-
At risk for developing TB dz | Recent exposure to person w/ TB dz, or clinical condition/other factor assoc w/ increased risk of progression from LTBI to TB dz
Avoid routine testing of persons at low risk,1 but do test persons w/ any of the following risk factors for TB infxn (unless written documentation of previous positive TST/IGRA result): - Foreign-born person from, or recent travel to, high-prevalence area2
- Close contact w/ someone w/ infectious TB dz
- Resident/employee of high-risk congregate setting in places at risk for TB transmission3
- Immunosuppression4
- Medical conditions assoc w/ risk of progressing to TB dz if infected5
- Chest radiographs w/ fibrotic changes suggesting inactive or past TB
- S/sx of TB dz
- Children at risk6
Either IGRA or TST may be used w/o preference, w/ the following considerations: - IGRAs preferred if poor rate of return likely for TST testing (eg, homeless); IGRA preferred for persons who have received BCG vaccine; TST preferred for children <5 yo; TST safe and reliable during pregnancy7
- Administer TST (Mantoux tuberculin skin test) by intradermal injection of 0.1 mL of 5 TU PPD, read w/in 48h-72h8 and interpret based on mm of induration, pt’s risk of acquiring TB infxn, or risk of progression to dz if infected;9 interpret TST test rxns based on risk stratification regardless of BCG vaccination hx10
- If individual may be tested periodically (eg, HCW), perform “2-step method”11 at time of initial TST
- Draw whole blood for IGRAs (QTF-GIT, T-SPOT TB test)12,13
- Routine testing w/ both TST and IGRA not recommended, although both may be useful in some situations14,15
- Test HIV-infected persons for LTBI as soon as HIV status becomes known; consider annual testing if initial TST/IGRA negative and at risk for exposure to Mtb16
- For contacts17 of person w/ infectious TB dz w/ initial negative TST/IGRA, retest18 8-10wk after exposure has ended; also obtain CXR if <5 yo or immunosuppressed (eg, HIV-infected)
If positive TST/IGRA result: - Perform PE, obtain medical hx19
- Perform CXR; also warranted if high-risk contact w/o positive test result20
- Sputum exam for AFB smear and cx indicated if positive test result and either abnl CXR or presence of resp sx (even if CXR negative)
Differentiation btwn LTBI and TB dz: Footnotes 1 Routine TB testing not recommended. CDC and ATS do not recommend a testing approach that is independent of risk assessment. CDC discourages use of dx test for LTBI in individuals/populations at low risk for infxn w/ Mtb. Despite CDC recommendations, testing sometimes done to meet administrative/legal requirements for groups not considered at increased risk (eg, entrance requirements for certain schools and workplaces).
2 Non-U.S.-born pts w/ TB are most commonly from: Mexico, the Philippines, Vietnam, India, China, Haiti, and Guatemala; or other countries w/ high rates of TB. People born in Canada, Australia, New Zealand, Western or Northern Europe not considered high risk for TB unless they spent time in a country w/ a high rate of TB.
3 Congregate settings at high risk for TB transmission include: correctional facility, long term care facility, hospital, homeless shelter, residential home for HIV pts.
4 Examples of immunosuppressed pts:
• HIV
• Organ txp recipient
• Secondary to use of prednisone (equivalent of ≥15 mg/day for ≥1mo) or other immunosuppressive medication such as TNF-α antagonist
• Substance abuse (eg, smoking, alcohol abuse, or injection drug use)
5 Conditions assoc w/ increased risk of progression to TB dz: DM, silicosis, use of TNF-α inhibitors, head/neck CA, Hodgkin dz, leukemia, ESRD, substance use (ie, injection drug use), intestinal bypass/gastrectomy, chronic malabsorption syndrome, low body wt (≤10% below ideal).
6 Children, esp <5 yo, have higher risk of developing TB dz once infected—testing for TB infxn in children important if they are in one of the risk groups noted above.
7 Test pregnant women only if specific risk factors present for acquiring LTBI or for progression of LTBI to TB dz; if TST or IGRA positive, obtain CXR using proper shielding.
8 Training is essential for HCW to administer/interpret TST—should not be read by pt, family; interpretation of TST same for person w/ BCG vaccination since cross-reactivity wanes w/ time. A TST not measured and recorded in mm of induration must be repeated. Don't perform if prior positive TST or hx of tx for TB dz. CDC. TST Administration and Measurement, excerpted from CDC LTBI app: Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. PDF
9 TST rxn ≥5 mm induration positive if:
• HIV-infected
• Recent contact of person w/ infectious TB dz
• Fibrotic changes on CXR consistent w/ prior TB
• Pts w/ organ txps, other immunosuppression (incl prednisone ≥15 mg/day for ≥1mo, or TNF-α antagonists)
TST rxn ≥10 mm induration positive if:
• Recent arrival (w/in 5y) to U.S. from high-prevalence area
• Injection drug user
• Resident/employee or high-risk congregate settings (eg, correctional facilities, long-term care facilities, hospitals and other healthcare facilities, residential facilities for HIV/AIDS pts; homeless shelters)
• Mycobacteriology lab personnel
• Persons w/ clinical conditions that increase risk for progression to TB dz
• Children <5 yo
• Infants, children, adolescents exposed to adults in high-risk categories
TST rxn ≥15 mm induration positive if:
• No known risk factors for TB
10 Where TB is common, BCG used to protect infants, young children from miliary TB and TB meningitis (WHO recommendation); BCG not generally recommended in US. TST reactivity caused by BCG wanes w/ time, although periodic testing may prolong (boost) reactivity; persons w/ hx of BCG vaccination can be tested, and treated for LTBI if they react to TST. IGRA uses Mtb-specific Ag which do not x-react w/ BCG, therefore no false-positive rxn in BCG recipient.
11 Some people infected w/ Mtb may have negative TST if many yrs passed since infected and may have subsequent positive TST because initial test stimulated ability to react (“booster phenomenon”) or it may be misinterpreted as skin test conversion. Interpret results as follows:
• If 1st TST positive in 2-step testing: Consider infected and evaluate/treat accordingly
• If 1st TST negative: Repeat in 1-3wk
• If 2nd TST test positive: Consider infected and evaluate/treat accordingly
• If both TST tests negative: Consider uninfected, classify TST as negative at baseline.
Note: IGRA testing does not cause booster phenomenon, and thus no need for 2nd test.
12 Advantages of IGRAs:
• Require single visit
• No booster phenomenon
• Results not affected by HCW perception/bias
• Unaffected by BCG and most environmental Mycobacteria
• Results can be available w/in 24h
Limitations of IGRAs:
• Blood sample must be processed w/in 8h-30h of draw
• Limited data on children <5 yo, persons recently exposed to TB, immunocompromised persons, or those who will be tested repeatedly (serial testing)
13 Interpretation of IGRAs based on the amount of interferon-γ released (QFT) or on the number of cells that release interferon-γ (T-SPOT TB test). Labs should provide both qualitative and quantitative results:
• Qualitative results reported as positive, negative, indeterminate, or borderline
• Quantitative results reported as numerical values that include a response to the TB antigen and 2 controls (nil and mitogen). Quantitative results may be useful for clinical decision-making in individual cases, in combination w/ risk factors.
14 Results from both TST and IGRA testing may be useful in the following situations:
When initial test is negative and:
• Risk for infxn, progression to dz, and/or a poor outcome is high (eg, HIV-infected persons or children <5 yo exposed to person w/ infectious TB)
• There is clinical suspicion for TB dz (eg, s/sx and/or radiographic evidence suggestive of TB dz) and confirmation of Mtb infxn desired
• Taking a positive result from a 2nd test as evidence of infxn increases detection sensitivity
When the initial test is positive and:
• Additional evidence of infxn is required to encourage acceptance and adherence to tx (eg, foreign-born HCWs who believe their positive TST is due to BCG)
• Person has low risk of both infxn and progression to TB dz. Requiring a positive result from the 2nd test as evidence of infxn increases likelihood that the test reflects infxn. An alternative is to assume, w/o additional testing, that initial test is false-positive or the risk for dz does not warrant additional evaluation/tx, regardless of test results.
In addition, repeating an IGRA or performing a TST might be useful when the initial IGRA is indeterminate, borderline, or invalid and a reason for testing persists.
15 Multiple negative results from any combo of TST/IGRA tests cannot exclude Mtb infxn. Minimize unnecessary and misleading testing of persons at low risk; base selection of most suitable test or combo of tests on reasons/context for testing, test availability, overall cost of testing.
