Febrile neutropenia: Difference between revisions
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=== Low risk for infectious complications === | === Low risk for infectious complications === | ||
Antimicrobial prophylaxis is not routinely recommended in these patients. Antiviral agents may be considered in low risk patients with prior HSV episodes (Table 4). | Antimicrobial prophylaxis is not routinely recommended in these patients. Antiviral agents may be considered in low risk patients with prior HSV episodes (Table 4).<ref>{{Cite web | title = Prevention and Treatment of Cancer-Related Infections | accessdate = | url = http://www.nccn.org/professionals/physician_gls/PDF/infections.pdf }}</ref> | ||
=== Intermediate risk for infectious complications === | === Intermediate risk for infectious complications === | ||
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=== Antibacterial Prophylaxis === | === Antibacterial Prophylaxis === | ||
Levofloxacin (500-750 mg oral or IV daily) significantly reduce episodes of fever and the number of documented infections, most strikingly for gram-negative bacillary infections among high-risk patients with cancer expected to develop profound neutropenia >7 days in duration. The NCCN Guidelines advise that fluoroquinolone prophylaxis (levofloxacin is preferred) be considered in patients with an expected duration of neutropenia (ANC <1000 cells/mm<sup>3</sup>) for more than 7 days. This is in agreement with the recommendations of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Among patients with neutropenia who are at | Levofloxacin (500-750 mg oral or IV daily) significantly reduce episodes of fever and the number of documented infections, most strikingly for gram-negative bacillary infections among high-risk patients with cancer expected to develop profound neutropenia >7 days in duration. The NCCN Guidelines advise that fluoroquinolone prophylaxis (levofloxacin is preferred) be considered in patients with an expected duration of neutropenia (ANC <1000 cells/mm<sup>3</sup>) for more than 7 days. This is in agreement with the recommendations of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients with cancer.<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> Among patients with neutropenia who are at lowe risk of infectious complications, the main benefit of antibacterial prophylaxis is a reduction in fever rather than in documented infections. | ||
According to the NCCN guidelines, prophylaxis for pneumococcal infection with penicillin should be initiated 3 months after HSCT and be continued until at least 1 year following transplant regardless of prior administration of pneumococcal vaccines. Prophylaxis should be continued in patients with chronic GVHD until immunosuppressive therapy has been discontinued. | According to the NCCN guidelines, prophylaxis for pneumococcal infection with penicillin should be initiated 3 months after HSCT and be continued until at least 1 year following transplant regardless of prior administration of pneumococcal vaccines. Prophylaxis should be continued in patients with chronic GVHD until immunosuppressive therapy has been discontinued. | ||
Revision as of 17:18, 13 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; hot and low; hot leuk; neutropenic fever; neutropenic fever syndrome; neutropenic sepsis
Overview
Febrile neutropenia is a condition characterized by a decrease in neutrophils (neutropenia) associated with the development of fever, the latter indicating the presence of an infection.[1] The majority of patients have no identifiable site of infection and no positive culture results. Nonetheless, urgent treatment with empirical antibiotics is recommended in light of the possibility of rapid progression.[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 infections in cancer patients:
- 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.
- Altered microbiota
- Microbiota that 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. Solid tumors that overgrow their blood supply may undergo necrosis and form a nidus for infection.
- Immune defects associated with specific primary malignancies
- Patients with leukemias, non-Hodgkin's lymphoma, or myelodysplastic syndrome may be leukopenic due to malignant infiltration or marrow dysfunction. Absolute or functional hypogammaglobulinemia predisposes patients with chronic lymphocytic leukemia or multiple myeloma to recurrent sinopulmonary infections and septicemia caused by encapsulated pathogens such as Streptococcus pneumoniae and Haemophilus influenza.[6][7] An increased risk of infection has also been observed in patients with Hodgkin's lymphoma as a result of defective cell-mediated immunity.
- Hyposplenism
- Production of opsonizing antibodies takes place in the spleen. Hyposplenism, either as a complication of graft-versus-host disease or irradiation, may contribute to overwhelming infection with encapsulated bacteria.
