

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“…The median length of neutropenia was 18 days (range 5-33). Eighteen of 28 patients had AML with a median neutropenic length of 20 days (range 5-33), and 10/18 patients had ALL with a median neutropenic period of 13 days (range [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Time Framesmentioning

confidence: 99%

“…Group 3-a consisted of 37 AML patients with median length of neutropenia of 16 days (range 5-120), and 8 ALL patients with median of 17 days (range 7-40) of neutropenia. Group 3-b consisted of 23 AML patients with median neutropenia duration of 15 days (range 5-42), and 3 ALL patients with median neutropenia duration of 11 days (range [8][9][10][11][12][13][14][15][16][17][18][19][20]. In group 3-c 26 patients underwent allogeneic BMT in the hematology ward with a median neutropenic period of 15 days (range 9-26), and 168 patients underwent autologous BMT in the hematology ward with median neutropenic period of 10 days (range 7-25).…”

Section: Time Framesmentioning

confidence: 99%

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Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: Before and after chemoprophylaxis and institution of HEPA filters

et al. 2001

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during extensive hospital construction and indoor renovation, a nosocomial outbreak of invasive pulmonary aspergillosis occurred in acute leukemia patients treated in a regular ward that has only natural ventilation. The observed infection rate was 50%. Chemoprophylaxis with intravenous continuous low-dose amphotericin B was then instituted as a preventive measure. During the next 18 months invasive pulmonary aspergillosis developed in 43% of acute leukemia patients. After that period a new hematology ward was opened with an air filtration system through high-efficiency particulate air filtration (HEPA) filters, and a bone marrow transplantation program was started on the hematology service. During the following three years, none of the acute leukemia or bone marrow transplantation patients who were hospitalized exclusively in the hematology ward developed invasive pulmonary aspergillosis, although 29% of acute leukemia patients who were housed in a regular ward, because of shortage of space in the new facility, still contracted invasive pulmonary aspergillosis. Overall, 31 patients were diagnosed with invasive pulmonary aspergillosis during almost five years: 74% of patients recovered from invasive pulmonary aspergillosis, and 42% are long-term survivors; 26% of patients died of resistant leukemia with aspergillosis, but no one died of invasive pulmonary aspergillosis alone. In conclusion, during an on-going construction period, an extremely high incidence rate of invasive pulmonary aspergillosis in acute leukemia patients undergoing intensive chemotherapy was observed. Institution of low-dose intravenous amphotericin B prophylaxis marginally reduced the incidence rate of invasive pulmonary aspergillosis. Keeping patients in a special ward with air filtration through a HEPA system eliminated invasive pulmonary aspergillosis completely. Among patients who developed invasive pulmonary aspergillosis, early diagnosis and treatment are probably the explanation for the favorable outcome. Am. J. Hematol. 66:257-262, 2001.

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“…Itraconazole capsules had activity in the treatment of invasive aspergillosis 16 and had been used as prophylaxis in high-risk patients with variable results. [17][18][19][20] However, the bioavailability of itraconazole in capsule form was unpredictable between and within patients, 21 particularly if concomitant antacids were used. A new cyclodextrin-based oral itraconazole solution had recently become available.…”

Section: Gvhdmentioning

confidence: 99%

A pilot study of targeted itraconazole prophylaxis in patients with graft-versus-host disease at high risk of invasive mould infections following allogeneic stem cell transplantation

Grigg

Brown

Roberts

et al. 2004

Bone Marrow Transplant

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Summary:Patients with severe graft-versus-host disease (GVHD) requiring intensive immunosuppression are at high risk of invasive mould infections (IMI). Prophylaxis with an active, oral antifungal agents with reliable absorption in this context is desirable. A total of 44 patients at high risk of post-engraftment IMI received itraconazole solution 2.5 mg/kg b.d. as prophylaxis. Two of the first nine patients, in whom bioavailability was compromised due to significant vomiting and/or diarrhoea, died of probable or proven invasive aspergillus. None of the subsequent 35 patients, some of whom had severe gut GVHD and who received liposomal amphotericin B prophylaxis until itraconazole was reliably tolerated and absorbed, developed IMI. The overall incidence of IMI was substantially lower than in historical controls. Itraconazole was generally well tolerated, with five patients (11%) ceasing the drug due to intolerance or disturbed liver function. Targeted prophylaxis with oral or parenteral antifungal agents in high-risk allograft recipients appears to be effective in reducing the incidence of IMI. GVHDInvasive mould infections (IMI), particularly with aspergillus species, occur in up to 11% of patients after allogeneic BMT and may be increasing in incidence due to more invasive transplantation procedures in higher risk patients. 1 Characteristically, there is a bimodal pattern of IMI: an early peak during the initial period of neutropenia after conditioning and a late peak around 2-5 months post transplant, 2-4 the latter now comprising the majority of infections. Risk factors for later onset IMI include T-cell depletion, graft-versus-host disease (GVHD), use of highdose corticosteroids, CMV disease and neutropenia. 2,3,5,6 Risk factors for IMI and its incidence appear similar after nonmyeloablative conditioning. 7 Corticosteroids contribute to the risk of IMI independently of GVHD due to complex immunobiological dysregulatory effects; 8 both the duration and dose of corticosteroids are important. 2,9,10 In our institution, the overall incidence of IMI in allograft recipients from 1991 to 1998 was 8%, 11 rising to 20% in those with grades III-IV acute GVHD. 12 An analysis of risk factors for post-engraftment IMI identified prolonged (42 weeks) use of 40.25 mg/kg/day of prednisolone or equivalent corticosteroid as a major risk factor. 12 In order to reduce this incidence, in 1998, our unit examined available prophylactic fungal strategies. Various amphotericin B-based approaches such as low-dose IV 6,13 or inhaled 14 amphotericin B or liposomal amphotericin B 15 had been examined as prophylaxis with either negative or inconclusive results. Important problems with these strategies included the high cost of liposomal amphotericin B, the impracticality of prolonged parenteral delivery in the outpatient setting and renal toxicity.Key features of an ideal strategy included availability of an oral preparation with reliable and good bioavailability, activity against aspergillus and sufficient tolerability to enable admini...

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Oral itraconazole plus nasal amphotericin B for prophylaxis of invasive aspergillosis in patients with hematological malignancies

Cited by 46 publications

References 22 publications

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia

Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: Before and after chemoprophylaxis and institution of HEPA filters

A pilot study of targeted itraconazole prophylaxis in patients with graft-versus-host disease at high risk of invasive mould infections following allogeneic stem cell transplantation

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