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Antibiotic > Tuberculosis > Flashcards

Tuberculosis Flashcards

1
Q

Risk factors for TB infection

A
  • living in urban areas
  • residents of prisons, homeless shelters, nursing homes
  • close contact with someone with pulmonary TB ( the more prolonged the contact, the greater the risk )
  • elderly ( Reactivation of infection acquired years earlier)
  • co infection with HIV
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2
Q

Risk factor for active diseases TB

A
  • Lifetime risk of developing active disease ~10% (highest risk during first 2 years after infection)
  • Extremes of age (<2yrs and >65 years)
  • underlying immune suppression
    ( disease-related : Renal failure , cancer)
    ( Drugs )
  • co- infection with HIV (annual risk ~10%; ~29X more likely to develop active disease)
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3
Q

Clinical presentation of TB

A
  • gradual onset
  • SNS
WT lost 
Fatigue 
Fever 
Productive cough 
Night sweats
Hemoptysis
  • Physical examination
    Dullness on percussion
    Rales/rhonchi
  • X-ray
    Infiltrated in apical regions
    Cavitary lesions
    Granulomas
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4
Q

Clinical presentation of TB
In

HIV patient
Elderly

Extrapulmonary TB
Military TB

A

HIV infected patients

  • may not manifest typical symptoms
  • higher incidence of extra-pulmonary TB
  • screen for TB.

Elderly

  • weight loss
  • altered mental status
  • have a high index of suspicion

Extrapulmonary TB

  • bones
  • joints
  • spine ( Pott’s disease)
  • meningitis
  • adrenal glands

Military TB

  • disseminated form of disease
  • rapidly progressive
  • mortality up to 33%
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5
Q

Key to preventing spread of TB is early identification of infected individuals

A

Key to preventing spread of TB is early identification of infected individuals

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6
Q

Latent TB infection

(LTBI) definition

A

Presumptive infection with
M tuberculosis as evidenced by a positive tuberculin skin test and or positive gamma interferon release assay without clinical or radiologic manifestation of disease.

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7
Q

Screening criteria LTBI

A

Implement selective testing based on risk of progression to active disease

Indicated only for those willing to undergo treatment with a positive test result.

CLEAR indication for screening

  • children and young adults with recent close contact
  • hiv infected individuals
  • candidates for tumors necrosis factor antagonist therapy
  • dialysis patients
  • organ/ hematologic transplant patients
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8
Q

Controversial groups for screening for LTBI

A

Vary from country to country
Immigrants from country with high incidence of TB

Healthcare workers
Prisoners
Homeless
Injection drug user

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9
Q

Detection of latent TB infection

Tuberculin skin test

A

Detection of Latent TB Infection
 Tuberculin skin test/Mantoux test/PPD test
- Singapore practice
- 0.1mL tuberculin purified protein derivative (PPD)
- Injected intra-cutaneously on volar aspect of forearm

 Read after 48 – 72 hours by experienced person
 Area of induration important, not area

 Interpretation depends on risk group and history of BCG vaccination
 Biggest limitation is low specificity
- Does not distinguish between infection with M. tuberculosis, prior BCG vaccination, or environmental contact with non-tuberculous mycobacteria

 BCG vaccinated population
 No universally accepted criteria
- UK NICE guidelines → ≥ 15mm induration

 Recent vaccination can result in false positive test
 Given in infancy → response wanes in ~ 5 yrs
 Given later in life → can persist > 10 yrs

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10
Q

Detection of LTBI gamma interferon release assays

A

Detection of Latent TB Infection
Gamma interferon release assays

 Detect gamma interferon released by sensitized T cells (mainly CD4) in response to antigens specific to M. tuberculosis
 Can be used in people with prior BCG vaccination
 Quantiferon® and T-Spot ® tests
 As good as, or even better, than skin testing
 Recommended as an alternative in any situation where skin testing would be used
 Results within a few hours

