Fever In Neutropenic Patients Research Articles

Antimicrobial use and appropriateness in neutropenic fever: a study of the Hospital National Antimicrobial Prescribing Survey data.

Neutropenic fever (NF) is a common complication in patients receiving chemotherapy. Judicious antimicrobial use is paramount to minimize morbidity and mortality and to avoid antimicrobial-related harms. To use an Australian national dataset of antimicrobial prescriptions for the treatment of NF to describe antimicrobial use, prescription guideline compliance and appropriateness; and to compare these findings across different healthcare settings and patient demographics. We also aimed to identify trends and practice changes over time. Data were extracted from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) database from August 2013 to May 2022. Antimicrobial prescriptions with a NF indication were analysed for antimicrobial use, guideline compliance and appropriateness according to the Hospital NAPS methodology. Demographic factors, hospital classifications and disease characteristics were compared. A total of 2887 (n = 2441 adults, n = 441 paediatric) NF prescriptions from 254 health facilities were included. Piperacillin-tazobactam was the most prescribed antimicrobial. Overall, 87.4% of prescriptions were appropriate. Piperacillin-tazobactam and cefepime had the highest appropriateness though incorrect piperacillin-tazobactam dosing was observed. Lower appropriateness was identified for meropenem, vancomycin, and gentamicin prescribing particularly in the private hospital and paediatric cohorts. The most common reasons for inappropriate prescribing were spectrum too broad, incorrect dosing or frequency, and incorrect duration. This study provides insights into antimicrobial prescribing practices for NF in Australia. We have identified three key areas for improvement: piperacillin-tazobactam dosing, paediatric NF prescribing and private hospital NF prescribing. Findings from this study will inform the updated Australian and New Zealand consensus guidelines for the management of neutropenic fever in patients with cancer.

Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( −) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( −) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

Antibiotic practice and stewardship in the management of neutropenic fever: A survey of US institutions

Background: Neutropenic fever management decisions are complex and result in prolonged duration of broad-spectrum antibiotics. Strategies for antibiotic stewardship in this context have been studied, including de-escalation of antibiotics prior to resolution of neutropenia, with unclear implementation. Here, we present the first survey study to describe real-world neutropenic fever management practices in US healthcare institutions, with particular emphasis on de-escalation strategies after initiation of broad-spectrum antibiotics. Methods: Using REDCap, we conducted a survey of US healthcare institutions through the SHEA Research Network (SRN). Questions pertained to antimicrobial prophylaxis and supportive care in the management of oncology patients and neutropenic fever management (including specific antimicrobial choices and clinical scenarios). Hematologic malignancy hospitalization (2020) and bone-marrow transplantation (2016–2020) volumes were obtained from CMS and Health Resources &amp; Services Administration databases, respectively. Results: Overall, 23 complete responses were recorded (response rate, 35.4%). Collectively, these entities account for ~11.0% of hematologic malignancy hospitalizations and 13.3% bone marrow transplantations nationwide. Of 23 facilities, 19 had institutional guidelines for neutropenic fever management and 18 had institutional guidelines for prophylaxis, with similar definitions for neutropenic fever. Firstline treatment universally utilized antipseudomonal broad-spectrum IV antibiotics (20 of 23 use cephalosporin, 3 of 23 use penicillin agent, and no respondents use carbapenem). Fluoroquinolone prophylaxis was common for leukemia induction patients (18 of 23) but was mixed for bone-marrow transplantation (10 of 23). We observed significant heterogeneity in treatment decisions. For stable neutropenic fever patients with no clinical source of infection identified, 13 of 23 respondents continued IV antibiotics until ANC (absolute neutrophil count) recovery. The remainder had criteria for de-escalation back to prophylaxis prior to this (eg, a fever-free period). Respondents were more willing to de-escalate prior to ANC recovery in patients with identified clinical sources (14 of 23 de-escalations in patients with pneumonia) or microbiological sources (15 of 23 de-escalations in patients with bacteremia) after dedicated treatment courses. In free-text responses, several respondents described opportunities for more systemic de-escalation for antimicrobial stewardship in these scenarios. Conclusions: Our results illustrate the real-world management of neutropenic fever in US hospitals, including initiation of therapy, prophylaxis, and treatment duration. We found significant heterogeneity in de-escalation of empiric antibiotics relative to ANC recovery, highlighting a need for more robust evidence for and adoption of this practice.Disclosures: None

