treatment of presenter tuberculosis course...factors affecting decision to initiate treatment...

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© 2017 Denver Public Health

Treatment of Tuberculosis

Bob Belknap M.D.

Denver Public Health

April 2019Propert

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Disclosures• No conflicts of interest

• Some of my slides were copied or adapted from Dr. Daley

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ObjectivesAfter participating in this lecture, you should be able to describe:

1. When empiric TB treatment should be started2. The medication regimens for treating likely or

confirmed drug‐susceptible TB3. Changes to TB treatment for patients with liver

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Nahid, CID October 1, 2016; 63(7): e147‐195Prop

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52 y/o male

• Born in the Pacific Islands; extensive travel in the U.S. military

• Prior BCG and (+) TST

• 1 month of cough, fever, weight loss

• Refused admissionProp

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Factors Affecting Decision to Initiate Treatment

Patient

Laboratory/Radiologic

Clinical status/suspicious

Favors Treatment Initiation Favors Delayed or no Treatment

Public Health

TB exposureRisk for progressionYoung age (< 2 yo)

No TB exposureRisk for AE

Radiograph c/w TBSmear positive, NAAT positiveSmear negative, NAAT positive

Radiograph not c/w TBSmear positive, NAAT negativeSmear negative, NAAT negative

Life threatening diseaseSymptoms c/w TBAlternative diagnosis unlikely

Stable diseaseSymptoms not c/w TBAlternative diagnosis likely

High transmission riskConcern for lost to f/u Low transmission risk

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The Story of Adam• 29 year old man originally from Chicago who developed headaches and fevers

• He went to an Urgent Care and was given an doxycycline for pneumonia (RUL opacity)

• He went to an Emergency Department and was given levofloxacin for pneumonia

• He saw a Pulmonologist who did a bronchoscopy and a biopsy

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The Story of Adam

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The Story of Adam• When he woke up confused, his fiancé took him to a hospital

• He was diagnosed with meningitis

• Started on empiric treatment for bacterial and fungal infections

• TB was considered but initial tests were negative

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The Story of Adam

• He got progressively worse despite treatment and began having strokes

• Adam died after 2 ½ weeks in the hospital

Cultures from his lungs and spinal fluid grew TB 2 weeks after his deathProp

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Factors Affecting Decision to Initiate Treatment

Patient

Laboratory/Radiologic

Clinical status/suspicious

Favors Treatment Initiation Favors Delayed or no Treatment

Public Health

TB exposureRisk for progressionYoung age (< 2 yo)

No TB exposureRisk for AE

Radiograph c/w TBSmear positive, NAAT positiveSmear negative, NAAT positive

Radiograph not c/w TBSmear positive, NAAT negativeSmear negative, NAAT negative

Life threatening diseaseSymptoms c/w TBAlternative diagnosis unlikely

Stable diseaseSymptoms not c/w TBAlternative diagnosis likely

High transmission riskConcern for lost to f/u Low transmission risk

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Deciding to start Empiric TB treatment

1. Clinical reasons– At risk for life‐threatening TB (e.g. < 50% of TB meningitis is culture positive)

2. Public health reasons– Return to work/school while cultures are pending, children at home, staying in a congregate setting (nursing home or homeless shelter)

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Basics of TB Treatment• Combination therapy is required to prevent failure and resistance

• Standard medications for drug sensitive TB– Isoniazid (INH, H, I)– Rifampin (RIF, R)– Pyrazinamide (PZA, Z) NOTE: some abbreviate with P but that usually refers to rifapentine

– Ethambutol (EMB, E)

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Treatment of TuberculosisStandard Regimen

Isoniazid

Rifampin

Pyrazinamide

Ethambutol

0 1 2 3 4 5 6months

Initial Phase Continuation Phase

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Role of each drug in the TB regimen

Never treat active TB with a single drug

Rapid killing of multiplying bacilli (bactericidal effect)

Achievement of relapse-free cure (sterilizing effect)

Protection against acquisition of drug resistance

INH

RIF, PZA

INH, RIF, EMBPropert

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23 y/o with lymphadenopathy

• Smear (‐), NAAT (+)

