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Timing of Empiric Antibiotic Administration Affects Outcomes in Febrile Neutropenia

February 2011, Vol 4, No 1

ANAHEIM—Antibiotics are being delayed in patients with febrile neutropenia, found George Varughese, PharmD.

After a patient is diagnosed with neutropenia, guidelines from the Infectious Diseases Society of America recommend prompt initiation of an antibiotic. “Ideally, prompt is considered to be administration in less than 1 hour,” said Varughese, a pharmacy resident at the University Hospital-Health Alliance of Greater Cincinnati at the University of Cincinnati at the time the study was conducted.

His retrospective chart review of 67 patients with a diagnosis of febrile neutropenia, covering 74 documented episodes, found that the guideline is not being followed.

“We wanted to see if it’s given within 1 hour or so in a hospital setting,” he said. “A secondary objective was to measure the impact of the timing of antibiotic administration on the patient’s clinical status [the incidence of septic shock, sepsis, and death] as well as the length of hospital stay after the diagnosis of neutropenic fever.”

The mean time to the first dose of an antibiotic after the diagnosis was 4.97 hours, and the median time was 3.67 hours.

The length of hospital stay after empiric antibiotic administration correlated weakly with the timing of antibiotic administration. Length of hospital stay was a median of 4 days in those patients treated with an empiric antibiotic in 4 hours or less, compared with a median of 7 days in patients who received an antibiotic more than 4 hours after diagnosis (P = .0003).

Antibiotic therapy was changed in 61 (82.4%) patients. Three (4%) patients died, and nine (12.2%) experienced sepsis. The incidence of negative composite clinical outcomes (sepsis, septic shock, length of intensive care unit stay, or death) was 31.1%, and negative composite outcomes occurred significantly more often (P = .0103) in the group that waited longer than 4 hours to receive an antibiotic.

“Diagnostic uncertainty of febrile neutropenia may cause delay in the administration of the antibiotic,” said Varughese. Another possible contributor to the delay is that emergency room physicians may have difficulty determining if the patient had a fever of 100.4°F for more than 1 hour, “which requires relying on the patient’s statement,” he said.

There were also times when emergency room physicians miscalculated the absolute neutrophil count (ANC) and “therefore the true time of febrile neutropenia was misinterpreted,” he continued.

“We need to educate emergency room physicians and all the nurses in the emergency room about measuring the patient’s fever and doing the ANC calculation and then getting the patient an antibiotic as soon as possible, hopefully within an hour.”

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