Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study.

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.

Clinical and Microbiological Characteristics of Febrile Neutropenia During Induction Chemotherapy in Adults With Acute Leukemia.

BACKGROUND: Few studies regarding infectious causes of febrile neutropenia (FN) in Mexico are available. AIMS: We aimed to describe clinical and microbiological characteristics of FN episodes during induction chemotherapy in adults with acute leukemia. METHODS AND RESULTS: This retrospective cohort from a Mexican tertiary care center included adults with newly diagnosed acute leukemia between January 2014, and December 2018. Clinical and microbiological characteristics were summarized using descriptive statistics. Univariate analyses for associations between clinical characteristics and FN and/or death were made; logistic regression analysis was performed to assess relationships with FN. Kaplan-Meier survival estimates were modeled for antimicrobial prophylaxis and FN. Ninety-five patients were included. Median age was 28 (IQR 20-43), 49 (52%) were males, and 74 (78%) developed FN (74/95). Among these, 98% had an identified source of infection (73/74) and 65% had >1. Common infections were urinary tract infection (24%), bacterial sinusitis (20%), and bacterial pneumonia (19%). Gram-negatives were the most frequently isolated microorganisms (69%), followed by Gram-positives (21%), and fungi (9%). Antimicrobial prophylaxis was inversely associated with FN (aOR = 0.07, CI 0.008-0.060, p = 0.02). Invasive fungal diseases were associated with 30-day mortality (aOR = 9.46, 95% CI 1.66-54.05). CONCLUSION: Infections caused 98% of the FN episodes. Gram-negative bacteria are the most common pathogens.

Yield of repeat blood cultures in acute myeloid leukemia patients with febrile neutropenia and bacteremia following allogeneic hematopoietic stem cell transplant.

INTRODUCTION: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. RESULTS: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. CONCLUSION: Among bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low.

[Microorganisms isolated from blood cultures and resistance profile in children with cancer and high-risk febrile neutropenia. Red PINDA, Chile, 2016-2021]. / Microorganismos aislados de hemocultivos y su perfil de resistencia en niños con cáncer y neutropenia febril de alto riesgo. Red PINDA, Chile, 2016-2021.

Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

Application value of metagenomic next-generation sequencing in hematological patients with high-risk febrile neutropenia.

Background: Metagenomic next-generation sequencing (mNGS) is a novel non-invasive and comprehensive technique for etiological diagnosis of infectious diseases. However, its practical significance has been seldom reported in the context of hematological patients with high-risk febrile neutropenia, a unique patient group characterized by neutropenia and compromised immune responses. Methods: This retrospective study evaluated the results of plasma cfDNA sequencing in 164 hematological patients with high-risk febrile neutropenia. We assessed the diagnostic efficacy and clinical impact of mNGS, comparing it with conventional microbiological tests. Results: mNGS identified 68 different pathogens in 111 patients, whereas conventional methods detected only 17 pathogen types in 36 patients. mNGS exhibited a significantly higher positive detection rate than conventional methods (67.7% vs. 22.0%, P < 0.001). This improvement was consistent across bacterial (30.5% vs. 9.1%), fungal (19.5% vs. 4.3%), and viral (37.2% vs. 9.1%) infections (P < 0.001 for all comparisons). The anti-infective treatment strategies were adjusted for 51.2% (84/164) of the patients based on the mNGS results. Conclusions: mNGS of plasma cfDNA offers substantial promise for the early detection of pathogens and the timely optimization of anti-infective therapies in hematological patients with high-risk febrile neutropenia.

Risk factors for resistant gram-positive bacteremia in febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. METHODS: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. RESULTS: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. CONCLUSIONS: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.

Mortality in patients with hematological malignancies, febrile neutropenia, and septic shock.

