Febrile Pediatric Oncology Patients Research Articles

Monitoring the efficacy of antibiotic therapy in febrile pediatric oncology patients with bacteremia using infrared spectroscopy of white blood cells-based machine learning

Bacteremia refers to the presence of bacteria in the bloodstream, which can lead to a serious and potentially life-threatening condition. In oncology patients, individuals undergoing cancer treatment have a higher risk of developing bacteremia due to a weakened immune system resulting from the disease itself or the treatments they receive. Prompt and accurate detection of bacterial infections and monitoring the effectiveness of antibiotic therapy are essential for enhancing patient outcomes and preventing the development and dissemination of multidrug-resistant bacteria. Traditional methods of infection monitoring, such as blood cultures and clinical observations, are time-consuming, labor-intensive, and often subject to limitations.This manuscript presents an innovative application of infrared spectroscopy of leucocytes of pediatric oncology patients with bacteremia combined with machine learning to diagnose the etiology of infection as bacterial and simultaneously monitor the efficacy of the antibiotic therapy in febrile pediatric oncology patients with bacteremia infections. Through the implementation of effective monitoring, it becomes possible to promptly identify any indications of treatment failure. This, in turn, indirectly serves to limit the progression of antibiotic resistance.The logistic regression (LR) classifier was able to differentiate the samples as bacterial or control within an hour, after receiving the blood samples with a success rate of over 95 %. Additionally, initial findings indicate that employing infrared spectroscopy of white blood cells (WBCs) along with machine learning is viable for monitoring the success of antibiotic therapy. Our follow up results demonstrate an accuracy of 87.5 % in assessing the effectiveness of the antibiotic treatment.

Developing and refining a theory of change to improve time to antibiotic administration for febrile pediatric oncology patients in real-world settings.

e18708 Background: From May 2019 to November 2020, 23 institutions participated in the first Mexico in Alliance with St. Jude Golden Hour Quality Improvement Collaborative (MAS Collaborative) and successfully reduced the TTA in fPHOP from 156.8 minutes to 59.4 minutes and demonstrated improved clinical outcomes The MAS Collaborative followed the Institute for Healthcare Improvement’s Breakthrough Series (BTS) model, which involves using a shared Theory of Change (TOC). This report describes the process followed to develop and refine the TOC, which is currently being used at-scale in the second MAS Collaborative. Methods: The theory of change was built over the course of four phases: pilot testing, driver diagram refinement, multisite deployment, and consolidation and dissemination. A driver diagram (DD) was used to organize and visualize the TOC. The first version of the TOC was built based on the experience of four institutions that piloted the Golden Hour in Mexico in 2018. It was then refined based on the input from a multidisciplinary expert panel. The DD was shared with teams from participating institutions and teams used Plan-Do-Study-Act cycles to test and adapt change ideas to their local context using. At the end of the first MAS Collaborative, teams reported the change ideas they tested and their degree of belief (low to high) that the change ideas had led to improved outcomes. This information was used to refine the TOC, which was validated with a second expert panel in preparation for the second MAS Collaborative. Results: The initial DD included five primary drivers, 16 secondary drivers, and 32 change ideas. The primary drivers were effective availability of medications and supplies, dynamic data learning systems, early detection of fever, process reliability, and effective teamwork. The 23 teams tested change ideas for all primary drivers and 34 of the change ideas were reported as having a high degree of belief. Based on the experience and feedback from participating teams, two secondary drivers were added to the DD for the second MAS Collaborative: 1) promoting wellbeing and resilience and 2) promoting early detection of fever at home. The final DD included five primary drivers, 18 secondary drivers, and 97 change ideas. A refined and robust TOC is currently being used for the second MAS Collaborative. Conclusions: The multiphase process followed to develop the TOC was key to the success of the first MAS Collaborative. Contrary to more prescriptive approaches to project implementation, the inherent flexibility of this TOC allowed teams to operate with a greater sense of agency, developing, adapting and testing implementing changes. This TOC provides practitioners with practice-based evidence to reduce TTA and improve clinical outcomes for children with cancer in resource-limited real-world settings in the context of the second MAS Collaborative and beyond.

Sampling Multiple Catheter Lumens to Improve Detection of Bloodstream Infection in Pediatric Oncology Patients.

