|
|
| (122 intermediate revisions by 5 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| {| class="infobox" style="float: right;" | | {{Siren|Febrile neutropenia}} |
| | style="vertical-align: middle; padding: 5px;" align=center | [[File:Siren.gif|30px|link=Cardiogenic shock resident survival guide]]
| | {{Febrile neutropenia}} |
| | style="vertical-align: middle; padding: 5px;" align=center | [[Febrile neutropenia resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
| |
| |}
| |
| {{CMG}} | | {{CMG}} |
|
| |
|
| {{SK}} F and N; fever and neutropenia; FN; neutropenic fever; neutropenic fever syndrome | | {{SK}} F and N; fever and neutropenia; FN; hot and low; hot leuk; neutropenic fever; neutropenic fever syndrome; neutropenic sepsis |
|
| |
|
| == Overview == | | ==[[Febrile neutropenia overview|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 granulocyte]]s (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.<ref name="pmid11850858">{{cite journal |author=Hughes WT, Armstrong D, Bodey GP, ''et al.'' |title=2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer |journal=Clin. Infect. Dis. |volume=34 |issue=6 |pages=730–51 |year=2002 |pmid=11850858 |doi=10.1086/339215| url=http://www.journals.uchicago.edu/doi/full/10.1086/339215 |month= March|issn=1058-4838}}</ref>
| |
|
| |
|
| == Historical Perspective == | | ==[[Febrile neutropenia historical perspective|Historical Perspective]]== |
|
| |
|
| | ==[[Febrile neutropenia pathophysiology|Pathophysiology]]== |
|
| |
|
| | ==[[Febrile neutropenia causes|Causes]]== |
|
| |
|
| == Pathophysiology == | | ==[[Febrile neutropenia epidemiology and demographics|Epidemiology and Demographics]]== |
|
| |
|
| A number of factors pose an increased risk for infection in patients with neutropenic fever:
| | ==[[Febrile neutropenia risk factors|Risk Factors]]== |
|
| |
|
| * '''Absolute or functional leukopenia'''
| | ==[[Febrile neutropenia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| :: [[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'''
| | ==Diagnosis== |
| :: [[Microbiome|Microbiota]] inhabit the skin, respiratory tract, and digestive tract may be altered by cancer and its treatment or the use of antibiotics.<ref>{{Cite journal | doi = 10.1056/NEJMct1210890 | issn = 1533-4406 | volume = 368 | issue = 12 | pages = 1131–1139 | last = Bennett | first = Charles L. | coauthors = Benjamin Djulbegovic, LeAnn B. Norris, James O. Armitage | title = Colony-stimulating factors for febrile neutropenia during cancer therapy | journal = The New England Journal of Medicine | date = 2013-03-21 | pmid = 23514290 | pmc = PMC3947590 }}</ref>
| | [[Febrile neutropenia diagnostic criteria|Diagnostic Criteria]] | [[Febrile neutropenia initial assessment|Initial Assessment]] | [[Febrile neutropenia history and symptoms|History and Symptoms]] | [[Febrile neutropenia physical examination|Physical Examination]] | [[Febrile neutropenia laboratory findings|Laboratory Findings]] | [[Febrile neutropenia CT|CT]] | [[Febrile neutropenia other diagnostic studies|Other Diagnostic Studies]] |
|
| |
|
| * '''Breaches of natural barriers'''
| | == Treatment == |
| :: [[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 [[commensal]]s into blood or subcutaneous tissues or serve as a [[biofilm]] which bacteria can colonize.
| | [[Febrile neutropenia medical therapy|Medical Therapy]] | [[Febrile neutropenia primary prevention|Primary Prevention]] |
|
| |
|
| * '''Immune defects associated with specific primary malignancies''' | | == Guideline Sources == |
| :: 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]]).
| | * Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America<ref>{{Cite journal | doi = 10.1093/cid/ciq147 | issn = 1537-6591 | volume = 52 | issue = 4 | pages = 427–431 | last = Freifeld | first = Alison G. | coauthors = Eric J. Bow, Kent A. Sepkowitz, Michael J. Boeckh, James I. Ito, Craig A. Mullen, Issam I. Raad, Kenneth V. Rolston, Jo-Anne H. Young, John R. Wingard, null Infectious Diseases Society of Americaa | title = Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = 2011-02-15 | pmid = 21205990 }}</ref> |
|
| |
|
| == Causes == | | * Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline<ref>{{Cite journal | doi = 10.1200/JCO.2012.45.8661 | issn = 1527-7755 | volume = 31 | issue = 6 | pages = 794–810 | last = Flowers | first = Christopher R. | coauthors = Jerome Seidenfeld, Eric J. Bow, Clare Karten, Charise Gleason, Douglas K. Hawley, Nicole M. Kuderer, Amelia A. Langston, Kieren A. Marr, Kenneth V. I. Rolston, Scott D. Ramsey | title = Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline | journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology | date = 2013-02-20 | pmid = 23319691 }}</ref> |
|
| |
|
| == Epidemiology and Demographics == | | * Guideline for the Management of Fever and Neutropenia in Children with Cancer and/or Undergoing Hematopoietic Stem-Cell Transplantation: American Society of Clinical Oncology Endorsement<ref>{{Cite journal | doi = 10.1200/JCO.2012.42.7161 | issn = 1527-7755 | volume = 30 | issue = 35 | pages = 4427–4438 | last = Lehrnbecher | first = Thomas | coauthors = Robert Phillips, Sarah Alexander, Frank Alvaro, Fabianne Carlesse, Brian Fisher, Hana Hakim, Maria Santolaya, Elio Castagnola, Bonnie L. Davis, L. Lee Dupuis, Faith Gibson, Andreas H. Groll, Aditya Gaur, Ajay Gupta, Rejin Kebudi, Sérgio Petrilli, William J. Steinbach, Milena Villarroel, Theoklis Zaoutis, Lillian Sung, International Pediatric Fever and Neutropenia Guideline Panel | title = Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation | journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology | date = 2012-12-10 | pmid = 22987086 }}</ref> |
|
| |
|
| | * Prevention and Treatment of Cancer-Related Infections: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology<ref>{{Cite web | title = Prevention and Treatment of Cancer-Related Infections | accessdate = | url = http://www.nccn.org/professionals/physician_gls/PDF/infections.pdf }}</ref> |
|
| |
|
| | * Management of Febrile Neutropenia: European Society for Medical Oncology Clinical Recommendations<ref>{{Cite journal | doi = 10.1093/annonc/mdp163 | issn = 1569-8041 | volume = 20 Suppl 4 | pages = 166–169 | last = Marti | first = F. Marti | coauthors = M. H. Cullen, F. Roila, ESMO Guidelines Working Group | title = Management of febrile neutropenia: ESMO clinical recommendations | journal = Annals of oncology: official journal of the European Society for Medical Oncology / ESMO | date = 2009-05 | pmid = 19454445 }}</ref> |
|
| |
|
| | == References == |
| | {{reflist|2}} |
|
| |
|
| == Risk Factors == | | == Related Chapters == |
| | | *[[Chemotherapy]] |
| == Natural History, Complications and Prognosis ==
| | *[[Fever]] |
| | |
| | |
| | |
| == 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.
| |
| | |
| {{cquote|
| |
| ==== Fever ====
| |
| Fever 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.<ref>{{Cite journal | doi = 10.1093/cid/ciq147 | issn = 1537-6591 | volume = 52 | issue = 4 | pages = 427–431 | last = Freifeld | first = Alison G. | coauthors = Eric J. Bow, Kent A. Sepkowitz, Michael J. Boeckh, James I. Ito, Craig A. Mullen, Issam I. Raad, Kenneth V. Rolston, Jo-Anne H. Young, John R. Wingard, null Infectious Diseases Society of Americaa | title = Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = 2011-02-15 | pmid = 21205990 }}</ref>}}
| |
| | |
| {{cquote|
| |
| ==== Neutropenia ====
| |
| Neutropenia is defined as an absolute neutrophil count (ANC) of <500 cells/mm<sup>3</sup> or an ANC that is expected to decrease to <500 cells/mm<sup>3</sup> during the next 48 hours.<ref>{{Cite journal | doi = 10.1093/cid/ciq147 | issn = 1537-6591 | volume = 52 | issue = 4 | pages = 427–431 | last = Freifeld | first = Alison G. | coauthors = Eric J. Bow, Kent A. Sepkowitz, Michael J. Boeckh, James I. Ito, Craig A. Mullen, Issam I. Raad, Kenneth V. Rolston, Jo-Anne H. Young, John R. Wingard, null Infectious Diseases Society of Americaa | title = Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = 2011-02-15 | pmid = 21205990 }}</ref>}}
