National Study Reveals Gram Negative Bacteremia on Contemporary Pediatric AML Protocol

National Study Reveals Gram Negative Bacteremia on Contemporary Pediatric AML Protocol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article National Study Reveals Gram Negative Bacteremia on Contemporary Pediatric AML Protocol Nira Arad-Cohen, Yoav Messinger, Shlomit Barzilai-Birenboim, Miriam Ben-Harosh, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3953893/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Bacteremia complicates more than 50% of childhood Acute myeloid leukemia (AML) patients with predominantly Gram-positive cocci )GPC). Objectives Assess bacteremia rates, risk factors, causative organisms, and antibiotic resistance in Israeli children with de-novo AML. Methods all chemotherapy courses for patients enrolled in the standard arm of the NOPHO-DBH 2012 AML protocol were included. Down syndrome, myelodysplastic syndrome, acute promyelocytic leukemia, secondary AML, and isolated granulocytic sarcoma were excluded. No routine antibacterial prophylaxis was applied. Results Among 69 patients, 7 had focal bacterial infections. Of the remaining 62, 77.4% had bacteremia episodes, ranging from 1 to 8 per patient. Out of 238 chemotherapy courses, 98 (41.2%) resulted in bacteremia, with 66 (67.3%) courses showing predominantly Gram-negative rods (GNR) and 28 (28.6%) courses with Gram-positive cocci (GPC). The most common was Escherichia coli ; followed by Klebsiella spp. Older age, Arab ethnicity, and presenting white blood cell count were associated with an increased risk of bacteremia in a univariate analysis. Six patients (9.7%) died, 3 of whom were from Gram-negative infection. Bacteremia resulted in a 7-fold increase in intensive care unit admissions. Empiric antibiotic treatment using piperacillin-tazobactam and vancomycin provided sufficient coverage in 75.5% of cases. Improved coverage was attained with amikacin (90.8%) or the combination of vancomycin and meropenem (94.7%). Quinolones were effective against GNR isolates in 42 cases (61.8%). Conclusions De-novo AML patients face high mortality from predominantly GNR bacteremia. Specific interventions are needed to reduce rates, but limited susceptibility to quinolones hampers prophylactic use. acute myeloid leukemia pediatric bacteremia gram-negative rods Figures Figure 1 Figure 2 Introduction Acute myeloid leukemia (AML) accounts for approximately 20% of acute leukemia cases in children and adolescents. The 5-year overall survival of pediatric patients with AML has improved, reaching almost 75% in various clinical trials. This improvement is mainly attributable to refinement in the risk classification, and treatment stratification as well as advances in supportive care [ 1 ]. However, AML chemotherapy is still one of the most intensive treatments in pediatric oncology. It is associated with a prolonged and profound period of neutropenia after each course of chemotherapy leading to a high risk of infections. Bacteremia have been documented in more than 50% of pediatric patients with AML and are associated with severe morbidity and a cumulative mortality that in the past had exceeded 10% [ 2 ]. Among bacteremia events in pediatric AML, Gram-positive cocci (GPC), mainly Viridans Group Streptococci (VGS) are much more prevalent than Gram-negative rods (GNR) [ 3 ][ 4 ]. Risk factors specific to bacteremia include diarrhea, recent receipt of blood products, and increased chemotherapy cycle number [ 5 ]. More broadly, risk factors for infection-related mortality in childhood AML include age older than 16 years, non-white ethnicity, and underweight status [ 2 ]. In this nationwide population-based study, we aimed to assess the proportion of patients and neutropenic courses complicated by bacteremia, risk factors for bacteremia, as well as the clinical and microbiological features and outcomes of bacteremia events in patients with de novo AML in Israel. Patients and methods Patients From October 1, 2016, to January 31, 2020, all data on neutropenic courses in patients < 18 years of age diagnosed with de novo AML and were enrolled on the standard arm of the NOPHO-DBH 2012 AML protocol in six tertiary pediatric hematology and oncology centers throughout Israel, were prospectively collected. This study was approved by the Institutional Review Board and Ethics Committee of all centers (RMB-661-19). The study compared the characteristics of neutropenic courses with bacteremia to neutropenic courses without bacteremia. Furthermore, the research sought to identify the primary bacterial species responsible for bacteremia events and assess their susceptibility to common antibiotic regimens. Children with Down syndrome, myelodysplastic syndrome, acute promyelocytic leukemia, secondary AML, and isolated granulocytic sarcoma were excluded. Children with focal bacterial complications in the absence of documented bacteremia were described but excluded from the statistical analysis. Children who underwent hematopoietic stem cell transplantation (HSCT) were censored on the day of transplantation. Definitions Fever was considered as either a single oral temperature of ≥ 38.3°C or a temperature of ≥ 38.0°C sustained over one hour. Bacteremia was defined as a positive blood culture for bacteria isolated from either peripheral blood or the central venous indwelling catheter consistent with clinical signs of infection. In the case of a blood culture isolate identified as a potential skin contaminant (e.g., coagulase-negative staphylococcus, at least two positive blood cultures obtained at different time points were required [ 6 ]. Repeated positive cultures of the same organism within 7 days were counted as a single event. However, repeated bacteremia events attributable to different organisms were considered separate bacteremia events. A course of chemotherapy was defined as the duration in days between the start of chemotherapy and the day prior to the start of the subsequent course of chemotherapy. The last course was defined from the start of the course until the absolute neutrophil count ≥ 500/µl. Neutropenia was defined as absolute neutrophil count < 500/µl and prolonged neutropenia as neutropenia ≥ 21 days. The bacteria were classified as GPC and GNR according to the Gram stain. All blood cultures were processed by the clinical microbiology laboratory using the BD BACTEC 9240 and BD BACTEC FX systems (Becton Dickinson, NJ, USA). Supportive Care Recommendations All patients received antifungal prophylaxis with itraconazole (suspension) or other triazoles as well as Pneumocystis jiroveci prophylaxis with cotrimoxazole, but routine antibacterial prophylaxis was not used. In the event of febrile neutropenia, empiric systemic antibiotics were started immediately. The choice of the antibiotic treatment regimen was at the discretion of the treating physician and according to institutional standards, which were based on the local epidemiology in each institution. The intent was to provide coverage against GNR with emphasis on anti-pseudomonas antibiotics, either alone or in combination with glycopeptide against resistant GPC mainly coagulase-negative staphylococci (CoNS) and VGS. AML treatment Patients were treated according to the control arm of the NOPHO-DBH-2012 protocol without randomizations (ClinicalTrials.gov identifier NCT01828489). Patients were stratified into either the standard-risk (SR) or the high-risk (HR) group. Response was evaluated by measurement of residual disease by flow cytometry(FCM). High-risk group included patients with ≥ 15% leukemic cells after 1st induction and/or ≥ 0.1% after 2nd induction. Regardless of response to treatment, all FLT3-ITD mutation without concurrent NPM1 mutation were also stratified to the high-risk group. Both risk groups received two induction treatments. Patients in the SR group received three consolidation courses with high-dose cytarabine except for those with Inv(16) who received two. HR patients were scheduled for HSCT with the best available donor after one consolidation course. Specifics of treatment courses are described in supplemental doc S1. Data were collected for all chemotherapy courses for SR patients whereas for HR patients until the phase of HSCT. For refractory disease (≥ 5% leukemic cells post 2nd induction), data were collected only from the first two inductions. Statistical analysis Data were analyzed using SPSS software (version 26). The characteristics of patients and neutropenic courses were summarized as counts and percentages for categorical variables, while for continuous variables; both mean and standard deviation as well as median and interquartile range were utilized. The association of categorical variables such as age, sex, ethnicity, and characteristics of leukemia including morphology, karyotype, and white blood cell count on admission, as well as risk stratifications, with the risk of bacteremia, was assessed using Chi χ2 test. The association between continuous variables such as age and age and bacteremia was assessed using Mann Whitney test. The variables with p-value < 0.3 from the univariate analysis were tested in a multivariable logistic regression model. The significance threshold for retaining variables in the model was a p-value of < 0.05. Results Patient characteristics Sixty-nine pediatric patients with AML were identified, of them 7 patients with focal bacterial infection without evidence of bacteremia were excluded (Fig. 1 ). The remaining 62 children with AML were included in this analysis, of them 14 (22.6%) had no bacterial complications and 48 (77.4%) had at least one bacteremia event (Table 1 ). The mean age was 9.1 ± 5.9 (range 0.1–17.9) years. There were 54.8% (34/62) Jewish patients and 45.2% (28/62) Arab patients. Almost half 48.4% (30/62) were females. A minority of patients (14, 22.6%) had presenting white blood counts (WBC) > 100,000. The most common FAB type was M4 (37.1%) followed by M5 (24.2%). Of these 62 patients, 45 (72.5%) were standard-risk patients and received the 2 inductions and 3 consolidation courses (except the inversion 16 in which the first consolidation was omitted). Ten patients (16.1%) were high risk and data was collected from only the 2 inductions and first consolidation courses. One patient (1.6%) had refractory disease and 6 patients (9.7%) died before the final risk stratification. All patients had an indwelling central venous catheter. Table 1 Characteristics of patients and neutropenic courses. Patients n (%) Neutropenic courses n (%) Total 62 238 Age Mean years ± SD Age Median years (Q1-Q3) 9.1 ± 5.9 8.9 (3.1–14.9) 