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11
Q

Suspicion of active TB disease

A

Active Disease
Suspect based on

 History
— Risk factors or exposure

 Clinical presentation
 Physical exam findings
 Chest X-ray findings

 Confirm with microbiological tests to identify/isolate organism

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12
Q

Sputum microscopy of TB

A

Sputum Microscopy
 Expectorated sputum sample or induced with aerosolized hypertonic saline
 WHO recommendations
—Send 2 specimens → increased yield
—Can send 2 specimens on the same day
 Ziehl-Neelsen stain for acid fast bacilli (AFB)
 Lower limit of detection = 8,000 – 10,000
organisms/mL
— Can be smear negative but still grow on culture

 Staining cannot determine species of Mycobacterium
 Cannot determine if organisms in original specimen were alive (viable) or dead
 If sputum is AFB positive → start treatment

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13
Q

Sputum culture TB

A

Sputum Culture
 Solid media
—Takes 4 – 8 weeks to grow and get confirmation
of TB
—Another 4 – 6 weeks for drug susceptibility testing results

 Liquid culture systems
— Can detect growth of M. tuberculosis within 1 – 3 weeks
— Another 1 – 2 weeks for drug susceptibility testing
— Can test first-line and second-line drugs
— Can be partially or fully automated
— Recommended by WHO as standard practice

 Molecular methods
— Real-time PCR assay
           Xpert MTB/RIF®
            — Detect M. tuberculosis and determine rifampin resistance < 2 hours
— WHO recommendations
       —
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14
Q

Confirming extrapulmonary TB

A 
Extrapulmonary TB
 Can perform AFB staining and culture on
 Draining fluid
 Bone biopsy specimen
 Tissue samples
 Cerebrospinal fluid (CSF)
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15
Q

Treatment LTBI principle

A

Treatment – LTBI
 Primary goal is to reduce the risk of progression to active disease
 Treatment reduces lifetime risk of active disease from ~10% to ~1%

 Must first exclude active disease
 Weigh risk of not treating (i.e., progression to active disease) vs. risk of adverse effects from treatment (i.e., primarily hepatotoxicity)
 Patients are asymptomatic and non-infectious

 Monotherapy is effective
 Lower bacterial burden vs. active disease
 Low risk of selecting out resistant organisms

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16
Q

LTBI treatment regimens first line

A 
Treatment Regimens – LTBI
 Isoniazid
 First-line for HIV positive and HIV negative
 5 – 10mg/kg daily (preferred) 
 Adults = 300mg standard dose

 Duration
 9 months → better efficacy
 6 months—

17
Q

Treatment regimens LTBI alternative First line

A

Treatment Regimens – LTBI
 Isoniazid plus rifapentine

 Rifapentine
— Long-acting rifamycin derivative
—

18
Q

Treatment regimens LTBI

For isoniazid resistance / cannot tolerate

A 
 Rifampin
 Adults
 600mg daily
 Duration
 US guidelines = 4 months
 UK NICE guidelines = 6 months

 Suspect isoniazid resistance or contacts of isoniazid-resistant active TB
 Cannot tolerate isoniazid

19
Q

Treatment regimens LTBI second line alternative

A

 Isoniazid plus rifampin
 Alternative second-line
 Duration = 3 – 4 months

 Rifampin plus pyrazinamide
 No longer recommended due to high rates of hepatotoxicity

Isoniazid 300mg (5-10mg/kg/ day) 
Rifampin 600mg daily
20
Q

Drug induced hepatotoxicity definition

A

Definition
 ALT > 3X upper limit of normal (ULN) with symptoms
OR
 ALT > 5X ULN without symptoms

21
Q

Rank order of drug for hepatotoxicity

A 
Risk of Hepatotoxicity
 Rank order
1. Pyrazinamide
2. Isoniazid
3. Rifampin
4. Ethambutol

 Second-line drugs
—

22
Q

Risk factors for drug induced hepatotoxicity

A 
Risk Factors
 Combination therapy
 Increasing age (> 35 years) 
 Female
 Underlying liver disease
 Heavy alcohol use
 Higher doses (pyrazinamide)
 Antiretroviral therapy

