Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers.

PURPOSE: The prompt initiation of a betalactam antibiotic in febrile neutropenic patients is considered standard of care, while the empiric use of vancomycin is recommended by guidelines in specific situations, with a low level of evidence. The objective of this study was to assess the utilization of vancomycin in the management of febrile neutropenia within four Brazilian medical centers that implemented more stringent criteria for its administration. METHODS: A comprehensive retrospective analysis was performed encompassing all instances of febrile neutropenia observed during the period from 2013 to 2019. The primary focus was to identify the reasons for initiating vancomycin therapy. RESULTS: A total of 536 consecutive episodes of febrile neutropenia were documented, involving 384 patients with a median age of 52 years (range 18-86). Chemotherapy preceded febrile neutropenia in 59.7% of cases, while 40.3% occurred after hematopoietic stem cell transplantation. The most prevalent underlying diseases were acute myeloid leukemia (26.5%) and non-Hodgkin's lymphoma (22%). According to international guidelines, vancomycin should have been initiated at the onset of fever in 145 episodes (27%); however, it was administered in only 27 cases (5.0%). Three episodes were associated with Staphylococcus aureus bacteremia, two of which were methicillin resistant. The 15-day and 30-day mortality rates were 5.0% and 9.9%, respectively. CONCLUSIONS: The results of this study underscore the notably low utilization rate of vancomycin in cases of febrile neutropenia, despite clear indications outlined in established guidelines. These findings emphasize the importance of carefully implementing guideline recommendations, considering local epidemiological factors, especially when the strength of recommendation is weak.

Infections in patients with chronic lymphocytic leukemia

ABSTRACT Introduction: Infection is a major complication in patients with chronic lymphocytic leukemia (CLL). Newly diagnosed patients are at high risk of developing infection caused by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophylus influenzae. Method and Results: However, once treatment is initiated, the spectrum of pathogens causing infection broadens, depending on the treatment regimens. With disease progression, cumulative immunosuppression occurs as a consequence of multiple treatment lines and the risk of infection further increases. On the other hand, the use of targeted therapies in the treatment of CLL have brought new risks of infection, with an increased incidence of invasive fungal diseases, particularly aspergillosis, in patients receiving Bruton kinase inhibitors. Conclusion: In this article, we review the epidemiology of infection in patients with CLL, taking into account the treatment regimen, and briefly discuss the management of infection.

Infections in patients with chronic lymphocytic leukemia.

INTRODUCTION: Infection is a major complication in patients with chronic lymphocytic leukemia (CLL). Newly diagnosed patients are at high risk of developing infection caused by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophylus influenzae. METHOD AND RESULTS: However, once treatment is initiated, the spectrum of pathogens causing infection broadens, depending on the treatment regimens. With disease progression, cumulative immunosuppression occurs as a consequence of multiple treatment lines and the risk of infection further increases. On the other hand, the use of targeted therapies in the treatment of CLL have brought new risks of infection, with an increased incidence of invasive fungal diseases, particularly aspergillosis, in patients receiving Bruton kinase inhibitors. CONCLUSION: In this article, we review the epidemiology of infection in patients with CLL, taking into account the treatment regimen, and briefly discuss the management of infection.

Should patients with acute myeloid leukemia treated with venetoclax-based regimens receive antifungal prophylaxis?

Invasive fungal disease (IFD) is a major complication in patients with acute myeloid leukemia (AML) receiving intensive induction chemotherapy, and the use of anti-mold prophylaxis is considered standard of care. On the other hand, the use of anti-mold prophylaxis in AML patients receiving less-intensive venetoclax-based regimens is not well established, basically because the incidence of IFD may not be high enough to justify primary antifungal prophylaxis. Furthermore, dose adjustments in venetoclax are needed because of drug interactions with azoles. Finally, the use of azoles is associated with toxicity, including liver, gastrointestinal and cardiac (QT prolongation) toxicity. In a setting of low incidence of invasive fungal disease, the number needed to harm would be higher than the number needed to treat. In this paper we review the risk factors for IFD in AML patients receiving intensive chemotherapeutic regimens, the incidence and risk factors for IFD in patients receiving hypomethylating agents alone, and in patients receiving less-intensive venetoclax-based regimens. We also discuss potential problems with the concomitant use of azoles, and present our perspective on how to manage AML patients receiving venetoclax-based regimens without primary antifungal prophylaxis.

