Management Of Febrile Neutropenia Research Articles

Update on Febrile Neutropenia in Pediatric Oncological Patients Undergoing Chemotherapy

Febrile neutropenia (FN) is a common complication of chemotherapy in oncological children and one of the most important causes of morbidity and mortality in these patients. The early detection of a bacteremia and the rapid therapeutic intervention are crucial to improve the outcome. We analyzed the literature in order to clarify the epidemiology of FN in children undergoing chemotherapy, the specific factors associated with a negative outcome, the most common etiology, and the value of biological markers as a tool to make an early diagnosis or to monitor the evolution of the infection. Several studies have tried to identify specific factors that could help the clinician in the detection of an infection and in its microbiological identification. However, due to the heterogenicity of the available studies, sufficient evidence is lacking to establish the role of these risk factors in clinical practice and future research on this topic appear mandatory. Determinations of risk factors, etiology, and markers of febrile episodes in these patients are complicated by the characteristics of the underlying illness and the effects of treatments received. Although some studies have tried to develop an evidence-based guideline for the empiric management of FN in pediatrics, validated predictive scores and algorithms are still lacking and urgently needed.

133 Value-based care for healthy children with first episode of febrile neutropenia

Abstract Primary Subject area Emergency Medicine - Paediatric Background While the management of febrile neutropenia in patients with cancer has clear, evidence-based guidelines, the management of previously healthy, immunocompetent children with a febrile illness and first episode of neutropenia is less understood. These patients are often similarly treated with empiric antibiotics and hospitalization despite studies demonstrating that this population, if they are well-appearing with a short history of neutropenia, is at low risk of serious bacterial infections. Therefore, less aggressive management should be considered in patients meeting low risk criteria. Objectives The aim of our quality improvement (QI) study was to decrease the number of unnecessary hospitalizations and empiric antibiotics prescribed by 50% over a 12-month period for otherwise healthy, well appearing patients presenting to the emergency department (ED) with a first episode of febrile neutropenia. Design/Methods A team of stakeholders from Hematology, Infectious Disease, Pediatrics and Emergency Medicine was assembled. A review of the literature, peer institutions and local practices of managing febrile neutropenia in healthy children was performed. Using the Model for Improvement, a guideline for the management of healthy children with first episode of febrile neutropenia was developed and refined using PDSA cycles. In January 2020, the guideline was launched for clinical use in the ED. Education, targeted audit and feedback, pathway modifications, and reminders were used to address knowledge gaps and staff turnover. A family of measures was analyzed using run charts and statistical process control (SPC) methods. Results Eighteen months of baseline data identified nineteen low risk patients with 84% either hospitalized and/or received antibiotics. It was also uncovered that many patients were misdiagnosed with neutropenia by excluding bands from the absolute neutrophil count (ANC). After the first twelve months of the intervention, sixteen patients met low risk criteria. Hospitalization and/or antibiotics use for this population decreased to 25% and all blood cultures were negative. Recognition of true severe febrile neutropenia also improved. Forty-one patients had a neutrophil count < 0.5, but an ANC > 0.5. Hospitalization and/or antibiotics use for this population decreased from 52% to 10%. Conclusion Through a multi-faceted, multidisciplinary QI study, we improved resource stewardship and value-based care by reducing unnecessary hospitalizations and antibiotics in low risk patients with a first episode of febrile neutropenia. Next steps include iterations to the guideline to increase impact along with sustainability planning. This work can easily be adopted by other pediatric and community sites caring for children.

Usefulness analysis of the 2018 ASCO/IDSA guideline for outpatient management of fever and neutropenia in adults treated for malignancy

