Lecture 7 - Respiratory 2 Flashcards
MDR resistance is resistance to…
both 1st line options
XDR tb is resistance to…
both 1st line, fluoroquinolone, and aminoglycosides
TB have to stained with…
Ziehl-Neelsen stain
keep red color after acid alcohol wash = acid fast bacilli
Most common TB spread
cough, sneezing, talking
infection risk inc in small, poorly vent room…cavitary disease and duration of exposure
disseminated TB
spread through blood/lymph if bacterial rep not controlled
PPD test result interpretation
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
How to diagnose TB?
AFB smear + culture = 3 samples in 8hrs
NAAT tests, 24-48hrs + rifampin resistance genes
Stain w/ Ziehl, Neelsen
how long after starting therapy are you infectious with TB?
2 weeks + have long course to prevent relapse
1st line TB therapy?
Rifamycins - Rifampin
Isoniazide
Pyrazinamide
Ethambutol
2nd line TB agents
Aminoglycosides
Fluoroquinolones
Cycloserine
Ethionamide
P-aminosalicylic acid
Alternative TB agents, XDR
Bedaquiline
Clofazimine
Delamanid = not FDA approved
Linezolid
Intensive phase for TB
RIPE, 1st 2 months
If RIF/INH susceptible then EMB can be D/c
Continuation phase
RIF + INH for 4 to 7 months
Daily>3X week > 2 X week
If pt has a cavitary lesion or positive AFB smear at end of intensive phase, they should do therapy for….
7 months
Rifamycin MOA
Bind to DNA-dependent RNA polymerase, blocking RNA synthesis
Common/significant ADE Rifamycin
Red/orange discoloration of all body fluids
Itching
Hepatotoxicity + minor LFT elevation so monitor monthly
Rifapentine is used….
in once weekly treatment in continuation phase or LTBI treatment in select patients
Isoniazid MOA
inhibit mycolic acid synthesis, resulting in disruption of bacterial cell wall
Isoniazid ADE
Peripheral neuropathy**, pyridoxine added on
Hepatitis
Lupus-like symptoms
Monitoring Isoniazide
LFT monthly & baseline
Adverse effects pyrazinamide
Nongouty polyarthralgia
potential hyperuriemia
Pyrazinamide monitoring
Baseline + Periodic LFTs
Joint pain
Ethambutol MOA
inhibits synthesis of metabolites, mostly there to prevent emergence of RIF resistance
Ethambutol Side effects
Retrobulbar neuritis = red/green color discirmination
Ethambutol monitoring
Visual acuity tests + color discrimination tests…BL & Monthly
Ethambutol DI
lowest risk, least interactions
some with Al containing antacids
Management of Hepatotoxicity
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
LTBI options
- ISN + RIF QW for 3 months
- RIF QD for 4 months
- ISN + RIF QD for 3 months
- Isoniazid for 6/9 months, QD or Twice weekly
Targets for antifungal agents?
Gluons and Sterols
Which drugs work by inhibiting ergosterol synthesis?
Azoles
Which Azole won’t prolong QTc?
isavuconazole
they can also all cause hepatotoxicity, inc LFTs
Fluconazole (FLU, Diflucan) info
Good CNS pen
1:1 IV to PO
Itraconazole (ITR, Sporanox) info
no more than 200mg/dose
Better absorption w/ suspension
new super-bioavail form
Voriconazole (VOR, Vfend) info
Good CNS pen
1:1 IV to PO
IV form contains cyclodextrin
can also cause visual disturbances
Posaconazole (POS, Noxafil) info
Suspension limited absorption, give 200mg QID w/ fatty meals
DR tab better absorption
IV for contains cyclodextrin
Isavuconazole (ISV, Cresemba)
Prodrug
1:1 IV to PO
Shortens QTc
Drugs that Inhibit 1,3-B-D-Glucan Synthase
Echinocandins
Echinocandins info
End in - Fungin
Only come as IV
All cause hepatotoxicity (Monitor LFTs)
Poor pen into CNS, Vitreous humor and Urine
Ibrexafungerp info
only comes in Oral formulation
Currently only approved for vulvovaginal candidiasis
Drugs that bind to ergosterol that create pores in membrane
Amphotericin B
Amphotericin B Toxicity
Nephrotoxicity = give 500ml before/after dose
Hypokalemia
Hypomagnesemia
Amphotericin B Infusion related reactions
Premed with Acetaminophen/Diphenydramine
can give meperidine, hydrocortisone, ibuprofen
Fungal that inhibits Fungal RNA synthesis
Flucytosine (5-FC, Ancobon)
Pyrimidine analog
Flucytosine info
good CNS pen
Resistance can develop quickly
can cause bone marrow suppression (monitor CBC) and hepatotoxicity (LFTs)
Key dosing info about azoles
All azoles get loading dose, always pick answer with loading dose
Fluconazole spectrum tips and tricks
Good for things that start with C (Candida, Cryptococcus, Coccilioides)
Itraconazole spectrum tips and tricks
Similar to Fluconazole
Aspergillus slight activity
Main role is endemic (dimorphic) fungi**
Voriconazole spectrum tips and tricks
1st line for Aspergillus
still works against Candida & Dimorphic
Posaconazole & Isavuconazole spectrum tips and tricks
Posa = prophylaxis of Mucor
Isa = treatment of Mucor
Echinocandin spectrum tips and tricks
Candida mostly
Amphotericin spectrum tips and tricks
Aspergillius terreus = not active against
overall broad spectrum
Therapeutic drug monitoring in Itraconazole and Voriconazole?
Troughs
Aspergillosis treatment
6-12weeks
1st line = Voriconazole
Liposomal Amphotericin B/ Isavuconazole alternatives
salvage: Posa-, Itraconazole, Echinocandins
Aspergillious prophylaxis, during high risk immunosuppression
Posaconazole = 1st line
Histoplasmosis traditionally in….
Ohio River valley, spread into eastern US tho
Blastomycosis traditionally in…
Mississippi River delta, spread into eastern US tho
Coccidioidomycosis traditionally in….
southwestern US
Mild Histoplasmosis, Chronic pulmonary, Mild Disseminated treatment is….
itraconazole 200mg QD or BID for 6-12weeks
** 12 months for Chronic pulmonary, disseminated ***
Severe Histoplasmosis or CNS or severe Disseminated treatment is…
L-AMB for 1-2 weeks then itraconazole 200mg BID for 12 weeks
** 12 months CNS, Disseminated **
Mild to moderate Blastomycosis treatment
itraconazole 200mg TID X 3 days, then BID 6-12 months
Severe or CNS Blastomycosis treatment
L-AMB 1-2 weeks (severe)
L - AMB 4-6 weeks (CNS)
Then switch to Itraconazole 6 to 12 months
Coccidioidomycosis treatment pneumonia
Not really treated unless severe disease
if treated use fluconazole > 400mg QD for 3-6 months