- Lymphotoxicity
- High-dose corticosteroids affect the distribution and function of lymphocytes as well as other immunocytes. Fludarabine, an adenosine analogue, depletes CD4+ lymphocytes and increases the risk of listeriosis, mycobacterial infections, and opportunistic infections.[8] Therapy with alemtuzumab, a humanized monoclonal antibody targeting CD52 on lymphocytes, heightened the risk for a wide variety of infections.[9][10][11] In addition, the use of anti-CD20 monoclonal antibodies such as rituximab and ofatumumab has been associated with an escalated risk for hepatitis B virus reactivation.[12]
Causes
| Table 1. Common Bacterial Pathogens in Neutropenic Patients |
|---|
| Gram-Positive Pathogens |
|
| Gram-Negative Pathogens |
|
Bloodstream infections caused by endogenous flora and reactivation of latent infections account for a majority of initial febrile episode in neutropenic patients with cancer. Common bacterial isolates that cause bacteremia in the setting of neutropenia are listed in Table 1.[13] Certain endogenous microorganisms may be reactivated and exit latency during immunosuppression. These include herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, hepatitis B and C viruses, and Mycobacterium tuberculosis. Exogenous pathogens carried by contaminated blood products, medical equipment and devices, water sources, and health care workers represent less common sources of infection. These include Clostridium difficile, respiratory syncytial virus, vancomycin-resistant enterococci, and other multidrug resistant bacteria.[14]
Fungal infections often take place in the setting of prolonged or profound neutropenia after administration of empirical therapy. Candidiasis may range in severity from mucosal or cutaneous infection to septicemia, endocarditis, or disseminated infection. Aspergillus, on the contrary, typically causes life-threatening infection of the sinuses and lungs, particularly after protracted neutropenia.[15]
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.[16]
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.[17]
Risk Factors
NCCN Overall Infection Risk Categories
The National Comprehensive Cancer Network (NCCN) devised a set of overall infection risk categories (low, intermediate, and high) in patients with cancer based on factors such as the underlying malignancy, disease status (eg, active disease, disease in remission), duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapies.[18]
Low risk for infectious complications
Patients with solid tumors undergoing standard chemotherapy regimens and who have an anticipated duration of neutropenia less than 7 days are considered at low risk for infectious complications.
Intermediate risk for infectious complications
Intermediate risk refer to patients with an anticipated duration of neutropenia of 7 to 10 days. Patients with lymphoma, multiple myeloma, or CLL; autologous HSCT recipients; or patients receiving treatment with purine analogue-containing regimens are also considered intermediate risk.
High risk for infectious complications
Patients with an anticipated duration of neutropenia longer than 10 days, patients undergoing intensive induction/consolidation therapy for acute leukemias, patients receiving treatment with alemtuzumab-containing regimens, allogeneic HSCT recipients, and those with GVHD following allogeneic HSCT are categorized as high risk for infectious complications.
Complications
| Table 2. Medical Complications Considered Serious | |
|---|---|
| |
|
† All reviewed by one investigator. Viral or fungal, microbiologically documented primary infection during the febrile episode, without any described complication and resolving under therapy, was considered a part of the infectious process and was not considered a serious complication. | |
High-risk patients as assessed by clinical judgment criteria or MASCC Risk Index are more likely to develop serious complications of febrile neutropenia including intensive care unit admission, confusion, cardiac complications, respiratory failure, renal failure, hypotension, bleeding, and death (Table 2).[19]
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.
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.[20]
Neutropenia
Neutropenia 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.[21]
Profound neutropenia
Neutropenia in which the ANC is <100 cells/mm3; a manual reading of the blood smear is required to confirm this degree of neutropenia.[22]
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.[23]
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.[24]
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.[25]
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.[26]
History
Pertinent history should include new site-specific symptoms, prior use of antimicrobial agents, potential infection exposures, previous documented infections or pathogen colonization, catheter or device placement, and co-existence of noninfectious causes of fever, such as blood product administration. Underlying co-morbidities, such as diabetes, chronic obstructive lung disease, and/or recent procedures, should also be noted.
Signs and Symptoms
In neutropenic patients, manifestations secondary to inflammation are attenuated and fever is often the only clue indicative of an underlying infection.
Physical Examination
The physical examination should focus on potential sites of infection.
Skin
Induration and erythema may be minimal. Pustule formation are uncommon in the absence of neutrophils.