Current guidelines recommend sampling each central-access lumen during the initial evaluation of febrile pediatric oncology patients. We investigated this recommendation's validity at centers implementing a diagnostic stewardship program to reduce blood cultures in critically ill children. Among 146 oncology patients admitted to the intensive care unit, there were 34 eligible blood culture-sets. Eleven (34%) sets yielded discordant results, most commonly cultivating a likely pathogen from one lumen and no growth from another. As hospitals move toward reducing testing overuse, these results emphasize the continued importance of culturing each central-access lumen to optimize the detection of bacteremia in the initial evaluation of critically ill pediatric oncology patients.

COVID-19-Related Reduction in Emergency Health Care Utilization Among Febrile Pediatric Oncology Patients.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic has disrupted normal health care utilization patterns worldwide, including decreasing emergency department (ED) visits for various medical emergencies. We examined whether this pattern was present in febrile pediatric oncology patients. In this single-center cohort study, we conducted a retrospective chart review of ED visits of febrile pediatric oncology patients during the first 4 months of the global SARS-CoV-2 pandemic and compared those data to the same time periods in the previous 2 years. During the first 5 months of the pandemic, 25 pediatric oncology patients with fever visited our ED; 65 children visited during the same time period in 2018; and 60 visited in 2019. Compared with 2018 and 2019, encounters for 2020 were decreased by 62% and 58%, respectively. A significantly higher percentage of febrile pediatric oncology patients (84%) were admitted to our hospital during the pandemic compared the previous years (58%). Of concern is the possibility that fear of exposure to coronavirus disease-19 (COVID-19) at our health care facility prompted caregivers of pediatric oncology patients to avoid seeking care for their child with fever. Consistent communication with families about the life-threatening nature of fever should be prioritized among pediatric oncology providers.

Rapid Absolute Neutrophil Count Testing Guides Targeted Antimicrobial Therapy in Febrile Pediatric Oncology Patients.

It is well established that early antibiotic administration leads to improved outcomes in febrile neutropenic patients. To achieve this, many institutions administer empiric antibiotics to all febrile oncology patients in the emergency setting, before knowing their neutropenic status. This study evaluates the role of rapid absolute neutrophil count (ANC) testing in the targeted antimicrobial management of nonneutropenic febrile oncology patients. We conducted a retrospective review of patients 19 years or younger presenting to the pediatric emergency service with an oncologic process and fever or history of fever. We examined the administration of antibiotics and outcomes in nonneutropenic patients. We included 101 patient encounters, representing 62 distinct patients. The rapid ANC test influenced antibiotic management in 94% (95/101) of patient encounters and resulted in no antibiotics or targeted antibiotic therapy in 88% (60/68) of nonneutropenic patients. Use of the rapid ANC test to guide treatment would have spared antibiotic administration in 68% (46/68) of well-appearing nonneutropenic patients with no alternate indication. No well-appearing, nonneutropenic patient had a positive blood culture, and only 1 required hospital admission on a repeat visit. The rapid ANC is a useful tool to balance the goal of early antibiotic administration in febrile neutropenic oncology patients while promoting antibiotic stewardship in this vulnerable population.

Rapid diagnosis of infection etiology in febrile pediatric oncology patients using infrared spectroscopy of leukocytes.

Rapid diagnosis of the etiology of infection is highly important for an effective treatment of the infected patients. Bacterial and viral infections are serious diseases that can cause death in many cases. The human immune system deals with many viral and bacterial infections that cause no symptoms and pass quietly without treatment. However, oncology patients undergoing chemotherapy have a very weak immune system caused by leukopenia, and even minor pathogen infection threatens their lives. For this reason, physicians tend to prescribe immediately several types of antibiotics for febrile pediatric oncology patients (FPOPs). Uncontrolled use of antibiotics is one of the major contributors to the development of resistant bacteria. Therefore, for oncology patients, a rapid and objective diagnosis of the etiology of the infection is extremely critical. Current identification methods are time-consuming (>24 h). In this study, the potential of midinfrared spectroscopy in tandem with machine learning algorithms is evaluated for rapid and objective diagnosis of the etiology of infections in FPOPs using simple peripheral blood samples. Our results show that infrared spectroscopy enables the diagnosis of the etiology of infection as bacterial or viral within 70 minutes after the collection of the blood sample with 93% sensitivity and 88% specificity.

