Copyright Hancock 2013 Neutropenic Sepsis in Patients with Cancer Barry Hancock Emeritus Professor of Oncology University of Sheffield 11 th October 2013

Copyright Hancock 2013 What Can Go Wrong? Cystitis

Copyright Hancock 2013

Bone Marrow Suppression

Copyright Hancock 2013

The importance of neutrophils

Copyright Hancock 2013 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 linecentral line

Copyright Hancock 2013 Neutropenic sepsis is a life threatening complication of anti-cancer treatment!

Copyright Hancock 2013 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?”

Copyright Hancock 2013 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.

Copyright Hancock 2013 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!

Copyright Hancock 2013 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 2013 Copyright restrictions may apply. Marti, F. M. et al. Ann Oncol :iv iv; doi: /annonc/mdp163 Initial management of febrile neutropenia

Copyright Hancock 2013 Assessing the patient with FN MASCC scoring index Characteristic Score Burden of illness: no or mild symptoms 5 No hypotension 5 No chronic obstructive pulmonary disease 4 Solid tumor or no previous fungal infection 4 No dehydration 3 Burden of illness: moderate symptoms 3 Outpatient status (at onset of fever) 3 Age <20 years 2 Scores >21 are at low risk of complications MASCC, Multinational Association for Supportive Care in Cancer

Copyright Hancock 2013 Copyright restrictions may apply. Marti, F. M. et al. Ann Oncol :iv iv; doi: /annonc/mdp163 Assessment of response and subsequent management

Copyright Hancock 2013 Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients Issued: September 2012 NICE clinical guideline 151 guidance.nice.org.uk/cg151

Copyright Hancock 2013 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?

Copyright Hancock 2013 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

Copyright Hancock 2013 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.

Copyright Hancock 2013 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

Copyright Hancock 2013 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 10 9 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

Copyright Hancock 2013 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.

Copyright Hancock 2013 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

Copyright Hancock 2013 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

Copyright Hancock 2013 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.

Copyright Hancock 2013 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

Copyright Hancock 2013 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.

Copyright Hancock 2013 Diagnose neutropenic sepsis in patients having anticancer treatment whose neutrophil count is 0.5×10 9 per litre or lower and who have either: - a temperature higher than 38 o C or - other signs or symptoms consistent with clinically significant sepsis. Confirming a diagnosis of neutropenic sepsis

Copyright Hancock 2013 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

Copyright Hancock 2013 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

Copyright Hancock 2013 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

Copyright Hancock 2013 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.

Copyright Hancock 2013 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

Copyright Hancock 2013 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.

Copyright Hancock 2013 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