Plínio Trabasso

Fusarium Infection in Hematopoietic Stem Cell Transplant Recipients

To characterize the epidemiology and prognostic factors of invasive fusariosis in hematopoietic stem cell transplant (HSCT) recipients, the records of HSCT recipients from 9 hospitals (7 in Brazil and 2 in the United States) were retrospectively reviewed. Sixty-one cases were identified: 54 in allogeneic HSCT recipients and 7 in autologous HSCT recipients. The incidence of fusariosis among allogeneic HSCT recipients varied between a range of 4.21-5.0 cases per 1000 in human leukocyte antigen (HLA)--matched related transplant recipients to 20.19 cases per 1000 in HLA-mismatched transplant recipients. The median time period between transplantation and diagnosis of fusariosis was 48 days. Among allogeneic HSCT recipients, a trimodal distribution was observed: a first peak before engraftment, a second peak at a median of 62 days after transplantation, and a third peak >1 year after transplantation. The actuarial survival was 13% (median, 13 days). Persistent neutropenia was the single prognostic factor for death identified by multivariate analysis.

Epidemiology of bacteremia and factors associated with multi-drug- resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients

The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75–30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60–34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.

Mycobacterial Infection: A Difficult and Late Diagnosis in Stem Cell Transplant Recipients

The Infectious Diseases Working Party of the European Blood and Marrow Transplant Group conducted a survey to obtain information about the frequency, presentation, and treatment of mycobacterial infection (MBI) in stem cell transplant (SCT) recipients. Among 29 centers, MBI was diagnosed in 0.79% of 1513 allogeneic and 0.23% of 3012 autologous SCT recipients during 1994-1998 a median of 160 days after transplantation. The mean interval between first symptoms and diagnosis was 29 days and was still longer for patients with atypical MBI or recipients of corticosteroid therapy. The prevalence of MBI was highest among those who received matched unrelated or mismatched STCs from related donors. Of 31 patients, 20 had tuberculosis, 8 had atypical MBI, and 3 had diagnoses based on histological findings only. Five patients (16%) died, all of whom had received an allogeneic SCT. Because of the increased numbers of unmatched donors and transplantation programs in countries with a high prevalence of tuberculosis, constant vigilance is required to early detect MBI in SCT recipients.

Trichosporon species infection in bone marrow transplanted patients.

Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invasive devices. Two cases of fungal infections caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.

Outbreaks of infectious diseases in stem cell transplant units: a silent cause of death for patients and transplant programmes

Summary:Following the closure of the National Blood and Bone Marrow Transplant Unit in Dublin, because of an outbreak of vancomycin-resistant enterococcal infection, a survey was carried out by the EBMT to investigate the occurrence of outbreaks of infection in SCT units and the impact on patient morbidity, mortality and the administration of the transplant programme over a 10-year period from 1991 to 2001. A total of 13 centres reported 23 outbreaks of infection involving 231 patients: 10 bacterial, eight viral and five fungal outbreaks were reported and 56 deaths were attributed to infection. All fungal and bacterial deaths and the majority of viral deaths occurred in allograft recipients. In all outbreaks, the infection was reported to be hospital acquired and in all the viral, and half the bacterial infections, cross-infection was a major factor. All viral, four of 10 bacterial and three of five fungal outbreaks occurred in HEPA filtered rooms. A total of 12 SCT units reported a partial or total closure. The introduction of mandatory quality management systems such as JACIE should result in a change in attitude to ‘incident reporting’ and together with future surveys should reduce the incidence of infectious outbreaks in SCT units.

Is the incidence of candidemia caused by Candida glabrata increasing in Brazil? Five-year surveillance of Candida bloodstream infection in a university reference hospital in southeast Brazil

From 2006 to 2010, a retrospective study was conducted in a university referral tertiary care hospital to study the frequency and distribution of Candida species in different medical specialties. The use of mechanical ventilation, central venous catheter, and urinary catheter were recorded per 1,000 patient-days and the use of antifungals was calculated using defined daily dose (DDD). A total of 313 episodes were identified and the overall incidence was 0.54 (0.41-0.71) episodes per 1,000 patient-days. Candida albicans caused 44% of the overall episodes, followed by C. tropicalis (21.7%), C. parapsilosis (14.4%), C. glabrata (11.2%), and C. krusei (3.5%). The incidence of C. glabrata significantly increased from 2006-2010 (range: 4.8-23.5%) (P = 0.024). Candida glabrata was associated with malignancies (P = 0.004) and C. krusei with hematologic malignancies (P < 0.0001). The use of antifungals was higher in the hematology/bone marrow transplant units and represented 40% of all fluconazole prescription in the hospital. There was no correlation with the use of fluconazole and the increasing ratio of C. glabrata (r = 0.60). The use of invasive devices was significantly higher in the intensive care units (ICUs) than the medical and surgical emergencies units (P < 0.001). In contrast, the emergencies had higher incidence of candidemia (2-2.1 episodes/1,000 patient-days) than the ICUs (1.6 episodes 1,000 patient-days). Candida glabrata candidemia showed a significant increase in contrast to the current national literature where C. parapsilosis remained the most important non-C. albicans Candida species in Brazilian hospitals. Our findings suggested that the increasing incidence of C. glabrata was not associated with use of fluconazole and other risk factors might play an important role.