10.5 ± 5.9 11.8 (6.6–16.1) Age categories (years) Less or equal to 2 15 (24.2) 62 (26.1) 2–10 18 (29) 65 (27.3) Greater than 10 29 (46.8) 111 (46.6) Ethnicity Jews 34 (54.8) 144 (60.5) Arabs 28 (45.2) 94 (39.5) Gender Male 32 (51.6) 119 (50) Female 30 (48.4) 119 (50) Presenting WBC 0–10,000 24 (38.7) 101 (42.4) 10,000-100,000 24 (38.7) 95 (39.9) > 100,000 14 (22.6) 26 (10.9) FAB Morphology M0 6 (9.7) 24 (10.7) M1 3 (4.8) 12 (5) M2 7 (11.3) 18 (7.6) M4 23 (37.1) 86 (36.1) M5 15 (24.2) 61 (25.6) M7 8 (12.9) 35 (14.7) Karyotype Other 21 (33.9) 86 (36.1) t(8;21) 8 (12.9) 22 (9.8) Inv(16) 6 (9.7) 27 (11.3) KMT2A excluding t(9;11) 7 (11.3) 27 (11.3) t(9;11) 5 (8.1) 19 (8.0) FLT3-ITD 5 (8.1) 11 (4.6) FLT3-ITD + NPM1‎ 1 (1.6) 1 (0.4) NPM1 2 (3.2) 9 (3.8) No aberration 7 (11.3) 24 (10.1) Risk Grouping Standard 45 (72.5) 186 (78.2) High risk 10 (16.1) 39 (16.4) Refractory 1 (1.6) 3 (1.3) Death in induction 6 (9.6) 10 (4.2) Treatment phase Induction * 121 (50.8) Consolidation * 117 (49.2) Duration of neutropenia 21 days * 166 (69.7) Bacteremia timing (n = 48 patients) Bacteremia during induction 16 (33.3) 49 (50.0) Bacteremia during consolidation 14 (29.2) 49 (50.0) Bacteremia during induction and consolidation 18 (37.5) * Number of bacteremia events per patient 0 14 (22.6) * 1 24 (38.7) * 2 11 (17.7) * 3 8 (12.9) * ≥ 4 (rang 4–8) 5 (8.1) * Median BSI/patient 1.5 (Range 1–8) Admission to ICU 10 (16.2) 33 (13.9) Outcome complete resolution 56 (90.3) * Sequela 1 (1.6) * Death 6 (9.7) * 30-days mortality 6 (8.1) * * Data are not relevant in this context. Risk Factors for Bacteremia When we compared the 48 patients who had bacteremia to the 14 patients without bacteremia no statistical differences were found (data not shown). Overall, 238 courses of chemotherapy (Fig. 2 ) and subsequent neutropenia (average 4 courses/patient) in 62 patients were analyzed. Fever was documented in 230/238 of the chemotherapy courses (96%). None of the eight non-febrile courses had a clinical or laboratory-documented bacterial infection. Neutropenia was documented in all the 238 chemotherapy courses, 98 (41.2%) had at least one bacteremia event, while 140 (57.9%) had no bacterial complications. Table 2 shows univariate and multivariate analysis of variables used to predict bacteremia. Univariate analysis revealed a significant association between older age, Arab ethnicity, and WBC at primary diagnosis of AML and developing bacteremia (p 0.013, 0.012, and 0.049 respectively). The rate of bacteremia in consolidation (high-dose cytarabine) was not significantly different compared to the rate in induction (low-dose cytarabine), p = 0.828. Neither did longer duration of neutropenia was associated with increased bacteremia rate, p-value of 0.296. Similarly, gender, FAB morphology, karyotype, and risk grouping were not statistically associated with bacteremia. (Table 2 ). Table 2 Univariate and multivariate analysis of variables predicting bacteremia Neutropenic courses with no bacteremia n (%), total = 140 Neutropenic courses with bacteremia n (%), total = 98 Univariate p-value Multivariate analysis P value Age Mean (y) ± Sd Age Median (Q1,Q3) 8.0 ± 5.8 7.7 (1.7–13.1) 10.5 ± 5.9 11.8 (6.6–16.1) 0.013 0.081 Age Groups ≤ 2 y 44 (71) 18 (29) 0.028 2–10 y 40 (61.5) 25 (38.5) > 10 y 56 (50.5) 55 (49.5) Gender Male 68 (57.1) 51 (42.9) 0.598 Female 72 (60.5) 47 (39.5) Ethnicity Jews 94 (65.3) 50 (34.7) 0.012 0.091 Arabs 46 (48.9) 48 (51.1) Presenting WBC 0–10,000 53 (52.5) 48 (47.5) 0.049 0.238 10,000-100,000 65 (68.4) 30 (31.6) > 100,000 22 (52.4) 20 (47.6) FAB Morphology M0 12 (46.2) 14 (53.8) 0.549 M1 6 (50) 6 (50) M2 12 (66.7) 6 (33) M4 51 (59.3) 35 (40.7) M5 35 (57.4) 26 (42.6) M7 24 (68.6) 11 (31.4) Karyotype Other 57 (66.30 29 (33.7) 0.609 t(8;21) 11 (40.7) 16 (59.3) Inv(16) 12 (44.4) 15 (55.6) KMT2A excluding t(9;11) 23 (67.6) 11 (32.4) t(9;11) 13 (68.4) 6 (31.6) FLT3-ITD 5 (45.5) 6 (54.5) FLT3-ITD + NPM1‎ 1 (100) 0 (0) NPM1 3 (33.3) 6 (66.7) No aberration 15 (62.5) 9 (37.5) Risk Grouping Standard risk 112 (60.2) 74 (39.8) 0.713 High risk 22 (56.4) 17 (43.6) Refractory 1 (33.3) 2 (66.7) Death in induction 5 (50.0) 5 (50.0) Treatment phase Induction 72 (59.5) 49 (40.5) 0.828 Consolidation 68 (58.1) 49 (41.9) Neutropenia 21 days 94 (56.6) 72 (43.4) Multivariate analysis including age, ethnicity, WBC on admission, and neutropenia duration failed to show significant independent risk factors after controlling for all other factors (p 0.081, 0.091, 0.232, and 0.560 respectively). Outcome Ten patients, 33 episodes were admitted to the ICU (Suppl. Table 1). Patients with bacteremia had ~ 7-fold increased likelihood to be admitted to ICU compared to no-bacteremia, 26 (26.5%) vs 7 (5%) respectively (p < 0.001, 95%CI 3-17.3, Suppl. Table 2). Of these 26 bacteremia events in which patients were admitted to ICU 18 (69.2%) were attributed to GNR and 8 events (30.8%) to GPC. There was no statistical significance in the admission rates to the ICU based on the type of bacteria, 18/70 (25.7%) in the GNR and 8/28 (28.6%) in the GPC (p = 0.772). A favorable outcome with complete recovery of bacteremia was noted in 55/62 (88.7%) of the patients, but 6 patients (9.7%) died, and one patient (1.6%) had severe neurological sequela (Suppl. Table 1). Thirty-day mortality occurred in 6 patients, three patients experienced GNR bacteremia prior to their death (2 due to Acinetobacter baumani, 1 due to pseudomonas aeroginosa), one had Enterococcus faecium bacteremia, one neonate died due to trichosporon asahi bloodstream infection and another neonate due to presumed culture negative sepsis. All died within 5 days of positive blood culture or clinically consistent with sepsis. Five out of the 6 deaths occurred during the first induction and one during the second induction. There were no deaths during the consolidation phases. No death occurred due to VGS. Bacteremia Organism and Antibiotics Table 3 shows the bacteria isolated from the blood cultures of these AML patients. Of the 98 bacteremia episodes, 66 (67.3%) were GNR, 28 (29.8%) were GPC and 4 (4.4%) were polymicrobial. The predominant GNR organisms were Escherichia coli (39.4%), Klebsiella spp (28.8%), and Pseudomonas aeruginosa (13.6%). Among GPC, Streptococcus viridans (39.3%) and CoNS (32.1%) were the most prevalent. Three of the four 3 polymicrobial bacteremia were Klebsiella spp with Escherichia coli. Thus, in total 69/98 (70.4%) bacteremia episodes were GNR organisms. Table 3 Bacteria isolated from blood cultures of patients with neutropenic episodes. Bacteria Number of bacteremia events (%) Total Isolates 98 Monomicrobial bacteremia 94 (95.9%) Gram-negative rods - total 66 (67.3%) Escherichia coli 26 (39.4) Klebsiella spp 19 (28.8) Pseudomonas spp. 9 (13.6) Acinetobacter spp 5 (7.6) Enterobacter cloacae 3 (3.2) Other Gram-negative rods 4 (6.1) Gram-positive cocci - total 28 (29.8%) Streptococcus viridans 11 (39.3) Coagulase-negative staphylococci 9 (32.1) Enterococcus faecium 5 (17.9) Rothia mucilaginosa 2 (7.1) Granulicatella adiacens 1 (3.6) Polymicrobial bacteremia 4 (4.4%) Escherichia coli + Klebsiella spp 3 (75) Enterobacter cloacae + Klebsiella spp 1 (25) The susceptibility of the microorganisms to the common antibiotic regimens is presented in Table 4 . Susceptibility to the combination of Vancomycin + Piperacillin/Tazobactam (PIP-TAZ) was noted in 75.5% of the cases, to Vancomycin + Meropenem in 94.7% and to Vancomycin + PIP-TAZ + Amikacin in 90.8%. The most common empiric treatment administered in 188/232 (81%) of the treated neutropenic episodes was PIP-TAZ, either as a sole agent or in combination with other agents. Notably, 42 (61.8%) of the GNR isolated from blood cultures were susceptible to quinolones (ciprofloxacin or levofloxacin, Table 4 ). Table 4 Susceptibility profile of Gram-positive cocci and Gram-negative rods to commonly used antimicrobial treatments Number (%) Gram-positive cocci antimicrobial susceptibility Penicillin (N = 24) 8 (33.3) Oxacillin (N = 5) 3 (60) Vancomycin (N = 26) 25 (96.2) PIP-TAZ (N = 24) 8 (33.3) Meropenem (N = 24) 8 (33.3) Gram-negative rods antimicrobial susceptibility PIP-TAZ (N = 68) 45 (66.2) Meropenem (N = 72) 67 (93.1) Gentamycin (N = 71) 50 (70.4) Amikacin (N = 71) 59 (83.1) Quinolones (N = 68) 42 (61.8) Susceptibility of isolates (GPC or GNR) to common antimicrobial regimens Vancomycin + PIP-TAZ (N = 94) 71 (75.5) Vancomycin + Amikacin (N = 99) 87 (87.9) Vancomycin + Meropenem (N = 98) 93 (94.7) Vancomycin + PIP-TAZ + Amikacin (N = 98) 89 (90.8) Vancomycin + Meropenem + Amikacin (N = 98) 95 (96.9) Abbreviations: PIP-TAZ - Piperacillin/Tazobactam Discussion Bacteremia in pediatric patients with AML constitutes a critical infectious complication, contributing significantly to increased mortality rates during the treatment phases. The intensified chemotherapy regimens result in extended and profound neutropenia, often accompanied by severe mucositis or gut toxicity. The presence of a central venous line (CVL) further augments the susceptibility to infections. In this population-based study, including all pediatric patients diagnosed in Israel with de-novo AML and enrolled in the prospective NOPHO-DBH2012 protocol between the years 2016–2020, more than three-quarters of patients (77.4%) developed at least one bacteremia event during the therapy. This is higher than the rate of 62.5% reported from a US center [ 5 ] or 39.7% noted in a recent report from the Children Oncology Group prophylactic study, on the control arm [ 18 ]. Interestingly, three-fourths of the bacteremia events were caused by GNR whereas the rest were GPC. Consequently, VGS accounted for only 10.7% of all bloodstream infections. These findings contrast with the reports by other international research groups noting the predominance of GPC of most bacteremia events. For instance, the AML-BFM 2004 clinical trial published in 2016 that almost three-fourths of the bloodstream infections among pediatric patients with AML were due to GPC [ 3 ]. The incidence of VGS bacteremia occurred in 20–33% of all bloodstream infections [ 3 ]. Other groups reported similar results noting the predominance of GPC over minority of GNR regardless of whether prophylactic therapy was used [ 7 ][ 8 ] or was not used [ 2 ][ 9 ][ 10 ][ 11 ]. Most GNR are presumed to be originating from the gut, possibly due to disruption of the gut integrity or changes in the microbiome. The chemotherapeutic drugs, especially cytarabine used all through AML therapy, and antibiotics that are frequently used in these patients are known to disturb the structural integrity of the gut barrier allowing infiltration of gut