A Risk-Prediction Nomogram for Neutropenia or Febrile Neutropenia after Etoposide-Based Chemotherapy in Cancer Patients: A Retrospective Cohort Study.

INTRODUCTION: This study was conducted to develop and validate a nomogram for predicting the risk of neutropenia or febrile neutropenia (FN) in tumor patients in the first cycle of etoposide-based chemotherapy. METHODS: This retrospective cohort study used an information system to monitor patients with non-Hodgkin's lymphoma or solid tumors receiving an etoposide regimen in the first chemotherapy cycle in our hospital from 2009 to 2020. Binary logistic regression analysis was used to identify the influencing factors of patients with neutropenia or FN. Those factors were then used to develop a nomogram. RESULTS: A total of 1,554 patients were divided into the development group (n = 1,072) and validation group (n = 482). Variables used to predict neutropenia or FN were Karnofsky performance status (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.81-0.89, p < 0.01), metastatic sites ≥3 (OR = 6.33, 95% CI = 2.66-15.11, p < 0.01), comorbidity of heart disease (OR = 4.88, 95% CI = 1.74-13.67, p < 0.01), recent surgery (OR = 7.96, 95% CI = 1.96-32.36, p < 0.01), administration of alkylating agents (OR = 4.50, 95% CI = 1.10-18.48, p < 0.01), total bilirubin ≥25 µmol/L (OR = 11.42, 95% CI = 4.00-32.61, p < 0.01), and lymphocyte count <0.7 × 109/L (OR = 4.22, 95% CI = 2.00-9.75, p < 0.01). CONCLUSION: This model can aid the early identification and screening of the potential risk of neutropenia or FN in the first cycle of treatment for patients using etoposide-based chemotherapy.

Survival of a case of Bacillus cereus meningitis with brain abscess presenting as immune reconstitution syndrome after febrile neutropenia - a case report and literature review.

BACKGROUND: Bacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome. CASE PRESENTATION: A 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC <100/µL, neutrophils 0/µL) and lumbar puncture yielded only mild pleocytosis. She was transferred to intensive care unit, and meropenem, linezolid and vancomycin was started. With intensive therapy, she recovered and once became afebrile. On day 19, however, her fever, meningism and consciousness level dramatically worsened despite recovery of bone marrow function. The antimicrobial chemotherapy was continued and finally she was cured with no complications. CONCLUSIONS: With early diagnosis and prompt initiation and of antibiotics, the case was successfully treated without any sequelae. It is important to remember that, even under optimal antimicrobial therapy, bone marrow recovery can cause transient reaggravation of the disease. In such cases, timely and appropriate evaluation should be done to make the clinical decision to change, continue, or intensify treatment.

Usefulness of serum galactomannan in initiating and modifying antifungal therapy in children with cancer and persistent high-risk febrile neutropenia.

BACKGROUND: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population. OBJECTIVES: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN. PATIENTS/METHODS: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds. RESULTS: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04). CONCLUSIONS: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

Intravenous itraconazole compared with liposomal amphotericin B as empirical antifungal therapy in patients with neutropaenia and persistent fever.

BACKGROUND: Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required. OBJECTIVE: We conducted a multicentre, open-label, randomised, non-inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever. METHODS: Patients with haematological malignancies who developed fever refractory to broad-spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d). RESULTS: Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model-based estimate of a 4% difference (90% CI, -12% to 20%), did not fulfil the statistical non-inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3-4 hypokalaemia-related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07). CONCLUSION: ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non-inferiority.

Evaluation of pharmacokinetic/pharmacodynamic and clinical outcomes with 6-hourly empiric piperacillin-tazobactam dosing in hematological malignancy patients with febrile neutropenia.

