Diagnostic approach to the adult cancer

patient with neutropenic fever

Author: John R Wingard, MD
Section Editor: Eric Bow, MD
Deputy Editor: Sheila Bond, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer
review process is complete.

Literature review current through: Jan 2023. | This topic last updated: Sep

12, 2022.

INTRODUCTION

Fever occurs frequently in patients with chemotherapy-induced

neutropenia. Factors that contribute to the pathogenesis of
neutropenic fever include the direct effects of chemotherapy on
mucosal barriers and immune deficits related to the underlying
malignancy or other immunosuppressive conditions or
therapies. Prior to the era of empiric antibiotic therapy,
infections accounted for most episodes of neutropenic fever
and approximately 70 percent of the mortality in neutropenic
acute leukemia patients [1]. Because of the routine use of
prompt empiric antibiotics, infections are documented less
frequently today.
Although the majority of patients with neutropenic fever do not
have a documented infection, consensus guidelines recommend
that all cancer patients with neutropenic fever be promptly
evaluated and treated with empiric broad-spectrum antibiotics
[2]. This approach is indicated since it is difficult to distinguish
life-threatening infections from less serious infections in this
patient population, and infection may progress rapidly in such
patients. Furthermore, better outcomes are seen with prompt
therapy [3].

The recommendations below are generally in keeping with the

2010 Infectious Diseases Society of America (IDSA) guidelines
for the use of antimicrobial agents in neutropenic patients with
cancer and the 2018 American Society of Clinical
Oncology/IDSA guidelines for outpatient management of fever
and neutropenia in adults treated for malignancy [2,4].

The diagnostic evaluation of cancer patients presenting with

neutropenic fever will be reviewed here. An overview of
neutropenic fever syndromes as well as the risk assessment
and management of patients with neutropenic fever are
presented separately. (See "Overview of neutropenic fever
syndromes" and "Risk assessment of adults with chemotherapy-
induced neutropenia" and "Treatment of neutropenic fever
syndromes in adults with hematologic malignancies and
hematopoietic cell transplant recipients (high-risk patients)" and
"Treatment and prevention of neutropenic fever syndromes in
adult cancer patients at low risk for complications" and
"Prophylaxis of infection during chemotherapy-induced
neutropenia in high-risk adults" and "Prophylaxis of invasive
fungal infections in adults with hematologic malignancies" and
"Prophylaxis of invasive fungal infections in adult hematopoietic
cell transplant recipients".)

DEFINITIONS

Fever — Fever in neutropenic patients is defined as a single oral

temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C
(100.4°F) sustained over a one-hour period [2]. The definition of
fever is discussed in greater detail separately. (See "Overview of
neutropenic fever syndromes", section on 'Fever'.)

Neutropenia — The definition of neutropenia may vary from

institution to institution, but neutropenia is usually defined as an
absolute neutrophil count (ANC) <1500 or 1000 cells/microL,
severe neutropenia is as an ANC <500 cells/microL or an ANC
that is expected to decrease to <500 cells/microL over the next
48 hours, and profound neutropenia as an ANC <100
cells/microL [2,4,5]. The risk of clinically important infection
rises as the neutrophil count falls below 500 cells/microL and is
higher in those with a prolonged duration of neutropenia (>7
days). For the purposes of this discussion, we are defining
severe neutropenia as an ANC <500 cells/microL.
The ANC can be calculated by multiplying the total white blood
cell (WBC) count by the percentage of polymorphonuclear cells
(PMNs) and bands (calculator 1). (See "Overview of neutropenic
fever syndromes", section on 'Neutropenia'.)

Assessment of the risk of neutropenia before the WBC and

differential results are available is discussed separately. (See
"Treatment of neutropenic fever syndromes in adults with
hematologic malignancies and hematopoietic cell transplant
recipients (high-risk patients)", section on 'Risk of neutropenia'.)

MICROBIOLOGY

Bacteremia is documented in only 10 to 25 percent of

neutropenic fever episodes, and clinically documented
infections are found in 20 to 30 percent [2]. Most documented
infections during neutropenia are due to bacteria. Although
gram-negative organisms predominated a few decades ago,
most documented infections are now due to gram-positive
organisms. Factors contributing to this trend include use of
long-term central venous catheters and empiric and prophylactic
antimicrobials that are primarily active against gram-negative
pathogens. Fungi and viruses can also be pathogens,
particularly in high-risk patients. (See "Overview of neutropenic
fever syndromes", section on 'Epidemiology'.)