Hahcifu

23
Q

Monitoring to avoid or detect hepatotoxicity for latent TB

Before tx

A

Monitoring to Avoid or Detect Hepatotoxicity

 Latent TB infection
— Screen for risk factors before starting treatment
— no risk factor —> start tx (no need chk Baseline)

W risk factor

  • chk Baseline LFT
  • normal —> start TX
  • abnormal —> defer tx

N/V, abdominal discomfort, unexplained fatigue = stop Tx

24
Q

Monitoring to avoid or detect hepatotoxicity

Active disease

A

Monitoring to Avoid or Detect Hepatotoxicity
 Active disease
— No risk factors
1) Baseline LFT’s
2) Re-check only if develop signs and symptoms

with risk factor

  • check Baseline LFT
  • recheck q 2-4 weeks
  • > 35yo = RF(?)
25
Q

What to do if develops hepatotoxicity

A 
With Hepatotoxicity
 Stop current treatment
 If severely ill and unsafe to completely stop
TB treatment
     — streptomycin , ethambutol, FQ

OR

Wait till SNS resolve and LFT normalize

  • restart drug 1 at a time
  • first drug - rifampin
  • monitor SNS and LFT
  • 3-7 days later at Isoniazid
  • if necessary, restart pyrazinamide
  • if symptoms it LFT abnormalities recur —> last drug added should be stopped
26
Q

Treatment regimens for hepatotoxicity

A

WHO Guidelines on Treatment Regimens
 Rifampin implicated
— Isoniazid + ethambutol + streptomycin x 2
months, then isoniazid + ethambutol x 10 months

 Isoniazid implicated
— rifampicin + pyrazinamide + ethambutol x 6-9months

 both Isoniazid and rifampin cannot be used
- streptomycin + ethambutol + FQ x 18 - 24 months

27
Q

Acute TB treatment regimen

Overall regimen no dose

A

Six month TB treatment

  • 2 month intensive phase
  • daily Ethambutol , isoniazid, rifampicin and pyrazinamide

Followed by

  • 4 month continuation phase of daily
  • rifampicin and isoniazid
    ( can be doses 3x weekly; dose for isoniazid be adjusted to 15mg/kg)

For patients who are unlikely to tolerate pyrazinamide (eg elderly, liver disease)
- 9 month regimens
- ethambutol, rifampicin, isoniazid for 2 months
Followed by
- rifampicin and isoniazid for 7months

28
Q

Dose for first line TB drugs active TB

A

Isoniazid
>= 15yo
- 5mg/kg/day, MAX 300mg/day
- 15mg/kg, MAX 900mg 3x/week

<15yo

  • 10-15mg/kg daily, MAX 300mg/day
  • 20mg/Kg, MAX 900mg 3x/week

Rifampicin
>=15yo
- 10mg/kg, MAX 600mg daily or 3x/week

<15yo

  • 10-20mg/Kg daily, MAX 600mg daily
  • 20mg/kg, MAX 600mg 3x/week

Ethambutol
>=15yo
- 15-20mg/kg daily for 1st two months then 15mg/kg daily
MAX: 1600mg/day

<15yo
- 15-25mg/kg, MAX 1600mg/ day

Pyrazinamide
>=15yo
- 25mg/kg daily, MAX: 2g/day

<15yo
- 25-35mg/kg MAX 2g/day

Streptomycin IM
>=15yo
- 15mg/kg daily, MAX 1g/day in person <= 59yo
- 10mg/kg daily, MAX 0.75g/day in persons > 59yo

<15yo
- 15-20mg/kg, MAX 1g daily.

29
Q

Latent TB hepatotoxicity during tx

A 
During tx
No risk factor for hepatotoxicity 
- no need chk LFT routinely 
- monitor SNS
- develops SNS —> stop TX and check LFT

Options (if develop hepatotoxicity)

  • stop Tx completely
  • restart Isoniazid after ALT <2x uln
  • switch to rifampicin x4 months

With risk factor
- monitor LFT q2-4weeks

Antibiotic (21 decks)

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