Transcript Clinical Slide Set. Tuberculosis

In the Clinic
TUBERCULOSIS
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
Who should be screened for latent TB
infection?
 Goal: identify and treat persons at increased risk for TB
 Persons with HIV infection, other immunocompromising
conditions
 Persons with recent close contact with person with active TB
 Persons with fibrotic changes consistent with old TB
 Recent (<5 y) arrivals from high-prevalence countries
 Mycobacteriology laboratory personnel
 Residents or employees in high-risk settings
 Persons with clinical conditions that put them at high risk for
active disease
 Children aged ≤4 years exposed to adults with TB
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What tests are used to screen for TB infection?
 Mantoux tuberculin skin test
 Interferon-release assays
 Use the test that best fits patient's needs
 Neither distinguishes between latent and active disease
 Neither should be sole investigation for active disease
 False-positives for TST: history of BCG vaccination or
infection with nontuberculous mycobacterium
 False-negatives: recent TB infection, overwhelming active
TB disease, recent live virus vaccination, recent viral
infection, anergy, age <6 mo
 Both tests more likely to yield false-negatives in persons
with advanced immunosuppression
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
Interpretation of TST Results: Criteria for
Tuberculin Positivity by Risk Group
 ≥5 mm size of induration
 HIV-positive persons
 Recent contacts of persons with active TB
 Persons with fibrotic changes consistent with old TB
 Patients who have immunosuppressive conditions
 ≥10 mm size of induration
 Recent (<5 y) arrivals from high-prevalence TB countries
 Injection drug users
 Residents or employees of high-risk congregate settings
 Persons at high risk due to comorbid conditions
 Mycobacteriology laboratory personnel
 Children aged ≤4 y
 ≥15 mm size of induration: No risk factors for TB
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What can patients do to decrease the
likelihood of infecting others?
 Promptly identify active TB
 Respiratory isolation if TB suspected/confirmed
 Hospital staff should wear fitted particulate respirators
(N95)
 Suspected TB: remove from isolation after 3 sputum
smears at least 8 h apart confirmed negative and
alternative diagnosis made
 Confirmed TB: remove from isolation after significant
clinical response and 3 sputum smears negative for AFB
 If patients are not too ill: send home after initiation
of therapy and isolate from outsiders
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
For patients with LTBI, what can be done to
decrease the likelihood of developing
active disease?
 Prophylaxis, especially in those with greater risk for
active disease
 HIV infection, immunosuppressive therapy
 Close contacts of persons with active TB in past 2 y
 Fibrotic changes (chest x-ray) consistent with old TB
 Medical conditions known to increase risk
 High-risk substance users
 Residents and employees in high-risk congregate settings
 Immunocompetent children <5 y: “window prophylaxis”
 Stop when TST/IGRA results are negative 8-10 weeks after
last contact with a contagious case
continued…
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
Treatment Regimens for Latent TB
 Isoniazid 9 months
o Daily: preferred treatment for individuals with HIV; children
aged 2–11 y; pregnant women (w/ pyridoxine/vitamin B6
supplements)*
o Twice weekly: pregnant women (w/ pyridoxine/vitamin B6)*
 Isoniazid 6 months
o Daily: Not indicated for HIV-infected persons, persons with
fibrotic lesions on chest radiographs, or children
 Isoniazid + rifapentine 3 mo
o Once weekly: treatment for persons ≥12 y
o Not recommended for persons <2 y; receiving ARV treatment;
presumed infected with INH- or RIF-resistant M tuberculosis;
pregnant or expect to become pregnant
 Rifampin 4 mo
o Daily: Not recommended for those receiving medications that
interact with rifamycins; who wear contact lenses; who are
pregnant or expect to become pregnant
*in pregnant women, may be delayed until after delivery and cessation of
breastfeeding except when there is increased risk of placental infection or
progression to active TB
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
How can patients with active TB protect
household members and other contacts
from infection?
 Cover their mouth and nose when they cough or sneeze
 Not sleep in a room with other household members
 Refrain from having home visitors until they are
noninfectious
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What are the physician's public health
responsibilities after diagnosing active TB?
 Notify the TB program about cases of suspected or
confirmed active TB within 24h
 State TB program must then notify the local board of health
of patient's residence within 24h
 To set up processes to screen potential contacts
 To take steps to avoid further transmission
 Providers must also report treatment progress
 Including patients who are nonadherent, leave medical
facilities AMA, or continue to place others at risk
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
CLINICAL BOTTOM LINE: Screening
and Prevention...