Although the clinical practice guideline for outpatient management of febrile neutropenia (FN) in adults treated for malignancy was updated by the ASCO/IDSA in 2018, most patients with FN in our hospital have been hospitalized. We performed this study to analyze the usefulness of the guideline. The medical records of patients hospitalized for FN in Kyungpook National University Chilgok Hospital from May 2016 to April 2018 were retrospectively reviewed. The feasibility of candidates for outpatient management according to the guideline was evaluated based on the outcomes. A total of 114 patients were enrolled and categorized into two groups, low-risk (38.6%) and high-risk (61.4%). The proportion of feasible candidates for outpatient management was 70.2% and was higher in the low-risk than in the high-risk group (90.0% vs. 57.1%; P < 0.001). The low-risk group had no mortality, no resistance to oral amoxicillin/clavulanate or ciprofloxacin, a higher rate of successful empirical antibiotics, and lower rates of glycopeptide or carbapenem administration. A significant number of hospitalized cancer patients treated for FN after chemotherapy were found to be feasible candidates for outpatient management. The guideline can be a useful tool to reduce labor of healthcare workers and hospitalization costs.

Evidence-based prevention and management of febrile neutropenia in patients undergoing chemotherapy for breast cancer

Evidence-based prevention and management of febrile neutropenia in patients undergoing chemotherapy for breast cancer

Evaluation of the clinical Index of Stable febrile neutropenia risk stratification system for management of febrile neutropenia in gynecologic oncology patients

ObjectiveScoring systems have been developed to identify low risk patients with febrile neutropenia (FN) who may be candidates for outpatient management. We sought to validate the predictive accuracy of the Clinical Index of Stable Febrile Neutropenia (CISNE) score alone and in conjunction with alternative scoring systems for risk of complications among gynecologic oncology patients. MethodsWe conducted a single institution retrospective cohort study of patients admitted to an academic gynecologic oncology service for FN. We examined the performance characteristics (sensitivity, specificity, positive and negative predictive value) of three scoring systems (Multinational Association of Supportive Care in Cancer (MASCC), CISNE cut-off 1 (Low risk = 0), CISNE cut-off 2 (Low risk = <3)), and the combination of MASCC and CISNE to predict complications: inpatient death, ICU admission, hypotension, respiratory/renal failure, mental status change, cardiac failure, bleeding, and arrhythmia. ResultsFifty patients were identified for study inclusion. No low-risk CISNE patients died during hospitalization. Fewer CISNE low-risk patients experienced complications compared to high-risk patients, regardless of cut-off. Sensitivity, specificity, positive and negative predictive values of the scoring systems were: CISNE 1–37.1%, 86.7%, 86.7%, 37.1%; CISNE 2–85.7%, 46.7%, 78.9%, 58.3%; MASCC-82.9%, 66.7%, 85.3%, 62.5%; MASCC + CISNE 1–37.1%, 93.3%, 92.9%, 38.9%; MASCC + CISNE 2–80%, 73.3%, 87.5%, 61.1%. ConclusionsThe CISNE scoring system is an appropriate tool for the identification of patients with gynecologic cancers and FN who may benefit from close outpatient management. CISNE cut-off 2 performed comparably to the MASCC, but CISNE cut-off 1 had a higher specificity and positive predictive value.

Survey of practices for the clinical management of febrile neutropenia in children in hematology-oncology units in Latin America

The management of febrile neutropenia (FN) in pediatrics is evolving. Our objective was to describe current practices for the care of patients with FN in pediatric oncology centers in Latin America and identify areas for practice improvement. We used an online survey to enroll eligible healthcare providers who treat children with cancer in Latin America. The survey addressed respondents’ characteristics, the environment of care, and FN care practices, including risk assessment, criteria for hospitalization, initial management of FN, evaluation, antibiotic administration, and discharge. From 220 surveys sent, we received 109 responses and selected 108 from 19 countries for analysis. Most (94%) respondents were working in specialized oncology centers, oncology units within a pediatric or general care hospital. The cohort included oncologists (42%) and infectious diseases physicians (30%). Most (67%) respondents had available guidelines; they used a risk-stratification scoring system (73%) for severe infection; and their guidelines had locally adapted risk stratification (34%) or published risk stratification (51%). The respondents used diverse FN definitions and concepts, including fever definitions, temperature-obtaining methods, neutropenia values for assigning risk, empiric antimicrobials administration, and length of hospitalization. Overall, we detected common practices aligning with standard published recommendations, as well as care variability. These findings can guide further evaluations of care resources and practices to prioritize interventions, and professional networks can be used for FN discussions and consensus in Latin America.

