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

AbstractIntroductionInvasive 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 methodsBetween 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.ResultsAmong 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.ConclusionA 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

Stewardship program for restricted use of antimicrobials in the elderly: a cohort study in a quaternary hospital in Brazil

Objective: The stewardship strategy refers to a consistent practice to promoting responsible antimicrobial use. Optimizing the use of antibiotics is critical to mitigating adverse effects and combating bacterial resistance. The pillars of a stewardship program include: i) clinical pharmacist and infectologist with expertise; ii) educational measures for prescribers, nurses and pharmacists; iii) prophylaxis and therapeutic protocol; iv) monitoring of indicators. In this scenario of antimicrobial rational use, the older population are more susceptible to infection because immunocenescence and, therefore, greater use of antimicrobials is expected. Thus, the aim of the present study is to evaluate the prescription compliance of antimicrobial whose use is restricted in a hospitalized elderly population. Method: observational, controlled study in a Brazilian hospital, from January 2021 to January 2022. Based on the electrotonic antimicrobial form, the compliance of the prescriptions was evaluated. The definition used for elderly corresponded to individuals over 60 years old, according to the Brazilian Nation Principles for Older Persons, ordinance number 2528, of October 2006. Restricted drugs were considered: carbapenems, polymyxin, ceftazidime-avibactam, linezolid, tigecycline, ceftaroline, echinocandins and amphotericin. Results: A total of 1.688 requests for restricted use were received, of which 53% corresponded use in elderly group. Neutropenic fever was more common in young people and the inpatient unit was the sector with the highest percentage of antimicrobials. Furthermore, teicoplanin was the main drug that required intervention. Conclusion: Faced with the increase in bacterial resistance, the rational use of antimicrobials is extremely important, especially in older age group

Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 2238) and 64% in arm B (95% CI 5771; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. (c) 2012 Wiley Periodicals, Inc.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CNPq (Conselho Nacional do Desenvolvimento Cientifico e Tecnologico)Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro

Recomendações no manejo das complicações infecciosas no transplante de células-tronco hematopoéticas Management of infectious complications after hematopoietic stem cell transplant

A infecção em receptores de transplante de células-tronco hematopoéticas (TCTH) está relacionada a altas taxas de morbidade e mortalidade. O tipo de transplante, a fonte de célula-tronco hematopoética, a utilização de doadores alternativos e outras medidas relacionadas ao procedimento influenciam diretamente no tipo e na intensidade da imunossupressão, modificando o risco de desenvolver uma infecção. Nesta seção são discutidas as estratégias para monitorização, diagnóstico e tratamento das infecções em receptores de TCTH em três fases: na fase pré-transplante, durante a fase de neutropenia, e na fase pós-pega do enxerto.<br>Infectious complications following stem cell transplantation are frequent and associated with high morbidity and mortality. Several factors related to the transplant procedure, such as type of transplant, the source of stem cells, the utilization of alternative donors are important determinants of the immune status of the host, and impact on the risk of infection. In this section we will discuss the different approaches for monitoring patients at risk and diagnosing and treating infectious complications in three time periods: before transplant, during neutropenia, and after engraftment

Earlier Diagnosis of Invasive Fusariosis with Aspergillus Serum Galactomannan Testing

Cross-reactivity of Fusarium species with serum galactomannan antigen (GMI) test has been observed. We sought to evaluate if GMI could help to early diagnose invasive fusariosis and to monitor treatment response. We reviewed the records of all patients with invasive fusariosis between 2008 and 2012 in three Brazilian hospitals. We selected patients who had at least 1 GMI test within 2 days before or after the date of the first clinical manifestation of fusariosis, and analyzed the temporal relationship between the first positive GMI test and the date of the diagnosis of invasive fusariosis, and the kinetics of GMI in relation to patients' response to treatment. We also selected 18 controls to determine the sensitivity and specificity of the test. Among 18 patients, 15 (83%) had at least one positive GMI (median 4, range 1-15). the sensitivity and specificity of was 83% and 67%, respectively. GMI was positive before the diagnosis of invasive fusariosis in 11 of the 15 cases (73%), at a median of 10 days (range 3-39), and after the diagnosis in 4 cases. GMI became negative in 8 of the 15 patients; 3 of these 8 patients (37.5%) were alive 90 days after the diagnosis of fusariosis compared with 2 of 7 (29%) who did not normalize GMI (p = 1.0). GMI is frequently positive in invasive fusariosis, and becomes positive before diagnosis in most patients. These findings may have important implications for the choice of antifungal therapy in settings with high prevalence of invasive fusariosis

Characteristics of 18 patients with invasive fusariosis.

*<p>Other underlying disease (1 case each): non-Hodgkin's lymphoma, chronic myeloid leukemia, aplastic anemia, myelodysplasia, chronic lymphoid leukemia, and myelofibrosis</p><p>HCT =  hematopoietic cell transplantation</p>**<p>Within 4 weeks before the diagnosis of invasive fusariosis.</p