Mycobacterial Tuberculosis
Download
Report
Transcript Mycobacterial Tuberculosis
Guidelines for Prevention and Treatment of Opportunistic
Infections in HIV-Infected Adults and Adolescents
Mycobacterial Tuberculosis Slide Set
Prepared by the AETC National Coordinating Resource Center based on
recommendations from the CDC, National Institutes of Health, and HIV
Medicine Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor
this intent.
- AETC National Coordinating Resource Center
http://www.aidsetc.org
www.aidsetc.org
May 2013
2
Mycobacterium tuberculosis (MTB) Disease
Epidemiology
Prevention
Diagnosis
Treatment
Clinical Manifestations
Considerations in Pregnancy
MTB: Epidemiology
Worldwide, 10 million people coinfected with HIV
and MTB
90% in developing countries
Most common cause of death in AIDS patients
In the United States, decline in HIV-related TB
since 1992, likely related to ART
www.aidsetc.org
May 2013
4
MTB: Epidemiology (2)
Infection via inhalation of droplet nuclei with MTB
organisms
Latent TB infection (LTBI): immune system
usually limits multiplication of TB bacilli, but
bacilli may persist
Persons with LTBI are asymptomatic and are not
infectious
Active TB disease: can develop immediately after
infection (primary TB) or with reactivation of LTBI
www.aidsetc.org
May 2013
5
MTB: Epidemiology (3)
Reactivation of latent TB:
More likely in HIV-infected patients; risk increases soon
after HIV infection
3-16% annual risk in HIV-infected patients; in HIV
uninfected, ~5% lifetime risk
TB disease can occur at any CD4 count, but risk
increases with progression of immunodeficiency
TB coinfection increases HIV viral loads and
progression of HIV
www.aidsetc.org
May 2013
6
MTB: Preventing Exposure
HIV-infected patients who travel or work in highprevalence settings should be counseled about
TB infection risk and tested for LTBI
Exposure risks in some health care and
correctional settings in the United States – usual
precautions
www.aidsetc.org
May 2013
7
MTB: Preventing Exposure (2)
Increased risk of MTB infection with time in
congregate settings such as correctional facilities,
homeless shelters, nursing homes
Patients with known or presumed infectious TB:
physically separate from other patients, especially
from HIV-infected patients
Patients with infections TB should not return to
settings in which others might be exposed until on
treatment (or completed treatment), with 3
consecutive negative AFB smear results, plus clinical
improvement
If MDR TB, some recommend that patients have negative
sputum culture
www.aidsetc.org
May 2013
8
MTB: Preventing Exposure (3)
Treatment of LTBI is effective in reducing TB
transmission: test all HIV-infected persons with
risk factors for TB, and treat all with LTBI
Treat presumptively for LTBI if significant history of TB
exposure, regardless of LTBI test results
BCG vaccination contraindicated in HIV infection:
risk of disseminated disease
www.aidsetc.org
May 2013
9
MTB: Preventing Disease
Diagnosis and treatment of LTBI is key aspect of
preventing active TB
Treatment of LTBI lowers risk of TB disease (by
62%) and death (by 26%)
www.aidsetc.org
May 2013
10
Latent TB Disease: Diagnosis
Screening
Test all for LTBI at time of HIV diagnosis (regardless of
TB risks)
If CD4 count <200 cells/µL and no indications for empiric LTBI
treatment, retest for LTBI when count rises to ≥200 cells/µL on
ART
Annual testing only for those at high risk or repeated or
ongoing exposure to active TB
www.aidsetc.org
May 2013
11
Latent TB Disease: Diagnosis (2)
Testing methods
Tuberculin skin test (TST):
0.1 mL purified protein derivative (PPD)
In HIV infection, positive is induration ≥5 mm at 48-72 hours
Specificity 56-95%
Requires 2 office visits; lower specificity in recipients of BCG
vaccination
Interferon-gamma release assay (IGRA):
IFN-γ release in response to MTB-specific peptides
Higher specificity (92-97%); less cross-reactivity resulting from
BCG vaccination or other non-TB mycobacterial exposure
Advanced immunosuppression may cause
false-negative results to both tests, perhaps less with IGRAs
www.aidsetc.org
May 2013
12
Latent TB Disease: Diagnosis (3)
In the U.S., only 47-65% complete TST
screening; use of IGRA may result in better rates
of screening
Use of both TST and IGRA is not recommended
in the U.S.