16 Risk of progression from LTBI to TB dz is 10x greater in HIV(+) pts (7%-10%/yr) vs HIV(-) pts (10%/lifetime); risk reduced w/ ART but still higher than in HIV(-) persons w/ LTBI; negative TST/IGRA does not r/o LTBI as ability to react to TB tests may be compromised. After initiation of ART, repeat testing for LTBI if previous TST/IGRA negative since immune response may be restored; anergy testing not recommended—not demonstrated to be useful.
17 Contacts are those w/ recent exposure to a person w/ known/suspected TB dz (eg, pulmonary/laryngeal TB w/ positive sputum smear).
18 Second test needed to determine if infxn occurred but was too recent to detect w/ initial test; children <5 yo and immunosuppressed contacts (eg, HIV) w/ negative initial TST/IGRA should have CXR; if CXR normal, start LTBI tx and repeat TST/IGRA 8-10wk after contact has ended; if repeat TST/IGRA positive, continue tx; if repeat TST/IGRA negative, tx can usually be discontinued, although for some high-risk contacts, a full course of LTBI may be warranted even if TST/IGRA negative—consult local TB control program; for repeat testing the same type of test (TST or IGRA) should be used; testing of adults in close social contact w/ infected child may be warranted—consult local TB control program.
19 Physical exam/hx includes info about previous positive tests for TB infxn, previous tx for LTBI or TB dz, and risk assessment for liver dz; written documentation for previous positive TST/IGRA result required, verbal hx not sufficient.
20 CXR indications/considerations:
• Positive TST/IGRA
• Absence of positive test for TB infxn when person is close contact of an infectious TB pt and tx for LTBI will be started (eg, “window prophylaxis” in a young child or immunocompromised person)
• Children <5 yo should have PA/lateral views, all others at least PA views
• Other views/additional studies should be based on HCP judgment
• Persons w/ nodular or fibrotic lesions consistent w/ old TB are high priority for tx of LTBI after TB dz excluded
• Persons w/ fully calcified, discrete granulomas, nodules, hilar lymph nodes, apical pleural capping don't have an increased risk for progression to TB dz, thus decision to treat is same as for person w/ normal CXR.
21 If pt refuses/unable to receive LTBI tx, f/u TST, IGRA, serial CXR unnecessary; educate pt about s/sx of TB dz.
22 Sx may include ≥1 of: fever, cough, chest pain, wt loss, night sweats, hemoptysis, fatigue, decreased appetite.
23 CXR may be normal in persons w/ advanced immunosuppression or extrapulmonary dz.
24 Smear/cx may be negative if extrapulmonary dz or minimal/early pulmonary dz. -
LTBI diagnosed (and TB dz R/O), awaiting tx
Adult/Adolescent, nonpregnant Choose LTBI tx regimen based on drug susceptibility results of presumed source case (if known), coexisting medical illness, and potential for drug-drug interactions: Consider shorter LTBI tx regimens as they result in higher completion rates Consider DOT esp for intermittent dosing; assess barriers for pt adherence; periodically assess pt progress to ensure safe/efficacious tx; provide pt ed8 - Use DOT in pts on intermittent dosing regimen, incl pts at esp high risk for TB dz who are suspected of nonadherence
- If pt exposed to known MDR-TB, consult expert in tx of MDR-TB
- Baseline/periodic lab testing not routine, unless high-risk pt or if sx of hepatitis develop on tx5,9
- Address barriers10-12 to pt adherence; recognize and address episodes of nonadherence ASAP. Adopt techniques for improvement13
- Clinical monitoring: Arrange for monthly pt visit; assess for compliance, s/sx of TB dz, and/or adverse effects, esp hepatitis (jaundice, loss of appetite, fatigue, and/or muscle/joint aches)
- If pt experiences possible AE, advise stopping meds immediately and contacting HCP; do not wait until next clinic visit
- At end of tx: Re-educate pt about s/sx of TB dz, provide tx documentation14
- Don’t re-treat TST/IGRA-positive contacts of person w/ known/suspected infectious TB (eg, pulmonary or laryngeal TB w/ (+) sputum smear) who can provide written documentation of prior adequate tx for LTBI; however, re-tx may be indicated for persons at high risk of becoming infected and progressing to TB dz (eg, immunosuppressed)
Footnotes 1 RPT and RIF may cause drug-drug interactions, incl reduced concentrations of methadone, warfarin, hormonal contraceptives, phenytoin. Advise women using hormonal contraceptives to consider alternative method (eg, barrier method).
2 RIF, an equal alternative to INH as tx for latent TB infxn, is the primary option for pts exposed to INH-resistant (rifamycin-susceptible) Mtb. Hepatotoxicity w/ transient asymptomatic hyperbilirubinemia may occur in 0.6% of pts taking RIF, more common if combined w/ INH. Cutaneous rxns, such as pruritus (w/ or w/o rash) may occur in 0.6% of pts taking RIF—generally self-limited, may not be true hypersensitivity, continued tx may be possible. Rarely, rifamycins may be assoc w/ hypersensitivity rxns, incl hypotension, nephritis or thrombocytopenia, and manifested by sx such as fever, HA, dizziness/lightheadedness, musculoskeletal pain, petechiae and pruritic. GI sx such as nausea, anorexia, abd pain rarely severe enough to d/c tx. Orange discoloration of body fluids common and harmless, but warn pts that soft contact lenses and dentures may be permanently stained.
3 RPT wt-based dosing:
• 10.0-14.0 kg: 300 mg
• 14.1-25.0 kg: 450 mg
• 25.1-32.0 kg: 600 mg
• 32.1-49.9 kg: 750 mg
• ≥50.0 kg: 900 mg max
RPT formulated as 150-mg tablets in blister packs that should be kept sealed until usage.
4 3HP (INH + RPT weekly x3mo)
• Consider 3HP as it results in higher tx completion rates vs INH 9-mo regimen, w/ equal safety and effectiveness.
• Approx 4% of all pts using 3HP experience flu-like or other systemic drug rxns, w/ fever, HA, dizziness, nausea, muscle/bone pain, rash, itching, red eyes, etc.
• Approx 5% of pts D/C 3HP d/t ADRS, incl systemic drug rxns, which typically occur after first 3-4 doses, and begin approx 4h after ingestion.
• Inform pt about possible adverse effects and instruct to seek medical attn when sx of possible ADR first appear; particularly drug hypersensitivity rxns, rash, hypotension, or thrombocytopenia.
• If sx suggestive of systemic drug rxn occur, pts should stop 3HP while cause is determined. Sx usually resolve w/o tx w/in 24h.
• Obtain baseline LFTs (at least AST) in pts w/ the following: liver disorders, HIV infxn, postpartum (<3mo after delivery), regular alcohol use, injection drug use, or use of meds w/ possible interactions. D/C 3HP if AST ≥5x ULN w/ no sx of ≥3x ULN w/ sx.
• Eval pts on 3HP regimens monthly (in person/by phone) to assess adherence and adverse effects.
• Monitor pts when 3HP prescribed w/ interacting meds (eg, methadone, warfarin).
• RPT can reduce effectiveness of hormonal contraceptives; advise women who use hormonal birth control to add/switch to barrier methods. Women should inform HCP if they decided to try to become pregnant or become pregnant during 3HP tx.
• Encourage pts on 3HP SAT to record med intake and report deviations from prescribed regimen.
5 INH-only regimens:
• 9-mo INH regimen preferred over 6-mo regimen due to higher efficacy. However, tx for 6 vs 9mo may be more cost-effective and result in greater adherence. If 6-mo regimen implemented, make every effort to ensure pt adheres to tx for minimum of 6mo.
• Asymptomatic elevation of serum liver enzymes occurs in 10%-20% of pts taking INH; this usually returns to normal even when tx continued. Withhold INH if pt’s transaminase level >3x ULN if assoc w/ sx, or >5x ULN if no sx. Clinical hepatitis occurs in 0.1% of pts taking INH, more common when combined w/ other hepatotoxic agents. Factors that increase liver enzymes or severity of hepatitis incl daily alcohol consumption, underlying liver dz or risks for liver dz, concurrent use of other meds metabolized in liver. Symptomatic hepatitis rare in pts <20 yo, but severe/fatal cases have been reported: Monitor w/ same precautions as older pts if at risk for liver dz.