BACKGROUND: Piperacillin-tazobactam is commonly used in neutropenic sepsis at standard doses that do not account for inter-individual differences in age, bodyweight and renal function. This study was designed to assess the rate of attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets in patients receiving piperacillin/tazobactam therapy and to evaluate the effect on clinical outcomes. METHODS: Patients undergoing intensive chemotherapy for aggressive hematological malignancies were enrolled and treated with piperacillin/tazobactam 4 g/0.5 g every 6 h as initial antimicrobial therapy for first fever. Plasma drug concentrations were assayed at 50% and 100% of the dosing interval and compared with target MIC breakpoint of 16 mg/L to calculate the primary endpoints of 50% and 100% time above MIC (fT > MIC), respectively. Secondary endpoints included time to clinical cure, length of hospital stay, duration of antibiotics, and clinical treatment success. RESULTS: Fifty-eight percent (14/24) of patients achieved 50% fT > MIC while only 4% (1/24) achieved 100% fT > MIC. Higher creatinine clearance was significantly associated with lower trough drug concentration and appeared to be the dominant reason for the poor PK/PD target attainment. Median time to clinical cure, duration of antibiotic therapy, and hospital length of stay was 3, 13 and 21 days, respectively. There were no statistically significant differences in these outcomes between patients who did and did not achieve 100% fT > MIC. CONCLUSIONS: A significant majority of febrile neutropenic patients fail to achieve PK/PD targets with 6-hourly piperacillin dosing, although the clinical implications of this finding are unclear. Larger studies are needed to assess any impact on morbidity and mortality. This trial is registered on the ANZCTR (ACTRN12618000110280).

Pelvic cellulitis caused by Raoultella planticola in a neutropenic patient.

Raoultella planticola is a gram-negative, encapsulated, aerobic bacterium within the Enterobacteriaceae family. It has been primarily described as pathogen in cases with pneumonia and gastrointestinal infections. Here we describe a case of severe pelvic cellulitis in a patient with neutropenia following induction therapy for myeloid sarcoma. The patient experienced a septic shock and was treated successfully with antibiotic therapy. A literature review is provided to put this case in context with previous reports on R. planticola. This report highlights that awareness for uncommon pathogens is crucial in the clinical management of infections in neutropenic patients.

Liver abscess due to Sterigmatomyces halophilus in a boy with acute lymphoblastic leukemia.

We report the first case of liver abscess due to Sterigmatomyces halophilus. Because this pathogen grows poorly in culture medium without added salts, it was identified by sequencing analysis targeting the rRNA gene internal transcribed spacer (ITS) region. This method could be useful for pathogens that cannot be cultured using standard methods.

Risk factors for bacteremia in children with febrile neutropenia

Background/aim: Bacteremia remains an important cause of morbidity and mortality during febrile neutropenia (FN) episodes. We aimed to define the risk factors for bacteremia in febrile neutropenic children with hemato-oncological malignancies. Materials and methods: The records of 150 patients aged ≤18 years who developed FN in hematology and oncology clinics were retrospectively evaluated. Patients with bacteremia were compared to patients with negative blood cultures. Results: The mean age of the patients was 7.5 ± 4.8 years. Leukemia was more prevalent than solid tumors (61.3% vs. 38.7%). Bacteremia was present in 23.3% of the patients. Coagulase-negative staphylococci were the most frequently isolated microorganism. Leukopenia, severe neutropenia, positive peripheral blood and central line cultures during the previous 3 months, presence of a central line, previous FN episode(s), hypotension, tachycardia, and tachypnea were found to be risk factors for bacteremia. Positive central line cultures during the previous 3 months and presence of previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. Conclusion: Presence of a bacterial growth in central line cultures during the previous 3 months and presence of any previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. These factors can predict bacteremia in children with FN.

Predictive Indicators to Identify High-Risk Paediatric Febrile Neutropenia in Paediatric Oncology Patients in a Middle-Income Country.

PURPOSE: To validate a clinical risk prediction score (Ammann score) to predict adverse events (AEs) in paediatric febrile neutropenia (FN). PATIENTS AND METHODS: Patients <16 years of age were enrolled. A risk prediction score (based on haemoglobin ≥ 9 g/dl, white cell count (WCC) < 0.3 G/l, platelet count <50 G/l and chemotherapy more intensive than acute lymphoblastic leukaemia maintenance therapy) was calculated and AEs were documented. RESULTS: In total, 100 FN episodes occurred in 52 patients, male:female ratio was 1.8:1 and median age was 56 months. At reassessment, AEs occurred in 18 of 55 (45%) low-risk FN episodes (score < 9) and 21 of 42 (55%) high-risk episodes (score ≥9) (sensitivity 60%, specificity 65%, positive predictive value 53%, negative predictive value 71%). Total WCC and absolute monocyte count (AMC) were significantly associated with AEs. CONCLUSION: This study identified total WCC and AMC as significantly associated with AEs but failed to validate the risk prediction score.