Comparison of the Power of Procalcitonin and C-Reactive Protein to Differentiate between Different Etiologies of Febrile Neutropenia in Patients with Prolonged Profound Neutropenia

Background: The management of febrile neutropenia in case of prolonged profound neutropenia remains challenging as there are many possible infectious and non-infectious causes for fever in these patients. In more than 60% of cases there is no documented infectious etiology and unresolved febrile neutropenia often results in multiple empirical modifications of antibacterial therapy and/or addition of antifungal therapy. Unfortunately, indiscriminate use of broad-spectrum antibiotics can lead to important collateral damage including toxicity, selection of multidrug resistant pathogens and an increased predisposition to other infections such as Clostridium difficile or yeasts/fungi. In this study, we investigated whether procalcitonin (PCT) is superior to C-reactive protein (CRP) in discriminating between different etiologies of fever.Methods: CRP and PCT were tested daily during 93 neutropenic episodes in 66 patients (Table 1). A linear mixed model was performed to evaluate the effects of different variables on the values of CRP and PCT over time. A total of 121 febrile episodes occurred during this study period and were classified into four categories based on clinical and microbiological findings: microbiologically documented infection (MDI); clinically documented infection (CDI); proven or probable invasive fungal disease (IFD); fever of unknown origin (FUO). The values of PCT and CRP on day 2 after onset of fever were considered for analysis of their performance in distinguishing etiologies of fever in receiver operating characteristic (ROC) curves and by calculation of sensitivity, specificity, positive & negative predictive values and efficiency.Results: In 61 out of 93 neutropenic episodes (66.7%) the evolution of PCT and CRP was clearly different. CRP seemed to be a more volatile parameter, rising above its ULN (3 mg/dL) during every neutropenic episode. Its reactivity to stimuli was also quite pronounced with a median of 2 surges above 100 mg/dL per neutropenic episode. In contrast, PCT did not rise above its ULN (0.5 ng/mL) in 50 out of 93 neutropenic episodes (53.8%). The only confounding factor on the evolution of CRP and PCT with a clinically relevant large effect size was administration of antithymocyte globulin (ATG), which led to an 11-fold increase of PCT versus a 2-fold increase of CRP.On the day of fever onset no significant difference in PCT values was observed between different etiologies of fever (p=0.314), whereas median CRP values were significantly higher in IFD versus all other etiologies (median 98.8 mg/dL vs 28.8 mg/dL, p=0.027). Both PCT and CRP reached their peak at a median of 2 days after onset of febrile neutropenia. Median PCT values on day 2 showed no statistically significant difference when comparing etiologies of fever (Figure 1A). There was a tendency towards higher median PCT values in MDI and IFD where they rose > 0.25 ng/mL, while they did not in CDI or FUO without prior administration of ATG. Median CRP values on day 2 after fever onset were significantly higher in IFD versus all other etiologies (median 172 mg/dL vs 78.4 mg/dL, p=0.002). In MDI median CRP values rose > 100 mg/dL, whereas they did not in CDI or FUO (Figure 1B).The discriminatory power between IFD and FUO of CRP on day 2 after onset of febrile neutropenia was superior to that of PCT. With the cut-off set at 200 mg/dL, CRP has a positive predictive value of 66.7% and a negative predictive value of 97% for the diagnosis of IFD versus FUO, leading to an efficiency of 94.5%.Conclusions: Both CRP and PCT are not able to predict neither etiology nor severity of infection at the onset of fever. When performing reassessment of antibiotic therapy 2 days after onset of febrile neutropenia, CRP has the better discriminatory power between etiologies of fever and shows higher peak values in clinically severe infections. As such we conclude that PCT has no added value over CRP for clinical management of febrile neutropenia. In our study a CRP value above 200 mg/dL has a positive predictive value of 66.7% and a negative predictive value of 97% for the diagnosis of IFD versus FUO (when MDI and CDI were ruled out by diagnostic workup). A high CRP in the absence of a clear focus of infection might prompt earlier investigation for IFD, leading to earlier treatment initiation and lower mortality. In view of the low numbers of IFD in our study it is important to note that this finding should be confirmed in a larger patient population. [Display omitted] DisclosuresVerlinden:MSD - Merck: Research Funding. Gadisseur:Bayer: Research Funding.