• Peripheral neuropathy occurs in <0.2% of pts taking INH at conventional doses; more likely in presence of other conditions assoc w/ neuropathy (eg, DM, HIV, renal failure, alcoholism). Pyridoxine (vitamin B6) is recommended only in such conditions (and in breastfeeding women).
• Lactation: INH can be used in breastfeeding women. Pyridoxine (vitamin B6) 10-15 mg/day recommended for nursing women and for breastfed infants. However, amount of INH in breast milk is inadequate for tx of LTBI in infants.
6 INH 15 mg/kg rounded up to the nearest 50 or 100 mg; INH formulated as 100-mg and 300-mg tablets.
7 Choose DOT vs self-administered tx (SAT) based on local practice, considerations such as individual pt factors, preferences, and risk for progression to severe forms of TB dz.
8 Pt ed:
• Explain dz process, rationale for meds in absence of sx, CXR abnormalities.
• Discuss possible side effects of LTBI meds incl fever, unexplained anorexia, dark urine (color of coffee/cola), icterus, rash, persistent paresthesia of hands and feet, persistent fatigue or weakness lasting ≥3 days, abd tenderness (esp RUQ), abnl bruising/bleeding, arthralgia, N/V.
• Discuss mgmt of common side effects and need to report to HCP.
• Instruct pts, at the start of tx and each monthly visit, to stop tx and seek medical attention immediately if sx of hepatitis develop and to not wait until the next clinic visit to stop tx.
9 Obtain baseline AST, ALT, bilirubin in pts w/ liver disorders, hx of liver dz (eg, hepatitis B or C, alcoholic hepatitis, or cirrhosis), regular alcohol use, risks for chronic liver dz, HIV infxn, pregnancy or immediate postpartum period (ie, w/in 3mo of delivery). Also consider baseline testing on an individual basis, esp for pts taking other meds for chronic conditions. Routine, periodic retesting recommended for persons w/ abnl initial tests and other persons at risk for hepatic dz; lab testing recommended any time pt develops sx of hepatitis (eg, fatigue, weakness, malaise, anorexia, N/V, abd pain, pale stools, dark urine, chills) or has jaundice. Instruct pt at every visit to stop tx and seek immediate medical attention if sx of hepatitis develop and not wait until next clinic visit to stop tx. Withhold meds if transaminase level exceeds >3x ULN if assoc w/ sx or >5x ULN if no sx.
10 Office-related barriers include:
• Long waiting time for appointment/referrals
• Long waiting time in provider’s office
• Inconvenient office hrs
• Complicated telephone system (not user-friendly)
11 Pt-related barriers include:
• Misinformation/confusion about certain issues, such as: meaning of the TST results (eg, a positive TST is thought to be normal/common in all foreign-born persons); differences btwn injections, vaccines, and TST; the words “positive” and “negative” as they relate to test results; modes of TB transmission/prevention; exposure vs becoming infected; safety of family/friends around LTBI pt
• Residential instability
• Lack of financial resources
• Poor access to health care
• Stigma associated w/ TB
• Coexisting medical conditions
• Culture and language
• Religious practices (eg, fasting from food)
12 Tx barriers include:
• Complexity and duration of tx
• Med side effects
• Obtaining refills
• Frequency of office visits
• Cost, incl insurance copayments
13 Techniques to improve adherence:
• Collaborate w/ local health dept to provide tx
• DOT, if pt is high risk (eg, HIV-infected, young child, or TB contact)
• Provide DOT w/ 12-dose and other intermittent regimens
• Case mgmt to coordinate care and services
• Rewards for adherence (incentives) (eg, grocery store/restaurant vouchers, nutritional supplements, cell phone minutes, movie tickets)
• Enablers to overcome barriers such as free van transportation, bus tickets
• Provide pt ed, instruction in pt’s primary language at every visit
• Ensure confidentiality
• Suggest/provide pt reminders such as pill box, calendar, or timer
14 Advise pt to contact HCP if s/sx of TB dz develop; provide documentation that includes TST/IGRA results, CXR results, name and dosages of meds and duration of tx. Instruct pt to present this document whenever future TB testing required. Serial/repeat CXR not indicated regardless of tx duration unless pt develops s/sx of TB dz. Choose LTBI tx regimen based on drug susceptibility results of presumed source case (if known), coexisting medical illness, and potential for drug-drug interactions; 1 if test for TB infxn negative, consider tx if HIV-infected pt had recent exposure to infectious TB Consider DOT esp for intermittent dosing; assess barriers for pt adherence; periodically assess pt progress to ensure safe/efficacious tx; provide pt ed11 - Use DOT in pts on intermittent dosing regimen, incl pts at esp high risk for TB dz who might be at risk of nonadherence
- If pt exposed to known MDR-TB, consult expert in tx of MDR-TB
- Obtain baseline/periodic liver tests12 in HIV-positive pts
- Address barriers13-15 to pt adherence; recognize and address episodes of nonadherence ASAP. Adopt techniques for improvement16
- Clinical monitoring: Arrange for monthly pt visit; assess for compliance, s/sx of TB dz, and/or adverse effects, esp hepatitis (jaundice, loss of appetite, fatigue, and/or muscle/joint aches)
- If pt experiences possible AE, advise stopping meds immediately and contacting HCP; do not wait until next clinic visit
- At end of tx: Re-educate pt about s/sx of TB dz, provide tx documentation17
- Don’t re-treat TST/IGRA-positive contacts of person w/ known/suspected infectious TB (eg, pulmonary or laryngeal TB w/ (+) sputum smear) who can provide written documentation of prior adequate tx for LTBI; however, re-tx may be indicated for persons at high risk of becoming infected and progressing to TB dz (eg, immunosuppressed)
Footnotes 1 See U.S. Department of Health and Human Services published AIDS info Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents for the most up-to-date info on drug-drug interactions and how they influence tx of latent TB infxn. Accessed online 5/8/18
2 RPT and RIF may cause drug-drug interactions, incl reduced concentrations of methadone, warfarin, hormonal contraceptives, phenytoin. Advise women using hormonal contraceptives to consider alternative method (eg, barrier method).
3 RPT wt-based dosing:
• 10.0-14.0 kg: 300 mg
• 14.1-25.0 kg: 450 mg
• 25.1-32.0 kg: 600 mg
• 32.1-49.9 kg: 750 mg
• ≥50.0 kg: 900 mg max
RPT formulated as 150-mg tablets in blister packs that should be kept sealed until usage.
4 3HP (INH + RPT weekly x3mo)
• 3-HP should ONLY be used in HIV-positive pts who are receiving ART w/ acceptable interactions btwn RPT and ART meds.
• Consider 3HP as it results in higher tx completion rates vs INH 9-mo regimen, w/ equal safety and effectiveness.
• Approx 4% of all pts using 3HP experience flu-like or other systemic drug rxns, w/ fever, HA, dizziness, nausea, muscle/bone pain, rash, itching, red eyes, etc.
• Approx 5% of pts D/C 3HP d/t ADRS, incl systemic drug rxns, which typically occur after first 3-4 doses, and begin approx 4h after ingestion.
• Inform pt about possible adverse effects and instruct to seek medical attn when sx of possible ADR first appear; particularly drug hypersensitivity rxns, rash, hypotension, or thrombocytopenia.
• If sx suggestive of systemic drug rxn occur, pts should stop 3HP while cause is determined. Sx usually resolve w/o tx w/in 24h.
• Obtain baseline LFTs (at least AST) in pts w/ the following: liver disorders, HIV infxn, postpartum (<3mo after delivery), regular alcohol use, injection drug use, or use of meds w/ possible interactions. D/C 3HP if AST ≥5x ULN w/ no sx of ≥3x ULN w/ sx.
• Eval pts on 3HP regimens monthly (in person/by phone) to assess adherence and adverse effects.
• Monitor pts when 3HP prescribed w/ interacting meds (eg, methadone, warfarin).
• RPT can reduce effectiveness of hormonal contraceptives; advise women who use hormonal birth control to add/switch to barrier methods. Women should inform HCP if they decided to try to become pregnant or become pregnant during 3HP tx.
• Encourage pts on 3HP SAT to record med intake and report deviations from prescribed regimen.
5 Recent research demonstrates no significant drug interactions between once-weekly RPT and either efavirenz or raltegravir in pts w/ HIV infxn who are treated w/ these antiretroviral meds.
