initial treatment of tuberculosis your name institution/organization meeting date international...
TRANSCRIPT
Initial Treatment of Tuberculosis
Your name Institution/organizationMeetingDate
International Standards 7, 8, 10, 13, 17, 21
ISTC TB Training Modules 2009
Initial Treatment of Tuberculosis
Objectives: At the end of this presentation,participants will have an understanding of:
Drug regimens used in the initial treatment of both pulmonary and extrapulmonary tuberculosis
The basis for the public health benefits of treating tuberculosis
The clinical and microbiological effects of treatment The rationale for patient monitoring and reporting The main adverse effects of antituberculosis drugs
ISTC TB Training Modules 2009
Initial Treatment of Tuberculosis
Overview: Effect of appropriate
treatment on public health First-line treatment
recommendations Treatment of extrapulmonary
tuberculosis Monitoring of treatment Adverse reactions Recording and reporting
International Standards 7, 8, 10, 13, 17, and 21
ISTC TB Training Modules 2009
Standards for Treatment
ISTC TB Training Modules 2009
Initial Treatment of TuberculosisStandards 7 & 8
ISTC TB Training Modules 2009
Standard 7: Public Health Responsibility
Any practitioner treating a patient for tuberculosis is assuming an important public health responsibility to prevent ongoing transmission of the infection and the development of drug resistance. To fulfill this responsibility the practitioner must not only prescribe an appropriate regimen, but also utilize local public health services and other agencies, when necessary, to assess the adherence of the patient and to address poor adherence when it occurs.
ISTC TB Training Modules 2009
Effect of Treatment on Public Health
Why is TB Treatment a Public Health Measure?
Effective treatment rapidly kills organisms, reducing the bacillary population in respiratory secretions, thus reducing the potential for transmission.
Effective multiple-drug treatment greatly reduces the risk of resistant organisms emerging.
Effective treatment decreases the duration and severity of illness and reduces the risk of death.
ISTC TB Training Modules 2009
Effect of Treatment on Public Health
100
120
140
160
180
200
220
1980 1985 1990 1995 2000
Pu
lmo
nar
y T
B c
as
es/1
00,0
00
DOTS 1990
PTB falling at 6%/yr
case finding
Effects of Treatment on the Incidence of Tuberculosis in Peru
ISTC TB Training Modules 2009
Standard 8: Initiation of Treatment
All patients (including those with HIV infection) who have not been treated previously should receive an internationally accepted first-line treatment regimen using drugs of known bioavailability. The initial phase should consist of two months of isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB).
(1 of 2)
ISTC TB Training Modules 2009
Mixed population (susceptible and resistant)
INH resistant bacilli
Emergence of INH resistant strain because of ineffective treatment (INH monotherapy)
Effective multi-drug therapy
Effect of Treatment on Bacillary Population
Weeks
Log
cfu
0 2 4 6 8 10 12 14 16 18 20 22 24
ISTC TB Training Modules 2009
Months of Rx 0 5 7 9
INH
RIF
EMB
Smear + + + +
Culture + + + +
Susceptibility
INH R* R R R
RIF S* R R R
EMB S* S S R
* Results not known to clinician
Unintended Monotherapy and Resistance
ISTC TB Training Modules 2009
Treatment Goals
Microbiological Goals of Antituberculosis Chemotherapy Kill tubercle bacilli rapidly
(early bactericidal effect) Prevent the emergence of drug
resistance Eliminate persistent bacilli to prevent
relapse (sterilizing effect)
ISTC TB Training Modules 2009
Activities of Antituberculosis Drugs
Highest ++++ High +++ Intermediate ++ Low +
DrugEarly
bactericidal activity
Preventing drug
resistance
Sterilizing activity
Isoniazid ++++ +++ ++
Rifampicin ++ +++ ++++
Pyrazinamide + + +++
Streptomycin ++ ++ ++
Ethambutol ++ - +++ ++ +
ISTC TB Training Modules 2009
Standard 8: Continuation of Treatment
The continuation phase should consist of isoniazid and rifampicin given for four months
The doses of antituberculosis drugs used should conform to international recommendations
Fixed-dose combinations (FDCs) of two (INH and RIF), three (INH, RIF, and PZA), and four (INH, RIF, PZA, and EMB) drugs are highly recommended
(2 of 2)
ISTC TB Training Modules 2009
Treatment Recommendations
1. Associated with higher rate of acquired drug resistance and must be given using directly-observed therapy. Where feasible, daily dosing is preferred. May consider daily initiation phase, then 3x week continuation phase. 3x weekly dosing not recommended if living with HIV or living in an HIV-prevalent setting.