Urine Cultures at the Onset of Febrile Neutropenia (FN) in Patients with Haematological Malignancies Rarely Impact Antibiotic Management in the Absence of Urinary Symptoms

IntroductionThe Choosing Wisely initiative aims to reduce wasteful testing. Our institution is participating in this initiative and hence has a focus on evidence-based approaches to the investigation of FN. We have previously shown that routine chest x-rays are not generally useful in this scenario. Urine cultures are also commonly performed in this context. However, specimen collection may delay the administration of antibiotics, laboratory costs are not inexpensive and the impact of culture results on subsequent antibiotic management is not well documented in patients receiving protocol specified broad spectrum antibiotics. We assessed this latter issue by evaluating the impact of urine cultures on the management of FN in haematology inpatients at a major tertiary hospital.Methods:A retrospective single-centre analysis of adult (≥16years) patients with haematological malignancy undergoing recent chemotherapy admitted to a large cancer centre with FN was performed over a 5-year period (2011-2015). FN was defined as fever ≥37.5°C and a neutrophil count <0.5 x 109/L or <1.5 x 109/L and predicted decline to <0.5 x 109/L over the next 48 hours. Local protocolised investigations for newly diagnosed FN included a urine culture. Empiric antibiotic therapy for FN consisted of IV tazocin in stable patients or, if systemically compromised, IV meropenem, gentamicin and vancomycin. Patients were identified from electronic hospital records. For each episode, baseline demographic data, urinary tract symptoms and signs (absence of which was termed ‘asymptomatic‘), beside urinalysis results (nitrites and leucocytes), urine culture results (chemistry, microscopy, culture and sensitivity) and any consequent change in antibiotic management were collected. A urine culture was considered positive if >108 organisms/L of a predominant organism were detected. Cultures were considered contaminated if mixed growth was present. Each positive culture and impact on antibiotic therapy was reviewed by an infectious disease physician.Results:Four hundred and thirty-three episodes of FN were identified in 317 patients, the baseline characteristics of which are summarized in Table 1. A urine culture was performed in 365 (84%) cases of which 16 (4.4%) were positive, 77 were contaminated (21%), and 272 (75%) had no growth. Cultures were positive in 7 of 317 (2.2%) asymptomatic patients; all were gram-negative bacteria of which 2 were extended spectrum beta-lactamase (ESBL) E. coli. Nine of 48 (19%) symptomatic patients had positive cultures of which 8 were non-ESBL E. coli. Four patients had a catheter, all of whom were asymptomatic with a negative culture. Bedside urinalysis was documented in 186 (43) patients who had urine cultures. Nitrites were detected in 5 of 12 evaluable patients with positive cultures compared with 4 of 174 patients with negative cultures; the positive and negative predictive values were 56%and 96%respectively. Only 5 patients (1.4%) had a change in antibiotic management due a positive urine culture: 3 of 48 (6.3%) symptomatic and 2 of 317 (0.6%) asymptomatic patients.Conclusion:Urinary tract infections are a rare source of infection in haematology patients with FN in the absence of focal urinary symptoms. Urine cultures rarely impact on antibiotic management in this context without urinary tract symptoms. As a result of this study we no longer perform urine cultures routinely in FN, restricting this investigation to symptomatic or catheterised patients without another clear source of infection, and those with nitrite positivity. [Display omitted] DisclosuresHawkes:Roche: Other: Travel expenses, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Other: Travel expenses; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Other: Travel expenses; Merck Serono: Research Funding; Merck Sharpe Dohme: Research Funding. Grigg:Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses.