www.aidsetc.org
May 2013
13
Latent TB Disease: Diagnosis (4)
TST or IGRA test results
If negative and CD4 count <200 cells/µL: retest after
ART initiation and increase in CD4 count to >200
cells/µL
If positive test: chest X ray and clinical evaluation to
screen for active TB
www.aidsetc.org
May 2013
14
Latent TB Disease: Treatment
Rule out active TB: chest X ray and clinical
evaluation
All HIV-infected persons should be treated, if no
evidence of active TB and:
Positive screening test for LTBI and no history of treatment
for active or latent TB
Close contact with someone with infectious TB, regardless
of LTBI test results
For HIV-infected persons who are anergic and no
recent contact with infectious TB: LTBI treatment not
recommended (no evidence of clinical benefit)
www.aidsetc.org
May 2013
15
Latent TB Disease: Treatment (2)
Preferred (duration: 9 months):
INH 300 mg PO QD (+ pyridoxine 25 mg PO QD, to reduce
risk of peripheral neuropathy)
INH or 900 mg PO BIW (+ pyridoxine 25 mg PO QD)
Alternative (duration: 4 months):
Rifampin: 600 mg PO QD
Rifabutin: dose adjusted according to concomitant ARVs
Note: potential drug interactions between rifamycins and
PIs, NNRTIs, integrase inhibitors; dosage adjustments may
be required; some combinations are contraindicated
For persons exposed to drug-resistant TB: consult
with experts
www.aidsetc.org
May 2013
16
Latent TB Disease: Treatment (3)
Regimens duration less than 9 months may
enhance adherence
3-month regimen of once weekly INH + rifapentine as
effective as 9-month INH regimen; not recommended
for HIV-infected persons on ART because of potential
interactions between some ARVs and rifapentine
2-month regimen of rifampin + pyrazinamide not
recommended: risk of severe hepatotoxicity
ART decreases risk of TB disease; use of both
ART and LTBI treatment is recommended
www.aidsetc.org
May 2013
17
Latent TB Disease: Monitoring
Monitor monthly for adherence and drug toxicity
Directly observed therapy (DOT) should be used with
intermittent dosing regimens
INH: liver toxicity possible, check baseline AST or
ALT, bilirubin; repeat if abnormal; monitor closely if
viral hepatitis
Asymptomatic patients: discontinue INH if AST increases >5
times upper limit of normal (ULN)
Symptomatic patients: discontinue INH if AST increases >3
times ULN
Baseline elevated transaminases: discontinue INH if AST
increases >2 times ULN
www.aidsetc.org
May 2013
18
TB Disease: Clinical Manifestations
Common symptoms included cough, fever,
sweats, weight loss, fatigue
May be subclinical or have few symptoms, even
if culture positive
Immune reconstitution following ART initiation
can unmask subclinical TB, with inflammatory
reactions at site of infection
www.aidsetc.org
May 2013
19
TB Disease: Clinical Manifestations (2)
Degree of immunosuppression influences
clinical, radiographic, and histopathologic
presentation of active TB
CD4 count >350 cells/µL: as in HIV uninfected
TB usually limited to lungs
Chest X ray: upper lobe infiltrates, +/− cavitation
Extrapulmonary disease (pleuritis, pericarditis,
meningitis, lymphadenitis), more common in HIV
infection, regardless of CD4 count
More common in advanced immunosuppression
www.aidsetc.org
May 2013
20
TB Disease: Clinical Manifestations (3)
Advanced HIV
TB may be systemic disease: high fevers, rapid progression,
sepsis syndrome
Extrapulmonary TB, with or without pulmonary disease, in
most TB patients with CD4 count <200 cells/µL
TB may be subclinical or with few symptoms
Chest X ray: lower lobe, middle lobe, interstitial, and miliary
infiltrates are common; cavitation less common
Intrathoracic lymphadenopathy is common
Granulomas may be poorly formed or absent
Sputum smear and culture may be positive even with
normal chest X ray
www.aidsetc.org
May 2013
21
TB Disease: Clinical Manifestations (4)
Chest X ray: TB manifesting as a
focal opacity in the right lung
