TB Flashcards
The most prevalent communicable infectious disease on earth and remains a leading infectious killer globally
Tuberculosis (TB)
Is mycobacteria fast or slow growing?
Slow growing
Once infected w/ M. tuberculosis, a person’s lifetime risk of active TB is approximately ___%
10
- What are the 2 most important drugs in tx of TB?
- Which age groups have a 2-5X greater risk for active disease compared w/ other age groups?
- Isoniazid & Rifampin
- <2y/o and >65y/o
____ should be used whenever possible to reduce tx failures and the selection of drug-resistant isolates
Directly Observed Treatment (DOT)
TB is more common in which 5 groups of people?
- Prison inmates
- IV drug abusers
- Immigrants
- HIV infected pts*
- Young minority adults
Sxs of TB
General ROS:
- Fatigue
- Fever
- Weight loss
- Night sweats
- Productive cough
- 2 or more antimicrobials are used in the tx of _____.
- Generally, __ drugs are given at the outset of tx
- Which 2 drugs are the best for preventing drug resistance
Active tuberculosis
4
Rifampin & Isoniazid
What are the 4 drugs used in Tx of Active TB in order of preference?
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
(IRPE)
- Monotherapy can be used only for infected pts who _____.
- Combination therapy is required for treating ____.
- do not have active TB (latent infection)
- Active TB (at least 2 drugs)
Regimens for treating TB:
- Intensive phase is ___months
- Continuation phase of either ___ or ___ months
(total of __ to ____ months of tx)
- 2
- 4 - 7
- 6 - 9
Which 2 TB meds are weight based?
- Pyrazinamide
- Ethambutol
Drugs given in:
- Initial Phase:
- Continuation Phase:
- Initial: all 4 - Isoniazid, Rifampin, pyrazinamide, ethambutol
- Continuation: Isoniazid & Rifampin
(Have best results in HIV patients + or -)
Which 2 drugs need to be adjusted for renal function? Why?
- Pyrazinamide
- Ethambutol
(they are weight based)
What is the tx for Latent TB?
Is latent or active more common?
- Isoniazid (6 or 9 months)
- Isoniazid & Rifampin (3 months)
- Rifampin (4 months)
Latent
- Does a pt w/ latent TB have active disease and are able to trasmit it to others?
- In what type of pt does latent TB become active?
- no!
- Immunocompromised
Which TB drug?
- Inhibits cell wall synthesis
- Isoniazid
- Ethambutol
Which TB drug?
- Inhibits RNA synthesis
Rifampin
Which TB drug?
- Exact target is unclear
- Disrupts Plasma Membrane
- Disrupts Energy Metabolism
Pyrazinamide
What is the 1st line tx for Active AND Latent TB?
Isoniazid
Which drug?
- Inhibits synthesis of mycolic acids, an essential component of mycobacterial cell walls
- First-line for active and latent TB
- PK: Hepatic clearance
Isoniazid
(1st line for active/latent TB)
What are the 2 ADEs of Isoniazid?
- Hepatic toxicity
- Peripheral neuropathy : VIt B6-pyridoxine
Which drug?
- Turns body fluids orange
- Inhibits DNA-dependent RNA polymerase (Blocking production of RNA)
- First-line for active and latent TB
Rifampin
Rifampin can be used for what other 3 infections?
- Atypical mycobacterial infections
- eradication of meningococcal colonization
- Staphylococcal infections
Which drug?
- PK: hepatic clearance & CYP inducer
-
ADEs:
- turns body fluids orange color**
- Cholestasis (hepatitis**)
- Rash
- Flu like syndrome w/ intermittent dosing
- Thrombocytopenia (bruising/bleeding)
- Nephritis**
Rifampin
Which drug?
- Used for disseminated M. avium infection in AIDS pts and is quite active against M. tuberculosis
- Most rifampin resistant organisms are resistant to this drug
- Less potent enzyme inducer than rifampin, it may be used for pts who are receiving protease inhibitors
- For HIV-positive pts, the ATS/CDC recommends regimens with 3 or more doses of the TB drugs / week
Rifabutin
Which drug?
- A long-acting rifamycin that can be used once weekly in the continuation phase of treatment (after the first 2 months) in carefully selected HIV-negative patients
- Approximately as potent an enzyme inducer as rifampin
similar drug interactions are likely
Rifapentine
Which drug?
- a sterilizing agent prescribed during the first 2 months of therapy
- Mechanism not fully understood
- Possibly disrupts plasma membrane
- Possibly energy metabolism
- Because it is a “sterilizing” agent the total duration of therapy for TB to be shortened to 6 months**
Pyrazinamide
Which drug?
- Hepatic clearance, metabolites renally cleared-reduced dose if <30mlmin clearance
-
ADE:
- hepatotoxicity
- hyperuricemia***
- rash
- GI disturbance
- arthralgias (don’t give acetaminophen bc/ hepatotoxic.)
Pyrazinamide
_____ is given until drug sensitivities are known
- Inhibits mycobacterial arabinosyl transferases, which are involved in the polymerization rxn of arabinoglycan, an essential component of the mycobacterial cell wall
Ethambutol
Which drug?