6 INH-only regimens:
• Asymptomatic elevation of serum liver enzymes occurs in 10%-20% of pts taking INH; this usually returns to normal even when tx continued. Withhold INH if pt’s transaminase level >3x ULN if assoc w/ sx, or >5x ULN if no sx. Clinical hepatitis occurs in 0.1% of pts taking INH, more common when combined w/ other hepatotoxic agents. Factors that increase liver enzymes or severity of hepatitis incl daily alcohol consumption, underlying liver dz or risks for liver dz, concurrent use of other meds metabolized in liver. Symptomatic hepatitis rare in pts <20 yo, but severe/fatal cases have been reported: Monitor w/ same precautions as older pts if at risk for liver dz.
• Peripheral neuropathy occurs in <0.2% of pts taking INH at conventional doses; more likely in presence of other conditions assoc w/ neuropathy (eg, DM, HIV, renal failure, alcoholism). Pyridoxine (vitamin B6) is recommended only in such conditions (and in breastfeeding women).
• Lactation: INH can be used in breastfeeding women. Pyridoxine (vitamin B6) 10-15 mg/day recommended for nursing women and for breastfed infants. However, amount of INH in breast milk is inadequate for tx of LTBI in infants.
7 Rifabutin dose may need to be adjusted when there is concomitant use of protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Nahid P, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016. Oct 1;63(7):e147-e195. PDF
8 INH 15 mg/kg rounded up to the nearest 50 or 100 mg; INH formulated as 100-mg and 300-mg tablets.
9 Choose DOT vs self-administered tx (SAT) based on local practice, considerations such as individual pt factors, preferences, and risk for progression to severe forms of TB dz.
10 Intermittent regimens must be provided via DOT (ie, HCW observes med ingestion); HIV-infected persons receiving ART should be treated w/ 9-mo regimen of INH.
11 Pt ed:
• Explain dz process, rationale for meds in absence of sx, CXR abnormalities.
• Discuss possible side effects of LTBI meds incl fever, unexplained anorexia, dark urine (color of coffee/cola), icterus, rash, persistent paresthesia of hands and feet, persistent fatigue or weakness lasting ≥3 days, abd tenderness (esp RUQ), abnl bruising/bleeding, arthralgia, N/V.
• Discuss mgmt of common side effects and need to report to HCP.
• Instruct pts, at the start of tx and each monthly visit, to stop tx and seek medical attention immediately if sx of hepatitis develop and to not wait until the next clinic visit to stop tx.
12 Obtain baseline AST, ALT, bilirubin in pts w/ liver disorders, hx of liver dz (eg, hepatitis B or C, alcoholic hepatitis, or cirrhosis), regular alcohol use, risks for chronic liver dz, HIV infxn, pregnancy or immediate postpartum period (ie, w/in 3mo of delivery). Also consider baseline testing on an individual basis, esp for pts taking other meds for chronic conditions. Routine, periodic retesting recommended for persons w/ abnl initial tests and other persons at risk for hepatic dz; lab testing recommended any time pt develops sx of hepatitis (eg, fatigue, weakness, malaise, anorexia, N/V, abd pain, pale stools, dark urine, chills) or has jaundice. Instruct pt at every visit to stop tx and seek immediate medical attention if sx of hepatitis develop and not wait until next clinic visit to stop tx. Withhold meds if transaminase level exceeds >3x ULN if assoc w/ sx or >5x ULN if no sx.
13 Office-related barriers include:
• Long waiting time for appointment/referrals
• Long waiting time in provider’s office
• Inconvenient office hrs
• Complicated telephone system (not user-friendly)
14 Pt-related barriers include:
• Misinformation/confusion about certain issues, such as: meaning of the TST results (eg, a positive TST is thought to be normal/common in all foreign-born persons); differences btwn injections, vaccines, and TST; the words “positive” and “negative” as they relate to test results; modes of TB transmission/prevention; exposure vs becoming infected; safety of family/friends around LTBI pt
• Residential instability
• Lack of financial resources
• Poor access to health care
• Stigma associated w/ TB
• Coexisting medical conditions
• Culture and language
• Religious practices (eg, fasting from food)
15 Tx barriers include:
• Complexity and duration of tx
• Med side effects
• Obtaining refills
• Frequency of office visits
• Cost, incl insurance copayments
16 Techniques to improve adherence:
• Collaborate w/ local health dept to provide tx
• DOT, if pt is high risk (eg, HIV-infected, young child, or TB contact)
• Provide DOT w/ 12-dose and other intermittent regimens
• Case mgmt to coordinate care and services
• Rewards for adherence, incentives (eg, grocery store/restaurant vouchers, nutritional supplements, cell phone minutes, movie tickets)
• Enablers to overcome barriers such as free van transportation, bus tickets
• Provide pt ed, instruction in pt’s primary language at every visit
• Ensure confidentiality
• Suggest/provide pt reminders such as pill box, calendar, or timer
17 Advise pt to contact HCP if s/sx of TB dz develop; provide documentation that includes TST/IGRA results, CXR results, name and dosages of meds and duration of tx. Instruct pt to present this document whenever future TB testing required. Serial/repeat CXR not indicated regardless of tx duration unless pt develops s/sx of TB dz. Choose LTBI tx regimen based on drug susceptibility results of presumed source case (if known), coexisting medical illness, and potential for drug-drug interactions; if test for TB infxn negative, still consider tx if HIV-infected pt had recent exposure to infectious TB Consider shorter LTBI tx regimens as they result in higher completion rates w/ fewer adverse events Consider DOT esp for intermittent dosing; assess barriers for pt adherence; periodically assess pt progress to ensure safe/efficacious tx; provide pt ed8 - Use DOT in pts on intermittent dosing regimen, incl pts at esp high risk for TB dz who might be at risk of nonadherence
- If pt exposed to known MDR-TB, consult expert in tx of MDR-TB
- Obtain baseline/periodic liver tests9 in HIV-positive pts
- Address barriers10-12 to pt adherence; recognize and address episodes of nonadherence ASAP. Adopt techniques for improvement13
- Clinical monitoring: Arrange for monthly pt visit; assess for compliance, s/sx of TB dz, and/or adverse effects, esp hepatitis (jaundice, loss of appetite, fatigue, and/or muscle/joint aches)
- If pt experiences possible AE, advise stopping meds immediately and contacting HCP; don't wait until next clinic visit
- At end of tx: Re-educate pt about s/sx of TB dz, provide tx documentation14
- Don’t re-treat TST/IGRA-positive contacts of person w/ known/suspected infectious TB (eg, pulmonary or laryngeal TB w/ (+) sputum smear) who can provide written documentation of prior adequate tx for LTBI; however, re-tx may be indicated for persons at high risk of becoming infected and progressing to TB dz (eg, immunosuppressed)
Footnotes 1 RPT and RIF may cause drug-drug interactions, incl reduced concentrations of methadone, warfarin, hormonal contraceptives, phenytoin. Advise women using hormonal contraceptives to consider alternative method (eg, barrier method).
2 RIF, an equal alternative to INH as a treatment for latent TB infxn, is the primary option for pts exposed to INH-resistant (rifamycin-susceptible) Mtb. Hepatotoxicity w/ transient asymptomatic hyperbilirubinemia may occur in 0.6% of pts taking RIF, more common if combined w/ INH. Cutaneous rxns, such as pruritus (w/ or w/o rash) may occur in 0.6% of pts taking RIF—generally self-limited, may not be true hypersensitivity, continued tx may be possible. Rarely, rifamycins may be assoc w/ hypersensitivity rxns, incl hypotension, nephritis or thrombocytopenia, and manifested by sx such as fever, HA, dizziness/lightheadedness, musculoskeletal pain, petechiae and pruritic. GI sx such as nausea, anorexia, abd pain rarely severe enough to d/c tx. Orange discoloration of body fluids common and harmless, but warn pts that soft contact lenses and dentures may be permanently stained.
3 RPT wt-based dosing:
• 10.0-14.0 kg: 300 mg
• 14.1-25.0 kg: 450 mg
• 25.1-32.0 kg: 600 mg
• 32.1-49.9 kg: 750 mg
• ≥50.0 kg: 900 mg max
RPT formulated as 150-mg tablets in blister packs that should be kept sealed until usage.
4 3HP (INH + RPT weekly x3mo)
• Consider 3HP as it results in higher tx completion rates vs INH 9-mo regimen, w/ equal safety and effectiveness.
• Approx 4% of all pts using 3HP experience flu-like or other systemic drug rxns, w/ fever, HA, dizziness, nausea, muscle/bone pain, rash, itching, red eyes, etc.
• Approx 5% of pts D/C 3HP d/t ADRS, incl systemic drug rxns, which typically occur after first 3-4 doses, and begin approx 4h after ingestion.
