Febrile neutropenia: Difference between revisions
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Generally, patients with febrile neutropenia are treated with empirical [[antibiotic]]s 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. | Generally, patients with febrile neutropenia are treated with empirical [[antibiotic]]s 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 [[cephalosporin]]s with activity against ''[[Pseudomonas aeruginosa]]'' (e.g. [[cefepime]]), or [[carbapenem]]s ([[imipenem]] or [[meropenem]]). | 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 [[cephalosporin]]s with activity against ''[[Pseudomonas aeruginosa]]'' (e.g. [[cefepime]]), or [[carbapenem]]s ([[imipenem]] or [[meropenem]]). 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.<ref name="pmid16344285">{{cite journal |author=Paul M, Yahav D, Fraser A, Leibovici L |title=Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials |journal=J. Antimicrob. Chemother. |volume=57 |issue=2 |pages=176–89 |year=2006 |pmid=16344285 |doi=10.1093/jac/dki448|url=http://jac.oxfordjournals.org/cgi/content/full/57/2/176 |month= February|issn=0305-7453}}</ref> | ||
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. | 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. | ||
Revision as of 21:22, 9 February 2015
|
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 a condition characterized by a decrease in neutrophils (neutropenia) associated with fever, the latter indicating the presence of an infection.[1] Most patients will have no infectious etiology documented; clinically defined infections occur in 20%–30% of febrile episodes.[2]
Historical Perspective
In 1966, Bodey et al. first described the quantitative association between leukocyte counts and the incidence of infection in a study of acute leukemia which demonstrated that the risk and the type of infection are related to the severity and duration of granulocytopenia.[3] Infection risk begins to increase when the absolute neutrophil count (ANC) decreases to less than 1000 cells/mm3 and rises markedly when the ANC drops to less than 500 cells/mm3. When the causative pathogen is identifiable, bacterial or viral etiology predominates within the first seven days of neutropenic fever, while infection with antibiotic-resistant bacteria or invasive fungi occurs more often in the setting of protracted neutropenia.[4]
Pathophysiology
A number of factors pose an increased risk for infection in patients with neutropenic fever:
- Absolute or functional leukopenia
- Leukocytes, particularly neutrophils, constitute one of the front-line defense mechanisms against invading microorganisms. Chemotherapy is associated with both qualitative and quantitative deficits in circulating neutrophils by lowering neutrophil counts and impairing chemotaxis and phagocytosis, respectively. In addition, patients receiving glucocorticoid-containing regimens, calcineurin inhibitors, or fludarabine are also predisposed to infection as a consequence of lymphocyte dysfunction.
- Altered microbiota
- Microbiota inhabit the skin, respiratory tract, and digestive tract may be altered by cancer and its treatment or the use of antibiotics.[5]
- Breaches of natural barriers
- Mucositis may occur as a direct adverse effect of chemotherapy or radiotherapy and disrupt the barrier function of the endothelial lining. Indwelling catheters and implanted devices allow access of skin commensals into blood or subcutaneous tissues or serve as a biofilm which bacteria can colonize.
- Immune defects associated with specific primary malignancies
- An increased risk of infection has been observed in patients with Hodgkin's lymphoma (as a result of defects in cell-mediated immunity) and in patients with chronic lymphocytic leukemia or multiple myeloma (as a result of hypogammaglobulinemia).
Causes
Epidemiology and Demographics
Approximately 10% to 50% of patients with solid tumors and more than 80% of those with hematologic malignancies will develop fever during courses of cytotoxic chemotherapy. However, an infectious etiology can be established in a minority of patients, and clinically defined infections occur in 20% to 30% of febrile episodes.[6]
Over the past few decades, there has been a shift in the spectrum of bacterial isolates from patients with febrile neutropenia. Gram-negative organisms prevailed in the era when cytotoxic chemotherapy was initially introduced, whereas Gram-positive skin flora including coagulase-negative staphylococci evolved as the most common isolates after widespread use of indwelling catheters and prophylactic antibiotics. In addition, there has been a drift in susceptibility patterns, with resistance seen in the general population of hospitalized patients now emerging in febrile neutropenic patients.[7]
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. Clinical judgment based on parameters in risk assessment also plays a critical role in tailoring the management.
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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.[8] |
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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.[9] |
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Profound neutropeniaNeutropenia in which the ANC is <100 cells/mm3; a manual reading of the blood smear is required to confirm this degree of neutropenia.[10] |
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Functional neutropeniaFunctional neutropenia refers to patients whose hematologic malignancy results in qualitative defects (impaired phagocytosis and killing of pathogens) of circulating neutrophils. These patients should also be considered to be at increased risk for infection, despite a normal neutrophil count.[11] |
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Microbiologically defined infectionThis can include both
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Clinically defined infectionThis is designated when a site of infection is diagnosed (e.g., pneumonia,cellulitis) but its microbiologic pathogenesis either cannot be proven or is inaccessible to examination.[13] |
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Unexplained feverIn the neutropenic patient, this is defined as a new fever that is not accompanied by either clinical or microbiologic evidence of infection.[14] |
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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).[15] 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.[16]
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). 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.[17]
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
- ↑ "NCI Thesaurus".
- ↑ 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) - ↑ Bodey, G. P. (1966-02). "Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia". Annals of Internal Medicine. 64 (2): 328–340. ISSN 0003-4819. PMID 5216294. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Pizzo, P. A. (1982-05). "Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes". Medicine. 61 (3): 153–165. ISSN 0025-7974. PMID 7078399. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Bennett, Charles L. (2013-03-21). "Colony-stimulating factors for febrile neutropenia during cancer therapy". The New England Journal of Medicine. 368 (12): 1131–1139. doi:10.1056/NEJMct1210890. ISSN 1533-4406. PMC 3947590. PMID 23514290. 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) - ↑ Ramphal, Reuben (2004-07-15). "Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 Suppl 1: –25-31. doi:10.1086/383048. ISSN 1537-6591. PMID 15250017.
- ↑ 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) - ↑ 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) - ↑ "From the Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Report of a consensus panel". The Journal of Infectious Diseases. 161 (3): 397–401. 1990-03. ISSN 0022-1899. PMID 2179421. Check date values in:
|date=(help) - ↑ "From the Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Report of a consensus panel". The Journal of Infectious Diseases. 161 (3): 397–401. 1990-03. ISSN 0022-1899. PMID 2179421. Check date values in:
|date=(help) - ↑ "From the Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Report of a consensus panel". The Journal of Infectious Diseases. 161 (3): 397–401. 1990-03. ISSN 0022-1899. PMID 2179421. Check date values in:
|date=(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 NCI Dictionary of Cancer Terms