Infectious Disease Flashcards
When is FQ ppx indicated?
ANTICIPATED neutropenia ANC< 100 for > 7 days
give while neutropenic
Notice: patient doesn’t have to be neutropenic if anticipated to be (heme cancer!!!
Can use 3rd gen cephalosporin if can’t take FQ
Who gets primary ppx w/ antifungal agent?
-acute leukemia pts receiving intensive remission INDUCTION therapy
-pre-engraftment phase following HCT
->10% risk candidiasis or >6% risk aspergillus
-give during periods of neutropenia!!! (don’t confuse with secondary ppx where it’s given for duration of tx)
-CONSIDER IF: Profound/prolonged neutropenia- ANC<100 for >7day
Antifungal primary ppx- AML/MDS
Posaconazole (category 1)
Alternate: voriconazole
These are mold active
Caution with IV forms of these if crcl<30 d/t cyclodextrin
Antifungal primary ppx- ALL
Fluconazole, echinocandin, or ampho B
Who gets secondary anti-fungal ppx?
IDSA: prior IFI and expected neutropenia duration 14+ days
NCCN: during subsequent chemo cycles or HCT in pts with prior IFI
Antifunal ppx is given for duration of immunosuppression even if neutropenia resolves (this is different than primary ppx which is given during periods of neutropenia
Who gets HSV ppx? Which drugs are used?
-pts undergoing acute leukemia induction
-CLL (if purine analog, bendamustine, or alemtuzumab, PIK3CA-inhibitors)
-alemtuzumab-regardless of CD4 count
-polatuzumab
-give during active therapy
-CD38 mAb
-consider for purine analog therapy
-consider for other hematologic malignancies
-hairy cell leukemia (x3 months after therapy and CD4 200+)
-acyclovir, valacyclovir, famciclovir
Who gets VZV ppx? Which drugs are used?
-pts w/ impaired cellular immunity (allogenic HCT)
-consider also for prolonged neutropenia, and t-cell depleting agents (Fludarabine, alemtuzumab- regardless of CD4) or proteosome inhibitors
-give during active therapy
-acyclovir, valacyclovir, famciclovir
Who gets pjp ppx? Which meds are used?
-Notice AML is not listed here
-chemo regimens w/ >3.5% risk
->= 20 mg pred x at least one month, or >30 mg x >3weeks (melanoma)
-purine analog based therapy for >1mo
-ALL throughout anti-leukemic therapy
-alemtuzumab
-PI3K inhibitors
-TMZ + RT
-polatuzumab
-give during active therapy or until CD4 count >200 for alemtuzumab
-CLL: bendamustine based immunotherapy
-hairy cell leukemia (x3 months after therapy and CD4 200+)
*Bactrim, dapsone, aerosolized or IV pentamidine, atovaquone
High risk ABX for cdif
FQ, clindamycin, cephalosporins
Aspergillus treatment
DOC: voriconazole
Alternatives: amphoterecin liposomal(esp if 3a4 interactions ), isavuconazole
Duration: 6-12 weeks or even months-years
don’t use echinocandin upfront
***Use TDM for voriconazole with a goal trough if 2-5 mcg/L
fever, chest pain, hemoptysis
Mold (e.g., aspergillus) ppx
Posaconazole (voriconazole is an alternative- don’t confuse with Tx of aspergillus where vori is preferred)
Use in AML/MDS induction
Triazole drug interactions (3A4)
Fluconazole and isavuconazole less severe
-vinca alkaloids
-irinotecan
-HD-cyclophosphamide
-thiotepa
-PO small molecules (e.g., dasatinib, venetoclax, midostaurin)
Separation of vaccines from chemo
-Live: give at least 4 wks before chemo (risk of infxn)
-Inactivated: give at least 2 weeks before chemo (vaccine won’t work- will need to repeat)
if can’t do before, give vaccine 3 months after chemotherapy
or 6 months after anti B-cell therapy
-Covid vaccine:
-solid tumor- vaccinate when available
-heme CA- hold until ANC recovers
-HCT or CAR-T- revaccinate 3 months after
Flu:
-anti-B cell antibodies: 6 mo after
-CAR-T/BiTE (blinatumomab)1 yr after
Flu vaccine
-give normal age appropriate
-these people should not get it:
-b cell antibodies within 6 months
-intensive chemo induction (acute leukemia)
-blinatumomab
-CAR-T
Pneumococcal
-PCV15 or PCV20 for newly diagnosed
-PPSV23 at least 8 weeks after PCV15 (but not after PCV20)
-if previous PPSV23- give either PCV15 or PCV20 at least 1 yr later
Herpes Zoster
RZV (shingrix) for immunocompromised adults >19y- 2 doses separated by 2-6 months
