Lecture 7 - Respiratory 2

Question 1

MDR resistance is resistance to…

Answer 1

both 1st line options

Question 2

XDR tb is resistance to…

Answer 2

both 1st line, fluoroquinolone, and aminoglycosides

Question 3

TB have to stained with…

Answer 3

Ziehl-Neelsen stain

keep red color after acid alcohol wash = acid fast bacilli

Question 4

Most common TB spread

Answer 4

cough, sneezing, talking

infection risk inc in small, poorly vent room…cavitary disease and duration of exposure

Question 5

disseminated TB

Answer 5

spread through blood/lymph if bacterial rep not controlled

Question 6

PPD test result interpretation

Answer 6

5m = HIV, recent contact, immunosuppressive, organ transplant
10 mm = recent immigrant, pts w/ comorbidites, < 5 yrs old, HCWs, IV drug use
15 mm = no TB risk factors

Question 7

How to diagnose TB?

Answer 7

AFB smear + culture = 3 samples in 8hrs
NAAT tests, 24-48hrs + rifampin resistance genes
Stain w/ Ziehl, Neelsen

Question 8

how long after starting therapy are you infectious with TB?

Answer 8

2 weeks + have long course to prevent relapse

Question 9

1st line TB therapy?

Answer 9

Rifamycins - Rifampin
Isoniazide
Pyrazinamide
Ethambutol

Question 10

2nd line TB agents

Answer 10

Aminoglycosides
Fluoroquinolones
Cycloserine
Ethionamide
P-aminosalicylic acid

Question 11

Alternative TB agents, XDR

Answer 11

Bedaquiline
Clofazimine
Delamanid = not FDA approved
Linezolid

Question 12

Intensive phase for TB

Answer 12

RIPE, 1st 2 months

If RIF/INH susceptible then EMB can be D/c

Question 13

Continuation phase

Answer 13

RIF + INH for 4 to 7 months
Daily>3X week > 2 X week

Question 14

If pt has a cavitary lesion or positive AFB smear at end of intensive phase, they should do therapy for….

Answer 14

7 months

Question 15

Rifamycin MOA

Answer 15

Bind to DNA-dependent RNA polymerase, blocking RNA synthesis

Question 16

Common/significant ADE Rifamycin

Answer 16

Red/orange discoloration of all body fluids
Itching
Hepatotoxicity + minor LFT elevation so monitor monthly

Question 17

Rifapentine is used….

Answer 17

in once weekly treatment in continuation phase or LTBI treatment in select patients

Question 18

Isoniazid MOA

Answer 18

inhibit mycolic acid synthesis, resulting in disruption of bacterial cell wall

Question 19

Isoniazid ADE

Answer 19

Peripheral neuropathy**, pyridoxine added on

Hepatitis
Lupus-like symptoms

Question 20

Monitoring Isoniazide

Answer 20

LFT monthly & baseline

Question 21

Adverse effects pyrazinamide

Answer 21

Nongouty polyarthralgia
potential hyperuriemia

Question 22

Pyrazinamide monitoring

Answer 22

Baseline + Periodic LFTs
Joint pain

Question 23

Ethambutol MOA

Answer 23

inhibits synthesis of metabolites, mostly there to prevent emergence of RIF resistance

Question 24

Ethambutol Side effects

Answer 24

Retrobulbar neuritis = red/green color discirmination

Question 25

Ethambutol monitoring

Answer 25

Visual acuity tests + color discrimination tests...BL & Monthly

Question 26

Ethambutol DI

Answer 26

lowest risk, least interactions some with Al containing antacids

Question 27

Management of Hepatotoxicity

Answer 27

ALT > 3X ULN w/ symptoms or ALT > 5X ULN w/o symptoms stop therapy until < 2 X ULN Then restart rifampin/ethambutol...recheck ALT and add isoniazid after 3-7 days, then can possibly reintroduce pyrazinamide if symptoms recur or ALT inc then d/x last added med

Question 28

LTBI options

Answer 28

1. ISN + RIF QW for 3 months 2. RIF QD for 4 months 3. ISN + RIF QD for 3 months 4. Isoniazid for 6/9 months, QD or Twice weekly

Question 29

Targets for antifungal agents?

Answer 29

Gluons and Sterols

Question 30

Which drugs work by inhibiting ergosterol synthesis?

Answer 30

Azoles

Question 31

Which Azole won't prolong QTc?

