Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus.

During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.

A retrospective review of 228 episodes of infective endocarditis where rheumatic valvular disease is still common.

Two hundred and twenty-eight episodes of infective endocarditis in adult patients (mean age 36 years) were reviewed retrospectively. There were 183 episodes (80%) of native valve, 15 (7%) early prosthetic valve and 30 (13%) late prosthetic valve endocarditis. The most common predisposing factor was rheumatic valvular disease (65%). None of the patients were intravenous drug users. According to the Duke criteria, the number of definite, probable and rejected episodes were 121 (53%), 94 (41%) and 13 (6%), respectively. Additional minor criteria increased the number of definite endocarditis to 82%. The Duke criteria are not primarily intended to influence treatment decisions but are helpful in standardising research activities. The choice of the level of sensitivity or specificity of the criteria may be adjusted according to the aim of the study and prevalence of disease in a particular area. More sensitive criteria may be valuable in those countries where the prevalence of rheumatic valvular disease is still high.

Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia.

Hematogenous candidiasis adds substantially to the morbidity and mortality rates of patients with cancer. Little is known about the risk factors and outcome in patients with breakthrough (BT) candidemia while on systemic antifungal therapy. All 479 episodes of candidemia in 474 consecutive patients with candidemia that was diagnosed at M. D. Anderson Cancer Center from 1988 through 1992 were studied retrospectively. A total of 49 patients had BT candidemia, defined as candidemia that developed after at least 5 days of systemic antifungal therapy. Risk factors for BT candidemia and predictors of mortality were investigated. Multivariate analysis revealed that intensive care unit stay, neutropenia, use of corticosteroids, and duration of neutropenia as significant risk factors for BT candidemia. Seventy-six percent of patients with BT candidemia died, compared with 50% of patients with non-BT infection. In multivariate analysis, intensive care unit stay, being and remaining neutropenic, APACHE III score, and disseminated disease were independent prognostic factors. In conclusion, identification of risk factors and predictors of a poor outcome in patients with cancer with BT candidemia may have important implications in early diagnosis and appropriate therapy of these patients.

Reliability of clinical research on invasive fungal infections: a systematic review of the literature.

The aim of this study was to assess the comparability and reliability of clinical research on invasive fungal infections (IFIs) which is accumulating in the medical literature. A Medline search strategy was developed covering the years 1985-1997. The 7,086 articles identified this way were further limited to 173 by reading the abstracts to studies involving immunocompromised patients and deep tissue infections. Diagnostic criteria used for definitions of IFIs were evaluated according to the level of confidence in diagnosis. For analysing the reliability, we used the sample of 397 patients from the European Organization for Research and Treatment of Cancer (EORTC) database. Each patient in the database was evaluated according to the definitions employed in each article. The level of overall agreement among the articles was very low (Kappa = 0.253). The results of this analysis show the discrepancy in the medical literature in diagnosing IFIs and the necessity for the standardization of definitions.

Prophylaxis and treatment of fungal infections associated with haematological malignancies.

Patients with haematological malignancies form one of the most susceptible host groups for microbial infection, especially during neutropenia. The incidence of invasive fungal infections has increased in recent years, highlighting the need for better diagnosis and more effective antifungal therapies. Amphotericin B is the drug of choice for many fungal infections, although toxicity and the need for intravenous infusion restrict its use. When possible, oral administration of antifungal agents is preferable but intravenous administration is often needed and current oral agents have their limitations: fluconazole because of a narrow spectrum of activity; itraconazole capsules because of erratic absorption. In this review, prophylactic and treatment options for systemic fungal infections are discussed. The specific needs of patients with different types of leukaemia and the benefits of new amphotericin B and itraconazole formulations are examined.

Invasive aspergillosis as an opportunistic infection in nonallografted patients with multiple myeloma: a European Organization for Research and Treatment of Cancer/ Invasive Fungal Infections Cooperative Group and the Intergroupe Français du Myélome.

We report the occurrence of invasive aspergillosis (IA) in nonallografted patients with multiple myeloma (MM) who were treated at hematology or oncology centers in Europe during 1984-1996. Thirty-one cases met the criteria for definitive (21 [68%]) or probable (10 [32%]) IA. Of these cases, 23 (74%) were reported during 1992-1996. Twenty-nine cases (94%) occurred in patients with Durie-Salmon stage 3 MM, and 2 (6%) occurred in patients with Durie-Salmon stage 2 MM. The median time between MM and IA diagnoses was 8 months (range, 1-75 months). Sixteen patients (51%) had a neutrophil count