 Screen close contacts of a person with active pulmonary TB
 Screen those who are at high risk for infection or progression
to disease once infected
 Prevent infection by identifying and treating persons with
active pulmonary TB
 Evidence of infection but not disease: offer LTBI therapy
 If patients suspected of having TB: order airborne isolation
 Notify public health authorities about cases of suspected
active TB
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What are the signs and symptoms of active TB?
History, ask about:
 TB exposure, infection, disease, or treatment
 patients with recent exposure to TB more likely to develop TB
 HIV infection or other medical conditions or demographic
factors that may increase the risk for or presentation of TB
 Fever
 but absence of fever does not rule out TB
 Malaise: night sweats are a classic symptom of TB
 Weight loss
 Especially in patients with advanced, extrapulmonary, or
disseminated disease
 Pelvic pain, menstrual irregularities, and infertility
continued…
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
Physical Examination
 Systemic signs: fever, wasting
 Hoarseness
 Palpable lymph nodes
 Pulmonary disease (most common presentation): signs of
consolidation or findings of pleural effusion
 Cardiac pericardial disease: Tachycardia, increased venous
pressure, pulsus paradoxus, friction rub
 Abdominal ascites, “doughy” abdomen, abdominal mass
 Hepatomegaly or splenomegaly
 Recurrent UTI with no organisms on culture
 Men: beaded vas deferens on palpation, draining scrotal sinus,
epididymitis or induration of prostrate or seminal vesicles
 Joint swelling, gibbus deformity, localized pain
 Neurologic: abnormal behavior, headache, seizure
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What are the signs and symptoms of active
TB among HIV co-infected patients?
 CD4 counts >350: more likely to present with classic
constitutional symptoms
 CD4 counts <200: more likely to have atypical and
asymptomatic presentation and extrapulmonary disease
 Use high index of suspicion for active TB when patients
with HIV who have been exposed to TB are cared for
 Use active microbiological screening
 Disease can be missed when screening based on signs and
symptoms alone
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
How is active TB diagnosed?
 3 serial sputum microscopy and mycobacterial cultures
collected ≥8h apart and chest radiography
 Signs of extrapulmonary disease: evaluate samples
from those areas (lymph nodes, pleural space)
 Gold standard: positive mycobacterial culture from
liquid medium
 AFB smears negative in half of patients with active
pulmonary TB, even higher % HIV co-infected persons
 Thus, perform mycobacterial cultures in all TB suspects,
even in patients with negative smears
continued…
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
 If disseminated TB suspected or person is highly
immunosuppressed: blood culture and first-void urine for
mycobacterial analysis in addition to sputum studies
 If active disease suspected, sputum samples negative:
bronchoscopy with bronchoalveolar lavage or biopsy;
consider empiric therapy as well and evaluate for treatment
response
 Confirm on culture when possible to avoid misdiagnosis
 Symptoms similar to TB: nontuberculous mycobacteria,
aspiration pneumonia, lung abscesses, Wegener
granulomatosis, actinomycosis, cancer
 Similar diseases on pathologic exam: sarcoidosis, syphilis,
nontuberculous mycobacteria, brucellosis, fungal diseases
 Nucleic acid amplification testing on sputum specimens
 Should not replace culture, but can facilitate earlier decision
making regarding whether to initiate treatment
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
How should drug susceptibility testing be
done, and in which patients?
 Do susceptibility testing if active TB is confirmed
 Ideally on the initial, pretreatment isolate
 Culture remains standard for drug susceptibility testing; genetic
testing available as well
 Drug-resistant TB refers to M tuberculosis with resistance to any of
the TB drugs
 Do drug susceptibility testing for both first-line and second-line drugs
 MDR TB: resistant to INH and RIF (requires second-line regimen)
 XDR TB: MDR TB + resistant to fluoroquinolone and an injectable
aminoglycoside: few options, extremely poor treatment outcomes
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
When should clinicians refer patients with
suspected active TB to an expert?
 Provider has little experience with TB
 Patient has a negative AFB smear and culture results
but pulmonary TB is still suspected clinically
 Patient has drug-resistant TB
 Patient has been treated previously for TB
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
CLINICAL BOTTOM LINE: Diagnosis...
 Test for TB if patients have prolonged cough, hemoptysis,
chest pain, or systemic symptoms
 Use higher clinical suspicion in patients who are HIV-positive
 Treat empirically if patients have negative microbiologic
testing but clinical suspicion is still high
 Refer patients to a TB expert if:
 Primary physician has little experience with TB
 Presentation is not straightforward
 Drug resistance present, patient doesn’t respond to therapy
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What is the standard drug treatment for
active TB in cases of drug-susceptible M
tuberculosis infection?
