Antifungal Prophylaxis in Immunocompromised Hosts

Reents, Stan; Goodwin, Shirley; Singh, Vrinderpal

doi:10.1177/106002809302700114

Cited by 28 publications

(16 citation statements)

References 37 publications

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“…However, unpleasant and potentially serious side effects associated with the intravenous administration of amphotericin B, such as nausea, fever, chills and nephrotoxicity, often lead to patients discontinuing treatment with this drug [7, 8, 9]. Lipid-associated formulations of amphotericin B have been developed to reduce the nephrotoxicity associated with this agent [10, 11], but withdrawal rates in clinical trials have been high [11, 12, 13].…”

Section: Introductionmentioning

confidence: 99%

Intravenous Itraconazole followed by Oral Itraconazole for the Treatment of Amphotericin-B-Refractory Invasive Pulmonary Aspergillosis

Caillot¹

2003

Acta Haematol

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The efficacy and safety of 2 weeks of intravenous itraconazole (200 mg twice daily for 2 days, then 200 mg once daily for 12 days) followed by 12 weeks of oral itraconazole capsules 200 mg twice daily were evaluated in a multicentre, open trial in 31 immunocompromised patients with invasive pulmonary aspergillosis (IPA). We report on a subset of 21 patients who had amphotericin-B-refractory IPA. All patients had haematological malignancies, 10 patients had failed prophylaxis, 12 patients had failed empirical therapy and 2 patients had failed treatment of confirmed infection with amphotericin B. By the second day of treatment, all patients assessed (n = 12) had trough plasma concentrations of itraconazole greater than 250 ng/ml. Mean trough plasma concentrations increased throughout the intravenous and oral treatment periods. Of the 10 patients who completed the 14 weeks of therapy, 9 (90%) had a complete or partial response and the remaining patient had stable disease. Overall, 11 of the 21 patients (52%) had a complete or partial response at their last assessment and three additional patients had stable disease. During intravenous treatment, 18 patients (86%) experienced adverse events; during oral treatment, 11 patients (52%) experienced adverse events. Most adverse events were not related to itraconazole treatment and all were expected in this patient population. In conclusion, intravenous itraconazole followed by oral itraconazole is an effective and well-tolerated treatment for amphotericin-B-refractory IPA.

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Section: Introductionmentioning

confidence: 99%

Intravenous Itraconazole followed by Oral Itraconazole for the Treatment of Amphotericin-B-Refractory Invasive Pulmonary Aspergillosis

Caillot¹

2003

Acta Haematol

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“…Patients at risk of acquiring IPA are patients on chronic glucocorticoid or immunosuppressive treatment (34,61), patients with impaired neutrophil/macrophage function such as in chronic granulomatous disease (16), patients with AIDS (21), and neutropenic patients with aplastic anemia (107) or chemotherapy-induced neutropenia (9,27,103,108). The risk of acquiring IPA correlates with the duration and degree of immunosuppression or neutropenia (27,108) and is the highest in patients with prolonged neutropenia of more than 20 days and in those with multiple risk factors, e.g., following allogeneic bone marrow transplantation (BMT) or other organ transplantations (9,22,51,62,71,82, 112).The still unsatisfactory diagnosis and treatment of IPA result in an overall mortality of more than 50% (9,22,27,28). The mortality of patients after BMT can even be as high as 95% (22,55,56,62).…”

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confidence: 99%

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Strategies in prevention of invasive pulmonary aspergillosis in immunosuppressed or neutropenic patients

