ID Exam 2 Mycobacterium Flashcards
TB stain, culture, and environment
Mycolic acid retains carbol fuchin stain Acid fast stain (won't de-stain) Cultures slowly (4-6wks solid, 2-3wks liquid) Lowenstein-Jenses medium Obligate aerobe
TB virulence factors
Respiratory spread
Mycolic acid
Cord factor: serpentine cross-linkage and granuloma formation, activates macrophages and walls off
Sufatides: prevents phago-lysosome formation
Outcomes of initial TB infection
No infection, caught and cleared
- Latent infection
- Progression to systemic bactermia(Milliary TB)
- Reactivation TB (TNFa inhibition, CNS, Pott’s)
Leprosy (Hansen dz)
Tuberculoid vs. Lepromatous
Prefers colder temps
Infects monocytes (Th1 and Th2)
Humans and armadillos only known hosts
TB infectious spread
Particle = droplet nuclei
Evaporates to small size which allows to reach alveoli
Can remain in air for up to 1 hr
Respiratory spread
Uncontrolled primary infection
5% of disease, failure of immunity to control dz
Targets middle and lower lobes of the lung
Caseous necrosis
Latent TB infection
Inactive, contained TST/blood tests usually positive Nml CXR Negative sputum and cultures No symptoms and not infectious
Reactivation TB
Upper lobes of lung
TNFa inhibition
Extra pulmonary TB manifestations
Bone (spine): Pott’s disease
CNS manifestations: cavitary lesion in brain
TB treatment
RIPE
Rifamin
Isoniazid
TB resistance and factors leading to
Acquired from mutations, not other bugs INH (prodrug) resistance = katG mutation (no phos) Factors: Long treatment course Inadequate regimens
Types of drug resistant TB
MDR TB: isoniazid and rifampin
XDR TB: above + FQ and at least one injectable
Risk factors for TB
HIV Transplant/immunosuppression Medical comorbidies -> diabetes Injection drug users From endemic country Contact with infectious cases
Drug treatment of TB and goals
Rapid cidal activity: INH Relapse free: RIF, PZA Prevent resistance: INH, RIF, EMB RIPE for initial RI for continuation
MDR-TB risk factors
Previous tx of TB Progressvie despite therapy Connection to MDR-TB endemic place Exposure to individual with MDR-TB (yeah, those last two are shocking)
MDR-TB treatment regimen
- FQs
- Injectables (KAM: Kanamycin, Amikacin, Capreomycin)
Two more groups with two drugs each
TB screening
$$$, at risk population only
TST/IGRA
CXR if positive
Active (abCXR) vs. latent (nmlCXR) treatment
TB skin test
> 5mm: at risk due to background/immunosuppresion
10mm: at risk due to potential exposure
15mm: no risk (probably shouldn’t be screened, false+)
Blood tests
Less false+ (including BCG vaccine)
ESAT-6 and CFP-10
M. ulcerans
Buruli ulcer Grows at 32˚c Contaminated water Mycolactone toxin: necrotic cell death, painless Tx: rifampin + streptomycin
NonTB mycobacterium lung dz: rapid vs slow
Slow: M avium, chimera, intracellulare
Rapid: M. abscessus, bolletti, massiliense
Infections are on the rise, often cleared
Why are NTM rates increasing?
Greater exposure to water sources Change to PVC from copper plumbing Better dx Host factors: older, more immunosuppression Increased virulence?
Risk factors for NTM
Underlying suppressive condition
Excessive exposure
Post menapausal, thin, pectus (think Marfanoid) women
NTM lung manifestations
Nodular bronchiectatic (thin, Marfanoid women)
TB like presentation
Can present really in any tissue
Leprosy treatment
Rifampin and dapsone
Add clofazimine for lepromatous
RIPE Treatment for TB
RIPE = initial (4 for 2 months) RI = continuation (2 for 4 months) Oral "Safe" during pregnancy (category C) Hepatoxicity (rise of LFT's)
Isoniazid indications (for solo) Mech
Can give isoniazid alone for latent (but NOT for active TB)
Inhibits synth of mycolic acids
Given as prodrug and activated katG (viral)
Static for resting, cidal for growing
Rifampin indications for solo
Mech
Adverse rxns
Monotherapy: prophylactic for close contacts of meningitis (H. flu, N. men)
Inactivates bacterial DNA dependent RNA polymerase
Cidal
Induce CYP450 (rif revs 450)
Orange/red discoloration of all body fluid
Ethambutol
Mech
Adverse rxns
Blocks arabinosyl transferase (inhibit carb formation at cell wall)
Bacteriostatic against TB
Cidal against other myco (MAC)
AR: optic neuritis (red/green colorblindness)
Pyrazinamide
Mech
Adverse rxns
Mech: probably targets wall somehow
AR: hyperurecemia (precipitate gout)
NTM treatment (specifically MAC)
Ethambutol (cidal)
Macrolides
Rifabutin (related to rifampin, less CYP450 induction)
INH adverse reactions
Injury to Nerves and Hepatocytes (INH)
AR: paraesthsia (B6 excretion), coadmin with vit B6
Hepatocyte injury (via nAT)
Risk depends on acetylation speed
Asians/inuits: fast acetylators (inc dose, inc tox)
Scandinavia/North Africans: slow acetylators
Drug SLE syndrome
Inhibit CYP450 (increase drugs eliminated by this)
MUDPLIES