Assessing Safe Discharge Criteria for Pediatric Oncology Patients Admitted for Febrile Neutropenia

Background: Febrile neutropenia is a common complication of myelosuppression secondary to chemotherapy. In many cases, no source of infection is found. Many pediatric oncology centers continue inpatient parenteral antibiotics therapy until myelorecovery is seen. Multiple studies suggest that outpatient therapy, oral antibiotics, or earlier discharge could be appropriate alternative treatments in some patients, supporting data are lacking. Current Children's Oncology Group guidelines recommend considering discontinuing empiric antibiotics at 72 hours in low risk patients with negative blood cultures for at least 24 hours irrespective of marrow recovery. However, this is a weak recommendation with only moderate quality evidence. With limited supporting evidence febrile neutropenia management and hospitalization duration vary by institution and individual provider.Methods: We performed a retrospective chart review of patients admitted to the Pediatric Hematology/Oncology service from September 2005 through October 2016, using ICD-9 or ICD-10 codes for “febrile neutropenia”, “neutropenia”, or “fever”, generating a list of 1555 charts. Duplicate charts, patients with fever or neutropenia but not both, and those with non-oncologic diagnoses, were eliminated, leaving 729 febrile neutropenia admissions. Of these, 131 were considered to be “early discharges” defined as discharged home at 4 or less days with discharge ANC < 500 and negative cultures. All were afebrile by the time of discharge and were released without outpatient antibiotics. These charts were then reviewed for subsequent readmission within the next 4 days.Results: 11 of the 131 patients (8%) were readmitted for reasons other than chemotherapy. 2 patients were called back from the initial admission for late positive cultures, one for Proprionibacter acnes bacterium for whom repeat cultures were negative and the second for coagulase negative staphylococcus, initially thought to be a contaminant but a second blood culture, collected prior to the initial discharge, was positive. The other 9 were readmitted with febrile neutropenia. Of these, 2 had positive cultures on readmission, 1 for pseudomonas aeruginosa and 1 for E. coli. All 4 patients with positive cultures remained stable and were safely treated with appropriate antibiotics. The remaining 7 patients had uneventful admissions and were discharged once again when afebrile with negative cultures. The mean age of the readmitted patients was younger than those not readmitted (4.2 yrs vs 7 yrs, p=0.003). The average ANC (standard deviation) at discharge was lower for the patients who were readmitted versus those not readmitted (69 (70) vs 198 (147), p=<0.001), as was APC on admission (165 (254) vs 321 (388), p=<0.001) and APC at discharge (97 (82) vs 453 (431), p=<0.001). The readmitted patients had a non-significant trend toward decline in ANC from initial admission to discharge, while those not readmitted had a slight increase in ANC (DANC -75 (211) vs +38 (209), p=0.065). Review of graphs of these values showed that use of the highest value for the readmitted patients as a cutoff would result in a large percentages of the non-readmitted patients remaining in the hospital. There was no difference with regard to gender, type of malignancy, or ANC on admission between the two cohorts.Conclusion: This retrospective review showed that low risk patients admitted with febrile neutropenia could be safely discharged prior to count recovery without oral antibiotics. Only a small percentage of patients required readmission for repeat fevers while still neutropenic, and those with bacterial infections were easily identified on readmission and appropriately treated. Not surprisingly, the readmitted group had a lower discharge ANC and APC than those not readmitted. However all patients remained stable and none suffered adverse events. Overall, 120/131 (92%) of patients deemed low risk were able to be discharged early without incident. Applying higher ANC or APC criteria for discharge would result in increased length of hospital stay for a significant population of low risk children without decreasing morbidity. [Display omitted] DisclosuresDucore:Octapharma: Research Funding; Bayer, Shire, HemaBiologics, Bioverativ, Octapharma, Spark Therapeutics: Other: Advisory board.

Management of Febrile Neutropenia in Children with Cancer

Febrile neutropenia (FN) is the most common complication of childhood cancer treatment with mortality rates of untreated patients up to 21%. The recognition and management of FN is fundamental to preserve the children health status and avoid life-threatening complications. Physical and laboratory assessments should be performed in every patient with FN to identify any potential site of infection to be promptly treated. Hence, an empiric antimicrobial therapy remains the gold standard for the management of these patients. Antimicrobial treatment should be based on local epidemiological data and antibiotic susceptibility; a combination of a fourth-generation antipseudomonal cephalosporin with an aminoglycoside is generally adopted. Empirical administration of glycopeptides, in absence of documented Gram-positive bacterial infection is not recommended for routine use. Despite the progress in the management of febrile neutropenia and its relatively low mortality, the emergence of resistant pathogens is increasing, and the development of new effective antimicrobials are needed. Established criteria for a risk adapted approach is still lacking and no definitive data supporting the duration of empiric treatment are present. De-escalation strategies should be implemented to reduce both antibiotic exposure and resistance as well as hospital stay.

Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia.

BackgroundStandard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management.MethodsThis prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results.ResultsPositive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases.Clinical Trials RegistrationNCT02912117ConclusionKT shows promise in the diagnosis and treatment optimization of FN.

Use of MASCC score in the inpatient management of febrile neutropenia: a single-center retrospective study

PurposeThe Multinational Association for Supportive Care in Cancer (MASCC) score is used to risk stratify outpatients with febrile neutropenia (FN). However, it is rarely used in hospital settings. We aimed to describe management, use of MASCC score, and outcomes among hospitalized patients with FN.MethodsWe conducted a retrospective cohort study of patients with cancer and FN. We collected patient demographics, cancer characteristics, microbiological profile, MASCC score, utilization of critical care therapies, documentation of goals of care (GOC), and inpatient deaths. Outcomes associated with low- (≥ 21) versus high-risk (< 21) MASCC scores are presented as absolute differences.ResultsOf 193 patients, few (2%, n = 3) had MASCC scores documented, but when calculated, 52% (n = 101) had a high-risk score (< 21). GOC were discussed in 12% (n = 24) of patients. Twenty one percent (n = 40) required intermediate/ICU level of care, and 12% (n = 23) died in the hospital. Those with a low-risk score were 33% less likely to require intermediate/ICU care (95% CI 23 to 44%) and 19% less likely to die in the hospital (95% CI 10% to 27%) compared to those with high-risk score.ConclusionsMASCC score was rarely used for hospitalized patients with FN, but high-risk score was associated with worse outcomes. Education efforts to incorporate MASCC score into the workflow may help identify patients at high risk for complications and help clinicians admit these patients to a higher level of care (e.g., intermediate/ICU care) or guide them to initiate earlier GOC discussions.

Correlation between Multidrug-Resistant Bacteria Colonization and Bloodstream Infections in Children with Hematolymphoid Malignancies at a Tertiary Cancer Center in India

Abstract Background Bloodstream infections with drug-resistant bacteria are associated with a higher morbidity and mortality. Based on previous studies in our institution demonstrating a rising incidence of multidrug resistant organism (MDR) bacteria in bloodstream infections (BSI) and high prevalence of enteric colonization with MDR, the “de-escalation” strategy for empirical antibiotics was adopted in the management of febrile neutropenia in children with hematolymphoid malignancies and MDR colonization. An audit was carried out to determine whether surveillance rectal swabs correlated with blood cultures in febrile neutropenia. Methods Patient data from January 2015 to July 2016 was examined. Rectal swabs of children with hematolymphoid malignancies were obtained at presentation. Blood cultures were taken during febrile neutropenia. Data were analyzed using SPSS version 24.0. The significance level was set at p &lt; 0.05. Results Most patients (62.1%) with confirmed BSI were colonized with either extended-spectrum β-lactamase producing organisms (ESBLO) (31.9%) or MDR (30.2%). Majority 116 (62.7%) developed BSI caused by either MDR or ESBLO. In contrast, only 12 (10.6%) patients colonized by sensitive bacteria, developed BSI caused by either MDR or ESBLO. These differences were statistically significant (p &lt; 0.001). Thus, the baseline rectal swab had a sensitivity and a specificity of 90.6% and 59.4%, respectively, in predicting BSI with either MDR or ESBLO. Conclusions We conclude that high prevalence of MDR colonization at presentation significantly results in MDR BSI, which further results in a significant increase in intensive care unit admissions and mortality. This would justify the use of a “de-escalation” antibiotic policy. Whether such a strategy has been successful in impacting outcomes, would need further study.

Optimising Antimicrobial Selection and Duration in the Treatment of Febrile Neutropenia in Children.

