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OU Module ID Fall 2018 > Antimycobacterials and Mycobacterial Infections Exam 4 > Flashcards

Antimycobacterials and Mycobacterial Infections Exam 4 Flashcards

1
Q

What are the antimycobacterial agents?

A
  • rifampin
  • isoniazid
  • ethambutol
  • pyrazinamide
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2
Q

rifampin MOA

A

inhibits RNA synthesis

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3
Q

isoniazid MOA

A

inhibits the synthesis of mycolic acids which are essential components of the bacterial cell wall

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4
Q

ethambutol MOA

A

Inhibits arabinosyl transferase III which disrupts the transfer of arabinose into arabinogalactan biosynthesis subsequently disrupting the assembly of the mycobacterial cell wall

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5
Q

pyrazinamide MOA

A

in acid environment, pyrazinamide is converted to pyrazinoic acid (POA), POA disrupts mycobacterial cell membrane metabolism and transport functions

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6
Q

rifampin treatment for TB

A
  • Rifampin: once daily
  • Rifabutin: once daily
  • Rifapentine: per week
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7
Q

rifampin ADE

A
  • Generally well tolerated
  • Most common significant adverse effects include rash, fever, nausea, vomiting, increased LFTs, immunologic reaction, flu like syndrome, GI
  • Causes an orange-tan discoloration of skin, urine, feces, saliva, tears, and contact lenses
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8
Q

Drug-drug interactions of rifampin

A
  • Potent inducer of CYPs 1A2, 2C9, 2C19, and 3A4
  • p-glycoprotein (efflux pump)
  • glucuronidation which decreases the Cmax and half-life of many medications ultimately reducing their therapeutic effects
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9
Q

Drug-drug interactions of rifabutin

A
  • Less potent inducer of CYPs than rifampin, both in potency and number of CYPs involved
  • Decreases the half-life of the following agents: Zidovudine, prednisone, digoxin, ketoconazole, propranolol, phenytoin, sulfonylureas, and warfarin
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10
Q

isoniazid treatment for TB

A

daily

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11
Q

isoniazid ADE

A
  • Hepatic injury
  • Peripheral neuritis
  • Neurologic toxicities
  • Mental abnormalities
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12
Q

isoniazid ADE

A
  • Hepatic injury
  • Peripheral neuritis
  • Neurologic toxicities
  • Mental abnormalities
  • Other hematologic reactions, vasculitis, arthritic symptoms, dry mouth, epigastric distress, tinnitus, and urinary retention, lupus like syndrome, hypersensitivity
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13
Q

isoniazid ADE: Hepatic injury

A

increased ALT/AST (often normalize after continuous use)

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14
Q

isoniazid ADE: Neurologic toxicities

A
  • convulsions in patients with seizure disorders, optic neuritis and atrophy, muscle twitching, dizziness, ataxia, paresthesias, stupor, and toxic encephalopathy
  • *Pyridoxine (vitamin B6) can serve as a prophylactic agent for peripheral neuritis and other CNS effects listed above
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15
Q

isoniazid ADE: Mental abnormalities

A
  • euphoria
  • transient memory impairment
  • loss of self-control
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16
Q

isoniazid ADE: Mental abnormalities

A
  • euphoria
  • transient memory impairment
  • loss of self-control
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17
Q

Drug-drug interactions of isoniazid

A

Inhibitor of CYP2C19, CYP3A, weak inhibitor of CYP2D6, and induces CYP2E1

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18
Q

Which agents needs renal dose adjustments?

A
  • Pyrazinamide

- Ethambutol

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19
Q

ethambutol treatment for TB

A

single daily dose

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20
Q

ethambutol ADE

A
  • Generally well tolerated
  • Retrobulbar neuritis
  • Rash, peripheral neuritis, drug fever
  • Other: pruritus, joint pain, GI upset, abdominal pain, malaise, headache, dizziness, mental confusion, disorientation, and possible hallucinations, skin reactions
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21
Q

ethambutol ADE: Retrobulbar neuritis

A
  • loss of visual acuity, inability to distinguish red-green color
  • Dose-related, rare at 15 mg/kg/d or less
  • Recommend periodic screening at high doses
  • Relative contraindication in children too young to assess visual acuity
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22
Q

pyrazinamide treatment for TB

A

daily dose

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23
Q

pyrazinamide ADE

A
  • Hepatic injury
  • Hyperuricemia
  • Other: arthralgias, anorexia, nausea, vomiting, dysuria, malaise, GI, polyarthalgia, rash, and fever
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24
Q

pyrazinamide ADE: Hepatic injury

A
  • increased ALT/AST
  • jaundice
  • hepatic necrosis
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25
Q