bacteria into the blood [ 12 ] [ 13 ]. The cause of the increased GNR in this population from Israel is not clear. We can only speculate that gut mucosal disruption was synergistic to microbiome diversity loss resulting in predominance of GNR in this childhood AML cohort. Our study showed a significant 30-day infectious death rate of almost 10% in Israel on the NOPHO-DBH2012 protocol, due to the high number of GNR which were the cause of 3 of the 6 death cases. This is similar to the cumulative infection-related mortality of 11% reported by Sung et al in 2007 [ 2 ]. A dramatically lower infectious death rate of 1.5% was reported by the BFM group although that group noted predominance of GPC [ 3 ]. In a separate study of randomized levofloxacin study no deaths at all in the study period [ 14 ]. The report from Colorado noted a 7.5% rate of central line–associated bloodstream infection (CLABSI ) events in 40 patients that contributed to death [ 5 ]. Despite this variable death rate, it became critical to address this issue and this analysis was preliminarily shared with the Israeli centers. Subsequently, the AML data committee in Israel noted a significant decline in death rate but this data is too immature for this paper (N.A.C. personal communication). It suggests that if prophylactic therapy will be considered, it should be directed to GNR as these were the majority of BSI, responsible for half of the death cases. Bacteremia resulted in a 7-fold increase in admissions to ICU, with all admissions being attributed to the bacteremia event. Additionally, it was numerically more commonly associated with GNR although this did not reach statistical significance. In the study from Colorado, ICU admissions were reported in 32.5% of patients, although it was not clear whether all were secondary to infections [ 5 ]. Prophylactic antibiotic use in pediatric AML is controversial due to limited randomized studies, the retrospective nature of most studies, exposure to diverse chemotherapy regimens, and many of them are single institution experiences. The only randomized childhood leukemia study was published in 2018 by the Children’s Oncology Group (COG, study ACCL0934). Levofloxacin prophylaxis, given during the first two courses of chemotherapy in patients with AML, relapsed ALL, and HSCT recipients, was compared to no prophylaxis in an open-label study of children at high risk of bacteremia. In acute leukemia (ALL & AML), the prophylaxis group, treated with levofloxacin, had a 21.9% likelihood of bacteremia compared to 43.4% in the control group (p = 0.001). The rate of bacteremia did not differ significantly among 128 randomized patients with AML, 23.4% in the prophylaxis group compared to 39.7% in the non-prophylaxis group, p = 0.05 [ 14 ]. Among retrospective studies, Boztug et al. reported that teicoplanin/vancomycin prophylaxis during periods of severe neutropenia eliminated the incidence of VGS sepsis compared to historical controls [ 15 ]. Weelderen et al. showed that prophylactic teicoplanin and ciprofloxacin had the best results in reducing BSI in children with AML [ 7 ]. In contrast to all these and unlike the recommendation for fluoroquinolone prophylaxis in adults [ 16 ], the 8th European Conference on Infections in Leukemia (ECIL-8) updated its 2021 recommendation on antibacterial prophylaxis for pediatric patients with AML, stating that routine use is not recommended based on evidence from randomized trials and meta-analyses [ 17 ]. At this time prophylaxis should only be utilized for specific patients after carefully assessing their risk profile and conducting a thorough evaluation of the risks and benefits. It may be that selected prophylaxis therapy in Israel will need to target GNR especially since they are responsible for three-quarters of the BSI and are responsible for half of the deaths. Unfortunately, the relatively low susceptibility (61.8%, Table 4 ) of GNR to quinolones decreases the utility of these agents for prophylaxis in the target population of the present study and requires alternative prophylactic treatments. While older age, Arab ethnicity, and WBC at diagnosis ( 100,000) were identified as factors correlated with bacteremia in the univariate analysis, these correlations did not attain statistical significance in the multivariate model, likely due to the limited sample size. Age older than 16 was noted as a risk factor for infectious death by Sung et al. [ 2 ] and age older than 14 was noted by Roger et al. as a risk factor for CLABSI [ 5 ]. Regarding ethnicity, prior reports also noted decreased childhood cancer survival of the Arabic population compared to the Jewish population, especially for leukemia and lymphoma, but that analysis included the years 1998–2009 [ 18 ][ 19 ]. A recent epidemiological analysis updated to 2017, notes a significant reduction of death rate from cancer in Arab boys. In the current study, 3/6 deceased patients were of Arab origin. Our study did not show an increased risk of bacteremia related to the phase of treatment either induction or consolidation. Induction courses include low-dose cytarabine and consolidation courses include only high-dose cytarabine. Prior reports note high-dose cytarabine as a risk factor for VGS [ 9 ][ 20 ] but was not confirmed by the BFM group [ 3 ]. Notably, these studies had predominant GPC vs our cohort which had predominant GNR. Similarly, we did not find gender, FAB morphology, cytogenetic group, or risk group associated with increased risk of bacteremia. Curiously duration of neutropenia was also not associated with bacteremia risk, in agreement with the report from Colorado [ 5 ]. The ECIL-8 European group for leukemia suggests empirical therapy of either an antipseudomonal beta-lactam, a fourth-generation cephalosporin, or a carbapenem. In instances where the patient's clinical condition is unstable, it is advisable to supplement treatment with a glycopeptide and consider the addition of a second agent effective against gram-negative bacteria. This approach also applies when there is suspicion of a resistant infection or in healthcare centers with a high incidence of resistant pathogens, as well as in cases involving profound mucositis [ 17 ]. In line with these recommendations, the present study demonstrates decreased susceptibility of GNR to the usual empiric antibiotic regimens, especially the resistance of GNR to PIP-TAZ in about one-third of cases, while this treatment was administered in 77.7% of neutropenic courses. This serious finding may call into question the appropriateness of PIP-TAZ as an empiric antimicrobial treatment in patients with AML with neutropenic fever and high suspicion of bacteremia. Furthermore, whether these resistance rates are also observed in patients with bacteremia in other malignancies needs to be explored. Importantly, any switch to a broad-spectrum antimicrobial regimen in patients with neutropenic fever should be accompanied by large population-based prospective studies because of the impact on the development of multidrug-resistant bacteria in patients and in the general population. The limitations of this study include the retrospective analysis of all courses and the lack of data regarding the association with mucositis and colitis that would have helped clarify factors responsible for the predominance of GNR in this population. Further, the variable empiric therapy given per physician choice and medical center guidelines precludes a strong statement about the utility of each antibiotic regimen for the treatment of fever and neutropenia in pediatric patients with AML. Finally, data about fungal infection especially candida was not collected and reported in this study. The strengths of this study include data collection for all de novo AML patients on a frontline uniform protocol in Israel. In conclusion, the current study found that three-quarters of patients on the NOPHO-DBH 2012 AML protocol in Israel between 2016 and 2019 experienced bacteremia, leading to a high mortality rate. Unlike prior investigations, our research identified a predominance of GNR, accounting for 50% of mortality cases, a noteworthy finding that has implications for choosing prophylactic treatments. Additionally, the high resistance to Quinolones limits its use as a prophylactic treatment, and the resistance to PIP-TAZ, the primary empirical treatment, underscores the necessity of broadening antibiotic coverage for patients with a high clinical suspicion of bacteremia or sepsis. Finally, more studies may clarify whether age or Arab ethnicity are potential independent risk factors for bacteremia in Israeli pediatric cancer patients. Abbreviations AML acute myeloid leukemia aOR adjusted odds ratio CLABSI central line-associated bloodstream infection CoNS coagulase-negative staphylococci CVL central venous line FCM flow cytometry GNR Gram-negative rods GPC Gram-positive cocci HR high-risk HSCT hematopoietic stem cell transplantation PIP-TAZ Piperacillin/Tazobactam SR standard-risk VGS Viridans Group Streptococci WBC white blood count Declarations This study was approved by the Institutional Review Board and Ethics Committee of all centers (RMB-661-19). The consent to participate was exempt by the IRB. It was not funded by any institution or grant. Summary of the data and material can be given upon request. No Conflict of Interest. Acknowledgments : We express our gratitude to the Israel Cancer Association, Chaim Association, and Israel Children’s Cancer Foundation for their generous support. Additionally, we extend our appreciation to all pediatric hematology-oncology departments in Israel for their devoted care of challenging patients References Elgarten CW, Aplenc R. Pediatric acute myeloid leukemia: updates on biology, risk stratification, and therapy, Curr. Opin. Pediatr. , vol. 32, no. 1, 2020, [Online]. Available: https://journals.lww.com/co-pediatrics/Fulltext/2020/02000/Pediatric_acute_myeloid_leukemia__updates_on.9.aspx . Sung L, Lange BJ, Feusner J, Alonzo TA, Gerbing RB. Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia. Blood. 2007;110(10):3532–9. 10.1182/blood-2007-05-091942 . Bochennek K et al. Jan., Infectious complications in children with acute myeloid leukemia: decreased mortality in multicenter trial AML-BFM 2004., Blood Cancer J. , vol. 6, no. 1, p. e382, 2016, 10.1038/bcj.2015.110 . ingentaconnect.com , Accessed: Mar. 05, 2019. [Online]. Available: https://www.ingentaconnect.com/content/wk/jpho/2017/00000039/00000003/art00004. Rogers AEJ, et al. Risk factors for bacteremia and central line-associated blood stream infections in children with acute myelogenous leukemia: A single-institution report. Pediatr Blood Cancer. Mar. 2017;64(3):e26254. 