Monitoring for Adverse Events During LTBI

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Monitoring for Adverse Events During LTBI

• Helene M. Calvet, MD
• Health Officer and TB Controller
• Long Beach Department of Health and Human Services

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Reported Tuberculosis Cases By YearCity of Long
Beach, 1997-2009
2009 TB Case rates CA 6.4, LB 8.9
Department of Health and Human Services
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Current TB Screening and LTBI RxLong Beach TB
Control Program

• Historically, TB screening limited to certain
  high-risk groups (contacts, B-1 immigrants, some
  drug treatment facilities and homeless programs)
• Routine, low-risk TB screening (school,
  employment) done in our Walk-In clinic for a fee
• Previously, any patients with positive TST and
  indication for treatment were offered LTBI
  treatment through TB clinic (600/yr)
• Currently, due to budget shortages and staffing
  cutbacks, only contacts and B-1 immigrants are
  treated through our program (150/yr), and others
  are referred for Rx to PMDs or community clinics

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LTBI Baseline AssessmentLong Beach TB Control
Program

• Baseline LFTs obtained on all over age 35, and
  those under 35 who have hx liver disease, are
  pregnant or less than 3 months post-partum, HIV,
  EtOH or drug abuse
• If baseline LFTs gt 3x ULN, risk-benefit
  assessment done and w/u for etiology of increased
  LFTs (Hep B and C)
• After orders signed off by MD, PHN does INH
  Start visit and educates patient on
  signs/symptoms of INH adverse effects

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LTBI Follow-Up Assessment Long Beach TB Control
Program

• All patients (or responsible adult if patient is
  a minor) are seen on a monthly basis by RN or PHN
  for refill, assessment of symptoms and review of
  compliance
• Repeat LFTs done on those who had baseline lab
  assessment monthly for the first 3 months
  further labs as ordered by MD
• LFTs done on any patient complaining of symptoms
  of hepatitis
• If follow-up LFTs increase, reviewed by MD with
  decision to continue or hold INH

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Case 1

• 11/2005 14 y.o. Hispanic male, arrived in US
  from Honduras 4 years prior, needing TB screening
  for school
• TST negative x 2 in past (2002, 2003) current
  TST positive at outside clinic 10 mm
• No known TB exposure
• CXR normal, no symptoms of TB, no past medical
  history, but c/o sore throat x 3 days referred
  to outside clinic for sore throat
• INH started 12/16/05

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Case 1

• Mother returns on Jan 13, 2006 for refill
• States patient has decreased appetite and feeling
  tired since November 2005 (before starting INH,
  but was not mentioned on INH start visit)
• Also learned that patient not been in school
  since January 2005
• Mother given INH refill but advised to bring
  patient in for evaluation ASAP
• Home visit by Spanish-speaking community worker
  later that day to investigate social situation
  and to reiterate need to bring patient in

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Case 1

• 1/30/06 patient still had not come in for
  evaluation referred to field nursing
• Field PHN finds that patient is still taking INH,
  c/o itching after taking medicine and vomited x1
  two days ago PHN advised mother to stop giving
  medication and to bring patient to clinic the
  next day
• No show to clinic
• 2/14/06 TB PHN spoke to patients mother, who
  now says patient looks pale yellow advised to
  bring patient in immediately

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Case 1Drug-Induced Liver Toxicity (DILI)

• 2/17/06 patient finally comes in, grossly
  icteric
• C/o fatigue and vomiting x 2 weeks, weight loss
  of 5 lbs
• Mother continued giving patient medication until
  4 days prior, despite advice to d/c meds over 2
  weeks previously

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Case 1 DILI

• Sent to hospital admission LFTs AST 3750, ALT
  2876, T.bili 26, INR 2.47
• Work-up done for other causes negative hepatitis
  panel, CMV neg, EBV IgG /IgM neg
• Patient denied taking Tylenol, EtOH, illicit
  drugs or herbal meds
• Patient stayed in hospital 1 month d/c labs AST
  94, ALT 111, T. bili 30, INR 1.13

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Isoniazid-Induced HepatitisComparison of Old
and New Data
N13,838 Hepatitis Age
(yr) Cases/1000 lt20 0.0 20-34
3.0 35-49 12.0 50-64 23.0 gt65 8.0
N11,141 Hepatitis Age
(yr) Cases/1000 0-14 0.0 15-34
0.8 35-64 2.1 65 2.8
Nolan CL et al. JAMA 19992811014
Kopanoff et al. Am Rev Resp Dis 1976117991
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Case 1 DILILessons Learned