Evaluation of the knowledge of hematologists about the management of infectious complications in hematologic patients.

INTRODUCTION: Infection is a serious complication among patients with hematologic malignancies (HMs) and in hematopoietic cell transplant (HCT) recipients. In most centers, the management of these complications is provided by the hematologist in person, thus demanding a knowledge of basic aspects of infection. METHODS: To evaluate the knowledge of the hematologist on infections, we invited clinicians to answer two questionnaires with 20 multiple-choice questions covering epidemiology, prophylaxis, diagnosis and treatment of infection in patients with HMs and HCT. RESULTS: We obtained 289 answers: 223 in survey 1 (febrile neutropenia) and 66 in survey 2 (infection in HCT). The median score was 5.0 in both surveys (range 0.5 - 9.0). In survey 1, the questions with the lowest number of correct answers were Q3 (8%), concerning the cefepime dose, and Q1 (9%), which asked about the epidemiologic link between the use of high dose cytarabine and viridans streptococcal bacteremia. In survey 2, two questions about cytomegalovirus (CMV) infection had the lowest percentage of correct answers (Q4, 12% and Q11, 18%). Clinicians attending to HCT recipients had higher scores, compared to clinicians attending to patients with HM only (median score of 5.0 and 4.5, p = 0.03, in survey 1 and 6.0 and 4.5, p = 0.001, in survey 2). In both surveys staff clinicians, residents and professors had similar scores. CONCLUSION: This is the first study in Brazil assessing the knowledge of hematologists on infectious complications. The low median score overall indicates an urgent need for continuous education. Such initiatives will eventually result in better patient care.

Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS) questionnaire: translation, cultural adaptation and validation to Brazilian Portuguese

ABSTRACT Introduction: Constitutional symptoms and thrombohemorrhagic events are common in patients with myeloproliferative neoplasms (MPNs). Hence, the treatment's primary goal is to control symptoms and improve the quality of life (QoL). In order to assess response to therapy, symptom burden, and QoL among patients with MPN, the "Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)" questionnaire was developed in the USA in 2012. Herein, we translated and validated the MPN-SAF TSS questionnaire to Brazilian Portuguese. Methods: The ten-item questionnaire was translated from the English language and its psychometric properties (reliability, convergent and construct validities) were evaluated in 101 MPN patients. Results: There were 41 patients with essential thrombocythemia, 39 with myelofibrosis and 21 with polycythemia vera. The median age of all patients at diagnosis was 68 years and 59% were female. The Cronbach's alpha coefficient for the overall questionnaire was 0.78, ranging from 0.73 to 0.79, if each item was deleted. Validity analyses showed that the strongest item-item correlation were between early satiety and abdominal discomfort. Strong correlations were also found between physician and patient perceptions of itching (r = 0.81) and fatigue (r = 0.70). The Pearson coefficient correlation between the MPN-SAF TSS global score and the EORTC QLQ-C30 functional scales ranged from 0.51 to 0.64. The exploratory factor analysis showed that seven of the ten symptoms loaded into one single factor. Conclusion: The Brazilian Portuguese version of the MPN-SAF-TSS showed good psychometric properties and can be an available tool to assess symptom burden in this group of patients.

Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS) questionnaire: translation, cultural adaptation and validation to Brazilian Portuguese.

INTRODUCTION: Constitutional symptoms and thrombohemorrhagic events are common in patients with myeloproliferative neoplasms (MPNs). Hence, the treatment's primary goal is to control symptoms and improve the quality of life (QoL). In order to assess response to therapy, symptom burden, and QoL among patients with MPN, the "Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)" questionnaire was developed in the USA in 2012. Herein, we translated and validated the MPN-SAF TSS questionnaire to Brazilian Portuguese. METHODS: The ten-item questionnaire was translated from the English language and its psychometric properties (reliability, convergent and construct validities) were evaluated in 101 MPN patients. RESULTS: There were 41 patients with essential thrombocythemia, 39 with myelofibrosis and 21 with polycythemia vera. The median age of all patients at diagnosis was 68 years and 59% were female. The Cronbach's alpha coefficient for the overall questionnaire was 0.78, ranging from 0.73 to 0.79, if each item was deleted. Validity analyses showed that the strongest item-item correlation were between early satiety and abdominal discomfort. Strong correlations were also found between physician and patient perceptions of itching (r=0.81) and fatigue (r=0.70). The Pearson coefficient correlation between the MPN-SAF TSS global score and the EORTC QLQ-C30 functional scales ranged from 0.51 to 0.64. The exploratory factor analysis showed that seven of the ten symptoms loaded into one single factor. CONCLUSION: The Brazilian Portuguese version of the MPN-SAF-TSS showed good psychometric properties and can be an available tool to assess symptom burden in this group of patients.