• Inform pt about possible adverse effects and instruct to seek medical attn when sx of possible ADR first appear; particularly drug hypersensitivity rxns, rash, hypotension, or thrombocytopenia.
• If sx suggestive of systemic drug rxn occur, pts should stop 3HP while cause is determined. Sx usually resolve w/o tx w/in 24h.
• Obtain baseline LFTs (at least AST) in pts w/ the following: liver disorders, HIV infxn, postpartum (<3mo after delivery), regular alcohol use, injection drug use, or use of meds w/ possible interactions. D/C 3HP if AST ≥5x ULN w/ no sx of ≥3x ULN w/ sx.
• Eval pts on 3HP regimens monthly (in person/by phone) to assess adherence and adverse effects.
• Monitor pts when 3HP prescribed w/ interacting meds (eg, methadone, warfarin).
• RPT can reduce effectiveness of hormonal contraceptives; advise women who use hormonal birth control to add/switch to barrier methods. Women should inform HCP if they decided to try to become pregnant or become pregnant during 3HP tx.
• Encourage pts on 3HP SAT to record med intake and report deviations from prescribed regimen.
5 INH-only regimens:
• 9-mo INH regimen preferred over 6-mo regimen due to higher efficacy. However, tx for 6 vs 9mo may be more cost-effective and result in greater adherence. If 6-mo regimen implemented, make every effort to ensure pt adheres to tx for minimum of 6mo.
• Asymptomatic elevation of serum liver enzymes occurs in 10%-20% of pts taking INH; this usually returns to normal even when tx continued. Withhold INH if pt’s transaminase level >3x ULN if assoc w/ sx, or >5x ULN if no sx. Clinical hepatitis occurs in 0.1% of pts taking INH, more common when combined w/ other hepatotoxic agents. Factors that increase liver enzymes or severity of hepatitis incl daily alcohol consumption, underlying liver dz or risks for liver dz, concurrent use of other meds metabolized in liver. Symptomatic hepatitis rare in pts <20 yo, but severe/fatal cases have been reported: Monitor w/ same precautions as older pts if at risk for liver dz.
• Peripheral neuropathy occurs in <0.2% of pts taking INH at conventional doses; more likely in presence of other conditions assoc w/ neuropathy (eg, DM, HIV, renal failure, alcoholism). Pyridoxine (vitamin B6) is recommended only in such conditions (and in breastfeeding women).
• Lactation: INH can be used in breastfeeding women. Pyridoxine (vitamin B6) 10-15 mg/day recommended for nursing women and for breastfed infants. However, amount of INH in breast milk is inadequate for tx of LTBI in infants.
6 INH 15 mg/kg rounded up to the nearest 50 or 100mg; INH formulated as 100-mg and 300-mg tablets.
7 Choose DOT vs self-administered tx (SAT) based on local practice, considerations such as individual pt factors, preferences, and risk for progression to severe forms of TB dz.
8 Pt ed:
• Explain dz process, rationale for meds in absence of sx, CXR abnormalities.
• Discuss possible side effects of LTBI meds incl fever, unexplained anorexia, dark urine (color of coffee/cola), icterus, rash, persistent paresthesia of hands and feet, persistent fatigue or weakness lasting ≥3 days, abd tenderness (esp RUQ), abnl bruising/bleeding, arthralgia, N/V.
• Discuss mgmt of common side effects and need to report to HCP.
• Instruct pts, at the start of tx and each monthly visit, to stop tx and seek medical attention immediately if sx of hepatitis develop and to not wait until the next clinic visit to stop tx.
9 Obtain baseline AST, ALT, bilirubin in pts w/ liver disorders, hx of liver dz (eg, hepatitis B or C, alcoholic hepatitis, or cirrhosis), regular alcohol use, risks for chronic liver dz, HIV infxn, pregnancy or immediate postpartum period (ie, w/in 3mo of delivery). Also consider baseline testing on an individual basis, esp for pts taking other meds for chronic conditions. Routine, periodic retesting recommended for persons w/ abnl initial tests and other persons at risk for hepatic dz; lab testing recommended any time pt develops sx of hepatitis (eg, fatigue, weakness, malaise, anorexia, N/V, abd pain, pale stools, dark urine, chills) or has jaundice. Instruct pt at every visit to stop tx and seek immediate medical attention if sx of hepatitis develop and not wait until next clinic visit to stop tx. Withhold meds if transaminase level exceeds >3x ULN if assoc w/ sx or >5x ULN if no sx.
10 Office-related barriers include:
• Long waiting time for appointment/referrals
• Long waiting time in provider’s office
• Inconvenient office hrs
• Complicated telephone system (not user-friendly)
11 Pt-related barriers include:
• Misinformation/confusion about certain issues, such as: meaning of the TST results (eg, a positive TST is thought to be normal/common in all foreign-born persons); differences btwn injections, vaccines, and TST; the words “positive” and “negative” as they relate to test results; modes of TB transmission/prevention; exposure vs becoming infected; safety of family/friends around LTBI pt
• Residential instability
• Lack of financial resources
• Poor access to health care
• Stigma associated w/ TB
• Coexisting medical conditions
• Culture and language
• Religious practices (eg, fasting from food)
12 Tx barriers include:
• Complexity and duration of tx
• Med side effects
• Obtaining refills
• Frequency of office visits
• Cost, incl insurance copayments
13 Techniques to improve adherence:
• Collaborate w/ local health dept to provide tx
• DOT, if pt is high risk (eg, HIV-infected, young child, or TB contact)
• Provide DOT w/ 12-dose and other intermittent regimens
• Case mgmt to coordinate care and services
• Rewards for adherence, incentives (eg, grocery store/restaurant vouchers, nutritional supplements, cell phone minutes, movie tickets)
• Enablers to overcome barriers such as free van transportation, bus tickets
• Provide pt ed, instruction in pt’s primary language at every visit
• Ensure confidentiality
• Suggest/provide pt reminders such as pill box, calendar, or timer
14 Advise pt to contact HCP if s/sx of TB dz develop; provide documentation that includes TST/IGRA results, CXR results, name and dosages of meds and duration of tx. Instruct pt to present this document whenever future TB testing required. Serial/repeat CXR not indicated regardless of tx duration unless pt develops s/sx of TB dz. Adult/Adolescent, pregnant Not @ risk (HIV-negative and no recent contact w/ TB) Delay LTBI tx until 2-3mo postpartum to avoid unnecessary meds during pregnancy; then choose LTBI tx regimen based on drug susceptibility results of presumed source case (if known), coexisting medical illness, and potential for drug-drug interactions Consider shorter tx LTBI regimens as they result in higher completion rates w/ fewer adverse events Consider DOT esp for intermittent dosing; assess barriers for pt adherence; periodically assess pt progress to ensure safe/efficacious tx; provide pt ed8 - Use DOT in pts on intermittent dosing regimen, incl pts at esp high risk for TB dz who are suspected of nonadherence
- If pt exposed to known MDR-TB, consult expert in tx of MDR-TB
- Obtain baseline/periodic lab tests9 in HIV-positive pts
- Address barriers10-12 to pt adherence; recognize and address episodes of nonadherence ASAP. Adopt techniques for improvement13
- Clinical monitoring: Arrange for monthly pt visit; assess for compliance, s/sx of TB dz, and/or adverse effects, esp hepatitis (jaundice, loss of appetite, fatigue, and/or muscle/joint aches)
- If pt experiences possible AE, advise stopping meds immediately and contacting HCP; do not wait until next clinic visit
- At end of tx: Re-educate pt about s/sx of TB dz, provide tx documentation14
- Don’t re-treat TST/IGRA-positive contacts of person w/ known/suspected infectious TB (eg, pulmonary or laryngeal TB w/ (+) sputum smear) who can provide written documentation of prior adequate tx for LTBI; however, re-tx may be indicated for persons at high risk of becoming infected and progressing to TB dz (eg, immunosuppressed)
Footnotes 1 RPT and RIF may cause drug-drug interactions, incl reduced concentrations of methadone, warfarin, hormonal contraceptives, phenytoin. Advise women using hormonal contraceptives to consider alternative method (eg, barrier method).