INTRODUCTION: Patients with severe neutropenia who develop septic shock (SS) have high mortality. This study aimed to evaluate the risk factors and mortality of SS in patients with HM and febrile neutropenia. METHODOLOGY: We included all patients with hematological malignancies (HM) who presented fever and severe neutropenia, admitted to an oncological tertiary care center in Mexico City for one year. RESULTS: Two hundred ninety-two episodes of fever and severe neutropenia were documented; 68 patients (23.2%) developed SS. Documented clinical infection was different between SS and non-SS patients (94.1% vs. 63.4%, p < 0.001); pneumonia was the most frequent infection (36.8% vs. 23.2%, p = 0.02). Also, in SS vs. non-SS, there were more positive cultures (69.1% vs. 38.4%, p < 0.001), higher frequency of Gram-negative bacteria (89.3% vs. 63.9%, p < 0.001), particularly Escherichia coli (68% vs. 44.2%) and Klebsiella spp. (23.4% vs. 15.1%). There were no differences when multidrug-resistant (MDR) microorganisms were compared. In the multivariate analysis, associated risk factors for SS were: prolonged neutropenia, a documented site of infection, and having received highly myelosuppressive chemotherapy. Risk factors for mortality at 30 days were: older patients, prolonged neutropenia, and SS. CONCLUSIONS: Severe and prolonged neutropenia was associated with SS development and mortality at 30 days. ICU management should be offered to all critically ill patients with HM if long-term survival of the underlying malignancy is expected.

Analysis of bacteremia at first-line antibiotic treatment for febrile neutropenia in children and adolescents: A retrospective, single-center analysis.

BACKGROUND: Control of bacterial and fungal infections is critical to improving outcomes in hematological neoplastic diseases of children and adolescents. In this study, a retrospective analysis of our previous studies on febrile neutropenia was performed to investigate bacteremia. PROCEDURE: From August 2008 to December 2023, five antibiotic studies were performed for febrile and neutropenic pediatric patients who had been treated with chemotherapy, immunosuppressive therapy, or had received stem cell transplantation in the pediatric unit at Sapporo Hokuyu Hospital. The rate of positive blood culture, detected bacteria, and susceptibility of several types of antibiotics in febrile episodes were investigated. RESULTS: Blood culture was positive in 133 of 1604 febrile episodes of 329 patients. Detected bacteria were Gram-positive cocci (61.2 %), Gram-negative bacilli (27.6 %), Gram-negative cocci (0.7 %), and Gram-positive bacilli (10.4 %). The incidence of bacteremia over time showed a decreasing trend with each passing year. In particular, the incidence of bacteremia was around 10 % in 2008-2013, whereas it was often below 5 % after 2020; this decrease was statistically significant. Although almost all detected bacteria and their susceptibilities to antibiotics (piperacillin/tazobactam, meropenem, ceftazidime, and cefozopran) did not change over time, all Escherichia coli detected after 2014 were extended-spectrum ß-lactamase-producing bacteria.

Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019).

BACKGROUND: The use of ill-suited antibiotics is a significant risk factor behind the increase in the mortality, morbidity, and economic burden for patients who are under treatment for hematological malignancy (HM) and bloodstream infections (BSI). Such unfitting treatment choices intensify the evolution of resistant variants which is a public health concern due to possible healthcare-associated infection spread to the general population. Hence, this study aims to evaluate antibiograms of patients with BSI and risk factors associated with septicemia. METHODS: A total of 1166 febrile neutropenia episodes (FNE) among 513 patients with HM from the National Center for Cancer Care and Research (NCCCR), Qatar, during 2009-2019 were used for this study. The socio-demographic, clinical, microbial, and anti-microbial data retrieved from the patient's health records were used. RESULTS: We analyzed the sensitivity of gram-negative and gram-positive bacilli reported in HM-FN-BSI patients. Out of the total 512 microorganisms isolated, 416 (81%) were gram-negative bacteria (GNB), 76 (15%) were gram-positive bacteria (GPB) and 20 (4%) were fungi. Furthermore, in 416 GNB, 298 (71.6%) were Enterobacteriaceae sp. among which 121 (41%) were ESBL (Extended Spectrum Beta-Lactamase) resistant to Cephalosporine third generation and Piperacillin-Tazobactam, 54 (18%) were Carbapenem-resistant or multidrug-resistant organism (MDRO). It's noteworthy that the predominant infectious agents in our hospital include E. coli, Klebsiella species, and P. aeruginosa. Throughout the study period, the mortality rate due to BSI was 23%. Risk factors that show a significant correlation with death are age, disease status, mono or polymicrobial BSI and septic shock. CONCLUSION: Decision pertaining to the usage of antimicrobials for HM-FN-BSI patients is a critical task that relies on the latest pattern of prevalence, treatment resistance, and clinical outcomes. Analysis of the antibiogram of HM-FN-BSI patients in Qatar calls for a reconsideration of currently followed empirical antibiotic therapy towards better infection control and antimicrobial stewardship.