Answer 31

isavuconazole they can also all cause hepatotoxicity, inc LFTs

Question 32

Fluconazole (FLU, Diflucan) info

Answer 32

Good CNS pen 1:1 IV to PO

Question 33

Itraconazole (ITR, Sporanox) info

Answer 33

no more than 200mg/dose Better absorption w/ suspension new super-bioavail form

Question 34

Voriconazole (VOR, Vfend) info

Answer 34

Good CNS pen 1:1 IV to PO IV form contains cyclodextrin can also cause visual disturbances

Question 35

Posaconazole (POS, Noxafil) info

Answer 35

Suspension limited absorption, give 200mg QID w/ fatty meals DR tab better absorption IV for contains cyclodextrin

Question 36

Isavuconazole (ISV, Cresemba)

Answer 36

Prodrug 1:1 IV to PO Shortens QTc

Question 37

Drugs that Inhibit 1,3-B-D-Glucan Synthase

Answer 37

Echinocandins

Question 38

Echinocandins info

Answer 38

End in - Fungin Only come as IV All cause hepatotoxicity (Monitor LFTs) Poor pen into CNS, Vitreous humor and Urine

Question 39

Ibrexafungerp info

Answer 39

only comes in Oral formulation Currently only approved for vulvovaginal candidiasis

Question 40

Drugs that bind to ergosterol that create pores in membrane

Answer 40

Amphotericin B

Question 41

Amphotericin B Toxicity

Answer 41

Nephrotoxicity = give 500ml before/after dose Hypokalemia Hypomagnesemia

Question 42

Amphotericin B Infusion related reactions

Answer 42

Premed with Acetaminophen/Diphenydramine can give meperidine, hydrocortisone, ibuprofen

Question 43

Fungal that inhibits Fungal RNA synthesis

Answer 43

Flucytosine (5-FC, Ancobon) Pyrimidine analog

Question 44

Flucytosine info

Answer 44

good CNS pen Resistance can develop quickly can cause bone marrow suppression (monitor CBC) and hepatotoxicity (LFTs)

Question 45

Key dosing info about azoles

Answer 45

All azoles get loading dose, always pick answer with loading dose

Question 46

Fluconazole spectrum tips and tricks

Answer 46

Good for things that start with C (Candida, Cryptococcus, Coccilioides)

Question 47

Itraconazole spectrum tips and tricks

Answer 47

Similar to Fluconazole Aspergillus slight activity Main role is endemic (dimorphic) fungi**

Question 48

Voriconazole spectrum tips and tricks

Answer 48

1st line for Aspergillus still works against Candida & Dimorphic

Question 49

Posaconazole & Isavuconazole spectrum tips and tricks

Answer 49

Posa = prophylaxis of Mucor Isa = treatment of Mucor

Question 50

Echinocandin spectrum tips and tricks

Answer 50

Candida mostly

Question 51

Amphotericin spectrum tips and tricks

Answer 51

Aspergillius terreus = not active against overall broad spectrum

Question 52

Therapeutic drug monitoring in Itraconazole and Voriconazole?

Answer 52

Troughs

Question 53

Aspergillosis treatment

Answer 53

6-12weeks 1st line = Voriconazole Liposomal Amphotericin B/ Isavuconazole alternatives salvage: Posa-, Itraconazole, Echinocandins

Question 54

Aspergillious prophylaxis, during high risk immunosuppression

Answer 54

Posaconazole = 1st line

Question 55

Histoplasmosis traditionally in....

Answer 55

Ohio River valley, spread into eastern US tho

Question 56

Blastomycosis traditionally in...

Answer 56

Mississippi River delta, spread into eastern US tho

Question 57

Coccidioidomycosis traditionally in....

Answer 57

southwestern US

Question 58

Mild Histoplasmosis, Chronic pulmonary, Mild Disseminated treatment is....

Answer 58

itraconazole 200mg QD or BID for 6-12weeks ** 12 months for Chronic pulmonary, disseminated ***

Question 59

Severe Histoplasmosis or CNS or severe Disseminated treatment is...

Answer 59

L-AMB for 1-2 weeks then itraconazole 200mg BID for 12 weeks ** 12 months CNS, Disseminated **

Question 60

Mild to moderate Blastomycosis treatment

Answer 60

itraconazole 200mg TID X 3 days, then BID 6-12 months

Question 61

Severe or CNS Blastomycosis treatment

Answer 61

L-AMB 1-2 weeks (severe) L - AMB 4-6 weeks (CNS) Then switch to Itraconazole 6 to 12 months

Question 62

Coccidioidomycosis treatment pneumonia

Answer 62

Not really treated unless severe disease if treated use fluconazole > 400mg QD for 3-6 months