Which trial do we need? Plasma metagenomic next-generation sequencing to diagnose infections in patients with haematological malignancies and febrile neutropenia: proposal for a randomized-controlled trial

Which trial do we need? Plasma metagenomic next-generation sequencing to diagnose infections in patients with haematological malignancies and febrile neutropenia: proposal for a randomized-controlled trial

Systematic Review of the Short-Term versus Long-Term Duration of Antibiotic Management for Neutropenic Fever in Patients with Cancer.

Early antibiotic discontinuation has been proposed in patients with hematologic malignancy with fever of unknown origin during febrile neutropenia (FN). We intended to investigate the safety of early antibiotic discontinuation in FN. Two reviewers independently searched for articles from Embase, CENTRAL, and MEDLINE on 30 September 2022. The selection criteria were randomized control trials (RCTs) comparing short- and long-term durations for FN in cancer patients, and evaluating mortality, clinical failure, and bacteremia. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. We identified eleven RCTs (comprising 1128 distinct patients with FN) from 1977 to 2022. A low certainty of evidence was observed, and no significant differences in mortality (RR 1.43, 95% CI, 0.81, 2.53, I2 = 0), clinical failure (RR 1.14, 95% CI, 0.86, 1.49, I2 = 25), or bacteremia (RR 1.32, 95% CI, 0.87, 2.01, I2 = 34) were identified, indicating that the efficacy of short-term treatment may not differ statistically from that of long-term treatment. Regarding patients with FN, our findings provide weak conclusions regarding the safety and efficacy of antimicrobial discontinuation prior to neutropenia resolution.

1022. The Role of Baseline Body Temperature in Neutropenic Fever

Abstract Background The management of neutropenic fever patients is challenging – from identification to diagnosis to treatment. We hypothesize that patients’ individual baseline body temperature provides diagnostic and prognostic value. Methods This is an analysis of 92 adult patients admitted for neutropenic fever to a tertiary medical center over 1 year period. We modelled the length of stay and the ability to find a definitive diagnosis using the change in body temperature from each patient’s outpatient baseline, the neutropenia level and overall patient acuity on admission, persistence of fever over 48-72 hours, and age. All temperatures were standardized to oral. Refer to Table 1 for the inclusion and exclusion criteria and statistical methods. Table 1.Inclusion and exclusion criteria and statistical methods. Results Refer to Tables 2 and 3 for demographics and descriptive statistics of temperature readings, to Table 4 for advanced statistical analyses. Importantly, the average baseline body temperature was at 36.7C; the average fever on admission was at 38.1C; based on the ≥ 38C cutoff, only 24% of patients had persistent fever over 48-72 hours but based on personalized cutoffs at &amp;gt; 2 standard deviations (SDs) or &amp;gt; 3 SDs above their outpatient baseline, 54% and 34% had persistent fever, respectively; the etiology of fever was identified in 48% of patients, all of which constituted infections; our multiple regression model demonstrated that a longer length of stay (LOS) of ≥ 4 days was predicted by larger deviation from baseline body temperature at admission and independently by fever persistence, after correcting for age, neutropenia level, and need for ICU level of care on admission. A similar model could not predict the ability to identify a fever-explaining diagnosis. Conclusion Given the average outpatient baseline body temperature of 36.7 +/- 0.3C, at 2 standard deviations (SDs) above this baseline, only 3% of patients would be at the 38C cutoff for fever, at 3 SDs, it would be 20%, thus rendering the standard 38C cutoff too high to be useful in identifying many neutropenic fever cases and supporting the use of personalized cutoffs based on patient’s baseline temperature. Further, consideration of the specific deviation from patients’ baseline body temperature could serve as a predictor for hospital LOS in patients admitted with neutropenic fever. Disclosures All Authors: No reported disclosures.