Beyer

Schwartz

Heinemann

et al. 1994

Antimicrob Agents Chemother

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Aspergillus species are increasingly recognized as major fungal pathogens in severely immunosuppressed or neutropenic patients (8,9,20,22,51,62,71,81,82,103,107, 112). As organ transplantations and aggressive antineoplastic chemotherapy regimens are becoming more frequent, increasing numbers of patients will be susceptible to an Aspergillus infection. Moreover, patients with AIDS probably have a higher incidence ofAspergillus infections than immunocompetent individuals (21). In the immunosuppressed or neutropenic host, invasive pulmonary aspergillosis (IPA), characterized by hyphal invasion and destruction of pulmonary tissue, is the most common manifestation of an Aspergillus infection, although local infections also occur in the sinuses, the skin, or intravenous catheters (1,8,9,20,82,89,101). Dissemination from these initial ports of entry to other organs can be a secondary event in about 20% or more of the cases (1,8,9,20,22,82,101). Aspergillus fumigatus, A. flavus, A. niger, and A. terreus strains were the most frequently observed strains in cases of documented infection (105).Aspergilli are respiratory pathogens, and pulmonary infections are usually acquired through the inhalation ofAspergillus conidia, which are universally present in unfiltered air (9,73,81,103). With a diameter of about 2.5 to 3.5 ,um, these conidia are able to reach small airways and the alveolar space, where the impaired host defense mechanisms allow hyphal germination of the aspergilli and subsequent tissue invasion (9,44,83,103,105). Some patients, however, may have Aspergillus colonization of the nasal sinuses and endogenous spread to the lungs, causing IPA (9, 89, 101). In these latter cases, the exact pathomechanisms of IPA manifestation and the way in which it disseminates from the sinuses to the lungs are less clear.The true incidence of IPA in susceptible patients is not known. In two relatively recent autopsy series, IPA was documented in about 10% of patients with hematological malignancies (8,20). In many cases the condition was not suspected clinically (20). Clinical reports show that the incidence of IPA differs greatly worldwide, at different treatment centers and even within the same institution, ranging from as low as 0% to 25% or more (8,9,28,62,82,88,103 (9,62,73,88). Spore counts in the hospital environment depend on the location and type of building and the type of air filtration used at the time the samples were taken. Without air filtration, spore counts of 5.0/m3 probably do not differ from outdoor samples, whereas by using high-efficiency particulate air (HEPA) filtration, concentrations of spores as low as 0.009/m3 can be achieved (73,88). Aspergillus infections occur more frequently when the spore counts are high. Numerous reports describe microepidemics of IPA coinciding with construction activity or with defective ventilation systems, and variable counts of 2.3 to 5.9 spores per m3 have been measured at these locations (9,72,73,81,88,103). A patient's susceptibility to anAspey*llus infection is determined ...

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“…Because of its water solubility, oral bioavailability and good safety profile, fluconazole is the current drug of choice in the management of oral candidiasis in HIV infection (reviewed in Stevens et al . 1991; Reents et al . 1993; Ellepola and Samaranayake 2000).…”

Section: What Are the Mechanisms And Significance Of Azole Resistancementioning

confidence: 99%

Fungal infections associated with HIV infection

Samaranayake

Naglik

et al. 2002

Oral Diseases

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Oral candidiasis is perhaps the commonest infection seen in HIV disease. The aim of this workshop was to provide a sketch of the multifarious aspects of the disease from a global perspective. To this end the panellists addressed issues such as the virulence of Candida, emergence of antifungal resistance, management of candidiasis and other exotic, oral mycotic diseases. An all-pervasive theme was the dramatic differences in the management of fungal infections consequential to the availability (or the lack) of anti-HIV drugs in the developed and the developing world. Further, the social stigmata associated with the HIV disease in many developing regions in Africa and Asia appears to modify the therapeutic strategies. Additionally, the lesser-known regional variations in the disease manifestations and therapeutic approaches were stark. Further work is direly needed to address these issues.

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Antifungal Prophylaxis in Immunocompromised Hosts

Cited by 28 publications

References 37 publications

Intravenous Itraconazole followed by Oral Itraconazole for the Treatment of Amphotericin-B-Refractory Invasive Pulmonary Aspergillosis

Intravenous Itraconazole followed by Oral Itraconazole for the Treatment of Amphotericin-B-Refractory Invasive Pulmonary Aspergillosis

Strategies in prevention of invasive pulmonary aspergillosis in immunosuppressed or neutropenic patients

Fungal infections associated with HIV infection

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