Consenso em criptococose: 2008

Divisao de Clinica de Molestias Infecciosas Hospital das Clinicas Universidade de Sao Paulo, Sao Paulo, SP

Infectious complications in patients randomized to receive allogeneic bone marrow or peripheral blood transplantation

Abstract: Very few data are available on the comparison of infectious complications in peripheral blood stem cell transplantation (PBSCT) and bone marrow transplant (BMT). The objective of this study was to evaluate the severity and frequency of infectious complications in patients randomized to receive PBSCT or BMT. We retrospectively reviewed the charts of all patients included in a randomized clinical trial comparing PBSCT (27 patients) and BMT (29 patients). We analyzed two periods: pre‐engraftment and post‐engraftment. In the pre‐engraftment period, we compared the two groups with respect to the duration of neutropenia, antibiotic use and hospitalization, and documentation of infection. In the post‐engraftment period, we analyzed the occurrence and severity of graft‐versus‐host disease (GVHD), duration of cyclosporine, corticosteroids, antibiotic, antiviral and antifungal prophylaxis, number of episodes of infection, and death rates. Patients receiving PBSCT had shorter duration of neutropenia, but there were no differences in the incidence of infections or duration of antibiotic therapy. Patients receiving PBSCT had a higher incidence of extensive chronic GVHD (65% vs. 39%, P=0.08), longer duration of cyclosporine use (risk ratio [RR] 1.97), corticosteroids (RR 1.66), antibacterial (RR 2.60), antifungal (RR 2.50), anti‐Pneumocystis carinii (RR 2.06) and anti‐cytomegalovirus (RR 1.44) prophylaxis, and more infectious episodes (3.65 vs. 2.32 per 1000 days at risk, RR 1.57). There were no differences in death rates. Multivariate analysis identified the use of steroids as the most significant variable associated with infectious episodes. PBSCT was associated with more infections in the post‐engraftment period.

Phaeohyphomycosis caused by Chaetomium globosum in an allogeneic bone marrow transplant recipient.

Bone marrow transplant recipients are highly susceptible to opportunistic fungal infections. This is the report, of the first case of a Chaetomium systemic infection described in Brazil. A 34 year-old patient with chronic myeloid leukemia underwent an allogeneic sibling matched bone marrow transplant. Seven months later, he developed systemic infection with enlargement of the axillary and cervical lymph nodes. Culture of the aspirates from both lymph nodes yielded Chaetomium globosum. The infection was successfully treated with amphotericin B. The increasing population of immunosupressed patients requires a careful microbiologic investigation for uncommon fungal infections.

Development of cycling probe-based real-time PCR system to detect Fusarium species and Fusarium solani species complex (FSSC)

In the present study, we developed a new real-time PCR system based on the cycling probe technology (CPT), which is composed of two single tube real-time PCR assays: the Fusarium genus-specific assay and the Fusarium solani species complex (FSSC)-specific assay with primers targeting the 28s ribosomal RNA gene. The Fusarium genus-specific assay was shown to be highly specific, detecting all reference Fusarium strains with no cross-reaction with other reference fungal strains, such as Aspergillus spp. and human DNA. The FSSC-specific assay also reacted very specifically with FSSC, except for a cross-reaction with Fusarium lunatum. To validate the real-time PCR system, we tested 87 clinical isolates of Fusarium spp. Identification results from the real-time PCR system were found to be 100% concordant with those from DNA sequencing of EF-1α gene. The sensitivity testing also demonstrated high sensitivity, enabling detection of one copy of standard DNA with good reproducibility. Furthermore, both assays were shown to be extremely sensitive even when fungal cells were mixed with human cells, detecting 3 germinated conidia spiked in 3mL of human blood. To apply our new real-time PCR system to the molecular diagnosis of fusariosis, we evaluated its efficacy using a mouse model of invasive F. solani infection. Plasma and whole blood samples of infected mice were tested using the real-time PCR system. The sensitivity of the real-time PCR system was found to be 100% (n=4) in plasma samples. In contrast, no amplification signal was detected in whole blood samples. This system could provide a rapid and precise diagnostic tool for early diagnosis, which is necessary for appropriate treatment and improvement of prognosis of disseminated fusariosis.