Vaccines for household members
-no live flu vaccine
-some other live are ok (MMR) while others are not (polio)
Vaccine during ICI therapy
No live for 1 month before or 3 months after
Covid vaccines
-Prefer mRNA (Pfizer/Moderna for primary series
-3 dose series for: tx of hematologic ca, organ transplant, CAR-T, HIV, steroids
-no need to delay following antibodies
->3 months after HCT/CAR-T
-no need to delay after mabs
-if heme-chemo wait til ANC recovers
-separate from surgery by a few days
-for solid tumor chemo just vaccinate when vaccine available
-4 wks before or 6 months after B cell therapy
-2 wks before immunosuppressive therapies
-don’t give Evusheld for at least 2 weeks after
Low v high risk FN
Low: MASCC >/=21, CISNE<3, talcotts group 4
High: MASCC<21, CISNE >/=3, talcotts 1-3
-assess MASCC and Talcotts first- if low risk proceed to CISNE to confirm only if pt has a solid tumor and had chemo recently
Proteosome inhibitor: ppx
VZV ppx
BTK inhibitors: Ppx
Acalabrutinib, ibrutinib, zanubrutinib
Consider pjp and VZV if additional risk factors
PI3K inhibitors: ppx
Copanlisib, idelalisib
-consider pjp
-monitor for cmv reactivation
JAK inhibits ppx
Ruxolitinib
-consider pjp, hsv, VZV
-screen/tx hep b and TB
IDH1 and IDH2 inhibitors
Enasidenib, ivosidenib
Differentiation syndrome may be difficult to distinguish from infection
FLT3 inhibitors inhibitors ppx
Gilteritinib, midostaurin
Differentiation syndrome may be difficult to distinguish from infection
CD19/CD3 mAb
Blinatumumab
-consider pjp, hsv, vzv
CD20 mAb
Obinutuzumab, ofatumumab, rituximab
-consider hsv/VZV ppx
-consider pjp if other risk factors
-screen/tx hep b
CD30 mAb
Brentuximab vedotin
-consider pjp, hsv, and VZV
-monitor for cmv reactivation
CD38 mAb
Daratumumab
-hsv/ vzv
- consider pjp
CD52 mab
Alemtuzumab
-pjp if CD4<200
-hsv, vzv
-monitor for cmv reactivation
-screen/tx hep b and TB
BRAF kinase inhibitors
Dabrafenib, encorafenib, vemurafenib
May develop drug fever
MEK inhibitors
Cobimetinib, trametinib
May develop drug fever
Hep B
-ppx for and HBsAg+ (chronic infxn) getting systemic therapy or HBcAb+ (past infxn) getting high risk therapy like CD20 mAb or HCT
-Ppx with entecavir or tenofovir (lamivudine less preferred)during cancer therapy and for 12 months after
-for people with past infxn (HBcAb+) not getting high risk therapy (CD20 mAb or HCT) just monitor HBsAg and ALT during therapy
-Above nuance is ASCO, but NCCN just says HbsAg+ or HbcAb+ you can give ppx
Note: so you can still treat the pt, just need to add ppx
IVIG may cause HBcAB+
Cdif
Initial:
FDX (PREFERRED) 200 mg po bid x 10d or VAN 125 mg po Q6h x10d
Initial fulminant:
VAN 500 po Q6h + MTZ 500 mg IV q8 h (consider rectal VAN if ileus)
Notice not using FDX for fulminant
Recurrent/subsequent:
-FDX or
-VAN tapered and pulsed
-could add bezlotoxumab
Secondary ppx
-fecal microbiota transplant or spores
-option for secondary ppx after recurrent CDI
Regimens with >20% risk of FN
Bladder:
DD-MVAC
Bone:
-VAI
-VDC-IE
-VDC
-VIDE
-cisplatin doxorubicin
Breast:
-DD- AC —>DD—>paclitaxel
-TAC (doc + dox + cyclo)
-TC (doc + cyclo)
-TCH (doc + carbo + trastuzumab)
Head/neck
-TPF (doc + cis + 5FU)
Hodgkin’s
-Brentuximab +AVD (dox + Vinblastine + Dacarbazine)
-BEACOPP
Kidney
-dox + gemzar
Non-Hodgkin’s
-Brentuximab + CHP (cyclo + dox + pred)
-dose adjusted EPOCH
-ICE (ifos + carbo + etop)
-DD-CHOP
-MINE (Mesna + ifos + mitoxantrone + etop)
-DHAP (dex + cis + Cytarabine)
-ESHAP (etop + Methylprednisolone + cis + Cytarabine)
HyperCVAD: cyclo + vin + dox + dex
Melanoma
-Dacarbazine + IL-2
Multiple myeloma
-DT-PACE: (dex + thalidomide + cisplatin + dox + cyclo + etop)
Ovarian
-topotecan
-docetaxel
Soft tissue sarcoma
-MAID: (Mesna + dox + ifos + Dacarbazine)
-dox
-ifos + dox
Small cell lung cancer
-topotecan
Testicular:
-VeIP: Vinblastine + ifos + cisplatin)
-VIP: etop + ifos + cisplatin
-TIP: pacli + ifos + cisplatin
When do we do FN ppx for pediatrics
Levofloxacin for pts with AML or RELAPSED ALL with anticipated nadir to <500 for 7 days or more
How long to continue ABX for in FN?