Febrile neutropenia (FN) is a frequent complication of cancer treatment in children. Owing to the potential for overwhelming bacterial sepsis, the recognition and management of FN requires rapid implementation of evidenced-based management protocols. Treatment paradigms have progressed from hospitalisation with broad spectrum antibiotics for all patients, through to risk adapted approaches to management. Such risk adapted approaches aim to provide safe care through incorporating antimicrobial stewardship (AMS) principles such as implementation of comprehensive clinical pathways incorporating de-escalation strategies with the imperative to reduce hospital stay and antibiotic exposure where possible in order to improve patient experience, reduce costs and diminish the risk of nosocomial infection. This review summarises the principles of risk stratification in FN, the current key considerations for optimising empiric antimicrobial selection including knowledge of antimicrobial resistance patterns and emerging technologies for rapid diagnosis of specific infections and summarises existing evidence on time to treatment, investigations required and duration of treatment. To aid treating physicians we suggest the key features based on current evidence that should be part of any FN management guideline and highlight areas for future research. The focus is on treatment of bacterial infections although fungal and viral infections are also important in this patient group.

How I Treat Febrile Neutropenia.

The management of febrile neutropenia is a backbone of treating patients with hematologic malignancies and has evolved over the past decades. This article reviews my approach to the evaluation and treatment of febrile neutropenic patients. Key topics discussed include antibacterial and antifungal prophylaxis, the initial workup for fever, the choice of the empiric antibiotic regimen and its modifications, and criteria for discontinuation. For each of these questions, I review the literature and present my perspective.

Potential reduction of hospital stay length with outpatient management of low-risk febrile neutropenia in a regional cancer center.

BackgroundFebrile neutropenia is a serious complication of chemotherapy. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score identifies patients at low risk of serious complications. Outpatient management programs have been successfully piloted in other Australian metropolitan cancer centers.AimTo assess current management of febrile neutropenia at our regional cancer center and determine potential impacts of an outpatient management program.MethodWe performed a retrospective review of medical records for all patients admitted at our regional institution with febrile neutropenia between 1 January 2016, and 31 December 2018. We collected information regarding patient characteristics, determined the MASCC risk index score, and if low risk, we determined the eligibility for outpatient care and potential reduction in length of stay and cost benefit.ResultsA total of 98 hospital admissions were identified. Of these, 66 had a MASCC low‐risk index score. Fifty‐eight patients met the eligibility criteria for outpatient management. Seventy‐one percent were female. The most common tumor type was breast cancer. Forty‐eight percent were treated with curative intent. The median length of stay was 3 days. The median potential reduction in length of stay for each admission was 2 days. The total potential reduction in length of stay was 198 days. No admission resulted in serious complications.ConclusionThis review demonstrates a significant number of hospital admission days can be avoided. We intend to conduct a prospective pilot study at our center to institute an outpatient management program for such low‐risk patients with potential reduction in hospital length of stay. This will have significant implications on health resource usage, service provision planning, and patient quality of life.

Burden of febrile neutropenia in paediatric oncology: Experience from Children’s Hospital Lahore Pakistan