Credit: L. Huang, MD; HIV InSite
www.aidsetc.org
Chest X ray: TB with bilateral hilar
lymphadenopathy and diffuse interstitial and
airspace opacities
Credit: L. Goozé, MD; C. Daley, MD; HIV InSite
May 2013
22
TB Disease: Clinical Manifestations (5)
Chest X ray: miliary pattern of TB in an HIV-infected patient with advanced immunosuppression
Credit: HIV Web Study (www.hivwebstudy.org) © 2006, University of Washington
www.aidsetc.org
May 2013
23
TB Disease: Diagnosis
Direct initial testing at site of symptoms or signs
Chest X ray
Perform in all with HIV+ with suspected TB, even if no
pulmonary symptoms – pulmonary involvement is common
Normal chest X ray does not rule out active pulmonary TB
Sputum samples for AFB smear and culture
3 samples recommended
Sputum smear negativity is common in HIV, especially in
severe immunodeficiency and noncavitary disease
AFB culture sensitivity not affected by HIV or
immunodeficiency
www.aidsetc.org
May 2013
24
TB Disease: Diagnosis (2)
Extrapulmonary TB: sample suspected tissue or
fluid
Lymph nodes: histopathology, smear, and culture
Pleural or pericardial fluid, ascites, CSF
Urine and blood cultures: sensitivity relatively high in
advanced immunodeficiency
www.aidsetc.org
May 2013
25
TB Disease: Diagnosis (3)
Nucleic acid amplification (NAA)
May rapidly identify M tuberculosis
NAA recommended on at least 1 specimen from all
patients with suspected pulmonary TB
In AFB smear-positive specimens, highly predictive of
TB
Can be used to direct therapy and make clinical decisions
More sensitive than AFB smear
Positive in 50%-80% of smear-negative, culture-positive
specimens
Licensed only for sputum samples
www.aidsetc.org
May 2013
26
TB Disease: Diagnosis (4)
TST or IGRA may be useful in unusual
circumstances (eg, if definitive culture evidence
for active TB cannot be obtained)
Evidence of previous infection increases likelihood of
TB
Negative test result does not rule out TB disease
www.aidsetc.org
May 2013
27
TB Disease: Diagnosis (5)
Drug susceptibility testing on initial isolates from
all patients with suspected TB
Test first-line TB drugs
Repeat if sputum cultures remain positive for
MTB at/after 4 months of treatment, or become
positive again after ≥1 month of negative cultures
Second-line drug susceptibility testing:
Only in reference laboratories, only on specimens with
resistance to first-line TB medications
www.aidsetc.org
May 2013
28
TB Disease: Diagnosis (6)
Conventional susceptibility testing is well validated
by requires culture of M tuberculosis; may take 6
weeks
Genotypic testing allows rapid detection of
resistance (24 hrs)
Commercial tests available for RIF and INH resistance
Commercial tests for other TB drugs are in development
CDC can provide rapid molecular testing for patients
who do not have local access to this testing
www.aidsetc.org
May 2013
29
TB Disease: Diagnosis (7)
Consider drug resistance testing:
Known exposure to drug-resistant TB
Country or area with high rates of drug-resistant TB
Persistently positive smear or culture results at/after 4
months of treatment
Previous TB treatment, particularly if no DOT of if
interrupted
www.aidsetc.org
May 2013
30
TB Disease: Diagnosis (8)
Multidrug resistant (MDR): resistance to at least
INH and RIF
Extensively drug resistant (XDR): resistance to
MDR TB plus resistance to a fluoroquinolone and
either kanamycin, amikacin, or capreomycin
High risk of treatment failure and relapse; consult
with specialist
www.aidsetc.org
May 2013
31
TB Disease: Treatment
For patients with clinical and radiographic
presentation suggestive of TB, start empiric
treatment for TB, after collection of specimens for
culture and molecular diagnostic tests
Early diagnosis and treatment are critical – TB can
progress rapidly in advanced immunodeficiency
www.aidsetc.org
May 2013
32
TB Disease: Treatment (2)
General principles
2 phases: intensive (2 months) and continuation (4+