Below is for fever of unknown etiology!! For known infxn you tx for appropriate duration of that infxn
Afebrile x48h and ANC>500
*emerging data that can stop if afebrile for several days but ANC not yet recovered
Tx of candida in non-neutropenic pts ?
Candidemia or invasive candidiasis: Echinocandin is gold standard
Fluconazole for step down therapy
Tx of candida in Neutropenia pts?
Candidemia: Echinocandin is gold standard also
Invasive candidiasis: Echinocandin or liposomal ampho B
Fluconazole for step down therapy
When should mold coverage be added for rx of FN?
After 4 days of persistent fever
Which vaccines should cancer pts get?
Influenza, pneumococcal, and RZV (shingrix) if 19+
Vaccines with immunotherapy
Inactivated okay but no live (lack of data)
FN indications for vanc
- HD instability
- MRSA colonized or PCN/ceph resistant pneumococci
- G+ blood cx
- PNA
- SSTI
- CVAD infection
Meaning of each hep b marker
HBsAB+: protective immunity: Limited value due to hep B vaccine
HBsAg+: chronic hep b infxn
HBcAB+: past hep b infxn
When to consider G-CSF for therapeutic use
double check but I think these require a fever- YES- pts presenting with FN
-expected neutropenia >10 days
-profound neutropenia (ANC<100)
-age >65 y
-PNA
-hypotension
-sepsis
-uncontrolled primary dx
-invasive fungal infection
-hospitalized at fever onset
-prior FN episode
-if pt received ppx G-CSF
BTK-I vaccine requirement
Zoster
Note: CLL also need flu, pneumococcal, and Covid vaccines- but they often have poor response to vaccines
Duration of ABX for infections tx
-Most things are 5-14days
-MRSA- 4 weeks after clear cxs
-fungal
-candida- 2 weeks after clear cxs
-mold- 12 weeks
-HSV/VZV- 7-10 days
-flu- 5 days maybe more
Mold therapy if drug interaction with azole
Ampho B
CAR-T
-Pjp ppx AND HSV/VZV ppx x1 year
-consider antibacterial and antifungal ppx while neutropenic
-consider mold ppx if additional risk fxs
-screen/tx HBV and TB
Positive galactomannan antigen assay
Aspergillus
Who is expected to have neutropenia that lasts greater than 7 days?
Chemo for hematologic malignancy or conditioning regimens for HCT
Chemo for solid tumors is usually neutropenic for less than 7 days
FN pearls
-triage within 15 mins and 1st dose within 60 mins
Outpatient
-first dose in clinic and monitor for 4hr (consider 2-12)
-lives within 1 hr of 24hr facility
-caregiver home 24hr/day
-telephone and transportation available 24hr/day
-daily monitoring clinic or home visit x72 hrs
Treatment of inpatient febrile neutropenia
Inpatient: IV anti-pseudomonal ABX (add vanc if appropriate)
-D/c vanc after 48-72hr if susceptible bacteria is not identified
-Use aztreonam as anti-pseudomonal only if PCN allergy
-don’t use FQ as anti-pseudomonal agent
-defervescence can take 2-7 days, don’t escalate ABX if clinically stable, can evaluate for fungal if >4 days
Timing of vaccines around anti-B-cell antibodies
Give vaccine 6 months after
