Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia

Gøtzsche, Peter C; Johansen, Helle Krogh

doi:10.1136/bmj.314.7089.1238

Cited by 105 publications

(69 citation statements)

References 41 publications

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“…Application of AmB has not been shown to be beneficial for prophylaxis of IPA in neutropenia [93]. Low dose intravenous cAmB, inhalation of cAmB as well as intranasal cAmB application are well tolerated, but failed to be effective in prevention of IPA [21,82,94,95].…”

Section: Amphotericin Bmentioning

confidence: 99%

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients

et al. 2001

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Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients. F. Reichenberger, J.M. Habicht, A. Gratwohl, M. Tamm. #ERS Journals Ltd 2002. ABSTRACT: Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in neutropenic patients.Microbiological and serological tests are of limited value. The diagnosis should be considered in neutropenic patients with fever not responding to antibiotics, and typical findings on thoracic computed tomography scan. Whenever possible, diagnosis should be confirmed by tissue examination. Newer techniques, such as polymerase chain reaction may change the current diagnostic approach.Therapeutic strategies consist of prophylaxis in risk groups and the early application of antifungal agents in suspected or probable disease. Amphotericin B as desoxycholate or lipid formulation is the current standard medication in invasive infection, although it has major side effects. Its role is challenged by the new azole derivates, such as itraconazole and voriconazole, and the new echinocandins. Additional therapies with cytokines, such as granulocyte macrophage colony stimulating factor and interferon-c, and with granulocyte transfusions are under evaluation. In selected cases lung resection is of proven diagnostic and therapeutic value.This paper analyses the current understanding of the pathogenesis and epidemiology of invasive aspergillosis and reviews the actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in neutropenic patients.

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Section: Amphotericin Bmentioning

confidence: 99%

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients

et al. 2001

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“…6 A recent meta-analysis 7 has been conducted of 24 trials in which antifungals were used, either as prophylaxis or as empirical therapy, in patients with cancer complicated by neutropenia. This meta-analysis showed that amphotericin B decreased mortality significantly although the studies were small, as was the difference in the number of deaths.…”

mentioning

confidence: 99%

Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study

Kelsey

Goldman

McCann

et al. 1999

Bone Marrow Transplant

157

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Summary:Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P ‫؍‬ NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P ‫؍‬ NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P ‫؍‬ NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P ‫؍‬ 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P Ͻ 0.01). Time to colonisation was significantly delayed in the group receiving AmBisome (P Ͻ 0.05). Treatment-related toxicity was modest and no additional toxicity was observed in patients receiving AmBisome. AmBisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or BMT. However, despite encouraging trends, prophylactic AmBisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy. Keywords: AmBisome; prophylaxis; neutropenia More than half the fatal infections in neutropenic patients are due to fungi 1 with candida and aspergillus the most commonly-observed pathogens. fungal infection increases with the severity and duration of neutropenia which, in the case of bone marrow transplantation (BMT) or chemotherapy for the treatment of haematological malignancies, can range from a few days to several weeks. The severe immunosuppression induced by high-dose corticosteroids given to recipients of allogeneic BMT to suppress graft-versus-host disease (GVHD) puts them at additional risk of fungal infections 2-4 whereas for patients receiving autologous stem cell support and treatment with growth factors the risk is much lower.5 This provides a rationale for the prophylactic use of antifungal agents.Orally administered agents such as the imidazoles, or non-absorbable amphotericin B, achieve only local decontamination and have little or no impact on invasive fungal infections. 6 A recent meta-analysis 7 has been conducted of 24 trials in which antifungals were used, either as prophylaxis or as empirical therapy, in patients with cancer complicated by neutropenia. This meta-analysis showed that amphotericin B decreased mortality significantly although the studies were small, as was the difference in the number of deaths. Antifungals as a group decreased the incidence of inv...

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“…The studies supporting these practices do not always reach a definitive conclusion in terms of modification of existing clinical practice. [1][2][3][4][5][6][7][8][9][10][11][12][13] Therefore, guidelines have been formulated for the prevention of infections following HSCT, 14,15 and have been endorsed by the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation. These evidence-based reviews have made weighted recommendations for the use of antimicrobial agents as prophylaxis for bacterial, viral, and fungal pathogens.…”

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confidence: 99%

Antimicrobial prophylaxis in hematopoietic stem cell transplant recipients: heterogeneity of current clinical practice

Trifilio

Verma

Mehta

2004

Bone Marrow Transplant

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Summary:Antimicrobial agents are commonly used after hematopoietic stem cell transplant (HSCT) to prevent bacterial, viral and fungal infections. A pharmacy practice survey was undertaken to evaluate prevailing practices. The 31 centers evaluated transplanted over 3400 patients in 2001. Over half used bacterial prophylaxis; all with fluoroquinolones. A significantly higher proportion (90-100%) used fungal and viral prophylaxis. Most centers used fluconazole for fungal prophylaxis, but the dose used varied from 400 mg (the recommended dose) to 100 mg. Itraconazole and amphotericin preparations were used by some centers for allograft recipients because of their activity against aspergillosis. Most centers used brief viral prophylaxis for autograft recipients aimed at preventing HSV reactivation. Viral prophylaxis for allograft recipients was usually much more prolonged, reflecting concern over cytomegalovirus infections. Overall, there was significant deviation from recommended guidelines in many of the practices. Our survey suggests that substantial variation exists among transplant centers in their approach to antimicrobial prophylaxis after HSCT. This probably stems from the lack of definitive studies and strong recommendations in several areas, availability of newer agents that have not been adequately studied in the HSCT setting, and a desire to improve outcome before definitive studies are available for newer agents, a process that could take several years.

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Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia

Cited by 105 publications

References 41 publications

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients

Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study

Antimicrobial prophylaxis in hematopoietic stem cell transplant recipients: heterogeneity of current clinical practice

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