• Started on INH, RIF, PZA, EMB

• At 1 month, complaint of losing his hair

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Isoniazid (INH)More common TipFatigue Sleep hygieneGI – anorexia, nausea, vomiting

Anti‐nausea (ondansetron), anti‐anxiety (hydroxyzine)

Hepatitis Stop if ALT/AST 3x ULN (>120) with symptoms or > 5x ULN (>200)

Maculopapular rash

Treat with topical lotions +/‐ steroid and anti‐histamines

Peripheral neuropathy

Mostly prevented with B6; can be problematic with DM and/or EtOH

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Isoniazid (INH)Less common TipAlopecia Temporary – can often continue

treatment and reassureOptic neuritis Typically think EMB or linezolid Seizure Unlikely the sole source, look for

other causes (CNS tuberculoma)Vasculitis Stop INH +/‐ steroidsAnemia StopThrombocytopenia Stop

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Rifampin (RIF)More common TipDrug‐druginteractions

Many are relatively minor (ex. HTN); Important to always review

Orange/Reddiscoloration of body fluids

Educate patients to prevent panic

GI – anorexia, nausea, vomiting

see INH

Maculopapular rash

see INH

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Rifampin (RIF)Less common ManagementHepatitis Less than PZA or INH; more often

associated with ↑ bilirubinHemolytic anemia Stop Rifampin

Thrombocytopenia Stop Rifampin

Acute renal failure Stop RifampinPropert

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Pyrazinamide (PZA)More common TipGI – anorexia, nausea, vomiting Both are more common with PZA

and worse with increasing ageHepatitis

Maculopapular rash

see INH

Arthralgias/myalgias

Acetaminophen or NSAIDS

Gout flare Anti‐inflammatoryProp

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Ethambutol (EMB)Less common TipOptic neuritis Counsel patients to notify you if

they develop blurred vision

Monitor visual acuity and Ishihara (red/green vision) monthly

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Monitoring for Treatment Response and Adverse Reactions

Shaded ‐ optional Nahid, CID October 1, 2016; 63(7): e147‐195Prop

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TB Treatment Duration

Regimen Duration, mos

Treatment Success

SM, PAS 18‐24 75%INH, SM, PAS 18‐24 95%INH, SM (or EMB), PZA 9 95%2 INH, RIF, SM/ 7 INH, RIF 9 95%2 INH, RIF, EMB/ 7 INH, RIF 9 95%2 INH, RIF, EMB, PZA/ 4 INH, RIF 6 95%

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Initial ContinuationReg Drugs Interval/Dose Drugs Interval/Dose

1 INHRIF

EMBPZA

7 days/wk (56) or 5 days/wk (40)

INH/RIF 7 days/wk (126) or 5 days/wk (90)

2 INHRIF

EMBPZA

7 days/wk (56) or 5 days/wk (40)

INH/RIF 3 days/wk (54)

Preferred Regimensdaily dosing

Effectiveness


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Alternative Regimensintermittent dosingInitial Continuation

Reg Drugs Interval/Dose Drugs Interval/Dose3* INH

RIFEMBPZA

3X wkly (24) INH/RIF 3X wkly (54)

4** INHRIFEMBPZA

7 days/wk (14) then twice wkly (12)

INH/RIF 2X wkly (36)

Effectiveness

*Use with caution in patients with HIV or cavitary disease**Do not use in patients with HIV or smear positive and/or cavitary disease


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Organization and Supervision of Therapy

We suggest using DOT rather than SAT (conditional recommendation, low quality of evidence)

2. Does self‐administered therapy (SAT) have similar outcomes compared to directly observed therapy (DOT) in patients with various forms of TB?

Studies DOT SAT Relative RiskTreatment Success 5 74.6% 73.0% 0.94 (0.89‐0.98)

No difference in mortality, treatment completion or relapseProp

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Directly Observed Therapy

ATS/CDC/IDSA TB Treatment MMWR 2003Prop

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Patient‐Centered Care• Patient education and reminders• Use of incentives and enablers

– Bus passes, food, compensation for time

• Coordination of care for other health issues– Mental health, DM, HIV etc.