PATIENT EVALUATION
In all cancer patients presenting with neutropenic fever, empiric
antibacterial therapy should be initiated immediately after blood
cultures have been obtained and before any other investigations
have been completed. (See 'Initiation of empiric therapy' below.)

All patients should undergo a careful history and detailed

physical examination as well as laboratory, microbiology, and
imaging studies; the approach to the diagnostic evaluation is
summarized in the following table ( table 1). Because
symptoms and signs of infection are attenuated due to the lack
of an inflammatory reaction, fever may be the sole sign of
infection. Thus, it is important to recognize that the absence of
the typical symptoms, signs, or laboratory findings suggestive of
infection typically seen in non-neutropenic patients cannot be
used to exclude the possibility of infection. The evaluation
should be performed promptly.

History — The history should probe for the development of new

symptoms that can lead to identification of a site of infection.
The initial clinical evaluation also focuses on assessing the risk
of serious complications. (See 'Risk assessment' below.)

The following key elements of the history should always be

included:

● Inquire about organ-specific symptoms. A review of systems

should be repeated daily. Determine if antimicrobial
prophylaxis had been given and which agent(s).
 ● Probe for a history of prior infection or colonization
(especially by antibiotic-resistant organisms).

● Determine if there might be noninfectious causes of fever

(eg, blood transfusion, uncontrolled cancer).

● Determine which comorbid conditions may be present. A

variety of comorbid conditions predispose to infectious
complications, such as immobility (decubitus ulcers), poor
nutrition, foreign bodies such as venous or bladder
catheters, prosthetic heart valves or orthopedic hardware,
diabetes mellitus, chronic respiratory conditions,
rheumatologic disorders, inflammatory bowel disease, etc.

Risk assessment — The initial clinical evaluation focuses on

assessing the risk of serious complications in addition to the
presence of a documented infection. The risk assessment
dictates the approach to therapy, including the need for inpatient
admission, intravenous (IV) antibiotics, and prolonged
hospitalization. The factors that are associated with serious
complications are summarized in the table ( table 2) and
discussed in greater detail separately. (See "Overview of
neutropenic fever syndromes", section on 'Risk of serious
complications' and "Risk assessment of adults with
chemotherapy-induced neutropenia".)

Physical examination — A thorough general physical

examination should be performed. The emphasis should be on
sites most likely to be infected, including the skin, catheter sites,
biopsy and bone marrow aspirate sites, teeth, oropharynx and
gingival surfaces, sinuses, lungs, abdomen, genitals, and
perianal area. As noted above, it is important to remember that
in the absence of neutrophils, signs of inflammation can be
extremely subtle.

Review of systems and a physical examination should be

repeated daily. In patients with persistent fever, new sites of
infection (eg, lungs, skin, and urinary tract) may become
apparent over time. In addition, as the neutrophil count recovers,
localizing symptoms and signs of infection often become
evident for the first time.

Lungs — The lungs are a common site of infection in patients

with chemotherapy-induced neutropenia and should be
examined for signs of pneumonia (eg, rales). Hypoxia,
tachypnea, and increased work of breathing are other signs of
pneumonia. (See "Approach to the immunocompromised patient
with fever and pulmonary infiltrates".)

Abdomen — An abdominal examination should be performed to

evaluate for peritoneal signs and/or abdominal tenderness,
which may represent neutropenic enterocolitis or Clostridioides
difficile colitis. Even when an abdominal process is present,
abdominal signs may be subtle or absent in neutropenic
patients. (See "Neutropenic enterocolitis (typhlitis)" and
"Clostridioides difficile infection in adults: Clinical
manifestations and diagnosis".)
Intravenous catheter sites — All IV catheter sites, especially
central venous catheter (CVC) sites, should be carefully
examined for subtle signs of infection; slight erythema or
tenderness may be the only evidence of a serious "tunnel"
infection. Fluctuance or exudates are unlikely since the lack of
inflammatory cells inhibits the development of inflammatory
reactions. IV catheters should also be assessed for any
malfunction; difficulty with infusion or blood drawing can also
be a sign of an infected venous thrombosis, even in the absence
of a problem with the exit site. Sites of recent IV catheters
should also be examined.

