Initial management of adults with chemotherapy-induced neutropenic fever

ANC: absolute neutrophil count; IV: intravenous; MASCC: Multinational Association for Supportive Care in Cancer risk index; CISNE: Clinical Index of Stable Febrile Neutropenia.
* The authors use an anticipated ANC threshold of <500 cells/microL for >7 days to consider a patient at high risk for serious complications. It should be noted that the Infectious Diseases Society of America and the National Comprehensive Cancer Network guidelines use an ANC threshold of ≤100 cells/microL for >7 days. At the time that the patient presents with neutropenic fever, it is not always possible to anticipate whether the patient will have severe neutropenia for >7 days. Severe prolonged neutropenia is most likely to occur following induction chemotherapy for acute leukemia and during the pre-engraftment phase of myeloablative hematopoietic cell transplantation (particularly allogeneic).
¶ Examples of active uncontrolled comorbid medical problems include but are not limited to:

• Oral or gastrointestinal mucositis that interferes with swallowing or causes severe diarrhea
• Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, or diarrhea
• Intravascular catheter infection, especially catheter tunnel infection
• New pulmonary infiltrate or hypoxemia
• Underlying chronic lung disease
• Complex infection at the time of presentation

Δ For additional details about the MASCC and CISNE scores, refer to the UpToDate topic review on risk assessment of adults with chemotherapy-induced neutropenia.
◊ Patients with a CISNE score of ≥3 are considered to be at high risk for medical complications, those with a score of 1 or 2 are considered to be at intermediate risk, and those with a score of 0 are considered to be at low risk. Intermediate CISNE scores (1 or 2) may require clinicians to judge the relative safety of outpatient oral therapy versus hospitalization for parenteral antibacterial therapy.
§ The appropriate regimen will depend upon patient-specific factors, including likely site of infection and severity of illness. Some patients will require regimens not included in this algorithm.
¥ Ceftazidime monotherapy has also been shown to be effective and continues to be used at some cancer centers with low rates of resistance. However, UpToDate authors generally avoid ceftazidime monotherapy because of rising resistance rates among gram-negative bacteria and its limited activity against gram-positive bacteria, such as streptococci, compared with newer alternatives. Ceftazidime monotherapy should not be used when there is concern for a gram-positive infection, such as infection caused by viridans group streptococci in patients with severe mucositis.