10.1002/pbc.26254 . CDC., Blood Culture Contamination: An Overview for Infection Control and Antibiotic Stewardship Programs Working with the Clinical Laboratory. pp. 5–7. [Online]. Available: https://www.cap.org/laboratory-improvement/accreditation/ . Van Weelderen RE, Klein K, Goemans BF, Tissing WJE, Wolfs TFW, Kaspers GJL. Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia: A Two-Center Retrospective Study. Cancers (Basel). 2022;14(13):1–15. 10.3390/cancers14133172 . Inaba H, et al. Feasibility, efficacy, and adverse effects of outpatient antibacterial prophylaxis in children with acute myeloid leukemia. Cancer. Jul. 2014;120(13):1985–92. Sung L, et al. Infections and association with different intensity of chemotherapy in children with acute myeloid leukemia. Cancer. 2009;115(5):1100–8. 10.1002/cncr.24107 . Castagnola E et al. Dec., Incidence of bacteremias and invasive mycoses in children with acute non-lymphoblastic leukemia: results from a multi-center Italian study., Pediatr. Blood Cancer , vol. 55, no. 6, pp. 1103–1107, 2010, 10.1002/pbc.22750 . Lehrnbecher T, Varwig D, Kaiser J, Reinhardt D, Klingebiel T, Creutzig U. Infectious complications in pediatric acute myeloid leukemia: Analysis of the prospective multi-institutional clinical trial AML-BFM 93, Leukemia , vol. 18, no. 1, pp. 72–77, 2004, 10.1038/sj.leu.2403188 . Berg RD. Bacterial translocation from the gastrointestinal tract. Trends Microbiol. Apr. 1995;3(4):149–54. 10.1016/s0966-842x(00)88906-4 . Keeney KM, Yurist-Doutsch S, Arrieta M-C, Finlay BB. Effects of antibiotics on human microbiota and subsequent disease. Annu Rev Microbiol. 2014;68:217–35. 10.1146/annurev-micro-091313-103456 . Alexander S, et al. Effect of levofloxacin prophylaxis on Bacteremia in children with acute Leukemia or undergoing hematopoietic stem cell transplantation a randomized clinical trial. JAMA - J Am Med Assoc. 2018;320(10):995–1004. 10.1001/jama.2018.12512 . Boztug H, et al. Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia. Ann Hematol. Jan. 2017;96(1):99–106. 10.1007/s00277-016-2833-5 . Taplitz RA, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Clin Oncol. 2018;36:3043–54. 10.1200/JCO.18.00374 . Lehrnbecher T et al. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation, Lancet Oncol. , vol. 22, no. 6, pp. e270–e280, 2021, 10.1016/S1470-2045(20)30725-7 . Rabinowicz R, Barchana M, Liphshiz I, Linn S, Futerman B, Ben-Arush MW. Cancer incidence and survival among infants in Israel, 1998–2007. Pediatr Hematol Oncol. 2013;30(7):646–54. 10.3109/08880018.2013.813099 . Berkun L, et al. Cancer incidence and survival among adolescents in Israel during the years 1998 to 2009. Pediatr Blood Cancer. 2013;60:1848–54. 10.1002/pbc.24651 . no. 11. Rossetti F, Cesaro S, Putti MC, Zanesco L. High-dose cytosine arabinoside and viridans streptococcus sepsis in children with leukemia. Pediatr Hematol Oncol. 1995;12(4):387–92. 10.3109/08880019509029589 . Additional Declarations No competing interests reported. Supplementary Files Supplement.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3953893","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272807394,"identity":"649e0f20-db06-4834-8f5d-49c01e894b05","order_by":0,"name":"Nira 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Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Yoav","middleName":"","lastName":"Messinger","suffix":""},{"id":272807396,"identity":"f47fd1bf-5e65-4528-b49f-ce6eb46067a0","order_by":2,"name":"Shlomit Barzilai-Birenboim","email":"","orcid":"","institution":"Schneider Children’s Medical Center of Israel","correspondingAuthor":false,"prefix":"","firstName":"Shlomit","middleName":"","lastName":"Barzilai-Birenboim","suffix":""},{"id":272807397,"identity":"af33975a-5e6d-45c5-856b-a52f723dbd0c","order_by":3,"name":"Miriam Ben-Harosh","email":"","orcid":"","institution":"Soroka Medical Center, Ben Gurion University","correspondingAuthor":false,"prefix":"","firstName":"Miriam","middleName":"","lastName":"Ben-Harosh","suffix":""},{"id":272807398,"identity":"7903310e-a195-4c39-a5d1-9af7aab45d04","order_by":4,"name":"Michal Golan-Malki","email":"","orcid":"","institution":"The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Michal","middleName":"","lastName":"Golan-Malki","suffix":""},{"id":272807399,"identity":"5575a217-b484-458f-97de-e0f51d03879c","order_by":5,"name":"Hila Rosenfeld-Kaidar","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hila","middleName":"","lastName":"Rosenfeld-Kaidar","suffix":""},{"id":272807400,"identity":"3941f165-801a-4e92-a30b-c6feb59d9391","order_by":6,"name":"Sigal Weinreb","email":"","orcid":"","institution":"Hadassah Hebrew University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sigal","middleName":"","lastName":"Weinreb","suffix":""},{"id":272807401,"identity":"e9874070-45b2-4842-b543-5312ab7b5721","order_by":7,"name":"Yael Shachor-Meyouhas","email":"","orcid":"","institution":"Ruth Rappaport Children’s Hospital, Rambam Health Care Campus","correspondingAuthor":false,"prefix":"","firstName":"Yael","middleName":"","lastName":"Shachor-Meyouhas","suffix":""},{"id":272807402,"identity":"95f97b78-ea58-43af-9120-581e9fc4d9ba","order_by":8,"name":"Halima Dabaja-Younis","email":"","orcid":"","institution":"Ruth Rappaport Children’s Hospital, Rambam Health Care Campus","correspondingAuthor":false,"prefix":"","firstName":"Halima","middleName":"","lastName":"Dabaja-Younis","suffix":""}],"badges":[],"createdAt":"2024-02-13 16:05:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3953893/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3953893/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51238386,"identity":"5bb48d10-0415-4ea9-8ed4-ee1539ca3cd3","added_by":"auto","created_at":"2024-02-16 16:49:38","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":234948,"visible":true,"origin":"","legend":"\u003cp\u003ePatient Flow Diagram\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3953893/v1/28f2b4f24a80ac9d65bb63d4.jpeg"},{"id":51236589,"identity":"478a8988-9e8f-418f-8589-e3503efa64c7","added_by":"auto","created_at":"2024-02-16 16:41:38","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":393175,"visible":true,"origin":"","legend":"\u003cp\u003eEpisodes Flow Diagram\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3953893/v1/f7dcd1dec1f27af83d331279.jpeg"},{"id":51341934,"identity":"393671a8-527b-4762-b22b-1dd672f1b3d0","added_by":"auto","created_at":"2024-02-20 00:28:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":604317,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3953893/v1/a327c002-9f65-4b2a-a6f7-acbc5a2381cf.pdf"},{"id":51236587,"identity":"0da011ca-df2c-4cf3-87fa-8f13fbb9dc42","added_by":"auto","created_at":"2024-02-16 16:41:38","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17657,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-3953893/v1/8de82670a34b63461909aa13.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"National Study Reveals Gram Negative Bacteremia on Contemporary Pediatric AML Protocol","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute myeloid leukemia (AML) accounts for approximately 20% of acute leukemia cases in children and adolescents. The 5-year overall survival of pediatric patients with AML has improved, reaching almost 75% in various clinical trials. This improvement is mainly attributable to refinement in the risk classification, and treatment stratification as well as advances in supportive care [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, AML chemotherapy is still one of the most intensive treatments in pediatric oncology. It is associated with a prolonged and profound period of neutropenia after each course of chemotherapy leading to a high risk of infections. Bacteremia have been documented in more than 50% of pediatric patients with AML and are associated with severe morbidity and a cumulative mortality that in the past had exceeded 10% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Among bacteremia events in pediatric AML, Gram-positive cocci (GPC), mainly \u003cem\u003eViridans Group Streptococci\u003c/em\u003e (VGS) are much more prevalent than Gram-negative rods (GNR) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRisk factors specific to bacteremia include diarrhea, recent receipt of blood products, and increased chemotherapy cycle number [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. More broadly, risk factors for infection-related mortality in childhood AML include age older than 16 years, non-white ethnicity, and underweight status [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this nationwide population-based study, we aimed to assess the proportion of patients and neutropenic courses complicated by bacteremia, risk factors for bacteremia, as well as the clinical and microbiological features and outcomes of bacteremia events in patients with de novo AML in Israel.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eFrom October 1, 2016, to January 31, 2020, all data on neutropenic courses in patients\u0026thinsp;\u0026lt;\u0026thinsp;18 years of age diagnosed with de novo AML and were enrolled on the standard arm of the NOPHO-DBH 2012 AML protocol in six tertiary pediatric hematology and oncology centers throughout Israel, were prospectively collected. This study was approved by the Institutional Review Board and Ethics Committee of all centers (RMB-661-19).\u003c/p\u003e \u003cp\u003eThe study compared the characteristics of neutropenic courses with bacteremia to neutropenic courses without bacteremia. Furthermore, the research sought to identify the primary bacterial species responsible for bacteremia events and assess their susceptibility to common antibiotic regimens. Children with Down syndrome, myelodysplastic syndrome, acute promyelocytic leukemia, secondary AML, and isolated granulocytic sarcoma were excluded. Children with focal bacterial complications in the absence of documented bacteremia were described but excluded from the statistical analysis. Children who underwent hematopoietic stem cell transplantation (HSCT) were censored on the day of transplantation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eFever was considered as either a single oral temperature of \u0026ge;\u0026thinsp;38.3\u0026deg;C or a temperature of \u0026ge;\u0026thinsp;38.0\u0026deg;C sustained over one hour. Bacteremia was defined as a positive blood culture for bacteria isolated from either peripheral blood or the central venous indwelling catheter consistent with clinical signs of infection. In the case of a blood culture isolate identified as a potential skin contaminant (e.g., coagulase-negative staphylococcus, at least two positive blood cultures obtained at different time points were required [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Repeated positive cultures of the same organism within 7 days were counted as a single event. However, repeated bacteremia events attributable to different organisms were considered separate bacteremia events. A course of chemotherapy was defined as the duration in days between the start of chemotherapy and the day prior to the start of the subsequent course of chemotherapy. The last course was defined from the start of the course until the absolute neutrophil count\u0026thinsp;\u0026ge;\u0026thinsp;500/\u0026micro;l. Neutropenia was defined as absolute neutrophil count\u0026thinsp;\u0026lt;\u0026thinsp;500/\u0026micro;l and prolonged neutropenia as neutropenia\u0026thinsp;\u0026ge;\u0026thinsp;21 days.