Skin and mucous membranes — The skin and mucous

membranes should be examined for signs of erythema, rash,
cellulitis, ulcers, furuncles, vesicles, paronychia, mucositis,
dental or peritonsillar cellulitis, perianal fissures, and pilonidal
disease. Skin lesions can often be a manifestation of a systemic
infection including:

● Ulcers – Fungi, atypical bacteria, nontuberculous

mycobacteria, viruses

● Vesicles – Viruses

● Nodules – Fungi, bacteria, nontuberculous mycobacteria

● Ecthyma gangrenosum – Large lesion with a necrotic center

that is classically seen with Pseudomonas aeruginosa but
 also with other bacteria, such as Staphylococcus aureus
( picture 1)

● Skin lesions with a necrotic center – Invasive fungal

infections (eg, Fusarium spp, Aspergillus spp, Mucorales) can
also cause skin lesions with a necrotic center ( picture 2
and picture 3)

Sometimes, skin lesions, such as erythema multiforme, can be

related to viral infections; alternatively, erythema multiforme can
be related to antibiotic therapy and may be associated with
fever, causing diagnostic confusion ( picture 4). (See
"Erythema multiforme: Pathogenesis, clinical features, and
diagnosis".)

Infections that can cause fever and rash in

immunocompromised hosts are discussed in greater detail
separately. (See "Fever and rash in immunocompromised
patients without HIV infection".)

Perianal region — The examination should also include

inspection of the perianal area. Erythema, pain on palpation, and
tender hemorrhoids are important signs of infection. However,
digital rectal examination (and rectal temperatures) should be
avoided so that one does not introduce infection by traumatizing
the fragile mucosa.

Routine laboratory tests — Laboratory evaluation should include

a complete blood cell count with differential, hepatic
transaminases, bilirubin, electrolytes, serum creatinine, blood
urea nitrogen, serum lactate, urinalysis, and cultures ( table 1)
[2].

In interpreting laboratory results in neutropenic patients, it is

important to recognize that the absence of the typical laboratory
findings suggestive of infection that are usually seen in non-
neutropenic patients cannot be used to exclude the possibility of
infection. Therefore, absence of abnormalities, such as
cerebrospinal fluid (CSF) pleocytosis, pyuria, or neutrophils on
sputum Gram stain, does not rule out infection.

Serum fungal markers — Checking fungal markers from the

serum, such as the Aspergillus galactomannan antigen and the
beta-D-glucan assay, should also be considered in high-risk
patients. Fungal markers are checked starting with onset of
neutropenia and continued until neutrophil recovery. They are
not routinely sent in low-risk patients except as part of an
evaluation for suspected fungal infection. Some centers
perform serial monitoring of these twice weekly in
hematopoietic cell transplant recipients and acute leukemia
patients not receiving anti-mold prophylaxis, where a positive
test may guide further evaluation or prompt pre-emptive therapy
[2]. In patients receiving an agent with antimold activity, the
value of this approach has not been established. The Aspergillus
galactomannan antigen is a specific test for invasive
aspergillosis, whereas the beta-D-glucan assay is a nonspecific
test for several invasive fungal infections, including aspergillosis
and candidiasis. (See "Diagnosis of invasive aspergillosis",
section on 'Galactomannan antigen detection' and "Diagnosis of
invasive aspergillosis", section on 'Beta-D-glucan assay' and
"Clinical manifestations and diagnosis of candidemia and
invasive candidiasis in adults", section on 'Beta-D-glucan assay'.)

Microbiology and other diagnostic testing — In all cancer

patients presenting with neutropenic fever, empiric antibacterial
therapy should be initiated immediately after blood cultures
have been obtained and before any other investigations have
been completed. The microbiologic evaluation should be
performed promptly. (See 'Initiation of empiric therapy' below.)

Specimens for the microbiology laboratory should include at

least two sets of blood cultures ( table 1) [2]. Each set should
have a volume of 20 mL (proportionally smaller volume in
children weighing <40 kg; eg, no more than 1 percent of
estimated patient total blood volume). In patients with a CVC,
we prefer to collect a set of blood cultures simultaneously from
each lumen and from a peripheral vein site. Some experts feel
that it is acceptable to collect both sets of cultures from the
CVC, especially in patients with difficult peripheral venous
access. In patients without a CVC, a set should be obtained from
each of two separate venipuncture sites. The diagnosis of CVC
infections is discussed in greater detail separately. (See
"Intravascular non-hemodialysis catheter-related infection:
Clinical manifestations and diagnosis".)