Procalcitonin versus C-Reactive Protein as a Biomarker for Prediction of Bacterial Infection in Children with Febrile Neutropenia in Acute Leukemia.

Febrile neutropenia (FN) is a frequently occurring treatment-related complication with significant morbidity and mortality for childhood acute leukemia. Early diagnosis and assessment of severity are essential steps for early comprehensive treatment to reduce FN-related morbidity and mortality. Biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) can be used to assess and predict the bacterial infection in children with febrile neutropenia. The objective of the study was to determine the role of procalcitonin and CRP as a biomarker for prediction of bacterial infection in children with FN in acute leukemia. This prospective observational study was conducted in the Department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from August 2020 to July 2021. Total 58 Children with acute leukemia aged 1 to <18 years with FN were analyzed in this study. A proper history and thorough physical examination were carried out. The blood sample was sent for biomarkers (Procalcitonin and CRP) within 24 hours of the onset of FN and other investigations, such as Complete blood count, Blood C/S, Urine R/E and C/S. Metabolic workup (SGPT, Serum Creatinine, Serum Electrolytes, Serum Ca+) was also done in every patient. Stool R/E & C/S, Chest X-ray, Wound swab for C/S were done when the patient presented with diarrhoea, cough, respiratory distress and focal sepsis respectively. In this study, the mean age of the patients was 6.62±4.07 years (1.10-16.0 years) and 34 patients (58.6%) were male. In 65.5% of patients, localizing signs of infection were not identified. Of the 58 patients, 12 patients (20.7%) showed positive blood culture and 2 patients (3.4%) showed positive urine culture. Klebsiella spp (41.0%) was the most frequent organism isolated followed by Acinetobacter (17.0%), Pseudomonas (17.0%) and E. coli (17.0%). The median PCT levels were significantly higher in patients with bacterial infection than patients without bacteremia (26.10µg/l versus 0.78µg/l, p=0.002) and PCT level >2µg/l was significantly associated with bacteremia. The median CRP levels in the bacteremia and without-bacteremia patients were 137.4mg/L and 54.17mg/L, respectively (p=0.036). In direct comparisons, PCT showed better overall performance than CRP with the AUC being 0.797 (95% CI 0.651-0.943) for PCT and 0.697 (95% CI 0.54-0.855) for CRP in predicting the bacterial infection. PCT and CRP both are useful biomarkers for the prediction of bacteremia, but PCT may be a superior early biomarker as compared to CRP to predict bacterial infection in children with febrile neutropenia in acute leukemia.

The use of serum endothelial adhesion molecules in pediatric patients with leukemia with febrile neutropenia to predict bacteremia.

OBJECTIVE: Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. We aimed to analyze the utility of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF) levels compared with C-reactive protein (CRP) and procalcitonin (PCT) during febrile neutropenia episodes of pediatric patients with leukemia. METHODS: Two plasma samples, on day 0 (initial of episode) and day 3 (48-72 h after episode), for VCAM-1, ICAM-1 and VEGF, CRP and PCT were prospectively collected concomitantly during each febrile neutropenic episode between December 2016 and December 2017. The primary outcome was bacteremia and the secondary outcome was intensive care unit (ICU) admission. RESULTS: Twenty-two (28.6%) acute lymphoblastic lymphoma (ALL), seventeen (22.1%) acute myeloblastic lymphoma (AML) patients and thirty-eight (49.3%) control patients with no known underlying disease or fever were included in this study. Of the 39 patients; 16 (41%) had bacteremia. Mean serum sVCAM1 and sICAM1 levels were significantly higher in control group, compared to FN patients (p < 0.001). Mean serum sVCAM2 level was significantly higher in FN patients with bacteremia compared to FN patients without bacteremia (144.97 ± 70.35 pg/mL vs 85.45 ± 53.76 pg/mL, p = 0.022). Mean sVCAM1 and 2 levels were higher in FN patients with ICU admission. In this study, we found that sVCAM-1 and VEGF, when combined to CRP and PCT, could predict gram-negative bacteremia in FN episodes of pediatric hematological malignancy. CONCLUSION: Serum endothelial adhesion molecules, excluding sVCAM-1, cannot predict bacteremia and ICU admission alone in FN patients; but may be associated with clinical outcome when used with PCT and CRP.