months)
If TB is suspected, empiric treatment should be started
and continued until diagnostic workup is complete
DOT is recommended for all
Addition of case management, other social support, and
linkage to HIV care further increases likelihood of successful
treatment (enhanced DOT)
Treatment duration based on total number of doses
ingested, rather than on duration of treatment
administration
www.aidsetc.org
May 2013
33
TB Disease: Treatment (3)
For drug-susceptible pulmonary TB
Intensive phase: 2 months
Isoniazid (INH), rifampin (RIF) or rifabutin (RFB), pyrazinamide
(PZA), ethambutol (EMB)
If concern about resistance to RIF, use expanded regimen
(consult with expert)
If organism is susceptible to INH and RIF, may discontinue
EMB
Continuation phase: ≥4 months
INH + RIF (or RFB)
www.aidsetc.org
May 2013
34
TB Disease: Treatment (4)
Frequency of dosing for HIV-infected patients:
Intensive phase
Daily therapy by DOT recommended (7 days/week for 56
doses or 5 days/week for 40 doses)
2-3 times weekly dosing: increased risk of treatment failure or
relapse, with rifamycin resistance
Continuation phase
Daily (5-7 days/week) or TIW dosing recommended
Less-frequent dosing: increased risk of treatment failure,
relapse, and rifamycin resistance
www.aidsetc.org
May 2013
35
TB Disease: Treatment (5)
Duration of treatment for HIV-infected patients
(drug-susceptible TB):
Optimal duration unknown; some data in high-burden
settings show higher rates of recurrence if treated 6
months vs 9 or 12 months
In the U.S., 6 months recommended for most with
drug-susceptible TB
9 months if sputum culture positive at 2 months
9-12 months if CNS involvement
6-9 months if bone and joint TB
6-9 months if extrapulmonary TB at other sites
www.aidsetc.org
May 2013
36
TB Disease: Treatment (Drug
Sensitive) (6)
Intensive phase (8 weeks), QD dosing (5-7 days/week):
INH 5 mg/kg (usual dose 300 mg) PO QD +
RIF* 10 mg/kg (usual dose 600 mg) PO QD (or RFB** 5 mg/kg
(usual dose 300 mg) PO QD) +
PZA 40-55 kg, 1,000 mg PO QD; 56-75 kg, 1,500 mg PO QD; >75
kg, 2,000 mg PO QD +
EMB 40-55 kg, 800 mg PO QD; 56-75 kg, 1,200 mg PO QD; >75
kg, 1,600 mg PO QD
For TIW regimens, see Guidelines
* Rifampin interacts with many ARVs and other drugs; consult
information on contraindicated combinations
** Adjust dosage for interacting ARVs
www.aidsetc.org
May 2013
37
TB Disease: Treatment (Drug
Sensitive) (7)
Continuation phase (≥16 weeks)
QD regimen (5-7 days/week):
INH 5 mg/kg (usual dose 300 mg) PO QD + RIF* 10 mg/kg (usual
dose 600 mg) PO QD (or RFB** 5 mg/kg [usual dose 300 mg] PO
QD)
OR
TIW regimens:
INH 15 mg/kg (usual dose 900 mg) PO TIW + RIF* 10 mg/kg
(usual dose 600 mg) PO TIW (or RFB** 5 mg/kg [usual dose 300
mg] PO TIW)
* Rifampin interacts with many ARVs and other drugs; consult
information on contraindicated combinations
** Adjust dosage for interacting ARVs
www.aidsetc.org
May 2013
38
TB Disease: Treatment (8)
Other therapies
Pyridoxine (25-50 mg QD) for all on INH (to
decrease risk of neuropathy)
Corticosteroids improve survival for CNS or
pericardial disease
www.aidsetc.org
May 2013
39
TB Disease: Starting ART
For optimal management of HIV-related TB, treat
both infections
Sequential treatment of TB followed by HIV treatment
is not recommended
www.aidsetc.org
May 2013
40
TB Disease: Starting ART (2)
Cotreatment :
Improves survival, particularly if CD4 count <50
cells/µL
Decreases risk of other OIs
Can achieve high rates of HIV suppression
May improve TB treatment outcomes
Risks of early ART:
Multidrug therapy for 2 infections, drug-drug interactions,
overlapping side effects, IRIS
www.aidsetc.org
May 2013
41
TB Disease: Starting ART (3)
ART-naive patients:
CD4 <50 cells/µL: start ART within 2 weeks
CD4 ≥50 cells/µL: start ART by 8-12 weeks
TB meningitis and low CD4: optimal timing of ART is
not clear; risk of severe adverse events with early ART;
consult with experts
