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Transcript of Febrile Neutropenia
However, infection can occur in neutropenic patients in the absence of fever.
This occurs more often in elderly patients and those receiving corticosteroids.
Presenting signs of infection in such patients may include hypothermia, hypotension, confusion, or clinical deterioration Introduction When?
What is it?
Why is it important?
How to treat? When Does Neutropenia Occur? Most chemotherapy agents/protocols cause neutropenia nadir at 10-14 days
But can see anytime from a few days after chemotherapy to up to 4-6 weeks later depending on the agents used Significance of Febrile Neutropenia? Infections in the neutropenic patient can be rapidly fatal if not managed properly
- Mortality rate in the 1960’s was 50%
- With proper management 5% today Significance of Febrile Neutropenia Most patients don’t have bacterial infection
30-50% will have infection Primary sites:
Skin Risk increases with lower counts (< 0.5 vs. < 0.1) and duration of neutropenia But no reliable way of knowing or predicting who is infected
So all are treated with empiric antibiotics
Fevers may be due to other infections or to non-infectious causes Assessment Good history and physical exam
Be aware that with ANC may not have inflammation - so redness swelling and infiltrates may not be seen
Mouth, pharynx, lower esophagus, lung, skin, anus and perineum are often sites of infection
Blood work - CBC, creat, BUN, liver profile
Blood cultures (include central line if present) Other cultures only indicated if symptoms
- If diarrhea should do C. Difficile toxin
- Urine if symptoms or catheter
CXR – if outpatient therapy or if symptomatic
Other – LP, lesion aspiration, wound cultures as indicated What Bugs? Traditionally - gram negatives
- Pseudomonas, E. Coli, Klebsiella
More recently - gram positives (60-70%)
- Staph epi, Staph aureus
- reason for switch may be central lines, prophylaxis with quinolones, or due to mucositis Importance Fever in a neutropenic patient should be considered a medical emergency.
Broad-spectrum antibiotics should be given as soon as possible and at full doses (adjusted for renal and/or hepatic function). Low Risk - Features Absolute neutrophil count 0.1 x 109 /L
Absolute monocyte count 0.1 x 109 /L
No acute process on CXR
Near normal liver and renal function
No IV catheter site infection
Peak temp. of < 39 ºC
No neurologic or mental changes
No abd. Pain
No cormorbid illness – COPD, DM, etc. What Initial Therapy? Monotherapy:
Cefepime or ceftazidime or imipenem or meropenem
Aminoglycoside plus antipseudomonal beta-lactam, cephalosporin (cefepime or ceftazidime), or carbapenem Oral Therapy? Oral therapy (only for low-risk adults)
Ciprofloxacin plus amoxicillin-clavulanate
In penicillin-allergic patients:
ciprofloxacin and clindamycin. Immediate Vancomycin? Generally not recommended- add in on basis of cultures
Recommended for the these situations: Suspected serious catheter infections
Known colonization with organisms resistant to other antibiotics
Positive blood cultures
Hypotension What If Patient Becomes Afebrile? Afebrile within first three to five days of treatment
If etiology identified:
If no etiology identified: Adjust to most appropriate treatment If low risk can change after 48 hours to oral antibiotics
- Adults: Ciprofloxacin/amoxicillin-clavulanate
- Children: Cefixime
If high risk then continue same antibiotics Persistent Fever Reassess on day three
If no change:
- Continue antibiotics;
- Stop vancomycin if cultures are negative
If progressive disease:
- Change antibiotics
If febrile after day five:
- Consider adding an antifungal drug with or without antibiotic changes first three to five days of treatment Central Line Infections Keep Line Most Staph. Epi
Some Staph. Aureus
Afebrile in 48-72hrs Tunnel or peri-port infection
Febrile after 48-72hrs
Pseudomonas ________________ ________________ Line Removal Required Duration of Therapy If ANC >= 0.5 - Two days
Afebrile X 48 hrs.
No infection If continued neutropenia
Continue until 5-7 days of afebrility
Then D/C If on IV
Can be switched to oral medication as directed by cultures
Or Ciprofloxacin/Clavulin and potentially discharge if stable Neutropenia Neutropenia — Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500/microL
ANC = WBC (cells/microL) x percent (PMNs + bands) ÷ 100
Neutrophilic metamyelocytes and younger forms are usually not included in this calculation Myeloid Growth Factors Colony Stimulating Factors Primary prophylaxis Age 65 and older
Poor performance status
Prior episodes of febrile neutropenia
Large radiation portals, or receiving combined chemoradiotherapy
Cytopenias due to marrow involvement
Poor nutritional status
Open wounds or active infection
Advanced cancer or other serious comorbidities Primary prophylaxis helps in reducing the frequency of hospitalization for antibiotic therapy, documented infection, and rates of febrile neutropenia
Used only with certain more toxic regimens or high risk patients . Secondary prophylaxis refers to the administration of a CSF in subsequent cycles after a neutropenic fever has occurred in a prior cycle
Secondary prophylaxis also includes the use of a CSF to speed recovery from neutropenia due to a previous cycle of chemotherapy Myeloid Growth Factors Colony Stimulating Factors Pegfilgrastim A pegylated formulation of G-CSF, has a prolonged half-life
Permitting the administration of a single dose rather than daily administration Peg + Filgrastim = Outpatient Therapy Not considered the standard but is often done
Must be reliable patient who doesn’t live alone, able to take oral antibiotics
Re-evaluate q 2days until ANC > 0.5 x 109/L and afebrile x 48hrs.
If complications or continued fever admit Neutropenia without fever If patient is ill and neutropenic, but doesn’t have fever still treat with same regimens
Beware in the elderly – might not mount a fever
Afebrile pt. with neutropenia and severe diarrhea – Ciprofloxacin recommended