When can antibiotics be discontinued in a patient with febrile neutropenia?

From the Guidelines

Antibiotics can be discontinued in a patient with febrile neutropenia when they have been afebrile for at least 48 hours, show clinical improvement, and have an absolute neutrophil count (ANC) greater than 500 cells/mm³, as recommended by the most recent guidelines 1. The decision to discontinue antibiotics in febrile neutropenia is based on several factors, including the patient's clinical stability, neutrophil count, and duration of fever.

• For low-risk patients who have responded well to therapy, antibiotics may be discontinued after 5-7 days even if neutropenia persists, provided they remain afebrile and clinically stable 1.
• However, high-risk patients (those with profound neutropenia with ANC less than 100 cells/mm³, expected prolonged neutropenia for more than 7 days, significant comorbidities, or clinically unstable) should continue antibiotics until neutrophil recovery occurs or for a longer duration as deemed necessary by the treating physician 1. The typical antibiotic regimen for febrile neutropenia includes an antipseudomonal beta-lactam such as piperacillin-tazobactam (4.5g IV every 6 hours), cefepime (2g IV every 8 hours), or meropenem (1g IV every 8 hours) 1.
• Blood cultures should be negative and any identified source of infection should be adequately treated before discontinuing antibiotics 1. Recent studies have shown that early cessation of antibiotics in clinically stable patients without proven infection and afebrile for 48 hours can reduce antimicrobial consumption without increasing mortality 1.
• This approach balances the need to treat potential life-threatening infections while avoiding prolonged unnecessary antibiotic exposure that could lead to resistance, Clostridioides difficile infection, or other adverse effects 1.

From the Research

Discontinuation of Antibiotics in Febrile Neutropenia

• The decision to discontinue antibiotics in patients with febrile neutropenia can be made based on certain criteria, including the resolution of fever and negative cultures 2, 3, 4.
• A study published in 1995 found that discontinuing antibiotics regardless of absolute neutrophil count (ANC) is safe in children with febrile neutropenia without an identifiable source of infection, as long as the patient is afebrile for at least 24 hours and has been treated for a minimum of 72 hours 2.
• Another study published in 2002 found that short courses of intravenous empirical antibiotic treatment can be safely discontinued in selected febrile neutropenic children with cancer, regardless of ANC or evidence of bone marrow recovery, as long as the patient is afebrile for at least 24 hours and has been treated for a minimum of 72 hours 3.
• A 2016 study found that broad-spectrum antibiotics can be safely de-escalated to oral fluoroquinolone prophylaxis prior to ANC recovery in select patients with febrile neutropenia, which may decrease the duration of broad-spectrum antibiotic exposure and associated complications 5.
• The criteria for discontinuing antibiotics may include:
  • Resolution of fever for at least 24 hours
  • Negative cultures for at least 48 hours
  • Improving blood count
  • Patient is clinically well
  • No source of infection is found 2, 3, 4

Patient Selection

• The decision to discontinue antibiotics should be made on a case-by-case basis, taking into account the individual patient's risk factors and clinical condition 5, 6.
• Patients with severe neutropenia, documented infections, or other high-risk features may require longer courses of antibiotic therapy 6, 4.
• Patients with solid tumors or leukemia may have different rates of documented infection, which should be taken into account when making decisions about antibiotic discontinuation 4.