pyrazinamide ADE: Hyperuricemia

A
  • may cause acute episodes of gout

- contraindicated in acute gout

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26
Q

pyrazinamide precaution

A
  • Avoid in pregnancy due to lack of data

- contraindicated in acute gout

27
Q

risk factors for infection of TB

A
  • Location and place of birth
  • Race, ethnicity, age, and gender
  • Co-infected with HIV
28
Q

risk factors for infection of TB: Location and place of birth

A
  • California, Florida, New York, and Texas are states commonly reported
  • 2 out of 3 cases are foreign born individuals majority originating from Mexico, Philippines, Vietnam, India, and China
29
Q

risk factors for infection of TB: Race, ethnicity, age, and gender

A
  • compared to non-Hispanic whites, the TB rate among non-Hispanic Asians was 29 times greater, and rates among non-Hispanic blacks and Hispanics were both 8 times greater
  • For US born ethnic groups, non-Hispanic blacks had the highest reported cases in 2014
  • Patients aged 45-64 have the highest reported cases
  • Male predominance after the age of 24
30
Q

risk factors for infection of TB: Co-infected with HIV

A
  • TB and HIV act synergistically making each infection worse
  • HIV does not increase the risk of getting TB but can increase the chances of progression to active disease
  • Higher mortality rates in patients who have multidrug-resistant (MDR) and extensive drug-resistant (XDR) TB
31
Q

risk factors for (active) disease

A
  • ~ 10% lifetime risk of developing active disease in those infected M. tuberculosis
  • Greatest risk occurs during the first 2 years after infection
  • Children less than 2 years and adults greater than 65
  • Immuno-compromised patients -> HIV patients are 100 times more likely to develop active TB than non-infected persons
32
Q

transmission of TB

A
  • Person to person by coughing or other mechanisms (sneezing, speaking, singing, etc…) that cause the organism to be aerosolized
  • The particles that are transmitted are called droplet nuclei which contains one to three organisms each
  • ~ 30% of people who experience sustained exposure with an infectious TB patient will become infected
  • Patient’s with latent tuberculosis that are not symptomatic do not transmit tuberculosis
33
Q

What is the area of induration?

A

in TB skin test (PPD), the “bump,” NOT the area of redness

34
Q

Reaction 5 mm of nduration means that you are positive for TB IF…

A
  • HIV positive
  • Recent contacts of TB case
  • Fibrotic changes on chest radiograph consistent with prior TB
  • Organ transplants and other immunosuppressed patients (receiving the equivalent of ≥ 15 mg/day of prednisone for ≥ 1 month)
35
Q

Reaction >= 10 mm of nduration means that you are positive for TB IF…

A
  • Recent immigrants (within 5 years) from high-prevalence countries)
  • Injection-drug users
  • Resident and employees of high risk congregate areas
36
Q

Reaction >= 15 mm of nduration means that you are positive for TB IF…

A

Persons with no risk factors for TB

37
Q

What are examples of high risk congregate areas?

A
  • prisons and jails
  • nursing homes and other long-term care facilities for elderly
  • hospitals and other healthcare facilities
  • residential facilities for patients with AIDS
  • homeless shelters
38
Q

How many patients will have a false negative test on the TB skin test?

A

20%

39
Q

What is the purpose of treating latent infection?

A

decreases the lifetime risk of active TB from ~10% to ~1%

40
Q

What is the preferred treatment of latent TB?

A
  • isoniazid

- All patients should be monitored monthly for adverse drug reactions and possible progression to active TB

41
Q

What are other agents that can be used for latent TB?

A
  • Rifampin

- Isoniazid and rifapentine

42
Q

What are the interval and duration of isoniazid that can be used for latent TB?

A
  • Daily for 9 months: May be administered concurrently with antiretroviral therapy (ART) for HIV patients; fibrotic lesions; children
  • Twice weekly for 9 months: Directly observed therapy (DOT) must be used
  • Daily for 6 months: Not indicated for HIV patients, patients with fibrotic lesions, or children
  • Twice weekly for 6 months: DOT must be used
43
Q

What are the interval and duration of rifampin that can be used for latent TB?

A
  • Daily for 4 months

- For persons who are contacts of patients with isoniazidresistant

44
Q

What are the interval and duration of isoniazid + rifapentine that can be used for latent TB?

A
  • Once weekly for 3 months
  • Directly observed therapy (DOT) must be used
  • Not recommended for children < 2
  • HIV patients on ART
  • isoniazid or rifampin resistant strains
  • pregnant women or women expecting to become pregnant within the 12 week regimen
45
Q

Standard treatment for active disease

A
  • RIPE: rifampin, isoniazid, pyrazinamide, ethambutol for 2 months
  • Followed by 4 months of isoniazid and rifampin (total of 6 months)
46
Q

What are the different dosing options for RIPE for active TB?