Two sets of blood cultures are typically repeated daily for

persistent fevers or rigors at least during the first two days
following initiation of empiric antibiotics [2]. Institutions may
have different guidelines for the frequency of obtaining blood
cultures. As an example, some centers stop collecting blood
cultures or reduce the frequency of collection after several days
if the initial cultures are negative for patients with a stable fever
pattern. If the cultures are positive, they should be repeated until
they become negative to ensure response to therapy and
intermittently thereafter.

Specimens should be obtained from other sites as clinically

indicated (eg, sputum, urine, CVC exit site, CSF, skin, stool).
Many neutropenic patients receiving cytotoxic chemotherapy are
also thrombocytopenic; in such patients, platelet transfusions
are often necessary in order to safely perform a lumbar puncture
or other invasive procedures. In general, indications for
collection of these additional samples are as follows [2]:

● Stool – If diarrhea is present, send a C. difficile toxin assay.

There is limited utility in sending stool samples for culture or
ova and parasites in hospitalized patients in the United
States; these studies can be sent in patients with recent
travel to or residence in areas that are endemic for enteric
pathogens or if there is another reason to suspect an enteric
 pathogen. (See "Clostridioides difficile infection in adults:
Clinical manifestations and diagnosis", section on
'Diagnosis'.)

● Urine – If symptoms of urinary tract infection are present,

send urine for bacterial culture and susceptibility testing.
(See "Sampling and evaluation of voided urine in the
diagnosis of urinary tract infection in adults".)

● Skin – If skin lesions are present, aspirate or biopsy lesions

for bacterial and fungal stains and cultures, and, if vesicles
are present, send for either herpes simplex virus and
varicella-zoster virus polymerase chain reactions (PCRs) or
culture plus direct fluorescent antibody testing. When a
biopsy is obtained, it should also be sent for histopathology.
(See "Epidemiology, clinical manifestations, and diagnosis of
herpes simplex virus type 1 infection", section on 'Diagnosis'
and "Diagnosis of varicella-zoster virus infection".)

● Respiratory – If productive cough is present, send sputum

for bacterial and fungal stains and cultures and assays for
respiratory viruses [6]. (See "Clinical evaluation and
diagnostic testing for community-acquired pneumonia in
adults".)

Neutropenic patients with pulmonary infiltrates often cannot

produce sputum; a more invasive approach, including
bronchoscopy with bronchoalveolar lavage ( table 3) or
video-assisted thoracoscopic surgery, may need to be
 pursued in order to make a microbiologic diagnosis. This
may be particularly important for patients with infiltrates on
chest radiographs or chest computed tomography (CT) who
continue to worsen despite 24 to 48 hours of empiric
antibiotic therapy. (See "Approach to the
immunocompromised patient with fever and pulmonary
infiltrates".)

In patients with an influenza-like illness (especially when

respiratory viruses are circulating), a nasopharyngeal swab
should be sent for influenza testing (ideally with a molecular
test, such as PCR), as well as testing for other respiratory
viruses (respiratory syncytial virus, adenovirus, parainfluenza
virus, human metapneumovirus). (See "Respiratory syncytial
virus infection: Clinical features and diagnosis", section on
'Laboratory confirmation' and "Diagnosis, treatment, and
prevention of adenovirus infection", section on 'Diagnostic
tests of choice for different adenovirus syndromes' and
"Human metapneumovirus infections", section on 'Diagnosis'
and "Seasonal influenza in adults: Clinical manifestations
and diagnosis".)

Testing for coronavirus disease 2019 (COVID-19) is also

discussed separately. (See "COVID-19: Diagnosis", section
on 'Diagnostic approach'.)

● Cerebrospinal fluid – If symptoms of meningitis (fever,

headache, nuchal rigidity, altered mental status) are present,
 send CSF for cell count, glucose, protein, and bacterial
culture and susceptibility testing. In addition, in patients with
clinical signs of meningitis and/or encephalitis, CSF should
also be sent for cryptococcal antigen testing and for PCR
testing for herpes simplex virus, cytomegalovirus, varicella-
zoster virus, and, in allogeneic hematopoietic cell transplant
recipients, human herpesvirus 6. Additional tests are
indicated if epidemiologic risk factors are present (eg,
testing for West Nile virus, Eastern equine encephalitis, and
other arthropod-borne encephalitides during the summer in
certain regions). (See "Clinical features and diagnosis of
acute bacterial meningitis in adults", section on
'Cerebrospinal fluid examination' and "Aseptic meningitis in
adults" and "Herpes simplex virus type 1 encephalitis",
section on 'Diagnosis' and "Clinical manifestations and
diagnosis of Cryptococcus neoformans
meningoencephalitis in patients without HIV" and
"Arthropod-borne encephalitides" and "Overview of
diagnostic tests for cytomegalovirus infection" and "Human
herpesvirus 6 infection in hematopoietic cell transplant
recipients", section on 'Diagnosis'.)