Pathogen Detection by Metagenomic Next-Generation Sequencing During Neutropenic Fever in Patients With Hematological Malignancies.

BackgroundFebrile neutropenia (FN) after chemotherapy is a major cause of morbidity during cancer treatment. The performance of metagenomic next-generation sequencing (mNGS) of circulating cell-free deoxyribonucleic acid from plasma may be superior to blood culture (BC) diagnostics for identification of causative pathogens. The aim of this study was to validate mNGS (DISQVER test) for the detection of pathogens in hematologic patients with FN.MethodsWe collected paired whole blood specimens from central venous catheter and peripheral vein during FN for BC and mNGS testing. We repeated paired sampling at the earliest after 3 days of fever, which was defined as 1 FN episode. All clinical data were retrospectively reviewed by an infectious disease expert panel. We calculated percent positive agreement (PPA), percent negative agreement (PNA), percent overall agreement (POA), and sensitivity and specificity.ResultsWe analyzed a total of 98 unselected FN episodes in 61 patients who developed predominantly FN after conditioning therapy for allogeneic (n = 22) or autologous (n = 21) hematopoietic stem cell transplantation. Success rate of mNGS was 99% (97 of 98). Positivity rate of mNGS was 43% (42 of 97) overall and 32% (31 of 97) excluding viruses compared to 14% (14 of 98) in BC. The PPA, PNA, and POA between mNGS and BC were 84.6% (95% confidence interval [CI], 54.6% to 98.1%), 63.1% (95% CI, 51.9% to 73.4%), and 66% (95% CI, 55.7% to 75.3%), respectively. Sensitivity for bacteria or fungi was 40% (95% CI, 28.0% to 52.9%) and 18.5% (95% CI, 9.9% to 30.0%), respectively.ConclusionsPathogen detection by mNGS (DISQVER) during unselected FN episodes shows 2-fold higher sensitivity and a broader pathogen spectrum than BC.

The long and short of antibiotic management for neutropenic fever in patients with haematological malignancy

Neutropenic fever is a common complication of therapy for haematological malignancy and in about 40% of episodes, no clinical focus or microbiological cause is identified. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 2 Averbuch D Orasch C Cordonnier C et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98: 1826-1835 Crossref PubMed Scopus (343) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar The optimal strategy for antibiotic management in the setting of neutropenic fever with no identified source is yet to be defined. Common strategies include early de-escalation from empiric therapy to antibiotic prophylaxis until neutrophil recovery or complete cessation of antibiotic therapy with different cessation thresholds used. 2 Averbuch D Orasch C Cordonnier C et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98: 1826-1835 Crossref PubMed Scopus (343) Google Scholar , 4 Freifeld AG Bow EJ Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52: e56-e93 Crossref PubMed Scopus (2014) Google Scholar A cellular recovery threshold (neutrophil count ≥0·5×109/L) for cessation has been recommended, 4 Freifeld AG Bow EJ Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52: e56-e93 Crossref PubMed Scopus (2014) Google Scholar but, new data suggest the use of clinically guided cessation using clinical stability and resolution of fever for earlier antibiotic cessation. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar Earlier antibiotic cessation compared with continuation until resolution of neutropenia is associated with lower antibiotic exposure and no significant difference in rates of clinical failure, safety, or mortality. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trialEarly discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. Full-Text PDF

Protocolo diagnóstico y tratamiento empírico de la infección sin focalidad en el paciente neutropénico

Neutropenic patients are at particularly high risk of infection, with fever being the only sign they present with in the majority of cases. An etiological diagnosis is made in just 20% to 30% of febrile episodes. Early diagnosis and effective treatment are crucial for decreasing morbidity and mortality in this population. The treatment of fever in neutropenic patients includes intravenous beta-lactam antibiotics such as cefepime. Multidrug-resistant pathogens are emerging and there are few new anti-infectious agents being developed. Therefore, a rational use of antimicrobial agents is fundamental.