Throat
Examination of the oropharynx may reveal ulcers or plaques suggestive of herpes or candidiasis. Mucositis owing to cytotoxic chemotherapy may be indistinguishable from herpetic gingivostomatitis.
Lungs
Auscultation of the lungs may reveal minimal adventitial sounds.
Abdomen
Abdominal pain in neutropenic patients may herald an intraabdominal catastrophe secondary to neutropenic enterocolitis or tumor necrosis.
Other
Examination of catheter sites may disclose erythema, tenderness, or discharge.
Laboratory Tests
Complete blood cell count with differential white cell count and levels of serum creatinine and urea nitrogen are required for determining the severity of neutropenia and monitoring potential drug toxicity. These tests should be performed at least every 3 days during the initial course of antibiotic treatment. At least weekly monitoring of transaminase levels is advisable for patients with suspected hepatocellular injury or cholestatic disease. Routine test of inflammation markers, such as C-reactive protein, IL-6, IL-8, or procalcitonin, to guide clinical decisions is not recommended.
At least two sets of blood culture samples, each consisting of ~20 mL of blood divided into 1 aerobic and 1 anaerobic blood culture bottle, should be obtained from both a peripheral vein and from each catheter lumen. In pediatric patients, the total sample limit would be 7 mL for a 10-kg patient and 28 mL for a 40-kg patient. Drawing blood samples from both peripheral vein and catheter may help determine the source of infection. Culture for coagulase-negative staphylococci requires two positive results to be considered a "true positive." After initial defervescence occurs with empirical treatment, any recrudescent fever should be evaluated as a new episode of possible infection.[27]
Stool
A stool specimen in a patient with diarrhea should be evaluated with Clostridium difficile toxin assays. There is limited value in sending a stool specimen for bacterial pathogen cultures or for ova and parasite examination for most patients unless there has been recent travel to or residence in areas of endemicity.[28]
Urine
Culture of urine samples is indicated if signs or symptoms of urinary tract infection exist, a urinary catheter is in place, or the findings of urinalysis are abnormal.[29]
Cerebrospinal Fluid
Examination and culture of the cerebrospinal fluid is indicated if meningitis is suspected. Platelet transfusion may be considered prior to lumbar puncture if thrombocytopenia is a concern.[30]
Skin Biopsy
Biopsy of skin lesions suspected of infection should be performed for Gram staining and culture.[31]
Respiratory Specimens
Sputum samples for routine bacterial culture should be obtained from patients with productive cough. Specimens obtained by bronchoalveolar lavage (BAL) are recommended for patients with a pulmonary infiltrate of uncertain etiology. Polymerase chain reaction testing, rapid antigen testing, or culture on nasal wash or BAL samples should be performed for respiratory viruses (including adenovirus, influenza A and B virus, respiratory syncytial virus, and parainfluenza virus) in patients with suggestive signs or symptoms during the winter season.[32]
Imaging Studies
Chest radiography should be reserved for patients with symptoms of respiratory tract infection. CT scan of the head, sinuses, abdomen, and pelvis may be performed if clinically indicated.[33]
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Initial Assessment
| Class A |
| "1. Laboratory tests should include a CBC count with differential leukocyte count and platelet count; measurement of serum levels of creatinine and blood urea nitrogen; and measurement of electrolytes, hepatic transaminase enzymes, and total bilirubin. (Quality of Evidence: III)" |
| "2. At least 2 sets of blood cultures are recommended, with a set collected simultaneously from each lumen of an existing CVC, if present, and from a peripheral vein site; 2 blood culture sets from separate venipunctures should be sent if no central catheter is present. (Quality of Evidence: III)" |
| "3. Culture specimens from other sites of suspected infection should be obtained as clinically indicated. (Quality of Evidence: III)" |
| "4. A chest radiograph is indicated for patients with respiratory signs or symptoms. (Quality of Evidence: III)" |
| Class C |
| "1. Blood culture volumes should be limited to <1% of total blood volume (usually ~70 mL/kg) in patients weighing <40 kg. (Quality of Evidence: III)" |
Risk Assessment
| Table 3. MASCC Risk Index Score | |
|---|---|
|
Characteristic
|
Weight 5
5
4
4
3
3
3
2
|
|
The maximum value of the score is 26. a Burden of febrile neutropenia refers to the general clinical status of the patient as influenced by the febrile neutropenic episode. It should be evaluated on the following scale: no or mild symptoms (score of 5); moderate symptoms (score of 3); and severe symptoms or moribund (score of 0). Scores of 3 and 5 are not cumulative. b Chronic obstructive pulmonary disease means active chronic bronchitis, emphysema, decrease in forced expiratory volumes, need for oxygen therapy and/or steroids and/or bronchodilators requiring treatment at the presentation of the febrile neutropenic episode. c Previous fungal infection means demonstrated fungal infection or empirically treated suspected fungal infection. | |
Infectious Diseases Society of America (IDSA) recommends that either the clinical judgment criteria or the MASCC assessment tool can be used to stratify risk for patients presenting with fever and neutropenia. Risk assessment should then inform decisions about the type of regimen and appropriate venue for delivery of empirical antibiotics, as well as the timing of hospital discharge. High-risk patients should initially receive IV empirical antibiotic therapy in the hospital, whereas low-risk patients may be candidates for oral and/or outpatient empirical antibiotic therapy.