Imaging — Imaging studies should be performed promptly but

should not delay initiation of empiric therapy. (See 'Initiation of
empiric therapy' below.)
In febrile neutropenic patients with respiratory signs or
symptoms, we suggest that a chest radiograph be obtained in
low-risk patients and a noncontrast intermediate- or high-
resolution chest CT be obtained in high-risk patients (see 'Risk
assessment' above). In contrast, the Infectious Diseases Society
of America guidelines recommend a chest radiograph as part of
the initial evaluation for neutropenic fever in patients with
respiratory symptoms without distinction by risk status [2]. It is
important to note, however, that chest radiograph findings are
often minimal or absent, even in patients with pneumonia or
pulmonary nodules. Intermediate- or high-resolution chest CT is
much more sensitive for detecting abnormalities in neutropenic
patients. One should be mindful that detection of small nodules
may represent benign granulomas in certain areas endemic for
certain infections rather than active infection, and therefore
caution in interpretation should be exercised.

In one study, high-resolution chest CT demonstrated pneumonia

in more than one-half of persistently febrile neutropenic patients
who had normal findings on routine chest radiograph [7]. It was
estimated that high-resolution CT scanning resulted in the
diagnosis being established five days earlier compared with the
exclusive use of chest radiographs but did not improve clinical
outcomes. Although CT scanning has not been shown to change
clinical outcomes, one should have a low threshold for ordering
a CT scan in both high- and low-risk neutropenic patients with
pulmonary symptoms to help guide the selection and duration of
treatment and to assess for radiographic evidence of invasive
fungal disease. Repeat chest imaging should be obtained for
increasing or persistent pulmonary symptoms and signs,
including cough, shortness of breath, and/or hypoxia [2].
Radiographic findings may become evident along with an
increase in symptoms as the neutropenia begins to resolve.

CT scanning of other sites (head, sinuses, abdomen/pelvis)

should be performed according to suggestive symptoms or
other risk factors [2]. In particular, patients with neutropenic
fever and any signs or symptoms suggestive of neutropenic
enterocolitis or C. difficile colitis (eg, abdominal pain or
tenderness, diarrhea) should undergo abdominal CT scanning
with IV and oral contrast. (See "Neutropenic enterocolitis
(typhlitis)", section on 'Diagnosis' and "Clostridioides difficile
infection in adults: Clinical manifestations and diagnosis".)

INITIATION OF EMPIRIC THERAPY

Fever in a neutropenic patient should be considered a medical

emergency ( algorithm 1). Early studies documented mortality
rates of up to 70 percent if initiation of antibiotics was delayed
[8]. Therefore, the evaluation of such patients should occur
promptly, and broad-spectrum antibiotics should be given as
soon as possible (within 60 minutes of presentation) and at full
doses (adjusted for renal and/or hepatic function). In all cancer
patients presenting with neutropenic fever, empiric antibacterial
therapy should be initiated immediately after blood cultures
have been obtained and before any other investigations have
been completed. (See "Overview of neutropenic fever
syndromes", section on 'Timing of antibiotics'.)

The aim of empiric therapy is to cover the most likely and most
virulent pathogens that may rapidly cause serious or life-
threatening infection in neutropenic patients [2]. Empiric therapy
approaches are discussed separately. (See "Treatment of
neutropenic fever syndromes in adults with hematologic
malignancies and hematopoietic cell transplant recipients (high-
risk patients)" and "Treatment and prevention of neutropenic
fever syndromes in adult cancer patients at low risk for
complications".)

EVALUATION OF PERSISTENT OR RECURRENT

FEVER

Persistent or recurrent fever should prompt a thorough search

for a source of occult infection. Repeat cultures of blood and
other cultures or diagnostic tests should be performed on the
basis of symptoms and signs. Diarrhea should be evaluated with
a C. difficile toxin assay.