Loss of microbiota-derived protective metabolites after neutropenic fever

Neutropenic fever (NF) is a common complication of chemotherapy in patients with cancer which often prolongs hospitalization and worsens the quality of life. Although an empiric antimicrobial approach is used to prevent and treat NF, a clear etiology cannot be found in most cases. Emerging data suggest an altered microbiota-host crosstalk leading to NF. We profiled the serum metabolome and gut microbiome in longitudinal samples before and after NF in patients with acute myeloid leukemia, a prototype setting with a high incidence of NF. We identified a circulating metabolomic shift after NF, with a minimal signature containing 18 metabolites, 13 of which were associated with the gut microbiota. Among these metabolites were markers of intestinal epithelial health and bacterial metabolites of dietary tryptophan with known anti-inflammatory and gut-protective effects. The level of these metabolites decreased after NF, in parallel with biologically consistent changes in the abundance of mucolytic and butyrogenic bacteria with known effects on the intestinal epithelium. Together, our findings indicate a metabolomic shift with NF which is primarily characterized by a loss of microbiota-derived protective metabolites rather than an increase in detrimental metabolites. This analysis suggests that the current antimicrobial approach to NF may need a revision to protect the commensal microbiota.

A Retrospective Study of Febrile Neutropenia From a Cancer Hospital

Background Fever in neutropenic patients is considered an emergency medical condition, requiring early recognition and prompt management. The aims of this study were to find the pathogen and time to antibiotic administration, and to identify predictive factors of mortality in patients with febrile neutropenia. Methods We retrospectively reviewed the clinical manifestations, pathogenic organisms, treatment regimens, and 30-day mortality of febrile neutropenic adult patients with solid tumor admitted to a cancer hospital in Thailand from January 2014 to December 2019. Results We enrolled 96 episodes of febrile neutropenia. Median age was 53 years. Sixty-two patients (64.6%) were female. The 2 most common cancers were head and neck (31.2%), followed by breast (30.2%), and 69.8% of all patients were in the advanced stage. Seven patients (7.3%) died within 30 days after onset. Bacteremia occurred in 7 episodes (7.8%). Source of infection was identified in 21 patients (21.8%). Gram-negative organism accounted for 85% of bacteremia and 79% of isolated pathogen. Pseudomonas aeruginosa was the most frequently identified causative organism. The most common empirical antibiotic was ceftazidime (67.7%). Median time to antibiotic administration was significantly shorter for nonsurvivors (32.5 minutes) than for survivors (62.0 minutes; P = 0.031). In the multivariate analysis, sepsis (odd ratio, 10.74; 95% confidence interval, 1.93–59.73; P = 0.007) was associated with increased 30-day mortality. Conclusions Gram negative was the predominant pathogen of neutropenic patients in this study. Shorter time to antibiotic administration did not contribute to a better outcome. Sepsis was an unfavorable predictive factor of death.

Rates of Neutropenic Fever in Patients with Hematologic Malignant Diseases with Central Venous Access

Background: Patients who are diagnosed with hematologic malignant diseases (HMD) almost invariably receive placement of central venous catheters (CVCs), whether temporary or permanent. These catheters are used for administration of various chemotherapies, antibiotics and even nutrition. Although the patients with HMD are immunocompromised, prophylactic use of antibiotics among these patients, especially related to CVC placement, remains controversial. This retrospective analysis evaluates the rates of development of neutropenic fever in patients with HMD with CVCs receiving prophylactic antibiotics.Methods: Data were collected retrospectively in a cohort of 268 patients with HMD who received treatment at our academic institution between 2002 to 2019. Demographic and other related data was abstracted and descriptive analysis was performed using Epi-Info - 7 software.Results: Of the 268 patients with HMD, 175 patients (65.3%) received prophylactic antibiotics and among these patients, 180 (67.2%) had a permanent CVC and 109 (40.7%) had a temporary CVC. Comparatively, 93 patients (34.7%) did not receive prophylactic antibiotics and among these individuals, 64 (68.8%) had a permanent CVC and 34 (36.6%) had a temporary CVC. In patients with a permanent central line, 84.3% of patients receiving prophylactic antibiotics developed neutropenic fever while 85% of those who did not receive prophylactic antibiotic also developed neutropenic fever. Among the individuals with a temporary CVC, 79.7% of patients receiving prophylactic antibiotics developed neutropenic fever and 65.4% of patients who were not receiving prophylactic antibiotics also developed neutropenic fever. None of the differences were statistically significant (p=0.8990 and p=0.1547 respectively).Conclusion: In this cohort of HMD patients, the rate of neutropenic fever development in patients with central venous access receiving prophylactic antibiotic was not significantly different compared to the rate of neutropenic fever development in patients with central venous access who did not receive any prophylactic antibiotic. This data suggests that there does not appear to be a significant clinical utility for prophylactic antibiotics in the prevention of neutropenic fever in patients with HMD who have central venous catheters in place. Further studies analyzing the impact of prophylactic antibiotics on true infections as an etiology for neutropenic fevers in patients with HMD and central venous catheters is warranted. DisclosuresNo relevant conflicts of interest to declare.