| |
| | |
| {{cquote|
| |
| ==== Profound neutropenia ====
| |
| Neutropenia in which the ANC is <100 cells/mm<sup>3</sup>; a manual reading of the blood smear is required to confirm this degree of neutropenia.<ref>{{Cite journal | doi = 10.1093/cid/ciq147 | issn = 1537-6591 | volume = 52 | issue = 4 | pages = 427–431 | last = Freifeld | first = Alison G. | coauthors = Eric J. Bow, Kent A. Sepkowitz, Michael J. Boeckh, James I. Ito, Craig A. Mullen, Issam I. Raad, Kenneth V. Rolston, Jo-Anne H. Young, John R. Wingard, null Infectious Diseases Society of Americaa | title = Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = 2011-02-15 | pmid = 21205990 }}</ref>}}
| |
| | |
| {{cquote|
| |
| ==== Functional neutropenia ====
| |
| Functional 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.<ref>{{Cite journal | doi = 10.1093/cid/ciq147 | issn = 1537-6591 | volume = 52 | issue = 4 | pages = 427–431 | last = Freifeld | first = Alison G. | coauthors = Eric J. Bow, Kent A. Sepkowitz, Michael J. Boeckh, James I. Ito, Craig A. Mullen, Issam I. Raad, Kenneth V. Rolston, Jo-Anne H. Young, John R. Wingard, null Infectious Diseases Society of Americaa | title = Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America | journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = 2011-02-15 | pmid = 21205990 }}</ref>}}
| |
| | |
| {{cquote|
| |
| ==== Microbiologically defined infection ====
| |
| This can include both
| |
| # bacteremia, either with a single organism or polymicrobial infection, but without a definable nonhematogenous site of infection, and
| |
| # a microbiologically defined site of infection (e.g., pneumonia, cellulitis) with or without concomitant bacteremia.<ref>{{Cite journal | issn = 0022-1899 | volume = 161 | issue = 3 | pages = 397–401 | title = 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 | journal = The Journal of Infectious Diseases | date = 1990-03 | pmid = 2179421 }}</ref>}}
| |
| | |
| {{cquote|
| |
| ==== Clinically defined infection ====
| |
| This 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.<ref>{{Cite journal | issn = 0022-1899 | volume = 161 | issue = 3 | pages = 397–401 | title = 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 | journal = The Journal of Infectious Diseases | date = 1990-03 | pmid = 2179421 }}</ref>}}
| |
| | |
| {{cquote|
| |
| ==== Unexplained fever ====
| |
| In the neutropenic patient, this is defined as a new fever that is not accompanied by either clinical or microbiologic evidence of infection.<ref>{{Cite journal | issn = 0022-1899 | volume = 161 | issue = 3 | pages = 397–401 | title = 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 | journal = The Journal of Infectious Diseases | date = 1990-03 | pmid = 2179421 }}</ref>}}
| |
| | |
| === 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).<ref name="pmid10944139">{{cite journal |author=Klastersky J, Paesmans M, Rubenstein EB, ''et al.'' |title=The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.|journal= J Clin Oncol. |volume=18 |issue=16 |pages=3038–51 |date=16 August 2000|pmid=10944139| url=http://jco.ascopubs.org/cgi/content/full/18/16/3038 |issn=0732-183X}}</ref> 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.
| |
| | |
| {|class="wikitable"
| |
| ! 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.<ref name="pmid17960431">{{cite journal |author=de Souza Viana L, Serufo JC, da Costa Rocha MO, Costa RN, Duarte RC |title=Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients |journal=Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer |volume=16 |issue=7 |pages=841–6 |year=2008 |month=July |pmid=17960431 |doi=10.1007/s00520-007-0347-3 |issn=0941-4355}}</ref>
| |
| | |
| == Treatment ==
| |
| 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]]).<ref name="pmid11850858"/> 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.
| |
| | |
| == See Also ==
| |
| *[[Neutropenia]] | |
| *[[Leukopenia]] | | *[[Leukopenia]] |
| *[[Fever]]
| |
| *[[Myelosuppression]] | | *[[Myelosuppression]] |
| *[[Chemotherapy]] | | *[[Neutropenia]] |
| | |
| ==References==
| |
| {{Reflist|2}}
| |
|
| |
|
| ==External Links== | | == External Links == |
| * [http://www.cancer.gov/dictionary?CdrID=415543 Febrile neutropenia] entry in the NCI Dictionary of Cancer Terms | | * [http://www.cancer.gov/dictionary?CdrID=415543 Febrile neutropenia entry in the NCI Dictionary of Cancer Terms] |