Clinical Judgment Criteria
Patients with febrile neutropenia can be stratified at presentation into those with high-risk versus low-risk for complications of severe infection by the clinical judgment criteria as follows:[34]
High-Risk Patient by Clinical Judgment Criteria
Patients with any of the following criteria are considered to be at high risk for serious complications during fever and neutropenia:
- Profound neutropenia (ANC ≤100 cells/mm3) anticipated to extend >7 days
- Presence of any co-morbid medical problems including but not limited to:
- — Hemodynamic instability
- — Oral or gastrointestinal mucositis that interferes with swallowing or causes severe diarrhea
- — Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, or diarrhea
- — Neurologic or mental-status changes of new onset d Intravascular catheter infection, especially catheter tunnel infection
- — New pulmonary infiltrate or hypoxemia, or underlying chronic lung disease
- Evidence of hepatic insufficiency (defined as aminotransferase levels greater than 5 times of normal values) or renal insufficiency (defined as a creatinine clearance of less than 30 mL/min).
High-risk patients should be hospitalized and receive intravenous empirical antibiotic therapy.
Low-Risk Patient by Clinical Judgment Criteria
Patients with all of the following criteria are considered to be at low risk for serious complications during fever and neutropenia:
- Neutropenia expected to resolve within 7 days
- No active medical co-morbidity
- Stable and adequate hepatic function and renal function.
In general, any patient who does not strictly fulfill criteria for being at low risk should be treated according to guidelines for high-risk patients. Low-risk patients may be candidates for oral and/or outpatient empirical antibiotic therapy.
MASCC Risk Index
The Multinational Association for Supportive Care in Cancer (MASCC) scoring system is a summation of weighted factors, including patient age, history, outpatient or inpatient status, acute clinical signs, the presence of medical comorbid conditions, and severity of fever and neutropenia as assessed by burden of illness. The MASCC Risk Index can be used to identify subgroups of febrile neutropenic patients with high-risk (score <21) or low-risk (score ≥21) for serious complications and death (Table 3). It is also a means to determine which patients require prolonged hospitalization and which may be candidates for oral or once-daily IV regimens and/or for early discharge from the hospital to complete the antibiotic course as outpatients.[35] A fundamental difficulty with the MASCC Risk Index is the indistinct nature of its major criteria: the "burden of febrile neutropenia" and associated symptoms. Without a clear standardized definition of this ‘‘burden’’ of disease, uniform application of the MASCC Risk Index may be confusing.[36]
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Risk Assessment
| Class A |
| "1. Assessment of risk for complications of severe infection should be undertaken at presentation of fever. Risk assessment may determine the type of empirical antibiotic therapy (oral vs IV), venue of treatment (inpatient vs outpatient), and duration of antibiotic therapy. (Quality of Evidence: II)" |
| "2. Most experts consider high-risk patients to be those with anticipated prolonged (>7 days duration) and profound neutropenia (absolute neutrophil count [ANC] ≤100 cells/mm3 following cytotoxic chemotherapy) and/or significant medical co-morbid conditions, including hypotension, pneumonia, new-onset abdominal pain, or neurologic changes. Such patients should be initially admitted to the hospital for empirical therapy. (Quality of Evidence: II)" |