Patients on ART:
Start TB treatment immediately
Optimize ART if needed to suppress HIV
Modify ART to reduce risk of drug interactions
www.aidsetc.org
May 2013
42
TB Disease: Starting ART (4)
Drug-drug interactions
Rifamycins (especially RIF)
Induce CYP3A metabolism of many drugs, including most
protease inhibitors (PIs) and nonnucleoside reverse
transcriptase inhibitors (NNRTIs)
Have other complex interactions with some ARVs
Dosage adjustments may be required, and some combinations
cannot be used
Considerable interpatient variations: consider therapeutic drug
monitoring for RFB and/or PIs or NNRTIs
Despite these issues, rifamycins should be used for treatment
of TB, if possible
www.aidsetc.org
May 2013
43
TB Disease: Starting ART (5)
NRTIs: no significant interactions with rifamycins
NNRTIs:
Efavirenz 600 mg QD + 2 NRTIs is preferred ART regimen
for patients taking RIF
Dosage adjustments for weight >60 kg appears not supported by
good data
Nevirapine- more significant interactions with RIF.
Can be used for patients unable to take efavirenz
Nevirapine + didanosine + lamivudine inferior to efavirenz with
the same NRTIs
Monitor HIV RNA closely
If on RIF for ≥2 weeks, omit lead-in dose of nevirapine
RFB: increased dosage of RFB needed if used with
efavirenz
www.aidsetc.org
May 2013
44
TB Disease: Starting ART (6)
PIs:
RIF lowers serum levels of most PIs, including ritonavirboosted PIs: contraindicated
RFB has little effect on levels of ritonavir-boosted PIs but all
PIs markedly increase RFB concentrations
Dosage reduction of RFB is needed, though optimal dosing is not
clear
150 mg QD recommended for those on boosted PI, at least during first
2 months of TB treatment
Some reports of acquired rifamycin resistance with 150 mg TIW dosing
of RFB + a boosted PI
Consider therapeutic drug monitoring for RFB
Closely monitor ART adherence (need to increase
RFB dosage if PI is stopped)
www.aidsetc.org
May 2013
45
TB Disease: Starting ART (7)
Integrase inhibitors:
Raltegravir: RIF decreases raltegravir levels
Raltegravir 800 mg BID recommended but not studied in clinical
trials
Elvitegravir + cobicistat: no data; drug interactions expected
to be similar to those with boosted PIs
Use only when required for ARV potency; consult with an
expert
CCR5 antagonist: RIF and possibly RFB decrease
maraviroc levels; few data; consult with expert
Fusion inhibitor: enfuvirtide not affected by rifamycins
www.aidsetc.org
May 2013
46
TB Disease: Monitoring
Close follow-up is essential to ensure treatment
success
Pulmonary TB: monthly sputum smear and
culture until 2 consecutive negative cultures
Sputum cultures usually convert to negative with 2
months of TB therapy; may be longer if high burden of
disease (eg, cavitary TB)
Positive cultures after 4 months: evaluate for possible
treatment failure and acquired drug resistance
Extrapulmonary TB: follow-up evaluation
depends on sites involved
www.aidsetc.org
May 2013
47
TB Disease: Monitoring (2)
Clinical and laboratory assessments at least
monthly (liver and renal function tests, CBC,
platelets, CD4)
At each visit, screen for lapses in adherence,
possible adverse effects
Patient on EMB: ask about blurred vision or scotomata;
test for visual acuity and color discrimination
Routine drug level monitoring is not
recommended (consider if slow response to
treatment)
www.aidsetc.org
May 2013
48
TB Disease: Adverse Events
First-line TB medications should not be stopped
permanently without strong evidence that a TB
drug was the cause of
a reaction
Consult with experts
www.aidsetc.org
May 2013
49
TB Disease: Adverse Events (2)
GI reactions: common with most TB drugs; usually can be
managed symptomatically; check AST and bilirubin
Rash: common with all TB drugs; if minor, use
antihistamines for symptomatic relief; if severe, stop all
TB drugs until rash is substantially better; restart TB
