Diagnostic-driven antifungal therapy in neutropenic patients using the D-index and serial serum galactomannan testing

Abstract Introduction Invasive mold disease is an important complication of patients with hematologic malignancies, and is associated with high mortality. A diagnostic-driven approach has been an alternative to the classical empiric antifungal therapy. In the present study we tested an algorithm that incorporated risk stratification using the D-index, serial serum galactomannan and computed tomographic-scan to guide the decision to start antifungal therapy in neutropenic patients. Patients and methods Between May 2010 and August 2012, patients with acute leukemia in induction remission were prospectively monitored from day 1 of chemotherapy until discharge or death with the D-index and galactomannan. Patients were stratified in low, intermediate and high risk according to the D-index and an extensive workup for invasive mold disease was performed in case of positive galactomannan (≥0.5), persistent fever, or the appearance of clinical manifestations suggestive of invasive mold disease. Results Among 29 patients, 6 (21%), 11 (38%), and 12 (41%) were classified as high, intermediate, and low risk, respectively. Workup for invasive mold disease was undertaken in 67%, 73% and 58% (p = 0.77) of patients in each risk category, respectively, and antifungal therapy was given to 67%, 54.5%, and 17% (p = 0.07). Proven or probable invasive mold disease was diagnosed in 67%, 45.5%, and in none (p = 0.007) of high, intermediate, and low risk patients, respectively. All patients survived. Conclusion A risk stratification using D-index was a useful instrument to be incorporated in invasive mold disease diagnostic approach, resulting in a more comprehensive antifungal treatment strategy, and to guide an earlier start of treatment in afebrile patients under very high risk.

Patogenia e inmunoterapia en la sinusitis alérgica fúngica (SAF) / Pathogeny and immunotherapy of allergic fungal sinusitis

Allergic fungal sinusitis is an atopic condition close related to fungus allergens that initiate a chronic inflammation dependent of the IgE system and LTCD4-TH2 cells whose cytokines and chemokines induced the clinical symptoms. Specific immunotherapy is recommended to avoid the recurrences and to improve the benefits of the surgical procedures of the affected sinuses. We suggest that Bipolaris sp Drechslera sp extracts must be included in the skin testing of the atopic patients suffering rhinosinusal symptoms as well as those who reveal intense response to fungal allergens in general.

Invasive aspergillosis in hematopoietic stem cell transplant recipients: a retrospective analysis

Invasive aspergillosis (IA) currently is an important cause of mortality in subjects undergoing hematopoietic stem cell transplants (HSCT) and is also an important cause of opportunistic respiratory and disseminated infections in other types of immunocompromised patients. We examined the medical records of 24 cases of proven and probable invasive aspergillosis (IA) at the Hospital de Clinicas of the Federal University of Parana, Brazil, from January 1996 to October 2006. During this period occurred a mean of 2.2 cases per year or 3.0 cases per 100 HSTC transplants. There was a significant relationship between structural changes in the bone marrow transplant (BMT) Unit and the occurrence of IA cases (p=0.034, relative risk (RR) = 2.47). Approximately 83 percent of the patients died due to invasive fungal infection within 60 days of follow up. Some factors tended to be associated with mortality, but these associations were not significant. These included corticosteroid use, neutropenia (<100 cells/mm³) at diagnosis, patients that needed to change antifungal therapy because of toxicity of the initial first-line regimen and disseminated disease. These factors should be monitored in BMT units to help prevent IA. Physicians should be aware of the risk factors for developing invasive fungal infections and try to reduce or eliminate them. However, once this invasive disease begins, appropriate diagnostic and treatment measures must be implemented as soon as possible in order to prevent the high mortality rates associated with this condition.

Fungal infections in the immunocompromised host

In recent years many remarkable changes occurred in our way of life, producing opportunities for microbes. All these changes are related to the recent emergence of previously unrecognized diseases, or the resurgence of diseases that, at least in developed countries, were thought to be under control. This concept is reviewed regarding fungal infections and their agents in the immunocompromised host. The changing pattern of these infections, the portals of entry of fungi into the human host, fungal pathogenicity and the main predisposing factors are analyzed. Opportunistic fungal infections in cancer, organ transplant and acquired immunodeficiency syndrome patients are reviewed, specially candidiasis and aspergillosis

Aspergillosis in immunocompromised children with acute myeloid leukemia and bone marrow aplasia: report of two cases

No presente trabalho sao registrados dois casos de aspergilose em criancas imunocomprometidas. O estudo micologico completo identificou Aspergillus flavus como agente de dois processos. A presenca cada vez mais frequente da aspergilose invasiva deve-se ao numero crescente de pacientes imunocomprometidos, muitos com hemopatias graves submetidos a quimioterapia. O diagnostico precoce em um dos casos possibilitou remissao do processo. Tratava-se de paciente com leucemia mieloide aguda, tendo sido isolado o fungo do sangue circulante. O segundo caso evoluiu para obito, com infeccao fungica generalizada.

La aspergilosis saprofítica intracavitaria pulmonar en Säo Paulo, Brasil

Se estudió la incidencia de la aspergilosis saprofítica pulmonar en la ciudad de Sao Paulo (Brasil), entre 105 pacientes que presentaron una imagen radiográfica compatible con aspergiloma y/o con cavidades pulmonares residuales. La contrainmunoelectroforesis (CIE) en gel de agarosa fue positiva en 18 (72%) pacientes que tenían una imagen radiográfica de un aspergiloma y en 7 (28%) de los casos que tenían una cavidad pulmonar vacía. La inmunodifusión (ID) fue positiva solamente en 20 (80%) de estos pacientes. La CIE detectó títulos de anticuerpos contra Aspergillus fumigatus en los 25 casos de aspergilosis pulmonar. La existencia del aspergiloma fue confirmada quirúrgicamente en 3 pacientes; del material de dos aspergilomas extirpados se cultivó el A. fumigatus. Aspegilos de la misma especie se cultivaron del esputo de 5 (25.7%) enfermos, de los 18 que tenían aspergiloma y en 3 de los 7 casos que tenían aspergilosis intracavitaria parietal