Predictors of Septic Shock or Bacteremia in Children Experiencing Febrile Neutropenia Post-Chemotherapy

Abstract

Background Febrile neutropenia (FN) is an early indicator of infection in oncology patients post-chemotherapy. We aimed to determine clinical predictors of septic shock and/or bacteremia in pediatric cancer patients experiencing FN and to create a model that classifies patients as low-risk for these outcomes. Methods This is a retrospective analysis with clinical data of a cohort of pediatric oncology patients admitted during July 2015 to September 2017 with FN. One FN episode per patient was randomly selected. Statistical analyses include distribution analysis, hypothesis testing, and multivariate logistic regression to determine clinical feature association with outcomes. Results A total of 865 episodes of FN occurred in 429 subjects. In the 404 sampled episodes that were analyzed, 20.8% experienced outcomes of septic shock and/or bacteremia. Gram-negative bacteria count for 70% of bacteremias. Features with statistically significant influence in predicting these outcomes were hematological malignancy (P < .001), cancer relapse (P = .011), platelet count (P = .004), and age (P = .023). The multivariate logistic regression model achieves AUROC = 0.66 (95% CI 0.56–0.76). The optimal classification threshold achieves sensitivity = 0.96, specificity = 0.33, PPV = 0.40, and NPV = 0.95. Conclusions This model, based on simple clinical variables, can be used to identify patients at low-risk of septic shock and/or bacteremia. The model’s NPV of 95% satisfies the priority to avoid discharging patients at high-risk for adverse infection outcomes. The model will require further validation on a prospective population.

Clinical description of pediatric oncology oncology patients with febrile neutropenia admitted to the intensive care unit of the national pediatric oncology unit

“…Among the oncological diagnoses identified in the study, as a disease prior to the development of NF, hematological neoplasms were the most frequent (81.99% of the total); Acute Lymphoblastic Leukemia (ALL) being the most common type of these, representing 70.14% of the total cases observed and Acute Myeloid Leukemia (AML) the remaining 11.85%. This behavior is similar to that described in multiple international studies 6,8,10,11,14,15 where Acute Lymphoblastic Leukemia (ALL) is also the most prevalent with a frequency ranging between 42% and 80.8%. Of these patients, 36.6% were in the induction phase at the time of developing NF and 22.27% had no treatment whatsoever, as they were in the diagnostic phase.…”

“…This finding differs from that described in the study performed at the Children's Hospital of Mexico, where patients who developed NF were more frequently in the maintenance phase. 6 Both findings are consistent with the Consensus of the Latin American Society of Pediatric Infectious Diseases 2021, 4 which describes that NF can develop at any time during the clinical course or phase in the treatment of oncology patients. However, it is important to highlight that our study takes into account only to patients admitted to the ICU for the first time, which explains why the highest frequency of admission is observed in the initial phases of the disease.…”

“…According to specialized publications on the subject, this disease is considered a medical emergency, since the delay in adequate treatment can cause an increase in the morbidity and mortality of affected patients. [3][4][5][6] The definition of neutropenia varies according to different authors, however, most of them agree in defining it as an absolute neutrophil count lower than 1,500 cells/mm3. 7 Depending on the level of neutrophils found, this disease can be classified as mild (1,000-1,500 cells/mm 3 ), moderate (500-1,000 cells/mm 3 ) or severe (< 500 cells/ mm 3 ).…”

Febrile illness in high-risk children: a prospective, international observational study

“…Some of these children are neutropenic. SBI during febrile neutropenia (FN) is a medical emergency associated with significant morbidity and mortality if left untreated [3,4]. One-third of neutropenic episodes in paediatric patients on cancer treatment or during haematopoietic stem cell transplant (HSCT) are associated with fever [5].…”

“…Differentiating viral, bacterial, and inflammatory illnesses on admission is challenging in HR patients: clinical syndromes are often non-specific, and at least 36-48 h is needed to culture microorganisms [4,6]. Because the risk of having SBI is significant [4,7], immunocompromised patients with febrile illness are virtually always admitted for intravenous antibiotic treatment, awaiting microbiological results, yet only around 20% will have a microbiologically documented infection [3,[8][9][10]. 41.3-62.3% will have no cause identified [11][12][13][14].…”