Do Cortisol Levels Predict the Outcome of Pediatric Oncology Patients Admitted to the PICU for Concerns of Sepsis

Introduction Sepsis is the leading cause of death in children worldwide and the diagnosis and treatment of sepsis in pediatric patients are often guided by studies of adult patients. Sepsis is a leading cause of morbidity and mortality in febrile pediatric oncology patients, with shock demonstrating even poorer outcomes. Steroid supplementation with hydrocortisone is recommended in patients with septic shock not responsive to fluid and vasopressors, despite the unknown underlying pathophysiological mechanism for …

Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.

Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790. © 2017 American Cancer Society.

Successful emergency department interventions that reduce time to antibiotics in febrile pediatric cancer patients

Children with cancer and fever are at high risk for sepsis related death. Rapid antibiotic delivery (< 60 minutes) has been shown to reduce mortality.We compared patient outcomes and describe...

Assessment of anaerobic blood cultures in pediatric oncology patients

IntroductionThe routine use of a single aerobic bottle for blood culture in pediatric patients has become commonplace, as anaerobic bacteria are not frequently involved in clinically significant infections. The aim of this study was to assess the usefulness of routinely performing anaerobic blood cultures in pediatric oncology patients. MethodsProspective study was conducted on pediatric (<18 years) patients affected with febrile syndrome after receiving chemotherapy for hematological or solid malignancies. Samples were inoculated into pediatric aerobic and standard anaerobic bottles (BacT/Alert automatic system). Strains were considered clinically significant, or deemed as contaminants, depending on isolation circumstances and clinical criteria. ResultsA total of 876 blood cultures from 228 patients were processed during the 21-month study period (January 2014 to September 2015). Baseline diagnosis included 143 solid tumors and 67/18 cases of leukemia/lymphoma. Bacterial growth was detected in 90 (10.2%) blood cultures for 95 different isolates, of which 62 (7.1%)/63 isolates were considered clinically significant. Among the latter, 38 (60.3%) microorganisms grew in both aerobic and anaerobic bottles, 18 (28.6%) only in aerobic bottles, and 7 (11.1%) only in anaerobic bottles. Gram-negative bacilli (33; 52.4%), mainly from the Enterobacteriaceae family, were the most frequently isolated microorganisms. Overall, only 3 out of 90 isolates (3.3%) were strict anaerobes (Propionibacterium acnes), and all of them were deemed contaminants. ConclusionStrict anaerobes did not cause significant infections in febrile pediatric oncology patients, and anaerobic blood culture bottles offered no additional advantages over aerobic media. Our results suggest that routine blood cultures should be solely processed in aerobic media in this group of patients.

Assessment of anaerobic blood cultures in pediatric oncology patients

IntroductionThe routine use of a single aerobic bottle for blood culture in pediatric patients has become commonplace, as anaerobic bacteria are not frequently involved in clinically significant infections. The aim of this study was to assess the usefulness of routinely performing anaerobic blood cultures in pediatric oncology patients. MethodsProspective study was conducted on pediatric (<18 years) patients affected with febrile syndrome after receiving chemotherapy for hematological or solid malignancies. Samples were inoculated into pediatric aerobic and standard anaerobic bottles (BacT/Alert automatic system). Strains were considered clinically significant, or deemed as contaminants, depending on isolation circumstances and clinical criteria. ResultsA total of 876 blood cultures from 228 patients were processed during the 21-month study period (January 2014 to September 2015). Baseline diagnosis included 143 solid tumors and 67/18 cases of leukemia/lymphoma. Bacterial growth was detected in 90 (10.2%) blood cultures for 95 different isolates, of which 62 (7.1%)/63 isolates were considered clinically significant. Among the latter, 38 (60.3%) microorganisms grew in both aerobic and anaerobic bottles, 18 (28.6%) only in aerobic bottles, and 7 (11.1%) only in anaerobic bottles. Gram-negative bacilli (33; 52.4%), mainly from the Enterobacteriaceae family, were the most frequently isolated microorganisms. Overall, only 3 out of 90 isolates (3.3%) were strict anaerobes (Propionibacterium acnes), and all of them were deemed contaminants. ConclusionStrict anaerobes did not cause significant infections in febrile pediatric oncology patients, and anaerobic blood culture bottles offered no additional advantages over aerobic media. Our results suggest that routine blood cultures should be solely processed in aerobic media in this group of patients.

Use of a fever fast track tool to reduce time to antibiotic dose in febrile pediatric oncology patients.