2 RIF, an equal alternative to INH as a tx for latent TB infection, is the primary option for pts exposed to INH-resistant (rifamycin-susceptible) Mtb. Hepatotoxicity w/ transient asymptomatic hyperbilirubinemia may occur in 0.6% of pts taking RIF, more common if combined w/ INH. Cutaneous rxns, such as pruritus (w/ or w/o rash) may occur in 0.6% of pts taking RIF—generally self-limited, may not be true hypersensitivity, continued tx may be possible. Rarely, rifamycins may be assoc w/ hypersensitivity rxns, incl hypotension, nephritis or thrombocytopenia, and manifested by sx such as fever, HA, dizziness/lightheadedness, musculoskeletal pain, petechiae and pruritic. GI sx such as nausea, anorexia, abd pain rarely severe enough to d/c tx. Orange discoloration of body fluids common and harmless, but warn pts that soft contact lenses and dentures may be permanently stained.
3 RPT wt-based dosing:
• 10.0-14.0 kg: 300 mg
• 14.1-25.0 kg: 450 mg
• 25.1-32.0 kg: 600 mg
• 32.1-49.9 kg: 750 mg
• ≥50.0 kg: 900 mg max
RPT formulated as 150-mg tablets in blister packs that should be kept sealed until usage.
4 3HP (INH + RPT weekly x3mo)
• Consider 3HP as it results in significantly higher tx completion rates vs INH 9-mo regimen, w/ equal safety and effectiveness.
• Approx 4% of all pts using 3HP experience flu-like or other systemic drug rxns, w/ fever, HA, dizziness, nausea, muscle/bone pain, rash, itching, red eyes, etc.
• Approx 5% of pts D/C 3HP d/t ADRS, incl systemic drug rxns, which typically occur after first 3-4 doses, and begin approx 4h after ingestion.
• Inform pt about possible adverse effects and instruct to seek medical attn when sx of possible ADR first appear; particularly drug hypersensitivity rxns, rash, hypotension, or thrombocytopenia.
• If sx suggestive of systemic drug rxn occur, pts should stop 3HP while cause is determined. Sx usually resolve w/o tx w/in 24h.
• Obtain baseline LFTs (at least AST) in pts w/ the following: liver disorders, HIV-infxn, postpartum (<3mo after delivery), regular alcohol use, injection drug use, or use of meds w/ possible interactions. D/C 3HP if AST ≥5x ULN w/ no sx of ≥3x ULN w/ sx.
• Eval pts on 3HP regimens monthly (in person/by phone) to assess adherence and adverse effects.
• Monitor pts when 3HP prescribed w/ interacting meds (eg, methadone, warfarin).
• RPT can reduce effectiveness of hormonal contraceptives; advise women who use hormonal birth control to add/switch to barrier methods. Women should inform HCP if they decided to try to become pregnant or become pregnant during 3HP tx.
• Encourage pts on 3HP SAT to record med intake and report deviations from prescribed regimen.
5 INH-only regimens:
• 9-mo INH regimen preferred over 6-mo regimen due to higher efficacy. However, tx for 6 vs 9mo may be more cost-effective and result in greater adherence. If 6-mo regimen implemented, make every effort to ensure pt adheres to tx for minimum of 6mo.
• Asymptomatic elevation of serum liver enzymes occurs in 10%-20% of pts taking INH; this usually returns to normal even when tx continued. Withhold INH if pt’s transaminase level >3x ULN if assoc w/ sx, or >5x ULN if no sx. Clinical hepatitis occurs in 0.1% of pts taking INH, more common when combined w/ other hepatotoxic agents. Factors that increase liver enzymes or severity of hepatitis incl daily alcohol consumption, underlying liver dz or risks for liver dz, concurrent use of other meds metabolized in liver. Symptomatic hepatitis rare in pts <20 yo, but severe/fatal cases have been reported: Monitor w/ same precautions as older pts if at risk for liver dz.
• Peripheral neuropathy occurs in <0.2% of pts taking INH at conventional doses; more likely in presence of other conditions assoc w/ neuropathy (eg, DM, HIV, renal failure, alcoholism). Pyridoxine (vitamin B6) is recommended only in such conditions (and in breastfeeding women).
• Lactation: INH can be used in breastfeeding women. Pyridoxine (vitamin B6) 10-15 mg/day recommended for nursing women and for breastfed infants. However, amount of INH in breast milk is inadequate for tx of LTBI in infants.
6 INH 15 mg/kg rounded up to the nearest 50 or 100 mg; INH formulated as 100-mg and 300-mg tablets.
7 Choose DOT vs self-administered tx (SAT) based on local practice, considerations such as individual pt factors, preferences, and risk for progression to severe forms of TB dz.
8 Pt ed:
• Explain dz process, rationale for meds in absence of sx, CXR abnormalities.
• Discuss possible side effects of LTBI meds incl fever, unexplained anorexia, dark urine (color of coffee/cola), icterus, rash, persistent paresthesia of hands and feet, persistent fatigue or weakness lasting ≥3 days, abd tenderness (esp RUQ), abnl bruising/bleeding, arthralgia, nausea/vomiting.
• Discuss mgmt of common side effects and need to report to HCP.
• Instruct pts, at the start of tx and each monthly visit, to stop tx and seek medical attention immediately if sx of hepatitis develop and to not wait until the next clinic visit to stop tx.
9 Obtain baseline AST, ALT, bilirubin in pregnant (or immediate postpartum, ie, w/in 3mo of delivery) pts w/ HIV infxn, as well in pts w/ liver disorders, hx of liver dz (eg, hepatitis B or C, alcoholic hepatitis, or cirrhosis), regular alcohol use, or risks for chronic liver dz. Also consider baseline testing on an individual basis, esp for pts taking other meds for chronic conditions. Routine periodic retesting recommended for persons w/ abnl initial tests and other persons at risk for hepatic dz; lab testing recommended any time pt develops sx of hepatitis (eg, fatigue, weakness, malaise, anorexia, N/V, abd pain, pale stools, dark urine, chills) or has jaundice. Instruct pt at every visit to stop tx and seek immediate medical attention if sx of hepatitis develop and not wait until next clinic visit to stop tx. Withhold meds if transaminase level exceeds >3x ULN if assoc w/ sx or >5x ULN if no sx.
10 Office-related barriers include:
• Long waiting time for appointment/referrals
• Long waiting time in provider’s office
• Inconvenient office hrs
• Complicated telephone system (not user-friendly)
11 Pt-related barriers include:
• Misinformation/confusion about certain issues, such as: meaning of the TST results (eg, a positive TST is thought to be normal/common in all foreign-born persons); differences btwn injections, vaccines, and TST; the words “positive” and “negative” as they relate to test results; modes of TB transmission/prevention; exposure vs becoming infected; safety of family/friends around LTBI pt
• Residential instability
• Lack of financial resources
• Poor access to health care
• Stigma associated w/ TB
• Coexisting medical conditions
• Culture and language
• Religious practices (eg, fasting from food)
12 Tx barriers include:
• Complexity and duration of tx
• Med side effects
• Obtaining refills
• Frequency of office visits
• Cost, incl insurance copayments
13 Techniques to improve adherence:
• Collaborate w/ local health dept to provide tx
• DOT, if pt is high risk (eg, HIV-infected, young child, or TB contact)
• Provide DOT w/ 12-dose and other intermittent regimens
• Case mgmt to coordinate care and services
• Rewards for adherence, incentives (eg, grocery store/restaurant vouchers, nutritional supplements, cell phone minutes, movie tickets)
• Enablers to overcome barriers such as free van transportation, bus tickets
• Provide pt ed, instruction in pt’s primary language at every visit
• Ensure confidentiality
• Suggest/provide pt reminders such as pill box, calendar, or timer
14 Advise pt to contact HCP if s/sx of TB dz develop; provide documentation that includes TST/IGRA results, CXR results, name and dosages of meds and duration of tx. Instruct pt to present this document whenever future TB testing required. Serial/repeat CXR not indicated regardless of tx duration unless pt develops s/sx of TB dz. At risk (HIV-positive or recent contact w/ TB) Consider immediate tx and monitor; choose LTBI tx regimen based on drug susceptibility results of presumed source case (if known), coexisting medical illness, and potential for drug-drug interactions - Preferred during pregnancy: isoniazid daily or twice weekly x 9mo or 6mo
- Don’t delay tx initiation on basis of pregnancy alone, even during 1st trimester
Consider DOT esp for intermittent dosing; assess barriers for pt adherence; periodically assess pt progress to ensure safe/efficacious tx; provide pt ed6 - Use DOT in pts on intermittent dosing regimen, incl pts at esp high risk for TB dz who are suspected of nonadherence
- If pt exposed to known MDR-TB, consult expert in tx of MDR-TB
- Obtain baseline/periodic liver tests7 in pregnant pts at risk (due to HIV or recent contact w/ TB)
- Address barriers8-10 to pt adherence; recognize and address episodes of nonadherence ASAP. Adopt techniques for improvement11
- Clinical monitoring: Arrange for monthly pt visit; assess for compliance, s/sx of TB dz, and/or adverse effects, esp hepatitis (jaundice, loss of appetite, fatigue, and/or muscle/joint aches)
- If pt experiences possible AE, advise stopping meds immediately and contacting HCP; do not wait until next clinic visit
- At end of tx: Re-educate pt about s/sx of TB dz, provide tx documentation12
- Don’t re-treat TST/IGRA-positive contacts of person w/ known/suspected infectious TB (eg, pulmonary or laryngeal TB w/ (+) sputum smear) who can provide written documentation of prior adequate tx for LTBI; however, re-tx may be indicated for persons at high risk of becoming infected and progressing to TB dz (eg, immunosuppressed)
Footnotes 1 INH-only regimens:
• 9-mo INH regimen preferred over 6-mo regimen due to higher efficacy. However, tx for 6 vs 9mo may be more cost-effective and result in greater adherence. If 6-mo regimen implemented, make every effort to ensure pt adheres to tx for minimum of 6mo.
