Mycobacteria Flashcards
What is the difference between a TB infection and TB disease?
TB Infection - Positive skin test
Normal immune function means that only 7-10% of people with TB infection will progress to develop TB Disease
TB Disease is active disease, commonly with upper lung infiltrate or cavitation
Which people are most likely to be infected with TB?
Close contacts of an active case
Foreign-born people
Medically underserved, low income
Homeless; Migrant farm workers
Who is more likely to progress from a TB infection to disease?
HIV infection (immunocompromised)
Recently infected with TB
Silicosis predisposes to TB
How is TB transmitted?
Airborne, so close contacts at high risk
Describe the basic pathogenesis of TB
TB gets inhaled and gains access to alveolar macrophages. May spread to regional lymph nodes and has a bloodborne spread.
Describe the basic immune response to TB infection
TB antigens swallowed and presented macrophages to CD4 T cells, which release cytokines to activate macrophages. See caseous necrosis with granulomas
What are the two potential outcomes of a Primary TB infection?
Latent TB infection (over 90%)
Progression to active TB disease (less than 10%)
What are the potential manifestations of TB Disease?
80-90% get an upper lung infiltrate with cavitation
10-15% get extrapulmonary manifestations from initial bloodborne spread (meninges, heart, bone, GU)
What is the Ghon focus?
The primary local area of infection, seen on CXR
What si the Ranke Complex?
When a Ghon focus becomes calcified, it becomes known as a Ranke Complex
What are common sites for Extrapulmonary TB?
Brain Epiphyses of long bones Kidneys Vertebral bodies Lymph nodes
Describe the PPD Skin Test
Intradermal inoculation of TB antigen. If there was a TB infection, you would see a lump of CD4 lymphocytes having a response a few days later
Describe the Quantiferon Gold Test
In vitro blood test that senses how much IFN-y is released when exposed to TB antigen
Describe the NAAT
NAAT= Nucleic Acid Amplification Test
Take a sputum sample, submit to lab, they do a PCR-like assay to assess for evidence of TB-like antigen
Rapid diagnosis!
Describe the use of Acid-Fast staining for TB detection
This stains the organisms red with blue background staining
Describe the use of bacterial culture in TB diagnosis
Liquid media can be more rapid, but in general, culture media can take many weeks to grow.
Where are nontuberculous mycobacteria most commonly acquired?
Bioaerosols
Water
Soil
Nosocomial
NOT human-to-human transmission
What are predisposing conditions for a Nontuberculous Mycobacteria infection?
Preexisting underlying lung abnormality (COPD, bronchiectasis, IPF, congenital abnormalities)
Where are infections with Nontuberculous Mycobacteria usually contained?
They are usually contained in the lung, but they may spread in AIDS patients
You suspect that a patient has TB. Is it more likely that they have TB or an NTM disease?
NTM disease
List some basic principles of TB treatment.
Multi-Drug Therapy (reducing emergence and enhancing response rates/cures)
Increase adherence
Long duration therapy (at least 6 months)
Isoniazid HCl (INH) Clinical Use
May be used as monotherapy in LATENT TB infection
First line drug for active pulmonary TB, used in combo with at least 2 others
Isoniazid HCl (INH) MOA
Prodrug, activated by catalase peroxidase (TB katG gene)
Targets inhA gene product, inhibiting TB cell wall synthesis (mycolic acid)
Isoniazid HCl (INH) Resistance Mechanisms
Mutations in either... katG gene (prevents activation of prodrug to active form)
inhA gene (cell wall/mycolic acid synthesis)
Isoniazid HCl (INH) Toxicity
Hepatotoxicity (monitor baseline liver enzymes and their changes over time)
Neurotoxicity
Hypersensitivity rxns
Rifampin
Clinical Use
First line drug for TB, always used in combo
Could also be used in combo for S. aureus, N. meningitidis (meninigitis prophylaxis)
Why can’t Rifampin be used alone as an antibacterial agent?
Rapid development of resistance
Rifampin
MOA
Inhibits DNA-dependent RNA polymerase encoded by rpoB gene
Rifampin
Resistance Mechanisms
rpoB mutations
Rifampin
Toxicity
Hepatotoxicity (increased with INH)
Red discoloration of urine and tears
Influenza syndrome - more common in intermittent dosing
Thrombocytopenia
Rifampin
Drug Interactions
Interacts with over 100 drugs
Accelerates clearance and reduces effective serum concentrations of….
Warfarin, Estrogen, Anticonvulsants, Antiretroviral drugs
Ethambutol
Clinical Use
“Helper” drug that inhibits resistance to other drugs
Ethambutol
MOA
Inhibits TB arabinosyl transferase encoded by embB gene
Ethambutol
Toxicity
Optic neuritis (blurred vision, could cause blindness) Periphral neuropathy
Pyrazinamide (PZA)
Clinical Use
First line TB drug for the 1st two months of therapy
Good penetration into CSF in tuberculous meningitis
Pyrazinamide (PZA)
MOA
Prodrug activated y TB pyrazinamidase, encoded by pncA gene
Pyrazinamide (PZA)
Toxicity
Hepatitis
Streptomycin
Clincial Use in TB infection
Second line TB drug
Streptomycin
MOA
Inhibits protein synthesis by binding ribosome
Streptomycin
Toxicity
Ototoxicity
Nephrotoxicity
What is the difference between primary and secondary resistance with TB?
Primary- infection of a TB disease that is ALREADY drug resistant
Secondary- an initially susceptuble TB population was selected for resistance
What are some factors that can select for drug resistance?
Too few drugs
Suboptimal drug dosing or absorption
How do you calculate the risk of multi-drug resistance developing?
Risk of evolution of resistance to two drugs is the PRODUCT of the risk of the development of resistance to each drug
Define Multi-Drug Resistant TB
Resistance to both INH and rifampin
When you discover that the TB disease is resistant to rifampin, how does that change your therapy?
Rifampin resistance eliminates short course (6 mo) TB therapy
Now, the pt will need 18-24 months of therapy
What is the typical multi-drug therapy for TB?
4 drug regimen = RIPE in initial phase Rifampin INH PZA Ethambutol
Continuation phase- only INH and rifampin
Describe the use of intermittent therapy for TB
2-3x weekly dosing
Only done with Directly Observed Therapy
A nurse visits the patient’s house multiple times weekly to dose them
What are the three methods used to treat a LATENT TB infection?
INH monotherapy for 9 months
Rifampin monotherapy for 9 months, daily
INH + Rifapentene (once weekly, DOT regimen)
Which drugs are used to treat both TB and NTM infections?
Rifampin
Ethambutol
Fluoroquinolones
Aminoglycosides
Which drugs are used to treat exclusively Non-tuberculous mycobacterial infections?
Clarithromycin
Azithromycin
What combination of drugs is used to treat leprosy?
Rifampin and Dapsone for 12 months, daily