• Parent of a 14 y.o. who has not been in school
  for one year is not a responsible adult
• No longer give INH refills to parents if any
  symptoms reported
• Learned to follow-up on no-shows to clinic more
  aggressively
• INH toxicity to this level is extremely rare, but
  can affect anybody (even adolescents with no
  identified risk factors), and is more common when
  INH continues to be administered after symptoms
  develop

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LTBI TreatmentRisk/Benefit Analysis

• Will offer treatment to any patients meeting
  CDCs criteria for treatment
• If patient at increased risk for DILI (advanced
  age or underlying liver disease), will counsel
  patient about risk for TB and risk of DILI and
  allow them to make the choice
• If patient at increased risk for DILI, will
  follow more closely
• If patient opts not to Rx LTBI, will educate the
  pt to self-monitor for symptoms of TB

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Case 2 To Treat or Not to Treat?

• 65 y.o. Cambodian man, referred for TB screening
  5/06 due to contact with patient with smear
  pulmonary TB disease (index died of TB)
• Patient in country for 25 years, cant remember
  any prior TST
• Hx of Hep C (on treatment) and partial lung
  resection in Cambodia in 60s
• TST 44 mm, c/o loss of appetite
• CXR reveals fibrolinear densities LLL,
  post-traumatic deformities left ribs,
  fibrocalcific density in L apex

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Case 1 To Treat or Not to Treat?

• Sputa x 3 obtained one showed rare AFB, but all
  specimens culture negative except for one with M.
  chelonae
• 7/06 Pt decides to defer LTBI treatment until
  HCV therapy finished

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Case 1

• Pt returns 2/07 Liver PMD advises Rx LTBI with
  INH since pt likely transplant candidate
• Patient also admits to cough x 3 weeks w/u for
  TB disease repeated
• Admitted with variceal bleed late 2/07
• Sputum cultures negative final 4/07, so INH
  started
• Baseline LFTs AST 51, ALT 13, T. bili 1.6, Alb
  2.7

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Case 1

• LFTs after one month AST 82, ALT 22, T. bili
  1.4 so far, so good!
• Near end of second month patient c/o bloating
  and increased fatigue, INH held pending LFTs
• LFTs AST 114, ALT 36, T. bili 2.1
• Patient admitted with new-onset ascites 5 days
  later
• Although no evidence of DILI on admission, pts
  disease obviously progressing and risk/benefit
  ratio thought to be too high, so INH stopped

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Case 3

• 71 y.o Hispanic male with c/o lower abdo pain x
  2-3 months admitted to hospital 2/4/09 because of
  hypercalcemia
• PMHx of Crohns disease, anemia, chronic kidney
  disease (CKD), and hx TST
• CXR read as no active lung lesion, but CT chest
  showed patchy inifltrate versus scarring right
  upper lobe, ?lytic lesions in thoracic vertebra
• Bronchoscopy done and specimen sent for AFB
  smear and culture negative

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Case 3

• Pt eventually diagnosed with multiple myeloma,
  and chemotherapy started
• Also diagnosed with liver disease, presumably due
  to prior EtOH abuse
• INH started by PMD, but stopped after one month
  due to increasing LFTs (no details available)
• Initial chemotherapy completed 6/09

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Case 3

• Patient readmitted to the hospital 11/3/09 with
  several month history of cough and 1 week history
  of altered mental status
• Admission CXR showed RUL infiltrate
• Ammonia level elevated, new onset ascites
• Sputa checked and now 3-4 AFB
• TB meds started

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Case 3

• Patient continued to have alteration of mental
  status, progressive elevation of bilirubin
• CKD worsened after trial of aminoglycosides for
  TB
• Eventually developed multi-organ failure and
  expired 12/6/09

Important points to remember TB can kill people,
and INH does help to prevent TB disease!
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TREATMENT OF LATENT TB INFECTIONHow long is
enough?
Calculated curve
5 4 3 2 1 0
Calculated values

• Lower TB rates among those who took 0-9 mo
• No extra increase among those who took gt9 mo

Observed values
Cases per 100
0 6 12 18 24
Months of Treatment
Comstock Int J Tuberc Lung Dis. 199910847