Neutropenic Sepsis in Patients
with Cancer
Barry Hancock
Emeritus Professor of Oncology
University of Sheffield
11th October 2013
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What Can Go Wrong?
Cystitis
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Bone Marrow Suppression
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The importance
of neutrophils
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An infection can occur
anywhere in the body. The
most common places are
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•
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The mouth and throat
The skin
The gut
The lungs
The kidneys and bladder, especially with
urinary catheter
• At the site of a drip or central line
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Neutropenic sepsis is a life
threatening complication of
anti-cancer treatment!
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Neutropenic sepsis has been highlighted as
an area of clinical priority in the UK, initially
by a publication from the National
Confidential Enquiry into Patient Outcome
and Death (NCEPOD) (Monaghan et al,
2008) then by a subsequent report from the
National Chemotherapy Advisory Group
(NCAG 2009)
“For better or for worse?”
“Chemotherapy Services in England:
Ensuring quality and safety?”
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Neutropenic sepsis
A significant inflammatory response to a
presumed bacterial infection in a person
with or without fever.
Febrile Neutropenia
The development of fever, often with
other signs of infection, in a patient with
neutropenia.
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Neutropenic sepsis
• 85% of infections are bacterial
• Previously Gram negative, now Gram positive
predominate
• Gram negative infections can still be fatal
• Classical signs and symptoms may be absent
• There is often no laboratory evidence
• Look at the whole patient!
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G-CSF - the six EORTC
recommendations
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The patient - age >65years, advanced disease, previous FN
The treatment - intensive, frequent
The purpose - curative, adjuvant
Assess FN risk - use prophylactic G-CSF if the FN risk is
>20%
• Consider G-CSF for ongoing FN not responding to expert
antimicrobial therapy
• Which G-CSF - filgrastim, lenograstim, pegfilgrastim?
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Initial management of febrile neutropenia
Marti, F. M. et al. Ann Oncol 2009 20:iv166-169iv; doi:10.1093/annonc/mdp163
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Assessing the patient with FN
MASCC scoring index
Score
Characteristic
Burden of illness: no or mild symptoms
No hypotension
No chronic obstructive pulmonary disease
Solid tumor or no previous fungal infection
No dehydration
Burden of illness: moderate symptoms
Outpatient status (at onset of fever)
Age <20 years
5
5
4
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3
3
3
2
Scores >21 are at low risk of complications
MASCC, Multinational Association for Supportive Care in Cancer
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Assessment of response and subsequent management
Marti, F. M. et al. Ann Oncol 2009 20:iv166-169iv; doi:10.1093/annonc/mdp163
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Neutropenic sepsis:
prevention and management
of neutropenic sepsis in
cancer patients
Issued: September 2012
NICE clinical guideline 151
guidance.nice.org.uk/cg151
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What is a Clinical Guideline?
Who is the Guideline Intended For?
Who Develops the Guideline?
What is the Remit of this Guideline?
What is the Process for Developing
the Guideline?
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Remit
‘To produce a clinical guideline on the
prevention and management of neutropenic
sepsis in cancer patients’
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Definition of Neutropenic Sepsis
Information, Support and Training
Preventative Treatment
Identification and Assessment
Initial and Subsequent Treatment
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Information, support and training
Provide patients having anticancer treatment
and their carers with written and
oral information, both before starting and
throughout their anticancer treatment,
on:
• neutropenic sepsis
• how and when to contact 24-hour specialist
oncology advice
• how and when to seek emergency care.
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Healthcare professionals and staff who come
into contact with patients having anticancer
treatment should be provided with training on
neutropenic sepsis. The training should be
tailored according to the type of contact
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Reducing the risk of septic complications
of anticancer treatment
For adult patients (aged 18years and older)
with acute leukaemias, stem cell transplants or
solid tumours in whom significant neutropenia
(neutrophil count 0.5 x 109 per litre or lower) is
an
anticipated consequence of chemotherapy,
offer prophylaxis with a fluoroquinolone
during the expected period of neutropenia only.
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• Rates of antibiotic resistance and infection
patterns should be monitored in treatment facilities
where patients are having fluoroquinolones for the
prophylaxis of neutropenic sepsis.
• Do not routinely offer G-CSF for the prevention
of neutropenic sepsis in adults receiving
chemotherapy unless they are receiving G-CSF
as an integral part of the chemotherapy regimen
or in order to maintain dose intensity.