drugs one by one at intervals of 2-3 days; if recurrence:
stop the last drug added
If generalized rash + fever or mucous membrane involvement,
stop all drugs, switch to alternative TB medications; consult with
expert
Fever after several weeks of TB treatment: exclude
worsening TB, superinfection, IRIS; if drug fever
suspected, stop all TB drugs; after resolution of fever,
restart as above
www.aidsetc.org
May 2013
50
TB Disease: Adverse Events (3)
AST elevation: common, may be caused by INH,
RIF/RFB, or PZA; risk higher in patients taking other
hepatotoxic drugs and in those with liver disease
If no symptoms and AST <3 times ULN, continue TB therapy
but increase frequency of monitoring
If AST ≥5 times ULN, or ≥3 times ULN with symptoms, or if
significant increase in bilirubin or alkaline phosphatase, stop
hepatotoxic drugs and evaluate patient (eg, for symptoms,
viral hepatitis, hepatotoxins)
Substitute nonhepatotoxic drugs, until alternative longer-term
regimen is designed
After AST decreases to <2 times ULN, may restart suspected TB
meds one at a time; if hepatotoxicity recurs, stop the last drug
added
www.aidsetc.org
May 2013
51
TB Disease: Adverse Events (4)
EMB may cause visual disturbances
Monthly review of symptoms
Monthly visual acuity and color discrimination testing
for all patients on dosages that are higher than
recommended and all patients on EMB >2 months
www.aidsetc.org
May 2013
52
TB Disease: IRIS
Paradoxical TB IRIS: temporary exacerbation of
symptoms, signs, or radiographic manifestations
of TB after initial improvement on TB treatment;
may include:
High fever
Worsening respiratory status
New or worsening lymphadenopathy
Worsening CNS lesions or symptoms
Worsening pulmonary infiltrates
Increasing pleural effusions
www.aidsetc.org
May 2013
53
TB Disease: IRIS (2)
Symptoms usually begin in the first 1-4 weeks
after starting ART, usually last 2-3 months
Risk factors: low CD4 count at start of ART (especially
<100 cells/µL), disseminated or extrapulmonary TB,
ART started shortly after start of TB therapy
(particularly within first 2 months of TB therapy)
No definitive tests; may be difficult to distinguish IRS
from worsening of TB, treatment failure, new infection,
adverse drug reaction, etc.
Evaluate thoroughly for other causes
www.aidsetc.org
May 2013
54
TB Disease: IRIS (3)
Management
Usually self-limited; can be prolonged and severe
Mild IRIS
Symptomatic treatment, NSAIDs
Aspiration of fluid collections, if indicated for symptomatic relief
Moderate-to-severe IRIS
Consider corticosteroids:
Some data show more rapid improvement, though no mortality benefit
in non-CNS TB IRIS
CNS TB IRIS: corticosteroids decreased mortality
Taper corticosteroids over 4 weeks or longer, based on clinical
assessment
Avoid in patients with Kaposi sarcoma
Continue TB therapy
Continue ART if possible (unless IRIS is life threatening)
www.aidsetc.org
May 2013
55
TB Disease: IRIS (4)
Unmasking TB IRIS: patients with unrecognized
TB when they start ART; may develop
accelerated and inflammatory presentation of TB
in the first weeks of ART
May have rapid onset of symptoms, features similar to
bacterial pneumonia, and/or abscesses and
lymphadenitis
Treatment: standard TB treatment; corticosteroids if
life-threatening manifestations
www.aidsetc.org
May 2013
56
TB Disease: Treatment Failure
Causes include
Undetected primary drug resistance, inadequate adherence
to therapy, incorrect or inadequate regimen, subtherapeutic
drug levels (malabsorption, drug interactions),
superinfection with resistant MTB, acquired drug resistance
Evaluate with history, physical exam, chest X ray
Review initial test results, therapy regimen,
adherence
Repeat culture and susceptibility testing; sample all
available sites
Perform rapid resistance testing on direct specimens or
positive cultures
www.aidsetc.org
May 2013
57
TB Disease: Treatment Failure (2)
Pending repeat culture and resistance test
