QuestionSBA
QuestionChoice
Fever in a patient undergoing chemotherapy should be taken seriously. This patient is at high risk for neutropenic sepsis, which suually presents 7-10 days after chemotherapy, when neutrophils are at their lowest. He requires urgent inpatient investigation and intravenous antibiotics through an emergency admission to hospital.
10017371
a
Emergency admission to hospital
QuestionChoice
The patient is at risk of neutropenic sepsis. Emergency admission to hospital should be arranged, rather than an urgent referral to haematology.
10017374
d
Urgent referral to haematology
QuestionChoice
This is inappropriate. The patient is at high risk of neutropenic sepsis, and should be admitted to hospital for IV antibiotics and investigations that are only available in hospital (e.g. blood cultures).
10017375
e
Reassure this is likely a viral infection and discharge with safety-netting
QuestionChoice
While an urgent full blood count will be required to check the neutrophil count, this should not be undertaken in the GP surgery. The priority should be admitting the patient to hospital for IV antibiotics. The GP is unlikely to be able to receive the results of blood tests in time to act on them in an emergency situation.
10017372
b
Urgent full blood count
QuestionChoice
Fever in a patient undergoing chemotherapy should be taken seriously. This patient is at high risk for neutropenic sepsis, which suually presents 7-10 days after chemotherapy, when neutrophils are at their lowest. He requires urgent inpatient investigation and intravenous antibiotics. Local guidelines vary, but the antibiotic of choice is usually IV piparicillin/tazobactam (in patients without a penicillin allergy).
10017373
c
Prescribe oral co-amoxiclav
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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Quesmed Tutorial: Infectious Diseases 
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Fever in a chemotherapy patient may indicate neutropenic sepsis, necessitating urgent hospital admission for assessment and intravenous antibiotics.
A patient presents to his GP feeling generally unwell. He has a background of Burkitt's lymphoma, for which he received chemotherapy 8 days ago. Observations show:

* Heart rate 83 beats/minute

* Blood pressure 132/83 mmHg

* Respiratory rate 13 breaths/minute

* Temperature 38.2 degrees Celcius

On examination, he looks tired but has no other signs of note.

What is the most appropriate next step in management?
a