QuestionSBA
QuestionChoice
This patient has neutropenic sepsis: a temperature of greater than 38.0°C, OR any symptoms and/or signs of sepsis, in a person with absolute neutrophil count of 0.5 x 10⁹/L or lower. They need cultures from possible infection sites and broad spectrum antibiotics as they are at high risk of deteriorating
33239
b
Admit the patient for observation for 24 hours
QuestionChoice
This patient has neutropenic sepsis and are at high risk of deteriorating and so should be admitted for cultures and broad spectrum antibiotics. CT scans can be used to identify the source of the infection, particularly if there any underlying collections, although it is not the first line investigation for determining the source. Cultures should be taken first and cross-sectional imaging to be considered if the source is still not identified despite this and the patient is still symptomatic
33242
e
Urgent CT Chest Abdomen and Pelvis
QuestionChoice
This patient has neutropenic sepsis: a temperature of greater than 38.0°C, OR any symptoms and/or signs of sepsis, in a person with absolute neutrophil count of 0.5 x 10⁹/L or lower. They need cultures from possible infection sites and broad spectrum antibiotics as they are at high risk of deteriorating
33241
d
Tranfuse one unit of packed red blood cells
QuestionChoice
The main concern in patients on chemotherapy with pyrexia is neutropenic sepsis. This is defined as a temperature of greater than 38.0°C, OR any symptoms and/or signs of sepsis, in a person with absolute neutrophil count of 0.5 x 10⁹/L or lower.
 

 These patients are severely immunosuppressed and cannot mount the normal immune response to infection that others can. They can look and feel completely well for some time, with relatively normal observations, before rapidly becoming unwell and deteriorating. Low threshold are needed to treat aggressively early and take cultures from any possible source to help guide choice of step-down antibiotics
33238
a
IV broad-spectrum antibiotics
QuestionChoice
This patient has neutropenic sepsis: a temperature of greater than 38.0°C, OR any symptoms and/or signs of sepsis, in a person with absolute neutrophil count of 0.5 x 10⁹/L or lower. They are at high risk of deteriorating and so should be admitted for cultures and broad spectrum antibiotics
33240
c
Discharge the patient and provide extensive safety-netting advice to return if develops any signs of infection
Concept
Chapter
# Summary

Neutropenic sepsis is a serious infection that can occur in immunocompromised patients. According to NICE, in patients undergoing cancer treatment, it is identified by a temperature exceeding 38<sup>o</sup>C or any signs of infection, coupled with a neutrophil count below 0.5 x 10<sup>9</sup>/l. This condition is most prevalent among those receiving anticancer therapies and is considered an oncological emergency. Risk factors include severe or prolonged neutropenia, advanced malignancies, and certain medical comorbidities. Clinical presentation may be subtle, necessitating a high index of suspicion for any febrile immunocompromised patient. Prompt investigation and management, including the sepsis six protocol and early senior input, are crucial, as untreated neutropenic sepsis carries a significant risk of mortality and complications from treatment, such as multi-drug resistant infections.



# Definition

In simple terms, neutropenic sepsis can be defined as the presence of both:

- Neutropenia, a low number of neutrophils in the blood.
- Sepsis, defined as a dysregulated response to infection causing life-threatening organ dysfunction.

NICE define neutropenic sepsis in patients receiving anticancer treatment as a temperature **above 38<sup>o</sup>C or any other signs of infection and a neutrophil count of less than 0.5x10<sup>9</sup>/l**.

It most commonly occurs in people receiving anticancer therapy, and is an oncological emergency. It can also occur in immunocompromise due to other causes, for example immunosuppression, HIV infection or congenital immunodeficiency syndromes.

Neutropenic fever is another commonly used term. It refers to a single temperature reading of above 38.3<sup>o</sup>C or two consecutive readings above above 38<sup>o</sup>C for two hours, along with a known or expected neutrophil count of less than 0.5x10<sup>9</sup>/l, and carries a greater risk of sepsis.

***In practice, any fever in the context of known or suspected neutropenia is a medical emergency which can be life-threatening if not treated promptly.***

# Aetiology

Risk factors for neutropenic sepsis include:

- Severe and/or prolonged neutropenia
- Extremes of age
- Previous febrile neutropenia
- Haematological or advanced malignancy
- Prolonged hospital admission or previous surgery
- Medical comorbidities
- Indwelling lines
- Concurrent corticosteroids

Pathogens which can cause neutropenic sepsis include:

- Gram-positive bacteria: Staphylococci sp. (including *S. aureus* & *S. epidermidis*), Enterococcus sp. and Streptococci sp.
- Gram-negative bacteria: *Escherichia coli*, Klebsiella sp., Enterobacter sp. and *Pseudomonas aeruginosa*
- Fungal infections with *Candida* or *Aspergillus* species
- Viral infections