results, broaden treatment using second-line TB
drugs (consult with expert)
Drug-resistant TB: optimal management not
established
Resistance to INH:
Evidence of increased risk of treatment failure with
baseline INH resistance
Substitute fluoroquinolone for INH, at least for first 2
months of therapy and perhaps for continuation phase,
with RIF and EMB; total duration 9 months
www.aidsetc.org
May 2013
58
TB Disease: Treatment Failure (3)
Resistance to RIF:
Treatment is more complex, less effective, and of
longer duration
Second- and third-line TB medications should be used,
based on drug susceptibility results
New drugs are in development
Consult with expert
www.aidsetc.org
May 2013
59
TB Disease: Management of Drug
Resistance
Resistance to INH:
(RIF or RFB) + EMB + PZA + (moxifloxacin or levofloxacin)
for 2 months, followed by RIF or RFB) + EMB +
(moxifloxacin or levofloxacin) for 7 months
Empiric therapy for suspected resistance to rifamycin
+/− resistance to other drugs:
INH + RIF or RFB + PZA + EMB + moxifloxacin or levofloxacin +
(an aminoglycoside or capreomycin)
Suspected resistance to rifamycins +/− resistance to
other drugs:
Individualize treatment and duration based on susceptibility,
clinical and microbiological responses
Manage with specialist
www.aidsetc.org
May 2013
60
TB Disease: Preventing Recurrence
Recurrence risk somewhat higher in HIV infection,
especially in TB-endemic settings, usually via
reinfection
In U.S., reinfection is uncommon
In high-burden settings (high risk of re-exposure),
treatment with INH for 6-9 months after completion of
standard TB therapy can decrease risk of reinfection
Not recommended in low-burden settings
ART probably decreases risk of reinfection with TB
www.aidsetc.org
May 2013
61
TB Disease: Considerations in
Pregnancy
All pregnant women should be tested (TST),
unless documented negative TST result
All at high risk of repeated or ongoing exposure should
be tested
Limited data on IGRAs in pregnant women
Diagnosis as in nonpregnant adults
(minimize fetal radiation exposure)
TB (pulmonary or extrapulmonary) may increase
complications, including preterm birth, low
birthweight, intrauterine growth retardation
www.aidsetc.org
May 2013
62
TB Disease: Considerations in
Pregnancy (2)
LTBI: consider treatment during pregnancy (after
ruling out active TB)
Weigh risk of INH toxicity against consequences of
active TB
High risk of maternal and infant mortality in HIV-infected
pregnant women with TB
ART decreases risk of progression from LTBI to active
TB
www.aidsetc.org
May 2013
63
TB Disease: Considerations in
Pregnancy (3)
TB disease:
Treat as in nonpregnant adults
Therapy should not be withheld because of pregnancy
www.aidsetc.org
May 2013
64
TB Disease: Considerations in
Pregnancy (4)
Treatment considerations (1)
INH: not teratogenic; hepatotoxicity may be more
frequent; monitor transaminases monthly through
postpartum period
RIF: not teratogenic
PZA: limited experience in human pregnancy (not
teratogenic in animals); WHO recommends routine
use, but limited data and not recommended in United
States; if PZA not used in initial treatment, minimum
duration of therapy is 9 months
www.aidsetc.org
May 2013
65
TB Disease: Considerations in
Pregnancy (5)
Treatment considerations (2)
EMB: teratogenic in animals at high doses; no
evidence of teratogenicity in humans; no evidence of
ocular toxicity in exposed infants
Second-line drugs: limited experience; some should be
avoided; consult with experts
www.aidsetc.org
May 2013
66
Websites to Access the Guidelines
http://www.aidsetc.org
http://aidsinfo.nih.gov
www.aidsetc.org
May 2013
67
About This Slide Set
This presentation was prepared by Susa Coffey,
MD, for the AETC National Coordinating
Resource Center in May 2013
See the AETC NCRC website for the most
current version of this presentation:
http://www.aidsetc.org
www.aidsetc.org
May 2013
68