Physical Examination Can Predict the Risk of Infection in Patients with Febrile Neutropenia (FN)
Authors: Tamai Yotaro , Imataki Osamu , Kawakami Kimihiro , Tanaka Terukazu 
Published: April 2020

Abstract
Purpose In patients with febrile neutropenia (FN) who undergo chemotherapy, it is not common that the infection focus can be accurately diagnosed and a pathogen identified. In the initial phase of standard treatment for FN, the CDC guidelines specify administration of broad-spectrum antibiotics. However, these antibiotics should be de-escalated as soon as the pathogen and infection focus are identified. In order to evaluate an infection focus, we must first hear from the patients about their conditions and carry out careful physical examinations. Therefore, we studied the contribution of physical examinations to the identification of infection focus in patients of FN.
Method We included patients who were admitted to the Division of Blood and Stem cell transplantation, Shizuoka Cancer Center Hospital, between February 2006 and July 2006, for treatment of hematological malignancies. We reviewed all events in patients whose axillary temperature reached 38.0 °C or higher during their chemotherapy courses. We studied the following items: the number of leukocytes and neutrophils at onset, duration of fever, concomitant catheter use, prophylactic antibiotics, regimen of empirical treatment, isolated pathogen, infection focus, mortality and the cause of death. We treated cases of continuous fever of 38.0 °C or higher as a single set of events. If the temperature fell below 38.0 °C and then returned to 38.0 °C or higher after a period of 48 hours or longer, we treated the second occurrence as a new case. The findings of physical examinations were classified into the following 4 categories: oral site, respiratory site, gastrointestinal site, and skin site (if any, including the portion of catheter insertion). The true infection focus was determined depending on the results of culture, otherwise, with reference to the patient’s clinical course. Criteria for decision of infection are below:
a positive result of culture from an aseptic site, identification of a pathogen that can explain the patient’s clinical symptoms, or clinical course suggesting an infection supported by clinical examination or imaging.
Non-infectious diseases were diagnosed by clinical information and categorized as tumor fever, allergic reaction or unknown fever.
Results Overall, 85 FN episodes were observed. Patient characteristics included a median age of 56 years (range: 26–86) and a M:F ratio of 37:48. Of the 85 cases, there were 22 cases of acute myelogeneous leukemia, 16 acute lymphoblastic leukemia, 29 malignant lymphoma, 12 multiple myeloma and 6 others. The maximum degree of fever was 38.0–38.9°C in 68 cases (80%), 39.0–39.9°C in 13 cases (15%), and more than 40.0°C in 4 cases (5%). We detected at least one site of infectious focus in 63 cases (74.1%). The sites included 34 oral, 26 respiratory, 20 gastrointestinal and 11 skin. In some cases, infectious symptoms appeared in multiple sites; 2 sites in 15 cases, 3 in 2 cases and 4 in 5 cases. Of the 85 cases, the final diagnosis was infection in 17 cases (20%), tumor fever in 11 cases (13%), allergic reaction in 8 cases (9%) and unknown in 49 cases (58%). Among the 17 cases of infection, we were able to predict the infectious focus in 11. Multivariate analysis showed significant correlations between diagnosis of infection and three factors: first FN in treatment course (P=0.0021), bacterial prophylaxis (P=0.0054) and infectious findings of skin site (P=0.059, marginal).
Conclusion Detailed physical examinations enable early and advance diagnosis of infection in cases of FN during chemotherapy.