| "3. Low-risk patients, including those with anticipated brief (≤7 days duration) neutropenic periods or no or few co-morbidities, are candidates for oral empirical therapy. (Quality of Evidence: II)" |
| Class B |
| "1. Formal risk classification may be performed using the Multinational Association for Supportive Care in Cancer (MASCC) scoring system. (Quality of Evidence: I) i. High-risk patients have a MASCC score <21. All patients at high risk by MASCC or by clinical criteria should be initially admitted to the hospital for empirical antibiotic therapy if they are not already inpatients. ii. Low-risk patients have a MASCC score ≥21. Carefully selected low-risk patients may be candidates for oral and/or outpatient empirical antibiotic therapy." |
Treatment
Prophylaxis
| Table 4. Antimicrobial Prophylaxis for Cancer-Related Infections |
|---|
| Low Risk |
|
| Intermediate Risk |
|
| High Risk |
|
Low risk for infectious complications
Antimicrobial prophylaxis is not routinely recommended in these patients. Antiviral agents may be considered in low risk patients with prior HSV episodes (Table 4).[37]
Intermediate risk for infectious complications
For the intermediate risk patients, antibacterial prophylaxis with fluoroquinolones should be considered. Herpes simplex virus prophylaxis should be given during periods of neutropenia, and for autologous HSCT recipients, until at least 30 days following transplant. Prophylaxis for varicella zoster virus should be maintained for at least 1 year after HSCT. Antifungals may be considered during periods of neutropenia and for anticipated mucositis for intermediate risk patients.
High risk for infectious complications
For the high risk patients, antibacterial prophylaxis with fluoroquinolones should be considered. Herpes simplex virus prophylaxis should be given during periods of neutropenia, and for autologous HSCT recipients, until at least 30 days following transplant. Prophylaxis for varicella zoster virus should be maintained for at least 1 year after HSCT. Antifungals may be considered during periods of neutropenia for ALL, AML/MDS, allogeneic HSCT recipients, or patients with significant GVHD receiving immunosuppressive therapy. In addition, allogeneic HSCT recipients, patients with ALL, and patients treated with alemtuzumab are all at increased risk for infection with Pneumocystis jirovecii.
Antibacterial Prophylaxis
Levofloxacin (500-750 mg oral or IV daily) significantly reduce episodes of fever and the number of documented infections, most strikingly for gram-negative bacillary infections among high-risk patients with cancer expected to develop profound neutropenia >7 days in duration. The NCCN Guidelines advise that fluoroquinolone prophylaxis (levofloxacin is preferred) be considered in patients with an expected duration of neutropenia (ANC <1000 cells/mm3) for more than 7 days. This is in agreement with the recommendations of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients with cancer.[38] Among patients with neutropenia who are at lowe risk of infectious complications, the main benefit of antibacterial prophylaxis is a reduction in fever rather than in documented infections.
According to the NCCN guidelines, prophylaxis for pneumococcal infection with penicillin should be initiated 3 months after HSCT and be continued until at least 1 year following transplant regardless of prior administration of pneumococcal vaccines. Prophylaxis should be continued in patients with chronic GVHD until immunosuppressive therapy has been discontinued.