Combinational approach using in situ hybridization targeting 23S ribosomal RNA genes and blood cultures for bacterial identification in patients with neutropenia and fever.

BACKGROUND: A new 23S ribosomal RNA genes-targeted in situ hybridization (ISH) probe to detect global bacterial genomic DNA (59 species from 35 genera; referred to as the GB probe) phagocytized in leukocytes was recently developed. This method provided early and direct evidence of bacterial infection with high sensitivity and specificity in spontaneous bacterial peritonitis ascites. However, the utility of this method in febrile neutropenia (FN) is unknown. METHODS: We prospectively evaluated the utility of the ISH approach using the GB probe and previously reported probes in patients with neutropenia and fever undergoing chemotherapy at our institution between June 2011 and July 2013. Blood samples for culture analysis and ISH tests were collected simultaneously at the onset of fever; the latter were performed repeatedly. RESULTS: Fifty febrile episodes were evaluated. In 24 episodes of fever of unknown origin and 15 episodes of local infection (all negative for blood cultures), ISH tests identified causal bacteria in 21% and 13% of cases, respectively, at the onset of fever. In seven sepsis cases (all positive for blood culture), positive ISH test results at fever onset were achieved in 71%; for two patients with neutrophil counts of 0/µl and 171/µl, respectively, negative results were obtained. CONCLUSIONS: This new ISH approach could prove useful for early detection of bacteria in patients with neutropenia and blood culture-negative, with fever of unknown etiology after chemotherapy. Using this method in combination with blood culture, even in cases with extremely low neutrophil counts, might contribute to better management of FN.

A simple intervention to improve antibiotic treatment times for neutropenic sepsis.

OBJECTIVES: Patients with suspected Neutropenic sepsis require rapid antibiotic administration, but despite extensive education, only 67% of patients received antibiotics within 60 minutes . METHODS: A Neutropenic Sepsis Alert Card was created, as a Patient Specific Directive - this allows nurses to administer antibiotics to specific patients without prior medical review. RESULTS: Since the intervention, 301 patients presented with suspected neutropenic sepsis. 277 patients (92%) received their first dose of intravenous antibiotics within 1 hour of arrival into hospital, compared to 95 out of 143 patients (67%) presenting between January and June of 2014 (p=0.036). CONCLUSION: The Neutropenic Sepsis Alert Card can significantly improve door to antibiotic needle time for chemotherapy patients with suspected neutropenic sepsis. This intervention is inexpensive and easily replicable in other health care organisations.

Quantification of the effect of chemotherapy and steroids on risk of Pneumocystis jiroveci among hospitalized patients with adult T-cell leukaemia.

This study aimed to quantify the risks of Pneumocystis pneumonia (PCP) among adult T-cell leukaemia (ATL) patients without prophylaxis. We used hospital administrative data collected nationwide in Japan over 4 years. The research design was a retrospective cohort study. Subjects were 4369 patients diagnosed with ATL aged 18 years or older. The subjects were categorized into four treatment groups: no agent, chemotherapy, chemotherapy + steroids and steroids. We described the risks of PCP among ATL patients without prophylaxis. Risks of PCP were 3·2% for the no agent group, 9·7% for the chemotherapy group, 10·0% for the chemotherapy + steroids group and 16·6% for the steroids group. Logistic regression analyses showed that the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risk of PCP than did the no agent group [adjusted odds ratio (AOR) 3·30 (1·55-7·02), P = 0·002 for the chemotherapy group; AOR 3·35 (2·18-5·17), P < 0·001 for the chemotherapy + steroids group; AOR 6·12 (3·99-9·38), P < 0·001 for the steroids group]. In conclusion, the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risks of PCP. Prophylaxis for PCP among ATL patients being treated with chemotherapy, chemotherapy + steroids and steroids is highly recommended.

Improving the emergency department management of post-chemotherapy sepsis in haematological malignancy patients.

