copyright hancock 2013 neutropenic sepsis in patients with cancer barry hancock emeritus professor...

Copyright Hancock 2013

Neutropenic Sepsis in Patients with Cancer

Barry Hancock

Emeritus Professor of Oncology

University of Sheffield

11th October 2013


What Can Go Wrong?

Cystitis


Bone Marrow Suppression

Copyright Hancock 2013The importance of neutrophils


An infection can occur anywhere in the body. The most common places are

• 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

http://cancerhelp.cancerresearchuk.org/about-cancer/treatment/chemotherapy/having/iv-chemotherapy#central


Neutropenic sepsis is a life

threatening complication of

anti-cancer treatment!


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?”


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.


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!


G-CSF - the six EORTC recommendations

• 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?

Copyright Hancock 2013Copyright restrictions may apply.

Marti, F. M. et al. Ann Oncol 2009 20:iv166-169iv; doi:10.1093/annonc/mdp163

Initial management of febrile neutropenia


Assessing the patient with FNMASCC scoring index

Characteristic Score

Burden of illness: no or mild symptoms 5No hypotension 5No chronic obstructive pulmonary disease 4Solid tumor or no previous fungal infection 4No dehydration 3Burden of illness: moderate symptoms 3Outpatient status (at onset of fever) 3Age <20 years 2

Scores >21 are at low risk of complications

MASCC, Multinational Association for Supportive Care in Cancer

Copyright Hancock 2013Copyright restrictions may apply.

Marti, F. M. et al. Ann Oncol 2009 20:iv166-169iv; doi:10.1093/annonc/mdp163

Assessment of response and subsequent management


Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients Issued: September 2012 NICE clinical guideline 151 guidance.nice.org.uk/cg151


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?


Remit‘To produce a clinical guideline on the

prevention and management of neutropenic sepsis in cancer patients’

- Definition of Neutropenic Sepsis

- Information, Support and Training

- Preventative Treatment

- Identification and Assessment

- Initial and Subsequent Treatment


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.


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


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.

Reducing the risk of septic complications of anticancer treatment


• Rates of antibiotic resistance and infectionpatterns should be monitored in treatment facilities where patients are having fluoroquinolones for theprophylaxis of neutropenic sepsis.

• Do not routinely offer G-CSF for the preventionof 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.


• 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.

When to refer patients in the community for suspected neutropenic sepsis


• 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.

Managing suspected neutropenic sepsis in secondary and tertiary care


After completing the initial clinical assessmenttry 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.


• 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 patient-specific 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.

Starting antibiotic therapy


• 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.


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.

Confirming a diagnosis of 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.

Managing confirmed neutropenic sepsis


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.

Patients at low 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.

Patients at high risk of septic complications


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.


• 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.

Duration of empiric antibiotic treatment


• 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.


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

copyright hancock 2013 neutropenic sepsis in patients with cancer barry hancock emeritus professor...

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subsequent management

bone marrow suppression

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