• Asymptomatic elevation of serum liver enzymes occurs in 10%-20% of pts taking INH; this usually returns to normal even when tx continued. Withhold INH if pt’s transaminase level >3x ULN if assoc w/ sx, or >5x ULN if no sx. Clinical hepatitis occurs in 0.1% of pts taking INH, more common when combined w/ other hepatotoxic agents. Factors that increase liver enzymes or severity of hepatitis incl daily alcohol consumption, underlying liver dz or risks for liver dz, concurrent use of other meds metabolized in liver. Symptomatic hepatitis rare in pts <20 yo, but severe/fatal cases have been reported: Monitor w/ same precautions as older pts if at risk for liver dz.
• Peripheral neuropathy occurs in <0.2% of pts taking INH at conventional doses; more likely in presence of other conditions assoc w/ neuropathy (eg, DM, HIV, renal failure, alcoholism). Pyridoxine (vitamin B6) is recommended only in such conditions (and in breastfeeding women).
• Lactation: INH can be used in breastfeeding women. Pyridoxine (vitamin B6) 10-15 mg/day recommended for nursing women and for breastfed infants. However, amount of INH in breast milk is inadequate for tx of LTBI in infants.
• Pregnancy: There is potential for increased risk of hepatotoxicity during pregnancy and 1st 2-3mo postpartum.
2 RIF may cause drug-drug interactions, incl reduced concentrations of methadone, warfarin, hormonal contraceptives, phenytoin. Advise women using hormonal contraceptives to consider alternative method (eg, barrier method).
3 Consider RIF for pts who cannot tolerate INH or were exposed to INH-resistant (rifamycin-susceptible) Mtb. Hepatotoxicity w/ transient asymptomatic hyperbilirubinemia may occur in 0.6% of pts taking RIF, more common if combined w/ INH. Cutaneous rxns, such as pruritus (w/ or w/o rash) may occur in 0.6% of pts taking RIF—generally self-limited, may not be true hypersensitivity, continued tx may be possible. Rarely, rifamycins may be assoc w/ hypersensitivity rxns, incl hypotension, nephritis or thrombocytopenia, and manifested by sx such as fever, HA, dizziness/lightheadedness, musculoskeletal pain, petechiae and pruritic. GI sx such as nausea, anorexia, abd pain rarely severe enough to d/c tx. Orange discoloration of body fluids common and harmless, but warn pts that soft contact lenses and dentures may be permanently stained. For adolescents, AAP recommends RIF 10-20 mg/kg PO qd x4mo (max: 600 mg/day).
4 If pregnant pt is HIV-positive and on ART, the 6-mo INH regimen is not recommended. Use 9-mo tx instead.
5 INH 15 mg/kg rounded up to the nearest 50 or 100 mg; INH formulated as 100-mg and 300-mg tablets.
6 Pt ed:
• Explain dz process, rationale for meds in absence of sx, CXR abnormalities.
• Discuss possible side effects of LTBI meds incl fever, unexplained anorexia, dark urine (color of coffee/cola), icterus, rash, persistent paresthesia of hands and feet, persistent fatigue or weakness lasting ≥3 days, abd tenderness (esp RUQ), abnl bruising/bleeding, arthralgia, nausea/vomiting.
• Discuss mgmt of common side effects and need to report to HCP.
• Instruct pts, at the start of tx and each monthly visit, to stop tx and seek medical attention immediately if sx of hepatitis develop and to not wait until the next clinic visit to stop tx.
7 Obtain baseline AST, ALT, bilirubin in pts w/ HIV infxn, as well in pts w/ liver disorders, hx of liver dz (eg, hepatitis B or C, alcoholic hepatitis, or cirrhosis), regular alcohol use, or risks for chronic liver dz. Also consider baseline testing on an individual basis, esp for pts taking other meds for chronic conditions. Routine periodic retesting recommended for persons w/ abnl initial tests and other persons at risk for hepatic dz; lab testing recommended any time pt develops sx of hepatitis (eg, fatigue, weakness, malaise, anorexia, nausea/vomiting, abd pain, pale stools, dark urine, chills) or has jaundice. Instruct pt at every visit to stop tx and seek immediate medical attention if sx of hepatitis develop and not wait until next clinic visit to stop tx. Withhold meds if transaminase level exceeds >3x ULN if assoc w/ sx or >5x ULN if no sx.
8 Office-related barriers include:
• Long waiting time for appointment/referrals
• Long waiting time in provider’s office
• Inconvenient office hrs
• Complicated telephone system (not user-friendly)
9 Pt-related barriers include:
• Misinformation/confusion about certain issues, such as: meaning of the TST results (eg, a positive TST is thought to be normal/common in all foreign-born persons); differences btwn injections, vaccines, and TST; the words “positive” and “negative” as they relate to test results; modes of TB transmission/prevention; exposure vs becoming infected; safety of family/friends around LTBI pt
• Residential instability
• Lack of financial resources
• Poor access to health care
• Stigma associated w/ TB
• Coexisting medical conditions
• Culture and language
• Religious practices (eg, fasting from food)
10 Tx barriers include:
• Complexity and duration of tx
• Med side effects
• Obtaining refills
• Frequency of office visits
• Cost, incl insurance copayments
11 Techniques to improve adherence:
• Collaborate w/ local health dept to provide tx
• DOT, if pt is high risk (eg, HIV-infected, young child, or TB contact)
• Provide DOT w/ 12-dose and other intermittent regimens
• Case mgmt to coordinate care and services
• Rewards for adherence (incentives) (eg, grocery store/restaurant vouchers, nutritional supplements, cell phone minutes, movie tickets)
• Enablers to overcome barriers such as free van transportation, bus tickets
• Provide pt ed, instruction in pt’s primary language at every visit
• Ensure confidentiality
• Suggest/provide pt reminders such as pill box, calendar, or timer
12 Advise pt to contact HCP if s/sx of TB dz develop; provide documentation that includes TST/IGRA results, CXR results, name and dosages of meds and duration of tx. Instruct pt to present this document whenever future TB testing required. Serial/repeat CXR not indicated regardless of tx duration unless pt develops s/sx of TB dz. Choose LTBI tx regimen based on drug susceptibility results of presumed source case (if known), coexisting medical illness, and potential for drug-drug interactions - If pt is HIV-positive and on ART, use the 9-mo INH regimen
- If pt is HIV-positive, otherwise healthy, and not on ART, consider 3HP
Consider shorter LTBI tx regimens as they result in higher completion rates w/ fewer adverse events Consider DOT esp for intermittent dosing; assess barriers for pt adherence; periodically assess pt progress to ensure safe/efficacious tx; provide pt ed8 - Use DOT in pts on intermittent dosing regimen, incl pts at esp high risk for TB dz who are suspected of nonadherence
- If pt exposed to known MDR-TB, consult expert in tx of MDR-TB
- Baseline/periodic lab testing not routine, unless high-risk pt or if sx of hepatitis develop on tx9
- Address barriers10-12 to pt adherence; recognize and address episodes of nonadherence ASAP. Adopt techniques for improvement13
- Clinical monitoring: Arrange for monthly pt visit; assess for compliance, s/sx of TB dz, and/or adverse effects, esp hepatitis (jaundice, loss of appetite, fatigue, and/or muscle/joint aches)
- If pt experiences possible AE, advise stopping meds immediately and contacting HCP; do not wait until next clinic visit
- At end of tx: Re-educate parent/guardian about s/sx of TB dz, provide tx documentation14
- Don’t re-treat TST/IGRA-positive contacts of person w/ known/suspected infectious TB (eg, pulmonary or laryngeal TB w/ (+) sputum smear) who can provide written documentation of prior adequate tx for LTBI; however, re-tx may be indicated for persons at high risk of becoming infected and progressing to TB dz (eg, immunosuppressed)
Footnotes 1 RPT and RIF may cause drug-drug interactions, incl reduced concentrations of methadone, warfarin, hormonal contraceptives, phenytoin. RIF contraindicated in HIV-infected pts treated w/ certain antiretrovirals.