A
  • Daily for 8 weeks or 5d/wk for 8 weeks followed
  • Daily for 2 weeks, then 2/wk for 6 weeks or 5d/wk for 2 weeks, then 2x/wk for 6 weeks
  • 3x/week for 8 weeks
47
Q

What are the different dosing options for RIE for active TB?

A

Daily for 8 weeks or 5d/wk for 8 weeks

48
Q

If you dose RIPE at Daily for 8 weeks or 5d/wk for 8 weeks followed , how should you follow it?

A
  • Isoniazid / rifampin: Daily for 18 weeks or 5d/wk for 18 weeks
  • Isoniazid / rifampin: 2x/wk for 18 weeks
  • Isoniazid / rifapentine: 1x/wk for 18 weeks
49
Q

If you dose RIPE at Daily for 2 weeks, then 2/wk for 6 weeks or 5d/wk for 2 weeks, then 2x/wk for 6 weeks, how should you follow it?

A
  • Isoniazid / rifampin: 2x for 18 weeks

- Isoniazid / rifapentine: 1x/wk for 18 weeks

50
Q

If you dose RIPE at 3x/week for 8 weeks, how should you follow it?

A

Isoniazid / rifampin: 3x/wk for 18 weeks

51
Q

If you dose RIE at Daily for 8 weeks or 5d/wk for 8 weeks, how should you follow it?

A

Isoniazid / rifampin: aily for 31 weeks or 5d/wk for 31 weeks or 2x/wk for 62 weeks

52
Q

Treatment of TB is usually 6 months total. Under what conditions would you treat a pt for 9 months?

A
  • Patients with cavitation on presentation and positive cultures after 2 months of therapy
  • Patients who cannot take PZA (RIF/EMB/INH for 2 months and RIF/INH for 7 months)
53
Q

When would you isolate a pt due to airborne precautions?

A
  • They are coughing and/or have positive sputum cultures for acid fast bacilli (AFB)
  • AND they are not receiving appropriate TB treatment, have just started TB treatment, or have poor clinical response to TB treatment
  • Patients who have drug susceptible TB should remain under airborne precautions until they: produce 3 consecutive negative sputum smears and have received at least two weeks of standard TB treatment
54
Q

What happens if you have MDR-TB?

A
  • Resistance to isoniazid and rifampin
  • There is no standard regimen and should be referred to specialists
  • Avoid monotherapy and adding a single agent to a failing regimen
  • May take several months for a patient to become culture negative
55
Q

XDR-TB are resistant to which drugs?

A
  • soniazid
  • rifampin
  • a fluoroquinolone
  • one second-line injectable drug (amikacin, capreomycin, or kanamycin)
56
Q

Special populations in TB

A
  • Tuberculosis meningitis and extrapulmonary disease
  • Children
  • Pregnancy
  • HIV
57
Q

Special populations in TB: Tuberculosis meningitis and extrapulmonary disease

A
  • CNS TB is usually treated longer (9-12 months)
  • TB of the bone is usually treated for 9 months
  • Isoniazid, pyrazinamide, ethionamide, and cycloserine penetrate the CSF readily
  • Levofloxacin is the preferred quinolone
58
Q

Special populations in TB: Children

A
  • May be treated with regimens used for adults but some experts recommend a duration of 9 months
  • Doses of isoniazid and rifampin are on a mg/kg basis and are higher than adult doses
59
Q

Special populations in TB: Pregnancy

A
  • Women should be counseled against conceiving because TB carries a risk to the fetus and mother
  • Usual treatment for pregnant patients is isoniazid, rifampin, and ethambutol for 2 months and isoniazid and rifampin for 7 months
  • Aminoglycosides are reserved for critical situations due to the potential of hearing loss to the baby
  • Therapy with isoniazid for LTBI may be delayed until after pregnancy
60
Q

Special populations in TB: HIV

A
  • AIDS and other immuno-compromised patients can be treated with similar regimens for the immunocompetent
  • Extended continuation phase to 7 months (9 months total) recommended for HIV patients who do not start ART during TB therapy
  • Highly intermittent regimens (twice or once weekly) are not recommended
  • Rifapentine not recommended
  • Rifampin and rifabutin can interact with many antiretrovirals
61
Q

How should you take Rifampin?

A

food decreases Cmax (best on empty stomach)

62
Q

How should you take Rifapentine?

A

high fat meal ↑AUC (best with food)

63
Q

If we can’t use RIPE, what are alternative agents that we can use?

A
  • Aminoglycosides
  • Fluoroquinolones
  • Macrolides
  • Clofazamine
  • Ethionamide
  • Para-Aminosalicylate Acid (PAS)
  • Cycloserine
  • Dapsone

OU Module ID Fall 2018 (18 decks)

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