 Intensive phase: 4 drugs (INH, RIF, EMB, PZA) for 2 mo
 Continuation phase: 2 drugs (INH, RIF) for 4 mo
 If M tuberculosis isolate found susceptible to INH and RIF,
EMB can be stopped early in intensive phase
 Give pyridoxine (vitamin B6) with INH to all persons at risk
for neuropathy
 Preferred schedule: daily dosing during both intensive and
continuation phases with DOT 5 days/week
 Intermittent dosing possible for HIV-negative, pulmonary
TB cases caused by drug-susceptible organisms without
cavitation
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What is the best way to monitor the results
of treatment and to detect adverse effects
during active TB therapy?
 Baseline evaluation
 AFB smear and TB culture status
 Drug susceptibility of infecting isolate
 Chest radiograph to assess extent of cavitation
 Blood tests: general health, liver and kidney function
 Weight and baseline symptoms
 Screen for HIV, HBV, HCV, alcoholism, and diabetes
 Visual acuity test (e.g., Snellen test) and a color
discrimination test (e.g., Ishihara test) if starting EMB
continued…
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
 Follow-up evaluation
 Sputum specimen: months 1 and 2 to assess treatment
response
 If culture-positive at treatment month 3, repeat drugsusceptibility testing to assess acquired drug resistance
 Regular liver function tests for those at risk
 Monthly visual acuity and color discrimination tests for
patients on EMB-containing regimen
 Monitor for medication adverse effects
 Review symptoms and adherence
 End-of-treatment evaluation
 Repeat microbiology and imaging tests
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
When and why should the standard
treatment regimen be modified?
 Intensive phase
 Treatment interrupted ≥2 weeks: restart from beginning
 Treatment interrupted for ≤2 weeks: continue therapy until
all doses completed as long as this occurs within 3 months
 Continuation phase
 Further therapy may not be necessary if patient takes >80%
of all doses and AFB smear results were initially negative
 If AFB was positive: should take all doses until completed
 If >80% of all doses missed during <2 consecutive months,
patient can continue therapy until completion
 If >2 consecutive months missed: repeat full course of
therapy from the beginning
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
How should patients with extrapulmonary
TB be treated?
 6- to 9-months of INH- and RIF-containing regimens
 Exception: TB meningitis
 2 months of 4-drug regimen, then 10 months INH + RIF
 Addition of corticosteroids confers mortality benefit
 Monitor treatment response
 Bacteriologic evaluation often limited by difficulty
obtaining follow-up specimens
 Obtain sputum specimens with concurrent pulmonary TB
 Response to therapy often judged on clinical and
radiographic findings
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What is the approach to treatment of active
TB and HIV co-infection?
 HIV-infected patients receiving ART (all patients should
start ART except rare instances)
 Standard 6-month daily regimen for drug-susceptible TB
 HIV-infected patients who do not receive ART
 Extend continuation phase an additional 3 months
 Start TB medication as soon after diagnosis as possible
 Beware interactions between HIV and TB medications,
and paradoxical reactions
 Initiate ART early to reduce HIV disease progression
 Exception: HIV-infected patients with TB meningitis
 Be aware TB Rx + ART may worsen TB symptoms (IRIS)
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
What are the indications for DOT for
active TB?
 DOT = Directly Observed Therapy
 Standard of practice in U.S. and European TB programs
 Ingestion of each dose is witnessed
 Aids adherence to TB treatment
 Adherence to TB treatment is challenging but critical
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
When should patients be treated for drugresistant TB, and what is the basic approach?
 INH-monoresistant TB
 Treat with other 3 first-line drugs for full 6 months
 Or add fluoroquinolone to the 3-drug regimen (6 months)
 MDR TB or RIF-resistant TB
 Induction phase: treat with 5 drugs to which isolate is
susceptible
 Include fluoroquinolone and injectable aminoglycoside
 Continuation phase: treat with 4 of those drugs (remove
the injectable)
 “Shorter” MDR TB regimen: 7 drugs given for 9-12 months
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.
CLINICAL BOTTOM LINE: Treatment...
 Active TB: tailor regimen to patient characteristics and
organism susceptibility
 Hospitalize patients with complications or adverse drug
effects that cannot be managed at home
 Do not hospitalize patients solely for isolation
 Monitor patients at least monthly for clinical response, AEs
 Culture sputum monthly in patients whose initial cultures
are positive
 Consider using DOT
 Manage complicated patients in consultation with experts
© Copyright Annals of Internal Medicine, 2017
Ann Int Med. 166 (2): ITC17–ITC32.