\u003c/p\u003e \u003cp\u003eThe bacteria were classified as GPC and GNR according to the Gram stain. All blood cultures were processed by the clinical microbiology laboratory using the BD BACTEC 9240 and BD BACTEC FX systems (Becton Dickinson, NJ, USA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSupportive Care Recommendations\u003c/h2\u003e \u003cp\u003eAll patients received antifungal prophylaxis with itraconazole (suspension) or other triazoles as well as Pneumocystis jiroveci prophylaxis with cotrimoxazole, but routine antibacterial prophylaxis was not used.\u003c/p\u003e \u003cp\u003eIn the event of febrile neutropenia, empiric systemic antibiotics were started immediately. The choice of the antibiotic treatment regimen was at the discretion of the treating physician and according to institutional standards, which were based on the local epidemiology in each institution. The intent was to provide coverage against GNR with emphasis on anti-pseudomonas antibiotics, either alone or in combination with glycopeptide against resistant GPC mainly coagulase-negative staphylococci (CoNS) and VGS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eAML treatment\u003c/h2\u003e \u003cp\u003ePatients were treated according to the control arm of the NOPHO-DBH-2012 protocol without randomizations (ClinicalTrials.gov identifier NCT01828489).\u003c/p\u003e \u003cp\u003ePatients were stratified into either the standard-risk (SR) or the high-risk (HR) group. Response was evaluated by measurement of residual disease by flow cytometry(FCM). High-risk group included patients with \u0026ge;\u0026thinsp;15% leukemic cells after 1st induction and/or \u0026ge;\u0026thinsp;0.1% after 2nd induction. Regardless of response to treatment, all FLT3-ITD mutation without concurrent NPM1 mutation were also stratified to the high-risk group. Both risk groups received two induction treatments. Patients in the SR group received three consolidation courses with high-dose cytarabine except for those with Inv(16) who received two. HR patients were scheduled for HSCT with the best available donor after one consolidation course. Specifics of treatment courses are described in supplemental doc S1.\u003c/p\u003e \u003cp\u003eData were collected for all chemotherapy courses for SR patients whereas for HR patients until the phase of HSCT. For refractory disease (\u0026ge;\u0026thinsp;5% leukemic cells post 2nd induction), data were collected only from the first two inductions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using SPSS software (version 26). The characteristics of patients and neutropenic courses were summarized as counts and percentages for categorical variables, while for continuous variables; both mean and standard deviation as well as median and interquartile range were utilized.\u003c/p\u003e \u003cp\u003eThe association of categorical variables such as age, sex, ethnicity, and characteristics of leukemia including morphology, karyotype, and white blood cell count on admission, as well as risk stratifications, with the risk of bacteremia, was assessed using Chi χ2 test. The association between continuous variables such as age and age and bacteremia was assessed using Mann Whitney test. The variables with p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.3 from the univariate analysis were tested in a multivariable logistic regression model. The significance threshold for retaining variables in the model was a p-value of \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eSixty-nine pediatric patients with AML were identified, of them 7 patients with focal bacterial infection without evidence of bacteremia were excluded (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The remaining 62 children with AML were included in this analysis, of them 14 (22.6%) had no bacterial complications and 48 (77.4%) had at least one bacteremia event (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean age was 9.1\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.9 (range 0.1\u0026ndash;17.9) years. There were 54.8% (34/62) Jewish patients and 45.2% (28/62) Arab patients. Almost half 48.4% (30/62) were females. A minority of patients (14, 22.6%) had presenting white blood counts (WBC)\u0026thinsp;\u0026gt;\u0026thinsp;100,000. The most common FAB type was M4 (37.1%) followed by M5 (24.2%). Of these 62 patients, 45 (72.5%) were standard-risk patients and received the 2 inductions and 3 consolidation courses (except the inversion 16 in which the first consolidation was omitted). Ten patients (16.1%) were high risk and data was collected from only the 2 inductions and first consolidation courses. One patient (1.6%) had refractory disease and 6 patients (9.7%) died before the final risk stratification. All patients had an indwelling central venous catheter.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients and neutropenic courses.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeutropenic courses\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e238\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge Mean years\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;SD\u003c/p\u003e \u003cp\u003eAge Median years (Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.1\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.9\u003c/p\u003e \u003cp\u003e8.9 (3.1\u0026ndash;14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.5\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.9\u003c/p\u003e \u003cp\u003e11.8 (6.6\u0026ndash;16.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAge categories (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLess or equal to 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (26.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65 (27.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGreater than 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111 (46.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144 (60.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArabs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (39.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e119 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e119 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePresenting WBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;10,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101 (42.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10,000-100,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95 (39.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (10.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eFAB Morphology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (10.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (7.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (37.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86 (36.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (25.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (14.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eKaryotype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86 (36.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003et(8;21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (9.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInv(16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (11.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKMT2A excluding t(9;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (11.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003et(9;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFLT3-ITD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (4.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFLT3-ITD\u0026thinsp;+\u0026thinsp;NPM1\u0026lrm;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNPM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo aberration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (10.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eRisk Grouping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStandard\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (72.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e186 (78.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (16.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDeath in induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (4.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTreatment phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInduction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121 (50.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConsolidation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117 (49.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDuration of neutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;21 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (30.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;21 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166 (69.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBacteremia timing (n\u0026thinsp;=\u0026thinsp;48 patients)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBacteremia during induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBacteremia during consolidation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBacteremia during induction and consolidation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eNumber of bacteremia events per patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4 (rang 4\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian BSI/patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 (Range 1\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAdmission to ICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (13.