Neutropenic fever Flashcards
cause of fever in most neutropenic fever patients
endogenous microflora
medication associated with reaction of HSV and VZV
mTOR inhibitors (sirolimus, everolimus)
when ANC is expected to reach nadir with chemo treatment
12 to 14 days from day 1
cancer type in which neutropenic fever is most common
acute leukemia, substantially less common in solid organ
most frequent pathogens in neutropenic fever
gram-positive bacteria (anaerobes infrequent)
what is the term for G-CSF and GM-CSF agents?
colony stimulating factors
what is myeloid reconstitution syndrome?
Onset or progression of an inflammatory focus defined clinically or radiologically temporally related to neutrophil recovery.
evidence for antibiotic prophylaxis for high risk neutropenic patients?
Effective but high NNT, and there are a lot of downsides (cost, side effects, resistance), so should be limited to high risk patients.
risk of fungal infection?
Very low among patients for whom the anticipated duration of neutropenia (ANC <500 cells/microL) is anticipated to be seven days or fewer.
when risk of neutropenia is highest during chemo
typically during the first two cycles of chemotherapy
RF’s for neutropenic events
- age >65 years
- preexisting neutropenia or extensive bone marrow involvement by tumor
- more advanced cancer
- poor performance and/or nutritional status - renal or hepatic dysfunction
Guideline update on use of colony stimulating factors during COVID-19
NCCN and ASCO have lowered the threshold for the use of myeloid growth factors from those chemotherapy regimens which have a 20 percent or higher risk of febrile neutropenia to now include those regimens with a risk of 10 to 20 percent, which includes all of the intermediate-risk chemotherapy regimens.
General term for medications used to
Colony stimulating factors
Why don’t we use CSF’s to treat neutropenic fever?
1) Controversial and mixed results. (no effect on mortality, shorter hospital stays in studies, but also increased rates of side effects).
2) It takes several days for CSF to produce a response with increased circulating neutrophils, so antibiotics work faster.
Neupogen generic name
Filgrastim
neulasta generic name
Pegfilgrastim
optimal duration of GCSF per guidelines
No consensus, guidelines vary
NCCN guidelines suggest daily administration until the post-nadir ANC recovers to normal or near-normal levels by laboratory standards
Why neulasta is typically used
Multiple RCTs and a meta-analysis have shown that pegfilgrastim is at least as effective as and more convenient to administer than G-CSF for primary prophylaxis in patients requiring CSF treatment during myelosuppressive chemotherapy
Potential treatment side effect of CSFs
therapy related myeloid neoplasm (a small but real increased risk of therapy-related myeloid neoplasms (myeloid growth factor receptors are expressed by several hematopoietic and nonhematopoietic cell types)
Risk of complications in neutropenic fever is based on…
duration and severity of neutropenia
When do you modify initial antibiotic regimen?
IF fever persists after 4 days → add antifungal coverage
Positive infectious workup
Hemodynamic instability
*NOT for persistent with negative workup
when people are at increased risk of fungal infections
- prolonged duration of neutropenia (more than 7 days of persistent neutropenia)
- comorbidities
how long do you continue abx?
Discontinue once myeloid reconstitution (ANC>500) + afebrile x48h
Evidence for use of CSF’s in neutropenic fever
NOT recommended
Median time to deferfescence
- 5 days (in contrast to 2 for solid tumors)
* ***so patients take longer to deferfesce (antibiotic may be covering infection but delay in response)
IFI means…
invasive fungal infection
Fungitell tests for
b-d-glucan, which is present in a wide variety of fungal pathogens (candida, aspergillus, pneumocystis)
Galactomannan tests for
Aspergillus (important cell wall component)
Definition of neutropenic fever
- single fever + ANC less than 500
outpatient abx for neutropenic fever
Cipro + augmentin
Initial therapy for inpatient management of neutropenic fever
Anti-pseudomonal beta-lactam (Cefepime or zosyn)
Indications for adding gram-positive coverage
- suspected line sepsis
- hemodynamic instability
- skin infections
ANC cutoff defining neutropenic fever
1000
Fever definition
38.3 single oral temp or 100.4 for 1 hr
2 most impt variables determining high risk neutropenia
- duration
- comorbidities
Decision support tools guiding inpatient vs outpatient management
MASCC (liquid tumor) and CISNE (solid tumor)
outpatient abx for neutropenic fever
cipro + augmentin (gram positive coverage)
initial abx options
cefepime, zosyn, meropenem
IDSA time window for abx for high risk febrile neutropenia
within 1 hr
when are people generally speaking at risk for fungal infections?
prolonged neutropenia
most common fungus in myeloid malignancy patients with prolonged neutropenia?
aspergillus
Mold active azoles
posa, vori, isavuconazole
know regimens with 20% or higher risk of febrile neutropenia
(think about each cancer subtype) ddMVAC dose dense AC FOLFOXIRI TPF EPOCH Hyper-CVAD Topotecan others (look at NCCN)
