Management and Prevention of Febrile Neutropenia: Updated Guidelines

New clinical guidelines are providing guidance for clinicians on the diagnosis, prevention, and treatment of febrile neutropenia in adult patients with solid tumors.

The guidelines were developed by a panel of 10 experts in the management of immunocompromised patients with solid tumors, with the level of evidence and grade of recommendation following the Infectious Diseases Society of American-US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines.

“In patients with solid tumors, febrile neutropenia has an identifiable clinical focus in 65% of episodes; however, microbiological documentation is only possible in 20%-30% of the cases and blood cultures are positive in 10%-25%,” wrote the panel. The etiology of infection is typically bacterial, due to both Gram-negative bacilli, as well as Gram-positive cocci.

In recent years, according to the guidelines, there has been an increase in strains resistant to extended-spectrum β-lactamase or carbapenemases, and the risk of resistant microorganisms depends on previous colonization, invasive procedures, prior exposure to antibiotics, prior hospitalization, chronic comorbidity, and local pattern of resistances.

To identify the infectious focus, the panel concluded that a systematic physical examination is essential. Before administering empirical antibiotics, clinicians should take 2 sets of samples for blood cultures from different sites, as well as microbiological samples.

Severity is determined by signs and symptoms, and risk assessment scores should be applied only when the signs and symptoms rule out clinical instability. According to the guidelines, most patients with febrile neutropenia and solid tumors display clinical stability in the first 3 hours after diagnosis.

Patients with sepsis, septic shock, or severe undocumented infections, such as pneumonia, are at high risk or potentially unstable. In these unstable patients, the prevalence of mortality due to sepsis is 18.1%, compared with 2.7% among those without risk factors.

Treatment of febrile neutropenia should be based on the type and severity of infection, as well as the probability of the presence of antibiotic-resistant microorganisms.

“For all patients, intravenous administration of β-lactam with antipseudomonal activity but that conserves activity against Gram positive is recommended,” wrote the panel. But, the regimen must be modified depending on the patient’s prognosis and characteristics, such as high-risk patients, allergy to penicillin, and low-risk patients.

During follow-up, patients must receive a physical examination and their general daily status must be evaluated to rule out the appearance of new infectious foci. Vital signs should be taken every 8 hours, and supervision, prevention, and treatment of other complications are needed.

For prophylaxis, the risk of developing febrile neutropenia should be evaluated on a case-by-case basis at the beginning of each chemotherapy cycle. Prophylaxis with granulocyte colony-stimulating factors (G-CSF) is recommended when the risk of developing febrile neutropenia is over 20%, having demonstrated a decrease in incidence, duration, and severity, without significantly affecting tumor response or survival.

For patients at intermediate risk (10%-20%), treatment with G-CSF should depend on the presence of characteristics that increase the risk of infection, including age over 65 years and liver or kidney dysfunction. Meanwhile, for patients with solid tumors being treated with chemotherapy of mild-moderate intensity, the use of prophylaxis is not recommended, except in high-risk cases in which antineoplastic therapy cannot be delayed.

Reference:

Carmona-Bayonas A, Jimenez-Fonesca P, Castro EM, et al. SEOM clinical practice guidelines: management and prevention of febrile neutropenia in adults with solid tumors (2018). [published online November 23, 2018]. doi: 10.1007/s12094-018-1983-4.