OBJECTIVE: To review the result of the implementation of treatment protocol for post-chemotherapy sepsis in haematological malignancy patients. DESIGN: Case series with internal comparison. SETTING: Accident and Emergency Department, Queen Elizabeth Hospital, Hong Kong. PATIENTS: Febrile patients presenting to the Accident and Emergency Department with underlying haematological malignancy and receiving chemotherapy within 1 month of Accident and Emergency Department visit between June 2011 and July 2012. Similar cases between June 2010 and May 2011 served as historical referents. MAIN OUTCOME MEASURES: The compliance rate among emergency physicians, the door-to-antibiotic time before and after implementation of the protocol, and the impact of the protocol on Accident and Emergency Department and hospital service. RESULTS: A total of 69 patients were enrolled in the study. Of these, 50 were managed with the treatment protocol while 19 patients were historical referents. Acute myeloid leukaemia was the most commonly encountered malignancy. Overall, 88% of the patients presented with sepsis syndrome. The mean door-to-antibiotic time of those managed with the treatment protocol was 47 minutes versus 300 minutes in the referent group. Overall, 86% of patients in the treatment group met the target door-to-antibiotic time of less than 1 hour. The mean lengths of stay in the emergency department (76 minutes vs 105 minutes) and hospital (11 days vs 15 days) were shorter in those managed with the treatment protocol versus the historical referents. CONCLUSION: Implementation of the protocol can effectively shorten the door-to-antibiotic time to meet the international standard of care in neutropenic sepsis patients. The compliance rate was also high. We proved that effective implementation of the protocol is feasible in a busy emergency department through excellent teamwork between nurses, pharmacists, and emergency physicians.

The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.

A novel scoring system to predict the incidence of invasive fungal disease in salvage chemotherapies for malignant lymphoma.

The requirement of antifungal prophylaxis has not been established in the chemotherapies for malignant lymphoma. This study was conducted to explore the incidence of invasive fungal diseases (IFD) and their risk factors in patients receiving salvage therapies for malignant lymphoma. We retrospectively analyzed 177 consecutive patients who received these therapies (705 courses in total) at our institute. IFD were observed in 16 courses and the incidence was 2.3 %. A multivariate analysis showed that the factors associated with IFD were primary refractoriness (adjusted odds ratio (aOR), 4.22; 95 % confidence interval (CI), 1.38-13.0; p value = 0.012), two (aOR, 10.5, 95 % CI, 1.20-91.7; p = 0.033) or more (aOR, 26.2; 95 % CI, 3.27-210; p = 0.002) previous treatment lines, and the minimum neutrophil count during the therapies equal to or less than 500/µL (aOR, 9.69; 95 % CI, 1.25-74.9; p = 0.030). Using these factors, we created the IFD scoring model by assigning one point to each of primary refractoriness, two previous treatment lines and treatment that caused neutropenia (≤500/µL minimal neutrophil count) and two points to three or more previous treatment lines. The IFD incidence of lower risk group (IFD score <3) was 0.19 % and that of higher (IFD score ≥3) was 9.0 %. In conclusion, adequate prophylaxis for IFD might be required for patients with primary refractoriness, repeated therapies, or therapies which cause neutropenia. Furthermore, the IFD scoring model of this study underscores the need to account for disease and host factors in determining administration of adequate prophylaxis in salvage treatments for malignant lymphoma.

Aztreonam for febrile neutropenia in patients with beta-lactam allergy.

BACKGROUND: Beta-lactam antibiotics are the mainstay of empiric therapy for febrile neutropenia. Aztreonam may benefit certain patients because of a lack of cross-hypersensitivity to penicillins and cephalosporins. This is the first study, to our knowledge, to evaluate the efficacy of aztreonam as monotherapy for febrile neutropenia (FN). METHODS: Our study was a single-center retrospective chart review of patients ≥18 years of age receiving aztreonam for the treatment of FN. Primary outcome was treatment success of aztreonam monotherapy. Secondary analyses included need for modification to antimicrobial therapy, patients transitioned to aztreonam from another empiric regimen, and patients receiving aztreonam in combination with other antibacterial agents. RESULTS: In patients prescribed aztreonam for first fever, 11 of 27 (40.7%) patients who received aztreonam alone and 19 of 40 (47.5%) given aztreonam plus another antibiotic responded within 96 h (P = 0.62). Twenty-four (89%) patients prescribed aztreonam monotherapy were alive when FN resolved or treatment ended. Infectious mortality was low (1 patient, 3.7%). In patients prescribed aztreonam monotherapy following an adverse reaction to cefepime, 6 of 11 (54.5%) responded within 96 h of initiating aztreonam; 10 (91%) were alive when FN resolved or treatment ended. CONCLUSION: Aztreonam monotherapy may be acceptable for use in patients with a history of beta-lactam hypersensitivity or following an adverse reaction with another beta-lactam. Further studies are needed to compare efficacy of aztreonam monotherapy with other therapies for the treatment of FN.