222 Background: Given the risk of serious bacterial infection in immunocompromised cancer patients, fever should be promptly treated with empiric antibiotics. Our institutional standard is to administer antibiotics in ≤ 60 minutes from on-site fever or from arrival time with known fever. Review of our febrile outpatient pediatric oncology clinic patients from October-December 2013 revealed that 53% met this metric. Our aim: To achieve a sustained rate of 80% of febrile patients receiving antibiotics in ≤ 60 minutes within 8 weeks. Methods: We developed and implemented a fever fast track tool in our pediatric oncology clinic. Providers time stamped each step in the process from fever to antibiotic administration; additional time points were collected from the medical record. Interviews with staff were conducted to identify barriers. Five revisions of the fever fast track tool were made. We also streamlined same-day encounters for febrile patients in order to flag their acute visits and facilitate pre-arrival order entry. Results: 21 patients were treated for fever between 2/26/14 and 4/17/14. 4 fevers were documented in clinic. Time to antibiotics ranged from 23 minutes to 165 minutes. The median time to antibiotic administration was reduced from 58 minutes during the first four weeks to 40 minutes after the second 4-week block. Over the same period, patients receiving antibiotics in ≤ 60 minutes increased from 62% to 88%. Conclusions: Use of a fever fast track tool improved the proportion of febrile patients receiving antibiotics in ≤ 60 minutes. Modifications facilitating antibiotic order entry and pre-arrival awareness of febrile patients should prove helpful in sustaining this success.

Development and validation of a prediction model for diagnosing blood stream infections in febrile, non‐neutropenic children with cancer

Pediatric oncology patients are at increased risk for blood stream infections (BSI). Risk in the absence of severe neutropenia (absolute neutrophil count [ANC] ≥500/µl) is not well defined. In a retrospective cohort of febrile (temperature ≥38.0° for >1 hr or ≥38.3°) pediatric oncology patients with ANC ≥500/µl, a diagnostic prediction model for BSI was constructed using logistic regression modeling and the following candidate predictors: age, ANC, absolute monocyte count, body temperature, inpatient/outpatient presentation, sex, central venous catheter type, hypotension, chills, cancer diagnosis, stem cell transplant, upper respiratory symptoms, and exposure to cytarabine, anti-thymocyte globulin, or anti-GD2 antibody. The model was internally validated with bootstrapping methods. Among 932 febrile episodes in 463 patients, we identified 91 cases of BSI. Independently significant predictors for BSI were higher body temperature (Odds ratio [OR] 2.36 P < 0.001), tunneled external catheter (OR 13.79 P < 0.001), peripherally inserted central catheter (OR 3.95 P = 0.005), elevated ANC (OR 1.19 P = 0.024), chills (OR 2.09 P = 0.031), and hypotension (OR 3.08 P = 0.004). Acute lymphoblastic leukemia diagnosis (OR 0.34 P = 0.026), increased age (OR 0.70 P = 0.049), and drug exposure (OR 0.08 P < 0.001) were associated with decreased risk for BSI. The risk prediction model had a C-index of 0.898; after bootstrapping adjustment for optimism, corrected C-index 0.885. We developed a diagnostic prediction model for BSI in febrile pediatric oncology patients without severe neutropenia. External validation is warranted before use in clinical practice. Pediatr Blood Cancer 2015;62:262-268. © 2014 Wiley Periodicals, Inc.

Comparison of Antimicrobial Sensitivity to Older and Newer Quinolones versus Piperacillin-Tazobactam, Cefepime and Meropenem in Febrile Patients with Cancer in two Referral Pediatric Centers in Tehran, Iran.

BackgroundInfection in pediatric cancer patients has become a concerning problem due to increasing antimicrobial resistance. The goal of this study was to determine the antimicrobial resistance patterns of blood isolates from pediatric oncology patients in Iran to determine if there was significant resistance to quinolonesMethodsChildren with cancer who were admitted with or developed fever during admission to Aliasghar Children’s Hospital or Mahak Hospitals July 2009 through June 2011 were eligible for enrollment. Two blood cultures were obtained. Antimicrobial sensitivity test was performed for ciprofloxacin, moxifloxacin, gatifloxacin, meropenem, cefepime, and piperacillin-tazobactam on isolates from children who were bacteremic.ResultsBlood cultures were positive for 38 episodes in 169 enrolled children but 9 episodes were excluded as blood cultures were thought to be contaminated, yielding a bacteremia rate of 29/160 (18%). The mean age of children and the stage of malignancy did not differ between those with and without bacteremia. Meropenem was the most likely antibiotic to cover isolates (97%) with cefepime having the lowest coverage rate (21%). Quinolone coverage ranged from 63% to 76%.ConclusionQuinolones may not be suitable for use as empiric therapy in febrile pediatric oncology patients in Iran.

