Febrile neutropenia
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Resident Survival Guide |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: F and N; fever and neutropenia; FN; neutropenic fever; neutropenic fever syndrome
Overview
Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia (bacteria in the bloodstream) is present in approximately 20% of all patients with this condition.[1]
Historical Perspective
Pathophysiology
Causes
- Febrile neutropenia can develop in any form of neutropenia, but is most generally recognized as a complication of chemotherapy when it is myelosuppressive (suppresses the bone marrow from producing blood cells).
- Medication induced:caspofungin acetate, Cyclophosphamide, Eribulin, Nelarabine, Pertuzumab
Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
Common Causes
Causes by Organ System
| Cardiovascular | No underlying causes |
| Chemical / poisoning | No underlying causes |
| Dermatologic | No underlying causes |
| Drug Side Effect | No underlying causes |
| Ear Nose Throat | No underlying causes |
| Endocrine | No underlying causes |
| Environmental | No underlying causes |
| Gastroenterologic | No underlying causes |
| Genetic | No underlying causes |
| Hematologic | No underlying causes |
| Iatrogenic | No underlying causes |
| Infectious Disease | No underlying causes |
| Musculoskeletal / Ortho | No underlying causes |
| Neurologic | No underlying causes |
| Nutritional / Metabolic | No underlying causes |
| Obstetric/Gynecologic | No underlying causes |
| Oncologic | No underlying causes |
| Opthalmologic | No underlying causes |
| Overdose / Toxicity | No underlying causes |
| Psychiatric | No underlying causes |
| Pulmonary | No underlying causes |
| Renal / Electrolyte | No underlying causes |
| Rheum / Immune / Allergy | No underlying causes |
| Sexual | No underlying causes |
| Trauma | No underlying causes |
| Urologic | No underlying causes |
| Dental | No underlying causes |
| Miscellaneous | No underlying causes |
Causes in Alphabetical Order
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
The definitions of fever and neutropenia are used to identify patients in whom empirical antibiotic therapy must be initiated. However, neutropenic patients represent a heterogeneous population and treatment may be considered even when they do not meet these specific criteria. Additional parameters in risk assessment and clinical judgment also play a critical role in tailoring the management.
| “ |
FeverFever is defined as a single oral temperature measurement of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period.[2] |
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| “ |
NeutropeniaNeutropenia is defined as an absolute neutrophil count (ANC) of <500 cells/mm3 or an ANC that is expected to decrease to <500 cells/mm3 during the next 48 hours.[3] |
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History
Symptoms
Physical Examination
Laboratory Findings
Multinational Association for Supportive Care in Cancer (MASCC) Risk Index
The Multinational Association for Supportive Care in Cancer (MASCC) Risk Index can be used to identify high-risk patients (score <21) and low-risk patients (score ≥21 points) for serious complications of febrile neutropenia (including death, intensive care unit admission, confusion, cardiac complications, respiratory failure, renal failure, hypotension, bleeding, and other serious medical complications).[4] The score was developed to select patients for therapeutic strategies that could potentially be more convenient or cost-effective. The various variables and the weight of individual variables used in the MASCC risk index is as follows. To summarize, risk assessment helps determining the type of empirical antibiotic therapy, venue of the treatment, and duration of the antibiotic therapy.
| Characteristic | Score |
|---|---|
| No or mild symptoms in patients following an episode of febrile neutropenia | 5 |
| Absence of hypotension with a systolic blood pressure >90 mmHg | 5 |
| No chronic obstructive pulmonary disease (active chronic bronchitis, emphysema, decrease in forced expiratory volumes, need for oxygen therapy and/or steroids and/or bronchodilators) | 4 |
| Solid tumor or hematologic malignancy with no previously demonstrated fungal infection or empirically treated suspected fungal infection | 4 |
| Absence of dehydration that requires parenteral fluids | 3 |
| Moderate symptoms in patients following an episode of febrile neutropenia | 3 |
| Outpatient status | 3 |
| Age <60 years | 2 |
A prospective trial demonstrated that a modified MASCC score can identify patients with febrile neutropenia at low risk of complications as well.[5]
Treatment
Generally, patients with febrile neutropenia are treated with empirical antibiotics until the neutrophil count has recovered (Absolute neutrophil counts greater than 500/mm3) and the fever has abated; if the neutrophil count does not improve, treatment may need to continue for two weeks or occasionally more. In cases of recurrent or persistent fever, an antifungal agent should be added.
Guidelines issued in 2002 by the Infectious Diseases Society of America recommend the use of particular combinations of antibiotics in specific settings; mild low-risk cases may be treated with a combination of oral co-amoxiclav and ciprofloxacin, while more severe cases require cephalosporins with activity against Pseudomonas aeruginosa (e.g. cefepime), or carbapenems (imipenem or meropenem).[1] A subsequent meta-analysis published in 2006 found that cefepime was associated with more negative outcomes, and that carbapenems (while causing a higher rate of pseudomembranous colitis) were the most straightforward in use.[6]
In 2010, an updated guidelines was issued by the Infectious Diseases Society of America, recommending use of cefepime, carbapenems (meropenem and imipenem/cilastatin), piperacillin/tazobactam for high risk patients and co-amoxiclav and ciprofloxacin for low risk patients. Patients who do not strictly fulfill the criteria of 'low risk patients' should be admitted to the hospital and treat as high risk patients.
See Also
References
- ↑ 1.0 1.1 Hughes WT, Armstrong D, Bodey GP; et al. (2002). "2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer". Clin. Infect. Dis. 34 (6): 730–51. doi:10.1086/339215. ISSN 1058-4838. PMID 11850858. Unknown parameter
|month=ignored (help) - ↑ Freifeld, Alison G. (2011-02-15). "Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (4): 427–431. doi:10.1093/cid/ciq147. ISSN 1537-6591. PMID 21205990. Unknown parameter
|coauthors=ignored (help) - ↑ Freifeld, Alison G. (2011-02-15). "Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (4): 427–431. doi:10.1093/cid/ciq147. ISSN 1537-6591. PMID 21205990. Unknown parameter
|coauthors=ignored (help) - ↑ Klastersky J, Paesmans M, Rubenstein EB; et al. (16 August 2000). "The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients". J Clin Oncol. 18 (16): 3038–51. ISSN 0732-183X. PMID 10944139.
- ↑ de Souza Viana L, Serufo JC, da Costa Rocha MO, Costa RN, Duarte RC (2008). "Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients". Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 16 (7): 841–6. doi:10.1007/s00520-007-0347-3. ISSN 0941-4355. PMID 17960431. Unknown parameter
|month=ignored (help) - ↑ Paul M, Yahav D, Fraser A, Leibovici L (2006). "Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials". J. Antimicrob. Chemother. 57 (2): 176–89. doi:10.1093/jac/dki448. ISSN 0305-7453. PMID 16344285. Unknown parameter
|month=ignored (help)
External links
- Febrile neutropenia entry in the public domain NCI Dictionary of Cancer Terms