• Flexibility with directly observed therapy– Clinic, field and/or home visits– Use of video technology

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Completion of TB Therapy• Completion of therapy is defined as the number of doses taken

• Initial phase ‐ All doses should be taken within 3 months

• Continuation phase ‐ All doses should be taken within 6 months

• Thus, a 6‐month regimen should be completed within 9 months

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Interruptions in TreatmentTime point of interruption

Details of interruption Approach

Intensive Phase Lapse is < 14 days Continue treatment

Lapse is ≥ 14 days Restart treatment

Continuation Phase Received ≥ 80% of doses and was sm (‐) at diagnosis

Further treatment may not be necessary

Received ≥ 80% of doses and was sm (+) at diagnosis

Continue treatment unless 2 consecutive mos missed then restart

Received < 80% of doses and lapse < 3 mos

Continue treatment

Received < 80% of doses and lapse ≥ 3 mos

Restart treatment


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Relapse Rates By Cavitation and 2‐Month Culture Status

6‐month regimen Cav+C2m+

Cav+C2m‐

Cav‐C2m+

Cav‐C2m‐

Daily 6.0 2.2 1.8 0.6Daily IP + thrice weekly CP 6.1 3.3 2.2 1.2Daily IP + twice weekly CP 15.6 5.7 5.4 1.9Thrice weekly 14.5 5.3 4.6 1.7Daily IP with Rp in CP 25.3 9.0 8.4 3.0Thrice weekly IP with Rp in CP 36.1 12.9 12.0 4.3

IP – intensive phase, CP continuation phase, Rp – rifapentineCav – cavitary, C2m – 2 month culture status

Chang et al, AJRCCM 2006; 174;1153‐1158

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Cavi es ≠ Cavi es

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Extending the Duration of Therapy

• Either cavitation or positive sputum culture at 2 months of therapy plus:– >10% below ideal body weight– Smoker– Diabetes mellitus– HIV infection– Other immunosuppressive conditions– Extensive disease on chest radiograph

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60 y/o with cryptogenic cirrhosis and isolated rifampin resistant TB

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60 y/o with cryptogenic cirrhosis

Isolated RIF‐resistant TB

• Levofloxacin• Linezolid• EMB• Amikacin (TIW)• Imipenem Prop

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TB Treatment in Liver Disease

1. Mild– INH, RIF, EMB; no PZA

2. Moderate– Rif, EMB, FQ; no INH or PZA

3. Severe / Unstable– FQ, EMB, amikacin/streptomycin, linezolid,

carbapenem, cycloserine,

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FluoroquinolonesTip

Clearance Moxifloxacin (liver) Levofloxacin (Kidney but not removed by hemodialysis)

Prolonged QT ‐Arrhythmia

Moxifloxacin > Levofloxacin

Tendinitis Achilles, shoulder, other large joints

Hepatotoxicity Maybe Moxifloxacin > Levofloxacin

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FluoroquinolonesTip

GI – anorexia, nausea, vomiting

sometimes improved by switching moxi to levo or levo to moxi

CNS – headache, dizziness, fatigue

Usually can treat symptoms and continue

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TB and renal disease

70 y/o from MX with DM and ESRD (emergent HD)‐ Cough with blood‐ (+) QFT‐ Worsening CXR‐ Smear and geneXpertnegative

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Renal Dosing for Standard TB Treatment


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Objectives1. When should empiric TB treatment be started

– Severely ill and/or likely to worsen acutely– High risk if transmission

2. Regimens for treating likely or confirmed drug‐susceptible TB

– INH, RIF, PZA, EMB x 2 months then INH, RIF x 4 months– Extend the continuation phase to 7 months (9 months

total) if sputum culture (+) at 2 months or cavitation with extensive disease

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Objectives3. TB treatment for patients with liver disease

– Depends on the severity of disease – INH (if mild) rifampin or rifabutin (if moderate/severe but stable), levofloxacin, EMB, linezolid, amikacin, carbapenem, cycloserine

Renal disease– INH and rifampin daily– PZA and EMB daily dose given 3 times a week– Fluoroquinolone if needed

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Questions?

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treatment of presenter tuberculosis course...factors affecting decision to initiate treatment...

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