Early versus Late Fluconazole Prophylaxis in Autologous Hematopoietic Cell Transplantation.

Candidemia is a major complication in hematopoietic cell transplantation (HCT), and antifungal prophylaxis with fluconazole decreases the incidence of this complication. We compared 2 strategies for fluconazole prophylaxis in patients with hematologic malignancy undergoing autologous HCT between 1997 and 2017. From 1997 to 2003, fluconazole prophylaxis (400 mg/d) was given to all HCTs, started with the conditioning regimen (early prophylaxis), and given until neutrophil engraftment or the need of non-prophylactic antifungal therapy. From 2004 on, fluconazole (400mg daily) was started only if (and when) the patient developed oral mucositis (late prophylaxis). Among 571 HCT, 270 received early prophylaxis, 112 received late prophylaxis, and 189 did not receive fluconazole because they did not develop oral mucositis. The incidence of candidemia was 1.8% in the early prophylaxis group, 0% in the late prophylaxis group, and 1.1% in the no prophylaxis group (P = .31). Among patients receiving fluconazole, the median duration of prophylaxis was 17 days (range, 6-36 days) in the early prophylaxis group and 6 days (range, 2-16 days) in the late prophylaxis group (P < .001). The initiation of fluconazole prophylaxis guided by the occurrence of oral mucositis (late prophylaxis) was as good as early fluconazole prophylaxis.

EQUAL Fusariosis score 2021: An European Confederation of Medical Mycology score derived from current guidelines to measure QUALity of the clinical management of invasive fusariosis.

BACKGROUND: Invasive fusariosis is a serious infection affecting mostly patients with haematologic malignancies and hematopoietic cell transplant recipients. OBJECTIVES: To develop a scoring tool that evaluates guideline adherence in the management of invasive fusariosis. METHODS: We reviewed two guidelines, provided by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM), and selected the strongest recommendations for management quality as the bases for the scoring tool. RESULTS: We reviewed the recommendations regarding primary and secondary prophylaxis, diagnostics procedures (images, blood cultures, biopsy of skin lesions with direct examination, culture and histopathology, species identification, antifungal susceptibility tests and antigen detection), treatment choices and follow-up procedures. The tool comprises 18 items, with a maximum of 24 points. CONCLUSIONS: The EQUAL score Fusariosis is a tool that may help clinicians to measure guidelines adherence.

Shock and Early Death in Hematologic Patients with Febrile Neutropenia.

Empirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data. In order to characterize the epidemiology of early death and shock in FN, we reviewed all episodes of FN from 2003 to 2017 at University Hospital, Federal University of Rio de Janeiro, and looked at factors associated with shock at first fever and early death (within 3 days from first fever) by univariate and multivariate analyses. Among 1,305 episodes of FN, shock occurred in 42 episodes (3.2%) and early death in 15 (1.1%). Predictors of shock were bacteremia due to Escherichia coli (odds ratio [OR], 8.47; 95% confidence interval [95% CI], 4.08 to 17.55; P < 0.001), Enterobacter sp. (OR, 7.53; 95% CI, 1.60 to 35.33; P = 0.01), and Acinetobacter sp. (OR, 6.95; 95% CI, 1.49 to 32.36; P = 0.01). Factors associated with early death were non-Hodgkin's lymphoma (OR, 3.57; 95% CI, 1.18 to 10.73; P = 0.02), pneumonia (OR, 21.36; 95% CI, 5.72 to 79.72; P < 0.001), shock (OR, 11.64: 95% CI, 2.77 to 48.86; P = 0.01), and bacteremia due to Klebsiella pneumoniae (OR, 5.91; 95% CI, 1.11 to 31.47; P = 0.03). Adequate empirical antibiotic therapy was protective (OR, 0.23; 95% CI, 0.07 to 0.81; P = 0.02). Shock or early death was not associated with Gram-positive bacteremia; catheter-related, skin, or soft tissue infection; or inadequate Gram-positive coverage. These data challenge guideline recommendations for the empirical use of vancomycin at first fever in neutropenic patients.