Repeating and/or broadening the imaging evaluation is

warranted for persistent or recurrent fever. An abdominal
computed tomography (CT) scan should be considered to
evaluate for neutropenic enterocolitis when abdominal signs are
present (see "Neutropenic enterocolitis (typhlitis)"). CT scans of
the chest and sinuses are useful to evaluate for occult mold
infections. (See "Diagnosis of invasive aspergillosis", section on
'Imaging' and "Epidemiology and clinical manifestations of
invasive aspergillosis", section on 'Imaging' and "Mucormycosis
(zygomycosis)" and "Fungal rhinosinusitis".)

Management algorithms have been developed for the

reassessment of neutropenic patients with persistent fever after
two to four days ( algorithm 2) and after four or more days
( algorithm 3) [2]. The risk assessment and management of
patients with neutropenic fever is discussed in detail separately.
(See "Risk assessment of adults with chemotherapy-induced
neutropenia" and "Treatment of neutropenic fever syndromes in
adults with hematologic malignancies and hematopoietic cell
transplant recipients (high-risk patients)", section on 'Persistent
fever' and "Treatment and prevention of neutropenic fever
syndromes in adult cancer patients at low risk for
complications".)

The diagnosis and management of sepsis syndromes are also

discussed separately. (See "Sepsis syndromes in adults:
Epidemiology, definitions, clinical presentation, diagnosis, and
prognosis" and "Evaluation and management of suspected
sepsis and septic shock in adults".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from
selected countries and regions around the world are provided
separately. (See "Society guideline links: Neutropenic fever in
adults with cancer".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The

Basics" and "Beyond the Basics." The Basics patient education
pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are
best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade
reading level and are best for patients who want in-depth
information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this
topic. We encourage you to print or email these topics to your
patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the
keyword(s) of interest.)

● Basics topic (see "Patient education: Neutropenia and fever

in people being treated for cancer (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Fever is a medical emergency − Fever during chemotherapy-
induced neutropenia is a medical emergency requiring
prompt evaluation and treatment. Fever in neutropenic
patients is defined as a single oral temperature of >38.3°C
(101.0°F) or a temperature of >38.0°C (100.4°F) sustained
for >1 hour. We define severe neutropenia as an absolute
neutrophil count <500 cells/microL. (See 'Introduction' above
and 'Fever' above and 'Neutropenia' above.)

● Urgent empiric antibiotic treatment − In all cancer patients

presenting with neutropenic fever, empiric antibacterial
therapy should be initiated as soon as possible (within 60
minutes of presentation), immediately after blood cultures
have been obtained, and before any other investigations
have been completed ( algorithm 1). (See "Treatment of
neutropenic fever syndromes in adults with hematologic
malignancies and hematopoietic cell transplant recipients
(high-risk patients)" and "Treatment and prevention of
neutropenic fever syndromes in adult cancer patients at low
risk for complications".)

● Microbiology − Bacteremia is documented in only 10 to 25

percent of neutropenic fever episodes, and clinically
documented infections are found in 20 to 30 percent. Most
documented infections during neutropenia are due to gram-
 positive organisms. Fungi and viruses can also be
pathogens, particularly in high-risk patients. (See
'Microbiology' above.)

● Diagnostic evaluation − The diagnostic evaluation should

include a targeted history, physical examination, and
laboratory assessments ( table 1). This includes:

• Blood cultures and cultures obtained from other

suspected sites of infection.

• Chest imaging – In febrile neutropenic patients with

respiratory signs or symptoms, we suggest that a chest
radiograph be obtained in low-risk patients and a chest
computed tomography (CT) scan be obtained in high-risk
patients.

• Abdominal imaging – Patients with neutropenic fever and

any signs or symptoms suggestive of neutropenic
enterocolitis or Clostridioides difficile colitis (eg,
abdominal pain or tenderness, diarrhea) should undergo
abdominal CT scanning. (See 'Patient evaluation' above.)

● Persistent and recurrent fever − Persistent or recurrent fever

should prompt a thorough search for a source of occult
infection. Repeat cultures of blood and other cultures or
diagnostic tests should be performed on the basis of
symptoms and signs. Management algorithms have been
developed for the reassessment of neutropenic patients with
 persistent fever after two to four days ( algorithm 2) and
after four or more days ( algorithm 3). (See 'Evaluation of
persistent or recurrent fever' above.)

ACKNOWLEDGEMENTS

The UpToDate editorial staff acknowledges Dr. Gregory K

Robbins and Dr. Kieren A Marr, who contributed to earlier
versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

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7. Heussel CP, Kauczor HU, Heussel GE, et al. Pneumonia in

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