- Neutropenia, a decrease in the absolute neutrophil count (ANC), occurs frequently in recipients of chemotherapy.
- The greatest risk of infection occurs in patients who experience profound, prolonged neutropenia after chemotherapy, which is most likely to occur in the period prior to engraftment during hematopoietic cell transplantation and following induction chemotherapy for acute leukemia.
- Fever is often the only sign or symptom of infection, although clinicians should also be mindful that severely or profoundly neutropenic patients may present with suspected infection in an afebrile state, or even hypothermic.
- The rate of major complications (e.g., hypotension, acute renal, respiratory or heart failure) in the context of neutropenic fever syndromes is approximately 25-30%, and mortality up to 11%.
- In the setting of severe sepsis or septic shock, hospital mortality may be as high as 50%.
Triage to Initial Empirical Antibiotic Therapy
Figure 1. Triage to Initial Empirical Antibacterial Therapy—Footnotes
a Fever is defined as a single oral temperature of ≥38.3°C (101°F), or a temperature of ≥38.0°C (100.4°F) sustained over a one-hour period.
b In the absence of an alternative explanation, clinicians should assume that fever in a patient with neutropenia from cancer therapy is the result of an infection. The initial diagnostic approach should maximize the chances of establishing clinical and microbiologic diagnoses that may affect antibacterial choice and prognosis. A systematic evaluation should include:
- Complete history and physical examination to identify infectious foci.
- Complete blood count with leukocyte differential count, hemoglobin and platelet count; serum electrolytes; serum creatinine and blood urea nitrogen; serum lactate; and liver function tests including total bilirubin, alkaline phosphatase, and transaminases.
- At least two sets of blood cultures from different anatomic sites, including a peripheral site as well as at least one line lumen of a central venous catheter if present, although the Expert Panel recognizes that that some centers may modify this practice and use only peripheral cultures, given the potential for false positive results with blood cultures from the line lumen of a central venous catheter.
- Cultures from other sites such as urine, lower respiratory tract, CSF, stool, or wounds, as clinically indicated.
- Chest imaging study for patients with signs and/or symptoms of lower respiratory tract infection, and consider chest imaging for other patients.
- Patients with an influenza-like illness (sudden onset of a respiratory illness characterized by fever and cough and ≥ one of malaise, sore throat, coryza, arthralgias, or myalgias) in the setting of seasonal community-acquired respiratory illnesses should have a nasopharyngeal swab obtained for detection of influenza. In some settings, such as patients with such symptoms in the setting of hematologic malignancy and HSCT, strong consideration should be given to obtaining expanded viral panels for detection of additional respiratory viruses (Influenza virus, Parainfluenza virus, Adenovirus, Coronavirus, Respiratory syncytial virus, Human metapneumovirus, and Rhinovirus). (Moderate Recommendation; CB-L)
c Administration of empirical antibiotics:
- Assessment should occur soon (e.g., within 15 minutes) after triage for patients presenting with febrile neutropenia (FN) within 6 weeks of receiving chemotherapy. This assessment is intended to be a sensitive test with low specificity, emphasizing inclusivity rather than exclusivity.
- High-risk patients require hospitalization for IV empirical antibiotic therapy.
- The first dose of empirical therapy should be administered within one hour after triage from initial presentation. In addition, the following recommendations from the 2010 IDSA guidelines are endorsed:
- Patients who are seen in clinic or the ED for FN and whose degree of risk has not yet been determined to be high or low within one hour should receive an initial IV dose of therapy while undergoing evaluation.
- Monotherapy with an antipseudomonal β-lactam agent, such as cefepime, a carbapenem (meropenem or imipenem-cilastatin), or piperacillin-tazobactam, is recommended. Other antimicrobials (aminoglycosides, fluoroquinolones, and/or vancomycin) may be added to the initial regimen for management of complications (e.g., hypotension and pneumonia) or if antimicrobial resistance is suspected or proven.
- Vancomycin (or other agents active against microaerophilic Gram-positive cocci) is not recommended as a standard part of the initial antibiotic regimen for fever and neutropenia. These agents should be considered for specific clinical indications, including suspected catheter-related infection, skin or soft-tissue infection, pneumonia, or hemodynamic instability.
- Modifications to initial empirical therapy may be considered for patients at risk for infection with the following antibiotic-resistant organisms, particularly if the patient’s condition is unstable or if the patient has positive blood culture results suspicious for resistant bacteria. These include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase (ESBL)–producing Gram-negative bacteria, and Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. Risk factors include previous infection or colonization with the organism and treatment in a hospital with high rates of endemicity.
- MRSA: Consider early addition of vancomycin, linezolid, or daptomycin.
- VRE: Consider early addition of linezolid or daptomycin.
- ESBLs: Consider early use of a carbapenem.
- KPCs: Consider early use of polymyxin-colistin or tigecycline, or a newer β-lactam with activity against resistant gram negative organisms as a less toxic and potentially more effective alternative. (Strong Recommendation; CB-L)
Inducible sustained VT/VF