Viridans Group Streptococci in Pediatric Leukemia and Stem Cell Transplant: Review of a Risk-stratified Guideline for Empiric Vancomycin in Febrile Neutropenia.

Viridans group streptococci (VGS) are an important cause of sepsis in immunosuppressed children. We reviewed the effectiveness of risk-stratified addition of vancomycin to empiric febrile neutropenia therapy among 107 children with leukemia or undergoing an allogeneic transplant. Of 19 VGS bacteremia episodes, 78.9% were susceptible to risk-stratified antibiotics including 100% from high-risk patients. All blood cultures were flagged positive within 24 hours.

Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia.

Objectives: Febrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia. Methods: Thirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8-24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed. Results: The median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8-100%) and specificity of 89% (95% CI 80.0-95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes. Conclusion: Elevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.

Cytokine and chemokine profiles in episodes of persistent high-risk febrile neutropenia in children with cancer.

BACKGROUND: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO). METHODS: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes. RESULTS: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity. CONCLUSION: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Evaluation of Risk Factors for Mortality in Febrile Neutropenia.

INTRODUCTION: We aimed to evaluate the epidemiology of infections and factors associated with mortality in patients with febrile neutropenia (FEN). METHODOLOGY: The adult patients, who developed FEN after chemotherapy due to a hematologic malignancy or a solid tumor in a training and research hospital were evaluated, retrospectively. The demographic data of the patients, underlying malignancy, administered antimicrobial therapy, microbiological findings, and other risk factors associated with mortality were evaluated. RESULTS: A total of 135 FEN episodes of 115 patients, who comprised of 72 (63%) patients with 89 FEN episodes due to hematologic malignancies (hemato-group) and 43 (37%) patients with 46 FEN episodes due to solid organ cancers (onco-group), were evaluated in the study. The median age was 47 years (range: 17-75 years) and 66 (57%) patients were male. A total of 12 patients (8.8%) died during 135 episodes of FEN including nine cases from hemato-group and three cases from onco-group. Those factors including a presence of pneumonia, advanced age, persistent fever despite an antimicrobial treatment, and need for mechanical ventilation in intensive care unit (ICU) with were determined as risk factors associated with mortality. CONCLUSIONS: Morbidity and mortality are more common in patients with hematological malignancies compared to patients with solid organ cancers due to prolonged neutropenia. In case of persistent fever, an invasive fungal infection (IFI) should be kept in mind in patients with hematologic malignancies and then antifungal treatment should be initiated. Although a persistent fever is also common in patients with solid tumors, the necessity of antifungal therapy is rare due to the short duration of neutropenia.

The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia.

Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression profiling was feasible in children with FN who were undergoing cancer treatment. The blood transcriptome of the children (n = 63) was investigated at time of FN diagnosed as viral, bacterial, co-infection or unknown etiology, respectively, and compared to control samples derived from 12 of the patients following the FN episode. RNA sequencing was successful in 43 (68%) of the FN episodes. Only two genes were significantly differentially expressed in the bacterial versus the control group. Significantly up-regulated genes in patients with the other three etiologies versus the control group were enriched with cellular processes related to proliferation and cellular stress response, with no clear enrichment with innate responses to pathogens. Among the significantly down-regulated genes, a few clustered into pathways connected to responses to infection. In the present study of children during cancer treatment, the blood transcriptome was not suitable for determining the etiology of FN because of too few circulating immune cells for reliable gene expression analysis.