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When to refer patients in the
community for suspected
neutropenic sepsis
• Suspect neutropenic sepsis in patients
having anticancer treatment who
become unwell.
• Refer patients with suspected neutropenic
sepsis immediately for assessment
in secondary or tertiary care.
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Managing suspected neutropenic sepsis
in secondary and tertiary care
• Treat suspected neutropenic sepsis as an
acute medical emergency and offer
empiric antibiotic therapy immediately.
• Include in the initial clinical assessment of
patients with suspected neutropenic sepsis:
- history and examination
- full blood count, kidney and liver function
tests (including albumin), C-reactive
protein, lactate and blood culture.
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After completing the initial clinical assessment
try to identify the underlying cause of the
sepsis by carrying out:
- additional peripheral blood culture in patients
with a central venous access device if clinically
feasible
- urinalysis in all children aged under 5years.
Do not perform a chest X-ray unless clinically
indicated.
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Starting antibiotic therapy
• Offer beta lactam monotherapy with piperacillin with
tazobactam as initial empiric antibiotic therapy to
patients with suspected neutropenic sepsis who need
intravenous treatment unless there are patientspecific or local microbiological contraindications.
• Do not offer an aminoglycoside, either as
monotherapy or in dual therapy, for
the initial empiric treatment of suspected neutropenic
sepsis unless there are patient-specific or local
microbiological indications.
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• Do not offer empiric glycopeptide antibiotics
to patients with suspected neutropenic sepsis
who have central venous access devices
unless there are patient-specific or local
microbiological indications.
• Do not remove central venous access
devices as part of the initial empiric
management of suspected neutropenic
sepsis.
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Confirming a diagnosis of neutropenic
sepsis
Diagnose neutropenic sepsis in patients having
anticancer treatment whose neutrophil count is
0.5×109 per litre or lower and who have either:
- a temperature higher than 38oC or
- other signs or symptoms consistent with
clinically significant sepsis.
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Managing confirmed neutropenic
sepsis
A healthcare professional with competence
in managing complications of anticancer
treatment should assess the patient's risk of
septic complications within 24hours of
presentation to secondary or tertiary care,
basing the risk assessment on presentation
features and using a validated risk scoring
system.
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Patients at low risk of septic
complications
Consider outpatient antibiotic therapy for
patients with confirmed neutropenic
sepsis and a low risk of developing septic
complications, taking into account the
patient's social and clinical circumstances
and discussing with them the need to return
to hospital promptly if a problem develops.
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Patients at high risk of septic
complications
For patients with confirmed neutropenic sepsis and
a high risk of developing septic complications, a
healthcare professional with competence in
managing complications of anticancer treatment
should daily:
- review the patient's clinical status
- reassess the patient's risk of septic
complications, using a validated risk scoring
system.
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Offer discharge to patients having empiric antibiotic
therapy for neutropenic sepsis only after:
- the patient's risk of developing septic complications
has been reassessed as low by a healthcare
professional with competence in managing
complications of anticancer treatment using a
validated risk scoring system and
- taking into account the patient's social and clinical
circumstances and discussing with them the need to
return to hospital promptly if a problem develops.
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Duration of empiric antibiotic treatment
• Do not switch initial empiric antibiotics in patients
with unresponsive fever unless there is clinical
deterioration or a microbiological indication.
• Switch from intravenous to oral antibiotic therapy
after 48hours of treatment in patients whose risk of
developing septic complications has been
reassessed as low by a healthcare professional with
competence in managing complications of anticancer
treatment using a validated risk scoring system.
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• Continue inpatient empiric antibiotic therapy
in all patients who have unresponsive fever
unless an alternative cause of fever is likely.
• Discontinue empiric antibiotic therapy in
patients whose neutropenic sepsis has
responded to treatment, irrespective of
neutrophil count.
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This guidance represents the view of NICE, which
was arrived at after careful consideration of the
evidence available. Healthcare professionals are
expected to take it fully into account when
exercising their clinical judgement. However, the
guidance does not override the individual
responsibility of healthcare professionals to make
decisions appropriate to the circumstances of the
individual patient, in consultation with the patient
and/or guardian or carer, and informed by the
summary of product characteristics of any drugs
they are considering. Implementation of this
guidance is the responsibility of local
commissioners and/or providers
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