Antifungal Prophylaxis
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Antibacterial Prophylaxis
| Class A |
| "1. Levofloxacin and ciprofloxacin have been evaluated most comprehensively and are considered to be roughly equivalent, although levofloxacin is preferred in situations with increased risk for oral mucositis-related invasive viridans group streptococcal infection. A systematic strategy for monitoring the development of fluoroquinolone resistance among gram- negative bacilli is recommended. (Quality of Evidence: II)" |
| "2. Addition of a gram-positive active agent to fluoroquinolone prophylaxis is generally not recommended. (Quality of Evidence: I)" |
| "3. Antibacterial prophylaxis is not routinely recommended for low-risk patients who are anticipated to remain neutropenic for <7 days. (Quality of Evidence: III)" |
| Class B |
| "1. Fluoroquinolone prophylaxis should be considered for high-risk patients with expected durations of prolonged and profound neutropenia (ANC ≤100 cells/mm3 for >7 days). (Quality of Evidence: I)" |
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Antifungal Prophylaxis
| Class A |
| "1. Empirical antifungal therapy and investigation for invasive fungal infections should be considered for patients with persistent or recurrent fever after 4–7 days of antibiotics and whose overall duration of neutropenia is expected to be <7 days. (Quality of Evidence: I)" |
| "2. In low-risk patients, the risk of invasive fungal infection is low, and therefore routine use of empirical antifungal therapy is not recommended. (Quality of Evidence: III)" |
| "3. Prophylaxis against Candida infection is recommended in patient groups in whom the risk of invasive candidal infection is substantial, such as allogeneic hematopoietic stem cell transplant (HSCT) recipients or those undergoing intensive remission-induction or salvage-induction chemotherapy for acute leukemia. Fluconazole, itraconazole, voriconazole, posaconazole, micafungin, and caspofungin are all acceptable alternatives. (Quality of Evidence: I)" |
| "4. Prophylaxis against Aspergillus infection in pre- engraftment allogeneic or autologous transplant recipients. (Quality of Evidence: III)" |
| "5. Antifungal prophylaxis is not recommended for patients in whom the anticipated duration of neutropenia is <7 days. (Quality of Evidence: III)" |
| Class C |
| "1. A mold-active agent is recommended in patients with anticipated prolonged neutropenic periods of at least 2 weeks, or a prolonged period of neutropenia immediately prior to HSCT. (Quality of Evidence: III)" |
| Class B |
| "1. Data are insufficient to recommend a specific empirical antifungal agent for a patient already receiving anti- mold prophylaxis, but switching to a different class of anti- mold antifungal that is given intravenously should be considered. (Quality of Evidence: III)" |
| "2. Preemptive antifungal management is acceptable as an alternative to empirical antifungal therapy in a subset of high- risk neutropenic patients. Those who remain febrile after 4–7 days of broad-spectrum antibiotics but are clinically stable, have no clinical or chest and sinus computed tomography (CT) signs of fungal infection, have negative serologic assay results for evidence of invasive fungal infection, and have no recovery of fungi (such as Candida or Aspergillus species) from any body site may have antifungal agents withheld. Antifungal therapy should be instituted if any of these indicators of possible invasive fungal infection are identified. (Quality of Evidence: II)" |
| "3. Prophylaxis against invasive Aspergillus infections with posaconazole should be considered for selected patients >13 years of age who are undergoing intensive chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in whom the risk of invasive aspergillosis without prophylaxis is substantial. (Quality of Evidence: I)" |
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Antiviral Prophylaxis
| Class A |
| "1. EHerpes simplex virus (HSV)–seropositive patients undergoing allogeneic HSCT or leukemia induction therapy should receive acyclovir antiviral prophylaxis. (Quality of Evidence: I)" |
| "2. Yearly influenza vaccination with inactivated vaccine is recommended for all patients being treated for cancer. (Quality of Evidence: II)" |
| "3. Influenza virus infection should be treated with neuraminidase inhibitors if the infecting strain is susceptible. (Quality of Evidence: II)" |
| Class C |
| "1. Antiviral treatment for HSV or varicella-zoster virus (VZV) infection is only indicated if there is clinical or laboratory evidence of active viral disease. (Quality of Evidence: III)" |
| "2. In the setting of an influenza exposure or outbreak, neutropenic patients presenting with influenza-like illness should receive treatment empirically. (Quality of Evidence: III)" |
| Class B |
| "1. Respiratory virus testing (including testing for influenza, parainfluenza, adenovirus, respiratory syncytial virus [RSV], and human metapneumovirus) and chest radiography are indicated for patients with upper respiratory symptoms (eg, coryza) and/or cough. (Quality of Evidence: III)" |
