The updated guidelines from American Society of Clinical Oncology (ASCO) and Infectious Diseases Society of America (IDSA) will help clinicians identify which patients would be good candidates for outpatient management of neutropenia and what antimicrobial prophylaxis can be followed.

In patients receiving chemotherapy, a decrease in absolute neutrophil count (neutropenia) is commonly seen and this may compromise the host defences against bacterial and fungal infections. Therefore, this guideline was developed as an update from ASCO in partnership with IDSA for identifying patients for outpatient management of fever and neutropenia.

Recommendation 1

1. Clinicians should attribute fever, in any patient with neutropenia due to cancer therapy to be the result of an infection, if there is no other explanation for it.
2. In order to maximise the chances of confirmatory clinical and microbiologic diagnoses, an initial diagnostic approach is needed as it can affect the antibacterial choice and prognosis.

• A minimum of two sets of blood culture from varied anatomic sites should be taken and these may include a peripheral site, as well as from the lumen of a central venous catheter
• As clinically indicated, cultures from sites such as urine, lower respiratory tract, CSF, stool or wounds should be taken 
• Patients with signs and/or symptoms suggestive of LRTI should have chest imaging studies

3. In the setting of seasonal community-acquired respiratory illnesses, if a patient presents with symptoms of influenza-like illness, such as with sudden onset of fever and cough along with either malaise, sore throat, coryza, arthralgias, or myalgias, a nasopharyngeal swab should be done to detect for the influenza virus.
4. Within 1 hour after triage from the initial presentation, the first dose of empirical therapy should be given.
5. Patients should receive an initial intravenous dose of therapy within 1 hour at the time of evaluation for FN in the clinic or emergency department, even if their degree of risk has not been determined to be either low or high.
6. Monotherapy is recommended with an antipseudomonal β-lactam agent (cefepime), or piperacillin-tazobactam (carbapenem).
7. In cases of fever and neutropenia, vancomycin is not recommended as part of the standard antibiotic regimen.

Recommendation 2

Candidates should be identified for outpatient management only after proper clinical judgment.

1. Patients that can be candidates for outpatient management can be identified by recommended tools such as the Multinational Association for Supportive Care in Cancer index or Talcott’s rules.
2. Febrile neutropenic patients should be admitted and treated as inpatients if they are infected with fluoroquinolone-resistant gram-negative pathogens, or if they are also co-resistant to β-lactams/cephalosporins since they will then require carbapenem-based regimens in multiple doses per day. In-patient management should be opted for in patients with MRSA, VRE, or Stenotrophomonas maltophilia suspected infections.
3. The risk of major complications among patients with solid tumours that are clinically stable, after mild to moderate intensity chemotherapy, may be identified using the Clinical Index of Stable Febrile Neutropenia as an additional tool.

Recommendation 3

1. Febrile neutropenic patients must meet the following psychosocial and logistic criteria to be eligible for discharge and outpatient management:
2. Patient should be living within 30 miles (48 km) or within a travel time of less than 1 hour from the clinic or hospital.
3. Permission for outpatient management is granted from the oncologist or primary care physician.
4. All the logistic requirements, including regular clinic visits, can be complied with.
5. Family members and caregivers should be present and available at home for 24 hours.
6. Telephone and transportation should be fully accessible for 24 hours a day.
7. There should not be any prior history of treatment protocol refusal.
8. These extra measures are also recommended:

• Patients should be checked on a regular basis for at least 3 days in the clinic or at home
• Patient should be contacted daily or regularly on the telephone to confirm if their fever is present or it has resolved
• In cases of myeloid reconstitution, monitoring of absolute neutrophil count and platelet count is necessary
• Patient should return to the clinic repeatedly for visits

Recommendation 4

1. Only after the fever has been recognised and documented and blood samples collected, should patients having fever and neutropenia receive the first dose of empiric therapy in the clinic, emergency department or the hospital if they are suitable for outpatient management.
2. Before discharge, the patient should be kept under observation for 4 hours.
3. Outpatient regimen management can be considered in febrile neutropenia patients if they have a lower risk of medical complications and are stable clinically and they are responding to inpatient intravenous empiric antibiotic treatment for fever.

Recommendation 5

1. Oral empiric therapy with a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) plus amoxicillin/clavulanate (or clindamycin if allergic to penicillin) is recommended for FN patients that are undergoing outpatient antibiotic treatment.
2. Recommendations do not allow for outpatient management of FN using fluoroquinolones alone as initial empiric therapy.
3. Hospital admission and initial empirical antibacterial treatment of patients with carbapenems should be done in settings where there is a high incidence of ESBL-producing gram-negative bacilli or resistance to fluoroquinolones.

Recommendation 6

1. After 2 to 3 days of administering an initial, empiric, broad-spectrum antibiotic and not seeing defervescence, low-risk outpatients with febrile neutropenia need to be re-evaluated for hospitalisation consideration or identification of a new source of infection.
2. Admission to the hospital should also be considered for patients if conditions such as these are seen:

• Recurrence of fever after a fall in body temperature
• Patient is no longer able to tolerate oral medications
• New signs and symptoms of infections are seen in patients

3. It is compulsory to add an extra antimicrobial drug or change the empiric regimen according to the species identified in microbiologic testing when this occurs.