Serum Hepcidin and Prohepcidin Levels in Nonfebrile and Febrile Neutropenia.

To compare the prohepcidin and hepcidin levels in the afebrile neutropenic period and neutropenic fever in patients with hematological malignancy. Descriptive study. Department of Hematology, Pamukkale University Hospital, Denizli, Turkey, between January 2018 and December 2019. Neutropenic patients were compared with a healthy control group. Prohepcidin and hepcidin serum levels were to be measured in neutropenic and control groups. When fever occurred in neutropenic group, serum was taken again and the same values were compared, in addition to procalcitonin and CRP values. Prohepcidin and hepcidin levels were found to be significantly higher in the neutropenic group (n = 53) than the control group [n = 44, (med:166.65 ng/ml, IQR:147.66 - 187.38 ng/ml vs. med:47.49 ng/ml, IQR:15.61 - 82.51 ng/ml; p <0.001); (med:315 ng/ml, IQR:314.92 - 315 ng/ml vs. med:26.61 ng/ml, IQR:4.69 - 66.83 ng/ml; p <0.001)]. No significant difference was found in terms of these two analyses (167.29 ± 29.31 ng/ml vs. 167.15 ± 27.61 ng/ml; p = 0.979; 296.21 ± 37.19 ng/ml vs 299.16 ± 37.68 ng/ml; p= 0.629) in the neutropenic fever period compared to the afebrile neutropenic period. In neutropenic fever patients, procalcitonin and CRP (C-reactive protein) were found significantly higher than the afebnile neutropenic group (0.7 ± 1.2 ng/ml vs. 0.25 ± 0.76 ng/ml; p = 0.034; 10.27 ± 9.93 mg/dl vs 2.61 ± 2.78 mg/dl; p <0.001). Although there was no significant difference between afebnile neutropenia and neutropenic fever in patients in terms of hepcidin and prohepcidin levels, higher levels were found in both groups compared to the control group. Key Words: Hepcidin, Prohepcidin, Neutropenia, Febrile neutropenia.

Altered microbiota-host metabolic cross talk preceding neutropenic fever in patients with acute leukemia

AbstractDespite antibiotic prophylaxis, most patients with acute leukemia receiving mucotoxic chemotherapy develop neutropenic fever (NF), many cases of which remain without a documented etiology. Antibiotics disrupt the gut microbiota, with adverse clinical consequences, such as Clostridioides difficile infection. A better understanding of NF pathogenesis could inform the development of novel therapeutics without deleterious effects on the microbiota. We hypothesized that metabolites absorbed from the gut to the bloodstream modulate pyrogenic and inflammatory pathways. Longitudinal profiling of the gut microbiota in 2 cohorts of patients with acute leukemia showed that Akkermansia expansion in the gut was associated with an increased risk for NF. As a prototype mucolytic genus, Akkermansia may influence the absorption of luminal metabolites; thus, its association with NF supported our metabolomics hypothesis. Longitudinal profiling of the serum metabolome identified a signature associated with gut Akkermansia and 1 with NF. Importantly, these 2 signatures overlapped in metabolites in the γ-glutamyl cycle, suggesting oxidative stress as a mediator involved in Akkermansia-related NF. In addition, the level of gut microbial–derived indole compounds increased after Akkermansia expansion and decreased before NF, suggesting their role in mediating the anti-inflammatory effects of Akkermansia, as seen predominantly in healthy individuals. These results suggest that Akkermansia regulates microbiota-host metabolic cross talk by modulating the mucosal interface. The clinical context, including factors influencing microbiota composition, determines the type of metabolites absorbed through the gut barrier and their net effect on the host. Our findings identify novel aspects of NF pathogenesis that could be targets for precision therapeutics. This trial was registered at www.clinicaltrials.gov as #NCT03316456.