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecomplete resolution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (90.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSequela\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e30-days mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e* Data are not relevant in this context.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eRisk Factors for Bacteremia\u003c/h2\u003e \u003cp\u003eWhen we compared the 48 patients who had bacteremia to the 14 patients without bacteremia no statistical differences were found (data not shown). Overall, 238 courses of chemotherapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and subsequent neutropenia (average 4 courses/patient) in 62 patients were analyzed. Fever was documented in 230/238 of the chemotherapy courses (96%). None of the eight non-febrile courses had a clinical or laboratory-documented bacterial infection. Neutropenia was documented in all the 238 chemotherapy courses, 98 (41.2%) had at least one bacteremia event, while 140 (57.9%) had no bacterial complications.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows univariate and multivariate analysis of variables used to predict bacteremia. Univariate analysis revealed a significant association between older age, Arab ethnicity, and WBC at primary diagnosis of AML and developing bacteremia (p 0.013, 0.012, and 0.049 respectively). The rate of bacteremia in consolidation (high-dose cytarabine) was not significantly different compared to the rate in induction (low-dose cytarabine), p\u0026thinsp;=\u0026thinsp;0.828. Neither did longer duration of neutropenia was associated with increased bacteremia rate, p-value of 0.296. Similarly, gender, FAB morphology, karyotype, and risk grouping were not statistically associated with bacteremia. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analysis of variables predicting bacteremia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNeutropenic courses with no bacteremia\u003c/p\u003e \u003cp\u003en (%), total\u0026thinsp;=\u0026thinsp;140\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeutropenic courses with bacteremia\u003c/p\u003e \u003cp\u003en (%), total\u0026thinsp;=\u0026thinsp;98\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge Mean (y)\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;Sd\u003c/p\u003e \u003cp\u003eAge Median (Q1,Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.8\u003c/p\u003e \u003cp\u003e7.7 (1.7\u0026ndash;13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.5\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.9\u003c/p\u003e \u003cp\u003e11.8 (6.6\u0026ndash;16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAge Groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;2 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;10 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10 y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (49.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (60.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 (65.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (34.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArabs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (51.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePresenting WBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;10,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10,000-100,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (52.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eFAB Morphology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (42.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (68.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (31.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eKaryotype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (66.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003et(8;21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInv(16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKMT2A excluding t(9;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003et(9;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFLT3-ITD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFLT3-ITD\u0026thinsp;+\u0026thinsp;NPM1\u0026lrm;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNPM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo aberration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eRisk Grouping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStandard risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (60.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.713\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDeath in induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTreatment phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInduction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (40.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.828\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConsolidation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (58.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNeutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;21 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (63.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;21 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 (56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMultivariate analysis including age, ethnicity, WBC on admission, and neutropenia duration failed to show significant independent risk factors after controlling for all other factors (p 0.081, 0.091, 0.232, and 0.560 respectively).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOutcome\u003c/h2\u003e \u003cp\u003eTen patients, 33 episodes were admitted to the ICU (Suppl. Table\u0026nbsp;1). Patients with bacteremia had\u0026thinsp;~\u0026thinsp;7-fold increased likelihood to be admitted to ICU compared to no-bacteremia, 26 (26.5%) vs 7 (5%) respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, 95%CI 3-17.3, Suppl. Table\u0026nbsp;2). Of these 26 bacteremia events in which patients were admitted to ICU 18 (69.2%) were attributed to GNR and 8 events (30.8%) to GPC. There was no statistical significance in the admission rates to the ICU based on the type of bacteria, 18/70 (25.7%) in the GNR and 8/28 (28.6%) in the GPC (p\u0026thinsp;=\u0026thinsp;0.772).\u003c/p\u003e \u003cp\u003eA favorable outcome with complete recovery of bacteremia was noted in 55/62 (88.7%) of the patients, but 6 patients (9.7%) died, and one patient (1.6%) had severe neurological sequela (Suppl. Table\u0026nbsp;1). Thirty-day mortality occurred in 6 patients, three patients experienced GNR bacteremia prior to their death (2 due to Acinetobacter baumani, 1 due to pseudomonas aeroginosa), one had \u003cem\u003eEnterococcus faecium\u003c/em\u003e bacteremia, one neonate died due to trichosporon asahi bloodstream infection and another neonate due to presumed culture negative sepsis. All died within 5 days of positive blood culture or clinically consistent with sepsis. Five out of the 6 deaths occurred during the first induction and one during the second induction. There were no deaths during the consolidation phases. No death occurred due to VGS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eBacteremia Organism and Antibiotics\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the bacteria isolated from the blood cultures of these AML patients. Of the 98 bacteremia episodes, 66 (67.3%) were GNR, 28 (29.8%) were GPC and 4 (4.4%) were polymicrobial. The predominant GNR organisms were \u003cem\u003eEscherichia coli\u003c/em\u003e (39.4%), Klebsiella spp (28.8%), and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (13.6%). Among GPC, \u003cem\u003eStreptococcus viridans\u003c/em\u003e (39.3%) and CoNS (32.1%) were the most prevalent. Three of the four 3 polymicrobial bacteremia were Klebsiella spp with \u003cem\u003eEscherichia coli.\u003c/em\u003e Thus, in total 69/98 (70.4%) bacteremia episodes were GNR organisms.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBacteria isolated from blood cultures of patients with neutropenic episodes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of bacteremia events (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Isolates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonomicrobial bacteremia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (95.9%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGram-negative rods - total\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e66 (67.3%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (39.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKlebsiella spp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (28.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePseudomonas spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (13.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcinetobacter spp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (7.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterobacter cloacae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Gram-negative rods\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGram-positive cocci - total\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e28 (29.8%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus viridans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (39.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulase-negative staphylococci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (32.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus faecium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRothia mucilaginosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGranulicatella adiacens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePolymicrobial bacteremia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4 (4.4%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u0026thinsp;+\u0026thinsp;Klebsiella spp\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterobacter cloacae\u0026thinsp;+\u0026thinsp;Klebsiella spp\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe susceptibility of the microorganisms to the common antibiotic regimens is presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Susceptibility to the combination of Vancomycin\u0026thinsp;+\u0026thinsp;Piperacillin/Tazobactam (PIP-TAZ) was noted in 75.5% of the cases, to Vancomycin\u0026thinsp;+\u0026thinsp;Meropenem in 94.7% and to Vancomycin\u0026thinsp;+\u0026thinsp;PIP-TAZ\u0026thinsp;+\u0026thinsp;Amikacin in 90.8%. The most common empiric treatment administered in 188/232 (81%) of the treated neutropenic episodes was PIP-TAZ, either as a sole agent or in combination with other agents. Notably, 42 (61.8%) of the GNR isolated from blood cultures were susceptible to quinolones (ciprofloxacin or levofloxacin, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSusceptibility profile of Gram-positive cocci and Gram-negative rods to commonly used antimicrobial treatments\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGram-positive cocci antimicrobial susceptibility\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePenicillin (N\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxacillin (N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVancomycin (N\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (96.