Optimal antibiotics timing ‘likely differs’ among inpatients with cancer, neutropenic fever
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Key findings:
- Time to administration of antibiotics did not significantly affect OS at any time point evaluated after the start of neutropenic fever.
- Multivariable analysis showed multiple factors had a significant impact on hazard of death, including insurance status and Charlson Comorbidity Index.
Delaying antibiotic treatment beyond 1 hour from developing neutropenic fever did not affect OS among hospitalized patients with cancer, results from a retrospective study showed.
However, data from the analysis show several other factors associated with an increased risk for death among inpatients with neutropenic fever, including those treated quickly with antibiotics.
The results underline the need for additional research into management of patients who develop neutropenic fever in a hospital setting, with particular focus on the optimal timing of antibiotics, according to Adam F. Binder, MD, associate professor in the division of hematologic malignancies and hematopoietic stem cell transplantation at Sidney Kimmel Cancer Center at Thomas Jefferson University.
“A lot of work and effort goes into quality improvement initiatives, and we want to make sure that we are making change that is meaningful and really improving patient care,” Binder told Healio. “Larger multi-institutional studies need to be conducted to really evaluate the time frame in which antibiotics need to be administered in a closely monitored setting to avoid adverse clinical outcomes.”
Background
Neutropenic fever occurs in approximately 50% to 80% of patients who receive intensive cytoreductive chemotherapy regimens in a hospital setting, according to Binder.
The motivation for the study came from a quality improvement initiative at his institution to reduce the time to administration of antibiotics among inpatients with neutropenic fever. They established a goal— based on Infectious Disease Society of America (IDSA) and ASCO guidelines — to reduce time to antibiotics for these patients to less than 60 minutes.
“While we were going through the iterative process of that improvement initiative, we asked ourselves, [if] this reduction in time to antibiotics [was] relevant to patients who develop febrile neutropenia while being monitored in the inpatient setting,” Binder said.
Methodology
Binder and colleagues sought to determine whether delays in time to administration of antibiotics impacted OS among hospital-monitored patients with hematologic malignancies who developed febrile neutropenia.
The investigators performed chart reviews of 187 patients (mean age, 57.6 years; range, 20-81 years; 53.5% men; 61% white, 28.3% Black) with cancer who developed neutropenic fever while being treated at Thomas Jefferson University Hospital between July 1, 2016, and March 27, 2019.
Researchers considered five categories of time to administration of antibiotics, starting with less than 1 hour and ending with 4 or more hours.
OS at 180 days after occurrence of neutropenic fever served as the study’s primary endpoint.
Results
Univariate analysis showed time to administration of antibiotics did not significantly affect OS at any time point evaluated after the start of neutropenic fever.
Multivariable analysis showed multiple factors had a significant impact on OS.
Insured patients had significantly lower risk for death compared with the uninsured (HR = 0.28; 95% CI, 0.1-0.73), whereas patients with a Charlson Comorbidity Index score of 3 or higher had a significantly increased risk for death (HR = 2.72; 95% CI, 1.26-5.88).
In addition, patients treated with antibiotics within 40 minutes of developing neutropenic fever had a significantly higher risk for death than patients who received them later (HR = 5.74; 95% CI, 2.3-14.32). This finding at first surprised Binder and colleagues but is likely a limitation of the study’s retrospective nature and represents clinical bias, he told Healio.
“It is likely that patients who appeared sicker ... were prioritized and received antibiotics faster as opposed to someone who was neutropenic and had a fever but otherwise appeared well,” he said. “The faster administration of antibiotics thus represented a clinical bias of sicker patients, and those patients ultimately had worse outcomes. It is not that giving antibiotics faster was bad — it was just the clinical scenario that led to faster antibiotics that was resulting in poorer outcomes.”
Clinical implications
Overall, the study’s results are informative but not definitive due to the study’s retrospective nature, single-center design and small sample size, according to Binder. The results require validation via a larger multicenter study, he added.
“I do not want people to take away from this study that we can just ignore timely administration of antibiotics in patients with febrile neutropenia,” he said. “This study opens the door to asking what truly is the optimal time to antibiotics, and that question likely differs for different patients and different clinical scenarios.”
For more information:
Adam F. Binder, MD, can be reached at Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplant, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, 925 Chestnut St., Suite 420A, Philadelphia, PA 19107; email: adam.binder@jefferson.edu.
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