Antimicrobial prophylaxis and post-chemotherapy neutropenic fever in patients with leukemia: comparisons of C-reactive protein, procalcitonin and immediate fever outcome measures between those with and without prophylaxis, and the implications for practice

PurposeThe efficacy of prophylactic antimicrobial treatment renders challenges in patients with leukemias receiving chemotherapy. The study aimed to compare differences in C-reactive protein (CRP) and procalcitonin (PCT) at presentation and the immediate outcome measures of post-chemotherapy NF between patients with and without antimicrobial prophylaxis.MethodsA 5-year observational study included 282 NF episodes in 133 leukemia patients requiring hospital care from January 2014 to May 2019. We collected demographic characteristics, laboratory data of blood cell counts and inflammatory biomarkers, and immediate outcome measures of NF, including microbiologically diagnosed infections, presence of predominant pathogens, required modification of antibiotics during NF, adverse medical complications, total fever duration, and deaths. We evaluated data between patients with and without prophylaxis.ResultsOf patients, 77.3%, 68.4%, and 20.6% had antibiotic prophylaxis, antifungal prophylaxis, and no prophylaxis, respectively. There were totally 15 deaths—13 with antibiotic prophylaxis and 10 with antifungal prophylaxis. CRP, PCT, and immediate outcome measures of NF did not show significant differences between those with and without antimicrobial prophylaxis. Although between-group differences showed no statistical significance, higher median fever duration, CRP and PTC values, and higher proportions of NF requiring modification of antibiotics were found more frequently in those with antimicrobial prophylaxis than in those without.ConclusionThe benefits of using antimicrobial prophylaxis were less supported. Enhancing diagnostic laboratory and medical complication surveillance and periodic evaluation of institutional data during post-chemotherapy neutropenia and NF in relation to antimicrobial prophylaxis is promising in providing insights to redefine the risk–benefit accounts of using prophylaxis.

Delays in time to antibiotics in inpatient oncologic neutropenic fever do not predict decreased overall survival.

e18765 Background: Neutropenic fever (NF) is relatively common oncologic emergency. Present expert consensus is that anti-pseudomonas gram-negative antibiotics should be administered within 60 minutes of detecting NF. To date studies investigating this relationship in neutropenic fever patients have been either limited in size, or have failed to reliably establish a relationship between time to antibiotics (TTA) and clinical outcomes.While some studies have shown an association between TTA and outcomes in NF patients admitted from the Emergency Department, such studies do not control for the time that patients may have been febrile in the community. To address these factors, we conducted a retrospective study on the effect of TTA on mortality in oncologic patients who developed NF as inpatients. Methods: We performed retrospective chart review of all cases of NF at an NCI designated Cancer Center between 7/1/2016 and 3/27/2019. NF was defined as temperature of 101˚ F on one occasion, or 100.4˚ F sustained over 60 minutes, with an absolute neutrophil count (ANC) less than 500. TTA and survival were calculated via chart abstraction; patients lost to follow up within 180 days were censored to the 180-day mortality group. Relationship between TTA and overall survival (OS) was analyzed via multivariable Cox regression. We excluded patients that had non-cancer related NF, were transferred from another institution with NF, were admitted from the ED with NF, or transitioned to hospice. Only the first instance of NF in any admission was analyzed. Results: A total of 187 eligible cases were identified during the study period, mean age was 57.6 +/- 13.6, 100 (53.5%) cases were in males, 114 (61.0%) cases in Caucasians, 53 (28.3%) in Black People. The 3 most common disease subtypes were acute leukemia (42.8%), plasma cell dyscrasias (27.8%), and lymphoma (16.6%). TTA showed no significant correlation with OS at any timeframe studied. Low Charlson Comorbidity Index ( &lt; 3) correlated with increased survival through ̃360 days, however the effect was non-significant at longer timeframes. Immediate antibiotic treatment ( &lt; 40 mins) correlated with poorer patient prognosis and significantly decreased OS (HR 3.08;CI: 1.30-7.28; p 0.010). Conclusions: TTA was not associated with OS in our study. For inpatients with NF, even hours long TTA may not be long enough to result in adverse clinical outcomes. Unlike NF patients presenting to the ED, where true TTA may often be many hours or even days prior to arrival, a few hours-long TTA in the hospital may not be sufficiently long enough to cause significant patient harm. Interestingly, in our cohort, those who received antibiotics quickly had adverse outcomes. It may be that in patients who were clinically unstable, TTA was shorter given the urgency of the situation. Ultimately, this study’s findings question the applicability of the 60-minute guideline when used in the inpatient setting.

