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Neutropenic sepsis

15 November 2013
Dr. Hlne McDermott
Microbiology lecturer
RCSI
Lecture overview
Definition of neutropenia
Causes of neutropenia
Infections encountered in neutropenic
patients
Case of patient neutropenic sepsis
Management of patients with neutropenic
sepsis


Neutropenia
Neutropenia is defined as a neutrophil count
of <500 cells/mm
3
or a neutrophil count that
is expected to decrease to <500 cells/mm
3

during the next 48h
1
Infection occurs in 20-30% of febrile
episodes
1
Low numbers of neutrophils mean patients
are vulnerable to a variety of infections,
including those caused by opportunistic
pathogens
1
IDSA Guidelines, 2010

Function

Killing by phagocytosis

Oxygen dependent killing

Antimicrobial peptides

Severity & duration
Patients with an neutrphil count <500/microL
risk if neutrophil count <100/microL for more
than five days
Source of microbial invasion of the blood
chemotherapy-induced mucositis
breaks in the gastrointestinal lining

Neutropenic sepsis
Pathogens
Pyogenic or enteric bacteria (endogenous, e.g. S.
aureus from the skin and Gram-negative organisms
from the gastrointestinal and urinary tract)
Certain fungi
Isolated neutropenia does not increase the
susceptibility to viral or parasitic infection
Sites of infection
oral cavity, the skin, and perirectal and genital
areas, bacteremia, infections of the lung and
gastrointestinal tract, indwelling catheters or other
foreign bodies


909 episodes of bacteremia among 799
neutropenic febrile cancer patients
46% Gram positive organisms
42% to Gram negative organisms
12% were polymicrobial
Infection at a site was observed in 242 episodes
lung (about 40%)
skin and soft tissue (30%)
urinary tract, sinuses and oropharynx, skeletal,
enteric tract, meninges, and endocardium

Bacteria

Viruses

Fungi

Protozoa

Opportunistic pathogens
Neutrophil Dysfunction
Primary (Genetic)
Chronic granulomatous disease
Leucocyte adhesion defect
Hyper-IgE syndrome

Secondary Drugs eg steroids, chemotherapy
Diabetes mellitus
Malignancy
Clinical Case
Patient tolerates his first cycle of
chemotherapy
Cycle 2
Day 7 patient becomes neutropenic
White cell count 1.5 x10
9
/l (4.0-11.0 x10
9
/L)
Neutrophil count 0.7 x10
9
/l (2.0-7.5 x10
9
/L)
Day 11 patient is still neutropenic (0.2 x10
9
/l)
and spikes a temperature 38.5C
Patient feels unwell

History
Patient feels cold and shivery
He feels tired and weak, with no energy
He has no appetite and some nausea
Patient has no cough, shortness of breath
or chest pain
He has no pain passing urine
He has no diarrhoea
Clinical Examination
Vital signs
Temperature 38.8C
Heart rate 118bpm
Blood pressure 110/50
Respiratory rate - 32
Clinical Examination
General inspection
Flushed
No evidence of rash
Hickman line site is clean
Cardiovascular examination
Respiratory examination
Abdominal examination

Nothing abnormal detected
Investigations
Bloods
Chest x-ray
Microbiological investigations
Blood cultures
Central & peripheral
MSU
Sputum
Swab hickman line site
Diagnosis & treatment
Diagnosis?
Neutropenic sepsis

Treatment?
Piperacillin/tazobactam
Results
FBC
0.7 x10
9
/l
Neutrophils 0.2 x10
9
/l
Blood cultures
Sterile
MSU
Wcc 1/mm
3
, cc<1x10
6
Sputum
Not productive
Swab Hickman line site
No growth


CXR
Clinical Deterioration
At 2am the following morning
Pt feels unwell
Spike to 39.5C
Hypotensive
Tachycardic
Physical examination is unremarkable
What would you do?

Clinical Deterioration
Full septic screen
Blood cultures central and peripheral
Chest x-ray
Antibiotic therapy?
Add gentamicin 5mg/kg iv od

The following day
Patient still pyrexial, c/o pain at Hickman line
insertion site
O/E - Erythema




Phone call from the lab
positive blood culture
Gram stain

What changes to his treatment would
you make?
A. None, continue piperacillin-tazobactam and
gentamicin
B. Discontinue piperacillin-tazobactam and
gentamicin and start flucloxacillin
C. Discontinue piperacillin-tazobactam and
gentamicin and start vancomycin
D. Continue piperacillin-tazobactam and
gentamicin and add vancomycin


Patient makes good progress
Within 48h the microbiology laboratory
confirms the blood culture isolate as S.
epidermidis
The patient improves on vancomycin and
temperature decreases
However central blood cultures remain
positive for S. epidermidis and patient
continues to c/o pain at the line site
What would you do next?
A. Add rifampicin
B. Switch patient to linezolid
C. Remove the line
D. Increase the dose of vancomycin
Patient progress
When the line is changed blood cultures
become sterile, the patient remains
apyrexial and feels well
However, the patient remains neutropenic
despite finishing his chemotherapy
(neutrophil count 0.8 x10
9
/l) for a number
of weeks
Day 24 patient c/o of dry cough and
shortness of breath
CXR
CT thorax
Bronchoalveolar lavage
Toxoplasma gondii
Cerebral toxoplasmosis
Cryptosporidium parvum
Lung biopsy
Diagnosis and treatment
Diagnosis
A. Pulmonary aspergillosis
B. Pulmonary TB
C. CMV pneumonitis
D. PCP
Treatment
A. Fluconazole
B. Terbinafine
C. Linezolid
D. Voriconazole
Patient progress
Patient responds to treatment
Cough resolves and CXR
infiltrates resolve
Neutrophil count improves
and eventually returns to normal
Patient goes on to have his next cycle of
chemotherapy
Infections in neutropenic patients
Bacterial
Pseudomonas aeruginosa
Staphylococcus aureus
Nocardia asteroides
Salmonella typhi
Fungal
Candida spp.
Aspergillus spp.
IDSA guidelines,
2010
Treatment of Neutropenic Fever
Stage 1 Piperacillin/tazobactam +/-
gentamicin

Stage 2 Add vancomycin

Stage 3 Add an anti-fungal

Stage 4 Add anti-viral therapy
Summary
Definition of neutropenia
Causes of neutropenia
Infections encountered in neutropenic
patients
Case of a patient with
neutropenic sepsis
Management of patients with neutropenic
sepsis

Thank you

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