Background: Infection is the major cause of morbidity and mortality in children with cancer. Chemotherapy induced febrile neutropenia-associated mortality is much higher in low-middle-income countries than in high-income countries, emphasizing the need of prevention, early identification and timely management of infection related complications in these children. Objective of this prospective study was to analyze the burden of chemotherapy induced febrile neutropenia and to assess the leading risk factors.&#x0D; Patients and methods: Prospective cohort study was done in 100 patients with febrile neutropenia (fever of 38.3℃ and ANC &lt;500) admitted in the Haematology/Oncology Department of Children’s Hospital Lahore (CHL) from July to August 2016. All the children on curative chemotherapy were included in this study and children with relapse and on palliation were excluded from this study. Risk factors including knowledge of parents and caregivers about febrile neutropenia, travel time from home to hospital and duration of symptoms at home before seeking treatment and reasons for delayed response in these children’s febrile illness, were analyzed for duration of hospital stay considered as a burden on the Haematology/Oncology Department. Data regarding their age, sex, and clinical features, baseline CBC, course of therapy, hospital stay and understanding of caregivers regarding febrile neutropenia was analyzed. The first line therapy was IV Piperacillin-Tazobactam and IV Amikacin. SPSS-16 software was used to analyze the data and a p-value of &lt;0.05 was considered as statistically significant.&#x0D; Results: Total 100 patients with age ranging from &lt;1 to 15 years were included. Male to female ratio was 1.7:1, 72% of the cases had Acute Lymphoblastic Leukaemia and 28% with solid tumors. About, 28% had last chemotherapy received in 72 hours, 30% in last week and rest in more than a week time 36% had upper respiratory tract infections, 18% gastrointestinal infections, 20% mucositis, 10% no focus found and rest 16% had other manifestations. Only 2 % presented in less than one hour of start of symptoms, 27% &lt;24 hours, 61% in &lt;5 days and 10% &gt;5 days duration of symptoms. 45% had Hb &lt;8 gm/dL, 33% had platelets &lt;50,000 mm3, and 54% had WBC &lt;1000 and 63% had ANC &lt;100. 29% presented with the first episode while 51% had 3 or more febrile neutropenia episodes. 28% cases stayed 1 hour distance from CHL while 72% had to travel &gt;1-5 hours to reach the primary treatment center. 66% received paracetamol at home, 17 had oral antibiotics while 17% had no treatment before reaching hospital. Only 19% caregivers had adequate awareness regarding adequate management of febrile neutropenia, 72% had some understanding while 9% had no knowledge about febrile neutropenia. 46% had financial issues, 41% were unaware while, 13% showed negligence in seeking treatment. Only 2 patients stayed for a day, 46% stayed for 5 days and 48% for more than 5 days.&#x0D; Conclusion: Febrile neutropenia episodes accounted for 25% of monthly admissions of the Haematology/Oncology Department of Children’s Hospital Lahore. Majority of these caregivers had inadequate basic knowledge of standard management of febrile neutropenia aggravated by increased travel time from their homes to the hospital.

Reductions in vancomycin and meropenem following the implementation of a febrile neutropenia management algorithm in hospitalized adults: An interrupted time series analysis.

To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies. Quasi-experimental study. Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States. Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014-May 2016) and after the intervention (June 2016-December 2018). These data were compared using interrupted time series analysis. In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality. Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.

Retrospective analysis of 34 febrile neutropenia episodes - therapeutic implication of multiplex polymerase chain reaction in infection diagnosis

Hemato-oncologic patients on chemotherapy or undergoing bone marrow transplantation are susceptible to infections due to neutropenia. Incidences of febrile neutropenia (FN) in these patients are common, contributing to high mortality and morbidity. Lack of diagnosis of pathogens responsible for infections in these patients is a major healthcare challenge. Newer molecular diagnostics are increasingly becoming relevant. The objective of this retrospective study was to evaluate the effectiveness of Syndrome Evaluation System (SES), a multiplex molecular diagnostic platform for diagnosis of pathogens, and its impact on the management of FN. In total, 34 neutropenic episodes from 21 patients admitted during September 2013 to April 2015 were analyzed in this study. Clinical samples from patients were tested on SES and routine culture. Treatment was as per standard of care. SES showed a 5-fold higher clinical sensitivity (55.9%) as compared to automated culture (11.1%). SES results were available within 14 hours as compared to >72 hours for culture, and elucidated change in antimicrobial therapy in 50% of episodes. Mortality rates were lower when SES was used early in the episode. De-escalation of antimicrobials according to SES results was possible, which translated into substantial cost saving. Newer non-culture-based molecular technologies like SES are changing the way we manage FN. It is faster, has a higher diagnostic yield as compared to traditional culture, and helps in making rapid, evidence-based therapeutic decision-making including de-escalation of antimicrobials. It would potentially lead to a reduction in mortality and healthcare cost in the long run.

The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings.

Introduction:Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML.Method:This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included.Result:A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days (p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 (p = 0.063). Thirteen patients (23.63%) died during the study period.Discussion:Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections.Conclusion:Infections continues to be a major cause of morbidity and mortality among AML patients.