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIP-TAZ (N\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeropenem (N\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGram-negative rods antimicrobial susceptibility\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIP-TAZ (N\u0026thinsp;=\u0026thinsp;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (66.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeropenem (N\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (93.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGentamycin (N\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (70.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmikacin (N\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (83.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuinolones (N\u0026thinsp;=\u0026thinsp;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (61.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSusceptibility of isolates (GPC or GNR) to common antimicrobial regimens\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVancomycin\u0026thinsp;+\u0026thinsp;PIP-TAZ (N\u0026thinsp;=\u0026thinsp;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (75.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVancomycin\u0026thinsp;+\u0026thinsp;Amikacin (N\u0026thinsp;=\u0026thinsp;99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (87.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVancomycin\u0026thinsp;+\u0026thinsp;Meropenem (N\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (94.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVancomycin\u0026thinsp;+\u0026thinsp;PIP-TAZ\u0026thinsp;+\u0026thinsp;Amikacin (N\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (90.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVancomycin\u0026thinsp;+\u0026thinsp;Meropenem\u0026thinsp;+\u0026thinsp;Amikacin (N\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (96.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: PIP-TAZ - Piperacillin/Tazobactam\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eBacteremia in pediatric patients with AML constitutes a critical infectious complication, contributing significantly to increased mortality rates during the treatment phases. The intensified chemotherapy regimens result in extended and profound neutropenia, often accompanied by severe mucositis or gut toxicity. The presence of a central venous line (CVL) further augments the susceptibility to infections.\u003c/p\u003e \u003cp\u003eIn this population-based study, including all pediatric patients diagnosed in Israel with de-novo AML and enrolled in the prospective NOPHO-DBH2012 protocol between the years 2016\u0026ndash;2020, more than three-quarters of patients (77.4%) developed at least one bacteremia event during the therapy. This is higher than the rate of 62.5% reported from a US center [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] or 39.7% noted in a recent report from the Children Oncology Group prophylactic study, on the control arm [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInterestingly, three-fourths of the bacteremia events were caused by GNR whereas the rest were GPC. Consequently, VGS accounted for only 10.7% of all bloodstream infections. These findings contrast with the reports by other international research groups noting the predominance of GPC of most bacteremia events. For instance, the AML-BFM 2004 clinical trial published in 2016 that almost three-fourths of the bloodstream infections among pediatric patients with AML were due to GPC [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The incidence of VGS bacteremia occurred in 20\u0026ndash;33% of all bloodstream infections [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Other groups reported similar results noting the predominance of GPC over minority of GNR regardless of whether prophylactic therapy was used [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] or was not used [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Most GNR are presumed to be originating from the gut, possibly due to disruption of the gut integrity or changes in the microbiome. The chemotherapeutic drugs, especially cytarabine used all through AML therapy, and antibiotics that are frequently used in these patients are known to disturb the structural integrity of the gut barrier allowing infiltration of gut bacteria into the blood [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The cause of the increased GNR in this population from Israel is not clear. We can only speculate that gut mucosal disruption was synergistic to microbiome diversity loss resulting in predominance of GNR in this childhood AML cohort.\u003c/p\u003e \u003cp\u003eOur study showed a significant 30-day infectious death rate of almost 10% in Israel on the NOPHO-DBH2012 protocol, due to the high number of GNR which were the cause of 3 of the 6 death cases. This is similar to the cumulative infection-related mortality of 11% reported by Sung et al in 2007 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. A dramatically lower infectious death rate of 1.5% was reported by the BFM group although that group noted predominance of GPC [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In a separate study of randomized levofloxacin study no deaths at all in the study period [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The report from Colorado noted a 7.5% rate of central line\u0026ndash;associated bloodstream infection (CLABSI ) events in 40 patients that contributed to death [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite this variable death rate, it became critical to address this issue and this analysis was preliminarily shared with the Israeli centers. Subsequently, the AML data committee in Israel noted a significant decline in death rate but this data is too immature for this paper (N.A.C. personal communication). It suggests that if prophylactic therapy will be considered, it should be directed to GNR as these were the majority of BSI, responsible for half of the death cases.\u003c/p\u003e \u003cp\u003eBacteremia resulted in a 7-fold increase in admissions to ICU, with all admissions being attributed to the bacteremia event. Additionally, it was numerically more commonly associated with GNR although this did not reach statistical significance. In the study from Colorado, ICU admissions were reported in 32.5% of patients, although it was not clear whether all were secondary to infections [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eProphylactic antibiotic use in pediatric AML is controversial due to limited randomized studies, the retrospective nature of most studies, exposure to diverse chemotherapy regimens, and many of them are single institution experiences. The only randomized childhood leukemia study was published in 2018 by the Children\u0026rsquo;s Oncology Group (COG, study ACCL0934). Levofloxacin prophylaxis, given during the first two courses of chemotherapy in patients with AML, relapsed ALL, and HSCT recipients, was compared to no prophylaxis in an open-label study of children at high risk of bacteremia. In acute leukemia (ALL \u0026amp; AML), the prophylaxis group, treated with levofloxacin, had a 21.9% likelihood of bacteremia compared to 43.4% in the control group (p\u0026thinsp;=\u0026thinsp;0.001). The rate of bacteremia did not differ significantly among 128 randomized patients with AML, 23.4% in the prophylaxis group compared to 39.7% in the non-prophylaxis group, p\u0026thinsp;=\u0026thinsp;0.05 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Among retrospective studies, Boztug et al. reported that teicoplanin/vancomycin prophylaxis during periods of severe neutropenia eliminated the incidence of VGS sepsis compared to historical controls [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Weelderen et al. showed that prophylactic teicoplanin and ciprofloxacin had the best results in reducing BSI in children with AML [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In contrast to all these and unlike the recommendation for fluoroquinolone prophylaxis in adults [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], the 8th European Conference on Infections in Leukemia (ECIL-8) updated its 2021 recommendation on antibacterial prophylaxis for pediatric patients with AML, stating that routine use is not recommended based on evidence from randomized trials and meta-analyses [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. At this time prophylaxis should only be utilized for specific patients after carefully assessing their risk profile and conducting a thorough evaluation of the risks and benefits. It may be that selected prophylaxis therapy in Israel will need to target GNR especially since they are responsible for three-quarters of the BSI and are responsible for half of the deaths. Unfortunately, the relatively low susceptibility (61.8%, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) of GNR to quinolones decreases the utility of these agents for prophylaxis in the target population of the present study and requires alternative prophylactic treatments.\u003c/p\u003e \u003cp\u003eWhile older age, Arab ethnicity, and WBC at diagnosis (\u0026lt;\u0026thinsp;10,000 or \u0026gt;\u0026thinsp;100,000) were identified as factors correlated with bacteremia in the univariate analysis, these correlations did not attain statistical significance in the multivariate model, likely due to the limited sample size. Age older than 16 was noted as a risk factor for infectious death by Sung et al. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and age older than 14 was noted by Roger et al. as a risk factor for CLABSI [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Regarding ethnicity, prior reports also noted decreased childhood cancer survival of the Arabic population compared to the Jewish population, especially for leukemia and lymphoma, but that analysis included the years 1998\u0026ndash;2009 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e][\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. A recent epidemiological analysis updated to 2017, notes a significant reduction of death rate from cancer in Arab boys. In the current study, 3/6 deceased patients were of Arab origin.\u003c/p\u003e \u003cp\u003eOur study did not show an increased risk of bacteremia related to the phase of treatment either induction or consolidation. Induction courses include low-dose cytarabine and consolidation courses include only high-dose cytarabine. Prior reports note high-dose cytarabine as a risk factor for VGS [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] but was not confirmed by the BFM group [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Notably, these studies had predominant GPC vs our cohort which had predominant GNR. Similarly, we did not find gender, FAB morphology, cytogenetic group, or risk group associated with increased risk of bacteremia. Curiously duration of neutropenia was also not associated with bacteremia risk, in agreement with the report from Colorado [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe ECIL-8 European group for leukemia suggests empirical therapy of either an antipseudomonal beta-lactam, a fourth-generation cephalosporin, or a carbapenem. In instances where the patient's clinical condition is unstable, it is advisable to supplement treatment with a glycopeptide and consider the addition of a second agent effective against gram-negative bacteria. This approach also applies when there is suspicion of a resistant infection or in healthcare centers with a high incidence of resistant pathogens, as well as in cases involving profound mucositis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In line with these recommendations, the present study demonstrates decreased susceptibility of GNR to the usual empiric antibiotic regimens, especially the resistance of GNR to PIP-TAZ in about one-third of cases, while this treatment was administered in 77.7% of neutropenic courses. This serious finding may call into question the appropriateness of PIP-TAZ as an empiric antimicrobial treatment in patients with AML with neutropenic fever and high suspicion of bacteremia. Furthermore, whether these resistance rates are also observed in patients with bacteremia in other malignancies needs to be explored. Importantly, any switch to a broad-spectrum antimicrobial regimen in patients with neutropenic fever should be accompanied by large population-based prospective studies because of the impact on the development of multidrug-resistant bacteria in patients and in the general population.\u003c/p\u003e \u003cp\u003eThe limitations of this study include the retrospective analysis of all courses and the lack of data regarding the association with mucositis and colitis that would have helped clarify factors responsible for the predominance of GNR in this population. Further, the variable empiric therapy given per physician choice and medical center guidelines precludes a strong statement about the utility of each antibiotic regimen for the treatment of fever and neutropenia in pediatric patients with AML. Finally, data about fungal infection especially candida was not collected and reported in this study. The strengths of this study include data collection for all de novo AML patients on a frontline uniform protocol in Israel.\u003c/p\u003e \u003cp\u003eIn conclusion, the current study found that three-quarters of patients on the NOPHO-DBH 2012 AML protocol in Israel between 2016 and 2019 experienced bacteremia, leading to a high mortality rate. Unlike prior investigations, our research identified a predominance of GNR, accounting for 50% of mortality cases, a noteworthy finding that has implications for choosing prophylactic treatments. Additionally, the high resistance to Quinolones limits its use as a prophylactic treatment, and the resistance to PIP-TAZ, the primary empirical treatment, underscores the necessity of broadening antibiotic coverage for patients with a high clinical suspicion of bacteremia or sepsis. Finally, more studies may clarify whether age or Arab ethnicity are potential independent risk factors for bacteremia in Israeli pediatric cancer patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eAML\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003eacute myeloid leukemia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003eadjusted odds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eCLABSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ecentral\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eline-associated bloodstream infection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eCoNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ecoagulase-negative staphylococci\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eCVL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ecentral venous line\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eFCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003eflow cytometry\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eGNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003eGram-negative rods\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eGPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003eGram-positive cocci\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ehigh-risk\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eHSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ehematopoietic stem cell transplantation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003ePIP-TAZ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ePiperacillin/Tazobactam\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eSR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003estandard-risk\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eVGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003eViridans Group Streptococci\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.137724550898202%\" valign=\"top\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"68.8622754491018%\" valign=\"top\"\u003e\n \u003cp\u003ewhite blood count\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis study was approved by the Institutional Review Board and Ethics Committee of all centers (RMB-661-19). The consent to participate was exempt by the IRB.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIt was not funded by any institution or grant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSummary of the data and material can be given upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo Conflict of Interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: We express our gratitude to the Israel Cancer Association, Chaim Association, and Israel Children\u0026rsquo;s Cancer Foundation for their generous support. Additionally, we extend our appreciation to all pediatric hematology-oncology departments in Israel for their devoted care of challenging patients\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eElgarten CW, Aplenc R. Pediatric acute myeloid leukemia: updates on biology, risk stratification, and therapy, \u003cem\u003eCurr. Opin. Pediatr.\u003c/em\u003e, vol. 32, no. 1, 2020, [Online]. 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High-dose cytosine arabinoside and viridans streptococcus sepsis in children with leukemia. Pediatr Hematol Oncol. 1995;12(4):387\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/08880019509029589\u003c/span\u003e\u003cspan address=\"10.3109/08880019509029589\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute myeloid leukemia, pediatric, bacteremia, gram-negative rods","lastPublishedDoi":"10.21203/rs.3.rs-3953893/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3953893/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBacteremia complicates more than 50% of childhood Acute myeloid leukemia (AML) patients with predominantly Gram-positive cocci )GPC).\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eAssess bacteremia rates, risk factors, causative organisms, and antibiotic resistance in Israeli children with de-novo AML.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eall chemotherapy courses for patients enrolled in the standard arm of the NOPHO-DBH 2012 AML protocol were included. Down syndrome, myelodysplastic syndrome, acute promyelocytic leukemia, secondary AML, and isolated granulocytic sarcoma were excluded. No routine antibacterial prophylaxis was applied.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 69 patients, 7 had focal bacterial infections. Of the remaining 62, 77.4% had bacteremia episodes, ranging from 1 to 8 per patient. Out of 238 chemotherapy courses, 98 (41.2%) resulted in bacteremia, with 66 (67.3%) courses showing predominantly Gram-negative rods (GNR) and 28 (28.6%) courses with Gram-positive cocci (GPC). The most common was \u003cem\u003eEscherichia coli\u003c/em\u003e; followed by Klebsiella spp. Older age, Arab ethnicity, and presenting white blood cell count were associated with an increased risk of bacteremia in a univariate analysis. Six patients (9.7%) died, 3 of whom were from Gram-negative infection. Bacteremia resulted in a 7-fold increase in intensive care unit admissions. Empiric antibiotic treatment using piperacillin-tazobactam and vancomycin provided sufficient coverage in 75.5% of cases. Improved coverage was attained with amikacin (90.8%) or the combination of vancomycin and meropenem (94.7%). Quinolones were effective against GNR isolates in 42 cases (61.8%).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDe-novo AML patients face high mortality from predominantly GNR bacteremia. Specific interventions are needed to reduce rates, but limited susceptibility to quinolones hampers prophylactic use.\u003c/p\u003e","manuscriptTitle":"National Study Reveals Gram Negative Bacteremia on Contemporary Pediatric AML Protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-16 16:41:33","doi":"10.21203/rs.3.rs-3953893/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e32f249-e2d2-4deb-a350-24bb9af27039","owner":[],"postedDate":"February 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-20T00:19:54+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-16 16:41:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3953893","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3953893","identity":"rs-3953893","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}