- Given in four drug initial combination therapy for tuberculosis until drug sensitivities are known
- Hepatic & Renal clearance, dose reduction in renal failure
Ethambutol
What are the ADEs of Ethambutol?**
- Retrobulbar neuritis (reversible if drug stopped)
Multiple Drug Resistant - TB
- Caused by organisms that are resistant to at least ___ of the best anti-TB drugs: Isoniazid & Rifampin
2
Which drug?
- The first drug in a new class of anti-TB meds to be approved in more than 40 yrs
- Inhibits the proton transfer chain of mycobacterial ATP synthase required for energy generation of M. tuberculosis
-
Box warning:
- increased mortality
- QT prolongation >500ms (get EKG before giving this drug)
Bedaquiniline
MDR TB (multiple drug resistant) can take up to __ months to cure.
24
Bedaquiline monitoring:
- How often should you monitor for sxs: N, HA, hemoptysis, CP, joint pain, rash
- ECG before start of tx and repeat when?
- Monitor for ___ related adverse drug rxns w/ serum transaminases
- ____ drug monitoring should be considered in pts w/ severe renal impairment & when given w/ other drugs that induce/suppress the cytochrome P450 system
- once a week
- 2, 12, and 24 weeks after tx started
- liver-related
- Therapeutic drug monitoring
5 second line TB meds
- Streptomycin
- Capreomycin
- Amikacin/kanamycin
- Moxifloxacin
- p-Aminosalicylic acid
(SCAMP)
Which “other” med?
- Injectable agent given intramuscularly in doses of 15–30 mg/kg/day (maximal dose 1 g)
- Major toxicities include ototoxicity (both vestibular and cochlear) and nephrotoxicity
- If the medication must be used in older patients, the dose should not exceed 750 mg
•Capreomycin
Which “other” med?
- A phenazine dye used in the treatment of leprosy
- Active in vitro against M avium complex and Mycobacterium tuberculosis
- Given orally as a single daily dose of 100 mg for treatment of M avium complex disease
- Clinical efficacy for the therapy of tuberculosis has not been established.
- Adverse effects include nausea, vomiting, abdominal pain, and skin discoloration
•Clofazimine
Which “other” med?
- A bacteriostatic agent, is given in doses of 15–20 mg/kg (not to exceed 1 g) orally
- Used in re-treatment regimens and for primary therapy of highly resistant M tuberculosis
- Can induce a variety of central nervous system dysfunctions and psychotic reactions.
•Cycloserine
Which “other” med?
- Like cycloserine, bacteriostatic, given orally in a dose of 15–20 mg/kg (maximal dose 1 g)
- Used in combination therapy but is poorly tolerated with marked gastric irritation
•Ethionamide
Which “other” med?
- Particularly moxifloxacin
- Active in vitro against M tuberculosis, with MICs of 0.25–2 mcg/mL
- These medications demonstrated to be efficacious in treating tuberculosis in patients unable to take isoniazid, rifampin, and pyrazinamide
- Rapid emergence of resistance has been described in some series
- Combination of 6 months of the long-acting rifamycin, rifapentine, in combination with moxifloxacin, is as effective as standard therapy in the treatment of tuberculosis
•Fluoroquinolones
Which “other” med?
- effective in achieving culture conversion in patients with treatment-refractory, highly resistant pulmonary tuberculosis
- Long-term use of this agent for tuberculosis is associated with significant side effects, particularly the 600 mg daily dose
•Linezolid
ADE of which drug?
- Asymptomatic elevation of aminotransferases
- Clinical hepatitis / Fatal hepatitis
- Peripheral neurotoxicity / CNS effects
- Lupus-like syndrome
- Hypersensitivity
- Monoamine poisoning
- Diarrhea
Isoniazid
ADE of which drug?
- Cutaneous rxns
- GI rxns (N, anorexia, abd pain)
- Flu-like syndrome
- Hepatotoxicity
- Severe immunologic rxns
- Orange discoloration of bodily fluids (sputum, urine, sweat, tears)
- Drug interactions due to induction of hepatic microsomal enzymes
Rifampin
ADE of which drug?
- Hepatotoxicity
- GI sxs (N/V)
- Non-gouty polyarthralgia
- Asymptomatic hyperuricemia
- Acute gouty arthritis
- Transient morbilliform rash
- Dermatitis
Pyrazinamide
ADE of which drug?
- Retrobulbar neuritis
- Peripheral neuritis
- Cutaneous rxns
Ethambutol
Monitoring of which drug?
- LFT monthly in patients who have preexisting liver disease or who develop abnormal liver function that does not require discontinuation of drug; dosage adjustments may be necessary in patients receiving anticonvulsants or warfarin
Isoniazid
Monitoring of which drug?
- Liver enzymes and interacting drugs as needed (eg, warfarin)
Rifampin
Monitoring of which drug?
- Serum uric acid can serve as a surrogate marker for adherence; LFTs in patients with underlying liver disease
Pyrazinamide
Monitoring of which drug?
- Baseline visual acuity testing and testing of color discrimination; monthly testing of visual acuity and color discrimination in patients taking >15–20 mg/kg, having renal insufficiency, or receiving the drug for >2 months
Ethambutol