EVALUASI PENGGUNAAN ANTIBIOTIKA PADA PASIEN LEUKEMIA LIMFOBLASTIK AKUT DENGAN DEMAM NEUTROPENIA DI RUMAH SAKIT UMUM DAERAH ABDUL WAHAB SJAHRANIE SAMARINDA

ABSTRACT&#x0D; &#x0D; The use of antibiotics is one of the management of neutropenic fever in patients with acute&#x0D; lymphoblastic leukemia (ALL). Irrational and excessive antibiotics can promote resistance to&#x0D; certain bacteria. The aim of this study was to evaluate the use of antibiotics given to ALL patients&#x0D; with neutropenic fever qualitatively and quantitatively. This type of observational research was&#x0D; conducted with a descriptive method using a cross-sectional design. Retrospective data collection&#x0D; from medical records of ALL patients who received antibiotics during 2017-2018. The quality of&#x0D; antibiotic use was analyzed using the Gyssens method, while the quantity of antibiotic use was&#x0D; analyzed using the DDD method per 100 bed days. Based on the results of the study of 7 ALL&#x0D; patients with neutropenic fever, the rational (category 0) use of antibiotics was 50% and the&#x0D; irrational (category I-IV) use of antibiotics was 50%. The use of inappropriate antibiotic dose (category IIA) was 25%, the use of the antibiotic inaccurate interval of use (category IIB) was&#x0D; 10%, and there was no indication that antibiotic use (category V) was 15%. Quantitative&#x0D; evaluation of the use of antibiotics using the DDD method per 100 bed days showed that the total&#x0D; use of antibiotics was 7 types with a DDD value of 100 patient days of 19.15. The most widely used&#x0D; antibiotic is the cephalosporin class, namely cefotaxime with a DDD value of 6.51.&#x0D; &#x0D; Keywords: antibiotics, leukemia, quality, quantity

S0526 Mortality and Infectious Adverse Events in Neutropenic Patients Undergoing Gastrointestinal Endoscopic Procedures: A Systematic Review and Meta-Analysis