Incidence, treatment, and consequences of chemotherapy-induced febrile neutropenia in the inpatient and outpatient settings.

OBJECTIVE: To examine the incidence, treatment, and consequences of febrile neutropenia across inpatient and outpatient care settings. METHODS: Data were obtained from Humedica's National Electronic Health Record-Derived Longitudinal Patient-Level Database (2007-2010). The study population included adult patients who received myelosuppressive chemotherapy for a solid tumor or non-Hodgkin's lymphoma. For each patient, each chemotherapy regimen course and each cycle within each regimen course was characterized. Febrile neutropenia episodes were identified on a cycle-specific basis based on any of the following: (1) absolute neutrophil count <1.0 × 10(9)/L and evidence of infection or fever; (2) inpatient diagnosis of neutropenia, fever, or infection; (3) outpatient diagnosis of neutropenia and non-prophylactic antimicrobial use; or (4) mention of febrile neutropenia in physician notes. Febrile neutropenia episodes were categorized as inpatient or outpatient based on the initial setting of care (i.e. acute-care inpatient facility vs. ambulatory care facility). Febrile neutropenia consequences included hospital length of stay and mortality (inpatient cases only), as well as number of febrile neutropenia-related outpatient encounters. RESULTS: Among the 2131 patients in this study, 401 experienced a total of 458 febrile neutropenia episodes. Risk of febrile neutropenia during the chemotherapy regimen course was 16.8% (95% CI: 15.3, 18.4). In cycle 1 alone, risk of febrile neutropenia was 8.1% (7.1, 9.3). Most febrile neutropenia episodes (83.2%) were initially treated in the inpatient setting; the hospital mortality rate was 8.1% (5.8, 11.1), and mean hospital length of stay was 8.4 days (7.7, 9.1). Among febrile neutropenia episodes initially treated in the outpatient setting (16.8%), the mean number of outpatient management encounters was 2.6 (2.1, 3.1), most of which were in the physician's office (69.2%) or emergency department (26.9%). CONCLUSIONS: Febrile neutropenia remains a common occurrence among patients receiving myelosuppressive chemotherapy and typically results in extended hospitalization and, for many patients, death. A minority of patients are, however, treated exclusively on an outpatient basis.

A hematology consensus agreement on antifungal strategies for neutropenic patients with hematological malignancies and stem cell transplant recipients. Gruppo Italiano Malattie Ematologiche dell'Adulto, Gruppo Italiano Trapianto di Midollo Osseo, Associazione Italiana Ematologia ed Oncologia Pediatrica, Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Sorveglianza Epidemiologica delle Infezioni Fungine nelle Emopatie Maligne.

In the attempt to establish key therapy definitions and provide shared approaches to invasive fungal diseases in neutropenic patients, trials of empiric, preeemptive and targeted antifungal therapy (EAT, PAT and TAT) were reviewed, and a Consensus Development Conference Project was convened. The Expert-Panel concurred that all antifungal treatments, including EAT, should always follow an adequate diagnostic strategy and that the standard definition of PAT may be misleading: being PAT guided by the results of a diagnostic work-up, it should better be termed diagnostic-driven antifungal therapy (DDAT). The Expert-Panel agreed that radiological findings alone are insufficient for the choice of a TAT and that the identification of the etiologic pathogen is needed. The Consensus Agreement proceeded identifying which clinical and microbiological findings were sufficient to start a DDAT and which were not. Finally, an algorithm to rationalize the choice of antifungal drugs on the basis of clinical manifestations, antifungal prophylaxis, instrumental and laboratory findings was drawn up.