Tests
1st tests to order
CBC and differential
Test
Should be ordered immediately for any patient presenting with fever or other signs and symptoms of infection, who has recently received chemotherapy.
Result
absolute neutrophil count (ANC) <500 cells/microliter (or expected to decrease to <500 cells/microliter over the next 48 hours)
urinalysis and renal function tests (BUN and creatinine)
Test
Should be ordered immediately for any patient presenting with fever or other signs and symptoms of infection, who has recently received chemotherapy.
Evidence of kidney dysfunction has been associated with increased risk of complications from neutropenia.[3][25] Patients with abnormal renal function are not suitable for outpatient therapy.
Result
normal or abnormal urinalysis; normal or elevated BUN and creatinine
liver function tests (LFTs)
Test
Should be ordered for any patient presenting with fever or other signs and symptoms of infection, who has recently received chemotherapy.
Abnormal LFTs could indicate a hepatobiliary infection, but may also occur in the setting of chemotherapy or other drug-related toxicity, or progressive disease with liver involvement.
Low albumin (<3.5 g/dL), elevated bilirubin, and elevated liver enzymes (aspartate aminotransferase and alkaline phosphatase) in patients receiving chemotherapy for cancer are independent risk factors for febrile neutropenia and complications related to febrile neutropenia.[9][22][23][24]
Result
abnormal LFTs (low albumin [<3.5 g/dL]; elevated bilirubin; elevated aspartate aminotransferase; elevated alkaline phosphatase)
blood cultures
Test
Blood cultures should be obtained promptly from all patients with neutropenia who present with fever or report fever.
At least two sets of blood cultures should be obtained from separate sites/draws. At least one culture, and preferably both, should be obtained from blood drawn peripherally (to avoid contamination and risk of introducing infection through frequent access of central venous catheters). However, this should only be done if feasible and practical in a rapid timeframe that does not delay initiation of empiric antibiotics.
If fever persists after empiric antibiotics have been started, and assuming blood cultures are negative, then repeat blood cultures should be obtained on the next 2 days.[1] Continuing blood cultures after this time is not usually required, unless prompted by a clinical change.
Result
may be positive for a pathogen
chest x-ray
Test
Patients with febrile neutropenia can have pneumonia without cough or abnormal breath sounds; therefore, a plain film chest x-ray should be obtained with the initial fever evaluation in all patients.
Result
may identify pulmonary infiltrates
Tests to consider
gastrointestinal pathogen molecular assay
Test
Clostridioides difficile-associated disease is a common cause of colitis in patients with febrile neutropenia, in the context of frequent use of broad-spectrum antibiotics and extensive contact with the healthcare environment.
Stool evaluation can be carried out to identify the presence of C.difficile or other gastrointestinal pathogens, if and when suspicion arises.
Multiplex polymerase chain reaction (PCR)-based assays for gastrointestinal pathogens are increasingly preferred to stool culture.[51] These assays can provide rapid results with high sensitivity and specificity.[52]
Neutropenic enterocolitis (typhlitis), an acute inflammatory disorder of the intestinal tract (generally in the ileocecal region), should be evaluated with imaging studies (e.g., CT scan).
Result
positive for pathogen in gastrointestinal infection
urine culture
Test
Urinary tract infection is relatively common in patients with febrile neutropenia, but pyuria is likely to be absent in most cases, owing to leukopenia.[49][50]
Urine culture should be obtained to identify the presence of a pathogen if a patient has urinary tract symptoms (results should be interpreted cautiously if a urinary catheter is present).
Result
positive for a pathogen in urinary tract infection
lumbar puncture
Test
A lumbar puncture should be considered for patients with febrile neutropenia who demonstrate signs or symptoms possibly attributable to central nervous system (CNS) infection (e.g., headache, neck stiffness, photophobia, altered mental status, and/or lethargy).
CT head scan or other CNS imaging must be obtained prior to lumbar puncture in patients with febrile neutropenia to ensure that it is safe to proceed.
Result
elevated cerebrospinal fluid (CSF) opening pressure, protein, white or red blood cells; low CSF glucose in CNS infection
fungal cultures and serologies (beta-glucan and galactomannan)
Test
For patients who remain neutropenic and persistently febrile following 3 to 5 days of empiric antibiotics, nonbacterial infections (e.g., fungal infection, viral infection) and non-infectious causes of fever (e.g., drug fever, tumor fever) should be considered. For these patients (and any patient at increased risk for invasive fungal infection) serologic evaluation for Aspergillus and other fungi infection using the galactomannan assay and 1,3-beta-D-glucan, respectively, can be considered.
Chest and sinus imaging (preferably with CT) should also be considered as these are relevant sites of involvement with invasive mold infection in patients with neutropenia.
Result
positive for a fungal organism in fungal infection
viral molecular assay
Test
Viral molecular assays (e.g., polymerase chain reaction [PCR]) should be performed if viral infections are suspected based on history and possible exposures.
Multiplex PCR assays are typically used in the diagnostics workup for patients who present with signs or symptoms suggesting a specific type of infection; for example, respiratory multiplex panel testing may be considered for patients presenting with signs or symptoms suggesting a respiratory viral infection (e.g., cough, shortness of breath).
Result
positive for a virus in viral infection
echocardiogram
Test
An echocardiogram should be ordered in all patients with Staphylococcus aureus bacteremia to assess for infective endocarditis and possible complications.[54]
It should also be considered in patients with suspected infective endocarditis, including those with persistent high-grade bacteremia due to other gram-positive bacteria (e.g., enterococci or viridans group streptococci), Candida species, and occasionally gram-negative rods.
It is reasonable to start with a transthoracic echocardiogram (TTE), and to consider a transesophageal echocardiogram in patients for whom the TTE is nondiagnostic and the index of suspicion for infective endocarditis is moderate or high.
Result
sonographic evidence of a valvular vegetation by either transthoracic or transesophageal echocardiogram
CT scans of the chest, abdomen, and pelvis
Test
Chest CT imaging is more sensitive than chest x-ray and should be considered if chest x-ray is unrevealing and there is concern for respiratory tract infection and/or persistent fever despite 3 to 5 days of empiric guideline concordant antibiotics, or if findings on chest x-ray warrant further delineation.[53]
CT imaging of the abdomen and pelvis should be performed if there are signs or symptoms suggestive of intra-abdominal infection (e.g., abscess, perforation, colitis) or biliary tract process.
Result
pulmonary infiltrates on CT scan of the chest in pneumonia; an abscess on CT scan of the chest, abdomen, or pelvis; inflammation or obstruction of the intestines, gallbladder, pancreas and biliary tree, and genitourinary tract
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