INTRODUCTION: The safety of gastrointestinal endoscopy in neutropenic patients is unclear. American Society for Gastrointestinal Endoscopy guidelines state that patients with absolute neutrophil count (ANC) < 500 cells/µL and advanced hematologic malignancies are at increased risk for bacteremia and sepsis after endoscopy. Infectious Diseases Society of America guidelines state that endoscopy should be avoided in neutropenic patients. We performed a systematic review and meta-analysis to assess the safety of endoscopy in patients with neutropenia. METHODS: Bibliographic databases (Medline, EMBASE, Cochrane Library, Web of Science, Scopus, PubMed) were searched through November 2019 for studies in neutropenic patients (ANC < 1000 cells/µL) undergoing endoscopy with outcome data on infections, mortality, or fever. Abstracts from Digestive Disease Week, American College of Gastroenterology Annual Scientific Meeting, and United European Gastroenterology Week from January 2017 to January 2020 were also searched. Two independent reviewers identified studies meeting inclusion criteria, performed data extraction using a standardized form, and assessed risk of bias using the Newcastle-Ottawa scale. Co-primary outcomes were 30-day infection-related mortality and new infection within 30 days of endoscopy. Secondary outcomes included new bacteremia and new fever within 30 days. Random effects meta-analysis was used to calculate pooled proportions and effect estimates. RESULTS: Database search identified 2733 unique citations. Four studies from database search and 1 from conference abstract review met eligibility criteria (N = 928). All studies had high risk of bias. Overall proportion of infection-related mortality was 0.0% (95% CI: 0.0–0.4% I2: 0.0%) and infectious adverse events was 1.9% (95% CI: 0.0–6.4% I2: 77.0%) (Table 1). The proportion of neutropenic patients developing bacteremia was 1.7% (CI: 0.0-6.8% I2: 82.3%) and new fever was 0.0% (95% CI: 0.0–0.0% I2: 0.0%) (Table 2). Subgroup analysis was not performed due to zero events in a majority of studies and limited number of studies. However, data on antibiotic use prior to endoscopy was available in 3 studies; here the proportion of patients on antibiotics that developed new infections ranged from 0.0 to 1.2%. CONCLUSION: This systematic review and meta-analysis showed a low rate of mortality and infection following endoscopy in neutropenic patients. Additional large studies designed to assess the safety of endoscopy in neutropenic patients are needed.Figure 1.: PRISMA flow diagram summarizing study selection.Table 1.: Primary outcomes: 30 day infection-related mortality and infectious adverse events in neutropenic patients undergoing endoscopyTable 2.: Secondary outcomes: Bacteremia and new fever in neutropenic patients undergoing endoscopy

AML-294: Predictors of Short-Term and Long-Term Mortality in Leukemia Patients with Neutropenic Fever

Context Infections cause substantial morbidity and mortality in acute leukemia patients. Neutropenic fever (NF) frequently complicates leukemia chemotherapy, but the mortality rate of NF and predictors of mortality are not fully defined for adult leukemia patients. We examined factors that influence mortality and type of infection in NF patients admitted to the hematologic malignancy service of a referral hospital. Design Retrospective chart review of NF patients admitted to University of Louisville from April 2016 to July 2018 who had AML, ALL, CML, CLL, or MDS, excluding active transplant patients. We used logistic regression and Cox proportional hazard analysis to evaluate mortality predictors and the Kaplan-Meier method for survival. Median follow-up was 16.6 months. Results Sixty-two patients had 101 episodes of NF. Median age was 56. Frequent primary diagnoses were AML (70%), ALL (24%), CML (2%), and CLL (2%). Infections and bacteremia occurred in 72% and 54% of episodes, respectively. Mean length of stay was 19 +/- 12 days. Refractory/relapsed (R/R) disease (RR 1.53, p=0.034) and ANC nadir of 0 (RR 2.64, p=0.001) correlated with bacteremia. Thirty-day mortality was 14% and increased for R/R disease (OR 3.13, CI=0.99–9.92), bacteremia (OR 3.58, CI=0.94-13.7), and ICU-level care (OR 15.24, CI=4.11-56.5) in univariate analysis. ICU-level care (OR 29.1, CI=5.42–156) and R/R disease (OR 7.30, CI=1.43–37.4) retained significance in multivariate logistic regression. Gram +/- status, resistance pattern, neutropenia severity, age, and neutropenia duration did not influence short-term mortality. Eighty-six episodes had a high-risk MASCC score ( 60 (HR 2.16, CI=1.22–3.84), R/R disease (HR 5.58, CI=2.74–11.4) and ICU-level care (HR 4.96, CI=2.14–11.5) predicted long-term mortality. High-risk MASCC approached significance for OS; median OS 7.8 months (high-risk) versus not reached (low-risk, p = 0.076). Conclusions Bacteremia occurred in the majority of NF episodes we recorded. Thirty-day NF mortality was 14%. Mortality increases for patients with age > 60, R/R disease, and ICU-level care. Identification of high-risk factors in NF may guide the study of interventions such as myeloid growth factor support in appropriate populations.

Shock and Early Death in Hematologic Patients with Febrile Neutropenia.

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