2 RPT wt-based dosing:
• 10.0-14.0 kg: 300 mg
• 14.1-25.0 kg: 450 mg
• 25.1-32.0 kg: 600 mg
• 32.1-49.9 kg: 750 mg
• ≥50.0 kg: 900 mg max
RPT formulated as 150-mg tablets in blister packs that should be kept sealed until usage.
3 3HP (INH + RPT weekly x3mo)
• Consider 3HP (for children ≥2 yo) as it results in higher tx completion rates vs INH 9-mo regimen, w/ equal safety and effectiveness.
• Approx 4% of all pts using 3HP experience flu-like or other systemic drug rxns, w/ fever, HA, dizziness, nausea, muscle/bone pain, rash, itching, red eyes, etc.
• Approx 5% of pts D/C 3HP d/t ADRS, incl systemic drug rxns, which typically occur after first 3-4 doses, and begin approx 4h after ingestion.
• Inform parents/guardians about possible adverse effects and instruct to seek medical attn when sx of possible ADR first appear; particularly drug hypersensitivity rxns, rash, hypotension, or thrombocytopenia.
• If sx suggestive of systemic drug rxn occur, pts should stop 3HP while cause is determined. Sx usually resolve w/o tx w/in 24h.
• Obtain baseline LFTs (at least AST) in pts w/ the following: liver disorders, HIV infxn, postpartum (<3mo after delivery), regular alcohol use, injection drug use, or use of meds w/ possible interactions. D/C 3HP if AST ≥5x ULN w/ no sx of ≥3x ULN w/ sx.
• Eval pts on 3HP regimens monthly (consult w/ parents/guardians in person/by phone) to assess adherence and adverse effects.
• Monitor pts when 3HP prescribed w/ interacting meds (eg, methadone, warfarin).
• Encourage parents/guardians of pts on 3HP SAT to record med intake and report deviations from prescribed regimen.
4 Consider RIF for pts who cannot tolerate INH or were exposed to INH-resistant (rifamycin-susceptible) Mtb. Hepatotoxicity w/ transient asymptomatic hyperbilirubinemia may occur in 0.6% of pts taking RIF, more common if combined w/ INH. Cutaneous rxns, such as pruritus (w/ or w/o rash) may occur in 0.6% of pts taking RIF—generally self-limited, may not be true hypersensitivity, continued tx may be possible. Rarely, rifamycins may be assoc w/ hypersensitivity rxns, incl hypotension, nephritis or thrombocytopenia, and manifested by sx such as fever, HA, dizziness/lightheadedness, musculoskeletal pain, petechiae and pruritic. GI sx such as nausea, anorexia, abd pain rarely severe enough to d/c tx. Orange discoloration of body fluids common and harmless.
5 INH-only regimens:
• 9-mo daily INH regimen is for all children.
• Asymptomatic elevation of serum liver enzymes occurs in 10%-20% of pts taking INH; this usually returns to normal even when tx continued. Withhold INH if pt’s transaminase level >3x ULN if assoc w/ sx, or >5x ULN if no sx. Clinical hepatitis occurs in 0.1% of pts taking INH, more common when combined w/ other hepatotoxic agents. Factors that increase liver enzymes or severity of hepatitis incl daily alcohol consumption, underlying liver dz or risks for liver dz, concurrent use of other meds metabolized in liver. Symptomatic hepatitis rare in pts <20 yo, but severe/fatal cases have been reported: Monitor w/ same precautions as older pts if at risk for liver dz.
• Peripheral neuropathy occurs in <0.2% of pts taking INH at conventional doses; more likely in presence of other conditions assoc w/ neuropathy (eg, DM, HIV, renal failure, alcoholism). Pyridoxine (vitamin B6) is recommended only in such conditions.
• Note: The amount of INH in breast milk is inadequate for tx of LTBI in infants.
6 INH 15 mg/kg rounded up to the nearest 50 or 100 mg; INH formulated as 100-mg and 300-mg tablets.
7 Choose DOT vs self-administered tx (SAT) based on local practice, considerations such as individual pt factors, preferences, and risk for progression to severe forms of TB dz. Some experts still prefer DOT (by a clinician, not parent) for treating LTBI in children aged 2–5 yo, in whom risk for TB progression and severe disease is higher than that in older children and adults. 3HP administered via SAT hasn’t been studied in RCTs in pts <18 yo.
8 Pt ed for parents/guardians:
• Explain dz process, rationale for meds in absence of sx, CXR abnormalities.
• Discuss possible side effects of LTBI meds incl fever, unexplained anorexia, dark urine (color of coffee/cola), icterus, rash, persistent paresthesia of hands and feet, persistent fatigue or weakness lasting ≥3 days, abd tenderness (esp RUQ), abnl bruising/bleeding, arthralgia, N/V.
• Discuss mgmt of common side effects and need to report to HCP.
• Instruct parents/guardians, at the start of tx and each monthly visit, to stop tx and seek medical attention immediately if sx of hepatitis develop and to not wait until the next clinic visit to stop tx.
9 Obtain baseline AST, ALT, bilirubin in pts w/ liver disorders, hx of liver dz (eg, hepatitis B or C, or cirrhosis), risks for chronic liver dz, or HIV infxn. Also consider baseline testing on an individual basis, esp for pts taking other meds for chronic conditions. Routine periodic retesting recommended for persons w/ abnl initial tests and other persons at risk for hepatic dz; lab testing recommended any time pt develops sx of hepatitis (eg, fatigue, weakness, malaise, anorexia, N/V, abd pain, pale stools, dark urine, chills) or has jaundice. Instruct parents/guardians at every visit to stop tx and seek immediate medical attention if sx of hepatitis develop and not wait until next clinic visit to stop tx. Withhold meds if transaminase level exceeds >3x ULN if assoc w/ sx or >5x ULN if no sx.
10 Office-related barriers include:
• Long waiting time for appointment/referrals
• Long waiting time in provider’s office
• Inconvenient office hrs
• Complicated telephone system (not user-friendly)
11 Pt-related barriers include:
• Misinformation/confusion about certain issues, such as: meaning of the TST results (eg, a positive TST is thought to be normal/common in all foreign-born persons); differences btwn injections, vaccines, and TST; the words “positive” and “negative” as they relate to test results; modes of TB transmission/prevention; exposure vs becoming infected; safety of family/friends around LTBI pt
• Residential instability
• Lack of financial resources
• Poor access to health care
• Stigma associated w/ TB
• Coexisting medical conditions
• Culture and language
• Religious practices (eg, fasting from food)
12 Tx barriers include:
• Complexity and duration of tx
• Med side effects
• Obtaining refills
• Frequency of office visits
• Cost, incl insurance copayments
13 Techniques to improve adherence:
• Collaborate w/ local health dept to provide tx
• DOT, if pt is high risk (eg, HIV-infected, young child, or TB contact)
• Provide DOT w/ 12-dose and other intermittent regimens
• Case mgmt to coordinate care and services
• Rewards for adherence (incentives) (eg, grocery store/restaurant vouchers, nutritional supplements, cell phone minutes, movie tickets)
• Enablers to overcome barriers such as free van transportation, bus tickets
• Provide pt ed, instruction in pt’s primary language at every visit
• Ensure confidentiality
• Suggest/provide pt reminders such as pill box, calendar, or timer
14 Advise parents/guardians to contact HCP if s/sx of TB dz develop; provide documentation that includes TST/IGRA results, CXR results, name and dosages of meds and duration of tx. Instruct parent/guardian to present this document whenever future TB testing required. Serial/repeat CXR not indicated regardless of tx duration unless pt develops s/sx of TB dz.
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