# Signs and symptoms

Clinical features of neutropenic sepsis may be very difficult to distinguish, as neutropenic patients do not have a normal immune response. Therefore, you should have a low threshold for suspecting neutropenic sepsis in any immunocompromised person who becomes unwell. Clinical features may include:

- Focal signs of infection, for example dysuria, productive cough, diarrhoea
- Physiological derangement, including fever or hypothermia, elevated respiratory rate, tachycardia, hypotension, skin colour changes, altered mental state
- Any concern from the patient or relative

# Differential diagnosis

- **Sepsis** causing neutropenia: the person will have presented with symptoms of sepsis first and had a normal or high white cell count, before subsequently developing a neutropenia due to the infection.
- **Drug fever** can occur with many pharmacological agents. Patients may have associated eosinophilia, rash, hepatic or renal derangement. Tests for infection would be negative.
- **Tumour fever**: this is a low-grade fever caused by progression of a malignancy causing inflammation. Tests for infection would be negative and tumour fevers do not respond to antibiotics.
- **Venous thromboembolism**: patients would typically have concurrent symptoms of a deep vein thrombosis or pulmonary embolism (painful swollen leg, chest pain respectively). Definitive diagnosis would be via doppler ultrasound or the leg or CT angiogram of the chest.


# Investigations

It is important to initiate investigations and management for neutropenic sepsis as soon as it is suspected. Initial investigations to request alongside an A-E assessment are:

- Bedside: full set of observations, blood gas, glucose measurement, urine dip, ECG
- Bloods: FBC, CRP, U&E's, LFT's, clotting, lactate
- Cultures: blood cultures, urine, sputum, any indwelling lines or other potential sources of infection
- Imaging: chest X-ray, and any further imaging related to the potential source of infection as appropriate

# Management

**For any patient with suspected neutropenic sepsis, adopt an A-E approach, initiate the sepsis six and seek early senior input.**

This will include:

- Giving **oxygen** to maintain saturations above 94%
- IV access to give **fluids** to maintain blood pressure, take bloods and give antibiotics
- Giving IV broad-spectrum **antibiotics** according to local guidelines, to be given within an hour. Often, this is piperacillin/tazobactam.
- Close **monitoring** of urine output, observations with a NEWS2 chart, and the patient's overall clinical condition.
- **Senior** input may be the consultant on call for immediate management, but the relevant specialty, for example acute oncology, should also be contacted as soon as possible.

Neutropenic patients can become very unwell very quickly. **Critical care** input may be required, and patients should be discussed with them early.

For further details of the sepsis six, please see the *Sepsis* page.

# Complications

Untreated, neutropenic sepsis has a high mortality rate.

Complications of treatment with broad-spectrum antibiotics include:

- Fungal infections, local and systemic
- *C. difficile* infection
- Multi-drug resistant infections, which are much more difficult to treat

# NICE guidelines


[NICE CKS: Neutropenic sepsis](https://cks.nice.org.uk/topics/neutropenic-sepsis/)

# References

[BMJ Best Practice: Febrile neutropenia](https://bestpractice.bmj.com/topics/en-gb/950)
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Oncology and Palliative Care
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Quesmed Tutorial: Infectious Diseases 
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6648
Neutropenic sepsis in chemotherapy patients requires immediate IV broad-spectrum antibiotics.
A 44-year-old woman presents with a temperature of 38.1°C, 3 days after starting cycle 2 of chemotherapy for advanced colorectal cancer. She had T3a rectal cancer resected 8 weeks ago with an end colostomy.

She feels well, with normal observations. Examination shows moist, oral mucosa, a clear chest, a soft, non-tender abdomen, and a pink, warm colostomy producing type 5 stool. No focal neurological signs, meningism, rash, or cellulitis are present.

Investigations:

Urine dip: Clear
Beta-hCG: Negative
Chest X-ray: Unremarkable
  
 

| Serum | Result | Reference Range |
| ------------------------------------ | ------ | ------------------- |
| Haemoglobin | 95 | 115-155 mg/dL |
| White Cell Count | 2.1 | 3.0 - 10.0 x 10⁹ /L |
| Platelets | 160 | 150 - 400 x 10⁹/L |
| Neutrophils | 0.5 | 2.0 - 7.5 x 10⁹ /L |
| Sodium | 135 | 135 - 146 mmol/L |
| Potassium | 3.6 | 3.5 - 5.3 mmol/L |
| Urea | 2.8 | 2.5 - 7.8 mmol/L |
| Creatinine | 45 | 60 - 120 µmol/L |
| eGFR | >90 | \> 60 mL/min/1.73m2 |
| C reactive protein | 25 | < 5 mg/L |
| Lactate | 1.2 | 0.20-1.80 mmol/L |
  
 

Which of the following is the best next step in the management of this patient?
a