Haematology - Neutropenic fever Flashcards
Host immune defense in skin and mucosa?
Physicochemical barrier:
Skin: pH, sIgA, normal flora, osmotic pressure
Mucosa: pH, sIgA, normal flora, bile, digestiveenzymes, lysozyme, flushing/ peristalsis, lactoferrin, peroxidase
Immune defense against microbes in local tissues
Cellular arm of the innate immune response
Infiltration by phagocytes (neutrophil, macrophages, Langhan cells)
Exudation
Local inflammatory response (LIRS)
Examples of 4 pathogens that are not virulent but cause disease in immunocompromised host
Opportunistic: Candida albicans Bacillus cereus Staphylococcus epidermidis Cytomegalovirus (CMV)
Define immunocompromised host
Examples of immunocompromised state
Compromised host:
- Has >1 significant alterations in body’s natural defense mechanisms (innate & adaptive immunity)
- As a result of underlying diseases & their therapy
- Which predispose the host to severe infections / neoplasia
E.g.:
o Leukaemia, lymphoma
o Organ/ bone marrow transplant, use of immunosuppressives (e.g. steroid, anti-TNF)
o Severe burn, massive trauma
o Alcoholism, under-nutrition & intravenous drug abuse
Examples of acquired immunocompromised state
Most common = HIV
From most to least severe:
BMT
Solid organ transplant (heart and lung > liver > kidneys)
Cancers (hematological (leukemia, lymphoma) are more suppressed than the solid tumour)
Autoimmune disorder
Chronic diseases/ major organ failure (e.g. liver/ kidney failure)
Splenectomy
Malnutrition
Major mechanisms in compromising host immunity **
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- Granulocytopenia (neutropenia = commonest, e.g. chemotherapy-induced)
- Cellular immune dysfunction (low CD4 T lymphocytes, e.g. AIDS, immunosuppressives)
- Humoral immune dysfunction (related to antibody, B lymphocytes)
-
Anatomic-barrier damage involving the mucosa/ skin
- Severe burn/ massive trauma
- Chemotherapy-/ radiotherapy-induced mucositis Neutropenic fever most common - Complement deficiency
- Autoantibody against cytokines (e.g. IFN-γ, IL-6, GM-CSF)
- Medical/surgical procedures, indwelling devices, implant devices
- Antimicrobial therapy: Suppress normal flora
- Gastric hypochlorhydria
- Therapeutic biologics
-
Obstruction of conducting systems
- draining from a normally sterile anatomical site to a non-sterile one - Central nervous system dysfunction e.g. aspiration pneumonia
- Major organ dysfunction
- Others:
o Thrombocytopenia
o Malnutrition
o Chronic blood transfusion/ poorly controlled diabetes mellitus
Pathogenesis of chemo-/ radiotherapy induced mucositis and subsequent infection
Cytoreductive chemotherapy acts on rapidly replicating cells
(e.g. blood cells, epithelial cells in GIT), e.g. chemotherapy mucositis affecting GI tract
> > Damage to mucosa throughout the alimentary system
> > endogenous bacterial/ fungal flora (or transient flora acquired from hospital environment) translocates across the mucosa
> > seeds the bloodstream and causes the majority of neutropenic fever cases
Clinical presentation of chemo/ radiotherapy induced mucositis
- Oral mucositis (sore throat; erythema, ulceration)
- Oesophagitis (retrosternal pain on swallowing)
- Enterocolitis (watery diarrhea)
- Narrowest part of GI tract which undergo frequent distension: cricopharyngeal junction, oesophagogastric junction, ileocecal junction, anus
Sources of bacteria causing chemo/radiotherapy-induced mucositis
o Feces (bacteremia) o Skin (e.g. Hickman catheter exit site) o Air (pulmonary aspergillosis)
Post-chemotherapy neutropenia
- Explain why neutropenic fever must occur if neutropenia is not corrected after weeks
- What determines the recovery of neutrophil count
Neutrophil half-life is only 8 hours
Neutrophil count is maintained by bone marrow reserves for up to 2 weeks
If WBC does not return to normal, then mucositis and infection will occur during neutropenic state
Determinants of neutrophil recovery:
- Intensity of chemotherapy
- Hematopoietic stem cell function and proliferation rate to re-populate BM
- Type of chemotherapy affects quality (function) of neutrophils: O2-dependent
microbicidal activity, complement receptor, adhesiveness, motility,
chemotaxis, loss of sialic acid…
Neutropenic fever
- Define absolute neutrophil counts for severities of neutropenia
Absolute neutrophil count (ANC):
ANC<1.5:
neutropenia (abnormal)
ANC<0.5 (<500/μL):
severe neutropenia – rate of infections start to increase
ANC<0.1 (<100/μL):
profound neutropenia – when most bacteraemia occurr
First-line investigations for neutropenic fever
Full Hx & P/E (daily): Focus on SKIN, GIT, RESPIRATORY tract
Skin, perianal skin (fungal cellulitis/ abscess: pain on defecation), surgical site infections S/S
Oral, abdomen exam (ask for mucositis, esophagitis, enterocolitis, bowel habits)
Lung, sinus (Respiratory S/S, Sinusitis S/S e.g. fungal sinusitis from inspiration)
Ix:
General (CBP, LFT, RFT)
Blood cultures from central venous catheter through 2 different ports
Abdomen:
Abdomen CT scan
stool culture: Add-on Clostridium difficile cytotoxin & culture
Lungs:
CXR (low risk); CT thorax (high risk)
BAL for sampling, culture
Others:
Urine, skin, sputum culture
Neutropenic fever causes and predisposing conditions
conditions that decrease neutrophil production or increase neutrophil destruction:
- severe active infections such as sepsis, hepatitis, or tuberculosis
- bone marrow disorders like aplastic anemia or myelofibrosis;
- autoimmune diseases like systemic lupus erythematosus or rheumatoid arthritis.
- cancer treatments such as chemotherapy, radiation therapy, and hematopoietic stem cell transplant (HSCT)
Predisposing conditions:
o Chemotherapy induced mucositis
o Indwelling vascular catheter
Neutropenic fever presentation
Fever may be only symptom
Other S/S:
abdominal pain, mucositis of the gastrointestinal tract, and perirectal pain.
complications such as severe sepsis or septic shock
Treatment of neutropenic fever
Oral: Ciprofloxacin + Augmentin
IV:
- Piperacillin/Tazobactam
- Meropenem
+/- Glycopeptide, FLuoroquinolone
Explain how antimicrobial therapy can compromise host immunity and predispose nosocomial infection
Antimicrobial therapy:
o Suppress normal flora (anaerobes, relatively non-invasive)»_space; flora fails to resist colonization by the more virulent and antibiotic-resistant hospital-acquired organisms (e.g. Pseudomonas aeruginosa, Corynebacterium jeikium, yeasts)
Hospital-acquired organisms: introduced into the patient during hospitalization by:
Hands of medical personnel
Various diagnostic/therapeutic procedures (e.g. endoscopy, surgery, nursing activities)