Kanserli Çocuğa Sahip Ailelerin Ateş Konusundaki Bilgi ve Ölçme Yetenekleri

Purpose: We did not encounter a study dealing with the knowledge of fever and attitudes of having children with a diagnosis of malignant disease toward fever in English literature. Materials and Methods: Caregivers of 124 pediatric oncology patients and 72 patients without any malignant disease were recruited and interviewed using a 26-item questionnaire about fever and its management in two hospital clinics in Diyarbakir, Turkey. Results: Seventy point one percent of the mothers in oncology group were illiterate and in 75% of the cases, caregiver was the mother of the patient. Most of the in control group (72.2%) knew at least one harmful effect of high fever (p=0.001). The primary method of measurement however was palpation in both groups. 41.9% of the in oncology group knew the correct measurement of fever, but only 2.7% in control group (p=0.001). Resources of fever konowledge was mainly doctors and nurses in oncology group (p=0.001). Conclusion: Pediatric health care providers must have more initiative and exploit oppportunities on parental understanding of fever and its management. Educational interventions are needed to correct caregivers misconceptions about fever and to promote appropriate management of febrile pediatric oncology patients.

β-Herpesviruses in Febrile Children with Cancer

We conducted a cross-sectional study of beta-herpesviruses in febrile pediatric oncology patients (n = 30), with a reference group of febrile pediatric solid-organ transplant recipients (n = 9). One (3.3%) of 30 cancer patients and 3 (33%) of 9 organ recipients were PCR positive for cytomegalovirus. Four (13%) of 30 cancer patients and 3 (33%) of 9 transplant recipients had human herpesvirus 6B (HHV-6B) DNAemia, which was more common within 6 months of initiation of immune suppression (4 of 16 vs. 0 of 14 cancer patients; p = 0.050). HHV-6A and HHV-7 were not detected. No other cause was identified in children with HHV-6B or cytomegalovirus DNAemia. One HHV-6B-positive cancer patient had febrile disease with concomitant hepatitis. Other HHV-6B-positive children had mild "viral" illnesses, as did a child with primary cytomegalovirus infection. Cytomegalovirus and HHV-6B should be included in the differential diagnosis of febrile disease in children with cancer.

Evaluation of computed tomography (CT) in persistently febrile pediatric oncology patients

8549 Background: Routine clinical evaluation often does not reveal a focus of infection in persistently febrile pediatric oncology patients. Clinicians commonly use CT to investigate occult sources of fever although its effectiveness has not been well established. Objective: To determine the proportion of CT scans in persistently febrile pediatric oncology patients that were positive for infection that led to changes in therapy. Methods: Retrospective review of all pediatric inpatients excluding allogeneic transplant patients that had a CT scan during an episode of fever at our institution between 1/1/1996 and 12/31/2001. Results: CT was performed on 62 patients to evaluate 71 episodes of fever. Overall, 28 (39%) of the CT scans demonstrated an infectious finding leading to 13 (18%) changes in therapy and 16 (23%) scans revealed a non-infectious finding leading to 7 (10%) changes in therapy. 5 (18%) of the 27 negative scans also led to changes in therapy (discontinued antibiotics). Chest CT detected 25 (40%) abnormalities (17 infectious and 9 non-infectious) in 63 scans leading to 9 changes in therapy (14%) all from infectious causes. Abdominopelvic CT detected 18 (26%) abnormalities (8 infectious and 10 non-infectious) in 69 scans leading to 10 changes in therapy (15%) (7 due to infectious and 3 non-infectious causes). Head, neck, and sinus CT detected 5 (39%) abnormalities (4 infectious and 1 non-infectious) out of 13 scans leading to 2 changes in therapy (15%) (1 infectious and 1 non-infectious). CT scans done in association with clinical signs and symptoms in addition to fever detected 10 abnormalities out of 13 scans (77%). Conclusions: CT detects both infectious and non-infectious findings in a significant proportion of persistently febrile pediatric oncology patients that may lead to changes in therapy. Infectious findings were more likely to lead to a change in therapy than non-infectious findings. The presence of signs and symptoms in addition to fever was associated with a higher likelihood of a CT finding. No significant financial relationships to disclose.