Shock and Early Death in Hematologic Patients with Febrile Neutropenia

Abstract

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.

Understanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial Resistance

“…Therefore, the rate of sepsis and septic shock globally is relatively low for FN. In line with this, a recent Brazilian study evaluating the frequency and epidemiology of early death and shock in 1,305 episodes of FN in 826 hematologic patients collected from 2003 to 2017 found that shock occurred in 42 (3.2%) on the first day of FN and early death occurred in 1.1% ( 55 ). In this study, predictors of septic shock were bacteremia due to Escherichia coli [odds ratio (OR), 8.47; 95% CI 4.08–17.55; p < 0.001), Enterobacter sp .…”

“…There are several current studies evaluating the prevalence, clinical features, etiology, and outcomes of cancer patients with bacteremia, with reported rates of septic shock varying by series from 6 to 57% ( 11 , 13 , 15 , 18 – 20 ). Nevertheless, very few investigations have focused on patients presenting with sepsis or septic shock ( 31 , 36 , 48 , 49 , 52 , 55 , 87 , 88 ), and among these, some were retrospective, some used different sepsis definitions, and some did not provide comprehensive data. Table 1 summarizes the most relevant data for cancer patients with sepsis or septic shock.…”

“…Overall, patients with hematological malignancies, mainly acute leukemia, are at greatest risk of sepsis ( 36 , 48 , 49 ). Patients with multiple myeloma ( 36 , 48 , 87 ) and non-Hodgkin lymphoma ( 31 , 36 , 55 , 87 ) also seem to experience high rates of sepsis and septic shock. HSCT recipients have been included in only few series, but rates of sepsis range from 3 ( 87 ) to 12% ( 36 ), as reported in a recent large study of cancer with 2,062 patients admitted to seven European ICUs for sepsis or septic shock.…”

Disseminated Corynebacterium jeikeium Infection in Cancer Patients

“…These infections present a high risk of mortality due to resistance to antifungal therapy and the rapid dissemination of infection. Immediate initiation of empiric antibiotic therapy is thus a key factor in reducing mortality in febrile neutropenic patients with disseminated infection [ 11 ]. Like C. jeikeium , clinical manifestations from these organisms include skin lesions from hematogenous dissemination [ 12 ].…”

How I treat febrile neutropenia

“… 70 We have recently analyzed 1,305 febrile neutropenia episodes looking at factors associated with early death and shock. 71 None of the circumstances in which guidelines recommend the use of vancomycin was associated with shock or early death, including bacteremia due to Gram-positive organisms, catheter-related infection, skin or soft tissue infection, or inadequate Gram-positive coverage, suggesting that the empiric use of vancomycin in the first fever in neutropenic patients is likely unnecessary in the overwhelming majority of cases. Another study evaluated the impact of inappropriate antibiotic coverage at first fever in 1,605 episodes of bloodstream infections in neutropenic patients.…”