infection in chemo treated patients

Question 1

sources of organisms

Answer 1

both host microbiome and outside exposures- appliances, surgery, hospitalization, cancer growth, community, reactivation of previous infections

Question 2

risk factors

Answer 2

marrow suppression (neutropenia), host defense disruption (mucositis), immunosuppression of T/B cells
greatest risk with “traditional” chemo, lesser with targeted therapies like TKIs, immunotherapies

Question 3

NCCN guidelines for prophylaxis in high risk of infection say what?

Answer 3

high risk: acute leukemia, alemtuzumab, anticipated neutropenia >10 days, etc
Bacterial: quinolone prophylaxis during neutropenia
Fungal: PJP prophylaxis
Viral: during neutropenia and longer depending on risk

Question 4

coverage for bacterial prophylaxis in high risk?

Answer 4

levofloxacin daily when ANC falling rapidly and/or <500
(alternatives ciprofloxacin, amoxicillin)

Question 5

coverage for viral prophylaxis in high risk?

Answer 5

acyclovir/valacyclovir daily when history of HSV or + serology

Question 6

coverage for fungal prophylaxis in high risk?

Answer 6

anti-mold azole daily when ANC<500: posaconazole, voriconazole, isavuconazole
(if CYP3A4 drug interaction exists then micafungin pref)

Question 7

coverage for PJP prophylaxis in high risk?

Answer 7

bactrim MWF

Question 8

how to calculate ANC

Answer 8

WBC x (%polys + %bands)

Question 9

_______ are the first line for fighting bacterial pathogens

Answer 9

neutrophils

Question 10

what do the NCCN guidelines say for initial empiric therapy for uncomplicated fever & neutropenia

Answer 10

IV monotherapy: cefepime, imipenem/cilastatin, meropenem, piperacillin/tazobactam, ceftazidime
(if you used a drug for prophylaxis you don’t use it for treatment- no quinolones)

Question 11

monitoring for fever & neutropenia?

Answer 11

fever pattern
exam
ANC daily
blood cultures

Question 12

what if cultures are negative- do you stop antibiotics?

Answer 12

not unless:
cultures negative and no clinical infection (cellulitis)
fever has resolved
neutropenia has resolved (ANC>500)

Question 13

what to do if patient fever/neutropenia clinically worsening?

Answer 13

broaden coverage
consider adding G-CSF
consult ID
consider antifungal with activity against molds for fever continuing more than 4 days of antibiotic therapy

Question 14

what if fever continues with persistent neutropenia & cultures are negative?

Answer 14

1. continue antibacterial agents until fever & neutropenia resolve, regardless of cultures
   (must have 3 factors to stop: ANC>500, cultures negative, no fever)
2. assess for infections: may broaden to add new anti-infectives
   (ex C diff for diarrhea, MRSA for skin, anaerobes for mouth)
3. add empiric daily antifungal for duration of neutropenia
   (Echinocandin, triazoles except fluconazole, reserve ampho B)

Question 15

what is the most common dose-limiting toxicity of conventional chemotherapy (also some PO kinase inhibitors like sunitinib)

Answer 15

myelosuppression

Question 16

when does myelosuppression occur after chemo?

Answer 16

7-10 days

Question 17

what is the impact of myelosuppression on subsequent chemo?

Answer 17

subsequent chemo is delayed until minimum blood counts reached
dose reductions to reduce myelosuppression must be balanced with treatment goals (cure)

Question 18

neutropenia increases risk of ___

Answer 18

infection
especially when ANC<500 or prolonged duration or both

Question 19

when is the lowest WBC or “nadir”

Answer 19

typically 7-10 days after chemo
(usually recovers by 21-28 days)

Question 20

which chemotherapy has a high risk of bone marrow suppression & neutropenia

Answer 20

anthracyclines
alkylators: cisplatin, ifosfamide, cyclophosphamide
antimetabolites: etoposide, cytarabine

highest risk in high dose intensity regimens– AML, HSCT

Question 21

how to reduce the risk of infection from neutropenia?

Answer 21

G-CSF: stimulates proliferation & maturation of progenitors & release of neutrophils
neutropenia will still occur but not as severe, shorter duration

Question 22

pegfilgrastim shows ____ compared to no G-CSF

Answer 22

71% reduction in fever & neutropenia incidence

Question 23

what is the mechanism of G-CSF?

Answer 23

a WBC lineage specific growth factor
glycoprotein that regulates the production, maturation, and function of cell of the neutrophil lineage

Question 24

what are the 2 G-CSF agents used

Answer 24

filgrastim
pegfilgrastim

Question 25

when do we use G-CSF?

Answer 25

1. PRIMARY PROPHYLAXIS to prevent febrile neutropenia with 1st cycle of chemotherapy-- 20% or higher risk of febrile neutropenia (remember the 20%) OR 10-20% risk of febrile neutropenia with risk factors like age, pre-existing conditions 2. Secondary prophylaxis for a patient who experienced a febrile neutropenia complication from a prior cycle of chemotherapy.

Question 26

difference in dosing between filgrastim and pegfilgrastim?

Answer 26

Filgrastim 5 mcg/kg/dose SQ daily until post-nadir (7-10 days) and ANC increased >1000-1500. do not give chemotherapy within 24 hours of last dose. Pegfilgrastim 6 mg SQ x 1. do not give chemo within 14 days of pegfilgrastim.

Question 27

what are biosimilars

Answer 27

NOT A GENERIC EQUIVALENT compared & evaluated against reference product so no clinically meaningful differences, highly similar unique 4 letter suffix distinguishes shared core- not actual "Chemical"

Question 28

where to administer G-CSF

Answer 28

outer upper arm, abdomen, front middle thigh, upper outer buttocks area

Question 29

expected toxicities of G-CSF

Answer 29

allergic reactions (within 30 min)-- do not administer to patients who experienced (recurs in >50% of patients with rechallenge) ostealgia in lower back, iliac crest, sternum---- anecdotal improvement with pre-dose cetirizine or loratidine