| "2. Optimal timing of vaccination is not established, but serologic responses may be best between chemotherapy cycles (>7 days after the last treatment) or >2 weeks before chemotherapy starts. (Quality of Evidence: III)" |
| "3. Routine treatment of RSV infection in neutropenic patients with upper respiratory disease should not be given. (Quality of Evidence: III)" |
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Adjunctive Therapy
| Class A |
| "1. Prophylactic use of myeloid colony-stimulating factors (CSFs; also referred to as hematopoietic growth factors) should be considered for patients in whom the anticipated risk of fever and neutropenia is ≥20%. (Quality of Evidence: II)" |
| Class B |
| "1. CSFs are not generally recommended for treatment of established fever and neutropenia. (Quality of Evidence: II)" |
Guideline Sources
- Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America[39]
- Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline[40]
- 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[41]
- Prevention and Treatment of Cancer-Related Infections: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology[42]
- Management of febrile neutropenia: European Society for Medical Oncology Clinical Recommendations[43]
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) - ↑ Griffiths, H. (1992-09). "Predictors of infection in chronic lymphocytic leukaemia (CLL)". Clinical and Experimental Immunology. 89 (3): 374–377. ISSN 0009-9104. PMC 1554487. PMID 1516254. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Savage, D. G. (1982-01). "Biphasic pattern of bacterial infection in multiple myeloma". Annals of Internal Medicine. 96 (1): 47–50. ISSN 0003-4819. PMID 6976144. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Anaissie, E. J. (1998-10-01). "Infections in patients with chronic lymphocytic leukemia treated with fludarabine". Annals of Internal Medicine. 129 (7): 559–566. ISSN 0003-4819. PMID 9758577. Unknown parameter
|coauthors=ignored (help) - ↑ Moreton, Paul (2005-05-01). "Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 23 (13): 2971–2979. doi:10.1200/JCO.2005.04.021. ISSN 0732-183X. PMID 15738539. Unknown parameter
|coauthors=ignored (help) - ↑ Thursky, Karin A. (2006-01). "Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab*". British Journal of Haematology. 132 (1): 3–12. doi:10.1111/j.1365-2141.2005.05789.x. ISSN 0007-1048. PMID 16371014. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Keating, Michael J. (2002-05-15). "Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study". Blood. 99 (10): 3554–3561. ISSN 0006-4971. PMID 11986207. Unknown parameter
|coauthors=ignored (help) - ↑ "Drug Safety and Availability - FDA Drug Safety Communication: Boxed Warning and new recommendations to decrease risk of hepatitis B reactivation with the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab)" (WebContent).
- ↑ Pagano, L. (2012-05). "A prospective survey of febrile events in hematological malignancies". Annals of Hematology. 91 (5): 767–774. doi:10.1007/s00277-011-1373-2. ISSN 1432-0584. PMID 22124621. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ MD, John E. Niederhuber (2013-11-05). Abeloff's Clinical Oncology: Expert Consult Premium Edition - Enhanced Online Features and Print, 5e (5 edition ed.). Philadelphia, Pennsylvania: Saunders. ISBN 9781455728657. 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) - ↑ 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.
- ↑ "Prevention and Treatment of Cancer-Related Infections" (PDF).
- ↑ "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) - ↑ 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) - ↑ 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) - ↑ Allen, U. (1986-05). "The value of skin biopsies in febrile, neutropenic, immunocompromised children". American Journal of Diseases of Children (1960). 140 (5): 459–461. ISSN 0002-922X. PMID 3962940. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(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) - ↑ Klastersky, J. (2000-08). "The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 18 (16): 3038–3051. ISSN 0732-183X. PMID 10944139. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(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) - ↑ "Prevention and Treatment of Cancer-Related Infections" (PDF).
- ↑ 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) - ↑ Flowers, Christopher R. (2013-02-20). "Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 31 (6): 794–810. doi:10.1200/JCO.2012.45.8661. ISSN 1527-7755. PMID 23319691. Unknown parameter
|coauthors=ignored (help) - ↑ Lehrnbecher, Thomas (2012-12-10). "Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 30 (35): 4427–4438. doi:10.1200/JCO.2012.42.7161. ISSN 1527-7755. PMID 22987086. Unknown parameter
|coauthors=ignored (help) - ↑ "Prevention and Treatment of Cancer-Related Infections" (PDF).
- ↑ Marti, F. Marti (2009-05). "Management of febrile neutropenia: ESMO clinical recommendations". Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 20 Suppl 4: 166–169. doi:10.1093/annonc/mdp163. ISSN 1569-8041. PMID 19454445. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help)
External Links
- Febrile neutropenia entry in the NCI Dictionary of Cancer Terms