New Patients (not previously treated)
Initial Phase(2 months)
Continuation Phase(4 months)
INH, RIF, PZA, EMB daily INH, RIF daily
INH, RIF, PZA, EMB1 3x/wk. INH, RIF 3x/wk
ISTC TB Training Modules 2009
Dose Recommendations
Drug Daily 3x Week
INH 5 (4-6), max 300/d 10 (8-12), max 900/d
RIF 10 (8-12), max 600/d 10 (8-12) max 600/ d
PZA 25 (20-30), max 2000/d 35 (30-40), max 3000/d
EMB 15 (15-20), max 1600/d 30 (25-35), max 2400/d
Streptomycin 15 (12-18) 15 (12-18)
Adults: mg/kg (range)
ISTC TB Training Modules 2009
Standard 17: Treat Co-morbid Disease(1 of 2)
All providers should conduct a thorough assessment for co-morbid conditions that could affect tuberculosis treatment response or outcome
At the time the treatment plan is developed, the provider should identify additional services that would support an optimal outcome for each patient and incorporate these services into an individualized plan of care
ISTC TB Training Modules 2009
This plan should include assessment of and referrals for treatment of other illnesses with particular attention to those known to affect treatment outcome, for instance care for diabetes mellitus, drug and alcohol treatment programs, tobacco smoking cessation programs, and other psychosocial support services, or to such services as antenatal or well baby care
Standard 17: Treat Co-morbid Disease(2 of 2)
ISTC TB Training Modules 2009
Treatment of Extrapulmonary TB
ISTC TB Training Modules 2009
In general, extrapulmonary tuberculosis is treated the same as pulmonary tuberculosis
Some experts recommend extending the duration of therapy in patients with:
• Meningeal tuberculosis
• Bone/joint tuberculosis
Corticosteroids may be useful adjunctive treatment in some forms of extrapulmonary tuberculosis
Treatment of Extrapulmonary TB
ISTC TB Training Modules 2009
Treatment Duration and Use of Steroids
Site Length of Rx (mos.) Corticosteroids
Lymph node 6 No
Bone/Joint 6-9 No
Pleural 6 No
Pericarditis 6 Yes
CNS 9-12 Yes
Disseminated 6 No
Genitourinary 6 No
Abd/Peritoneal 6 No
Treatment of Extrapulmonary TB
ISTC TB Training Modules 2009
Monitoring Treatment for TBand Public HealthReportingStandards 10, 13, & 21
ISTC TB Training Modules 2009
Standard 10: Monitoring Treatment
1 of 2
Response to therapy in patients with pulmonary tuberculosis should be monitored by follow-up sputum smear microscopy (2 specimens) at the time of completion of the initial phase of treatment (2 months).
If the sputum smear is positive at completion of the initial phase, sputum smears should be examined again at 3 months and, if possible, culture and drug susceptibility testing should be performed.
(1 of 2)
ISTC TB Training Modules 2009
Standard 10: Monitoring Treatment
2 of 2
In patients with extrapulmonary TB and in children, the response to treatment is best assessed clinically.
(2 of 2)
ISTC TB Training Modules 2009
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
0 1 2 3 4 5 6Months
Initial Phase Continuation Phase
DiagnosticEnd of intensive phase
Assessment for failure
Completion
Monitoring: Timing of Sputum Specimens
[*Obtain if smear-positive at month 2]
ISTC TB Training Modules 2009
Treatment Outcomes for Pulmonary TB
98%64%
32%
20%18%
50%
10%
Dead
Sputum negative
Sputum positive
No Chemotherapy
PoorChemotherapy
Good Chemotherapy
0.8%
1.2%
Grzybowski S et al, Bull Int Union Tuberc 1978; (53)2: 70-5
ISTC TB Training Modules 2009
Monitoring: Adverse Reactions
• Drugs are listed in order of relative likelihood of causing adverse reaction.
• INH/RIF and RIF/PZA appear to have synergistic effects in causing hepatitis
Adverse Reaction
Drugs
Rash PZA, INH, RIF, EMB
Gastrointestinal intolerance
PZA, RIF
Liver toxicity
PZA, INH, RIF
Peripheral neuropathy
INH, (EMB)
Optic neuritis
EMB
Gout PZA
ISTC TB Training Modules 2009
Adverse Reactions: Rash
Severe skin rash from thioacetazone
Classic drug-related rash
ISTC TB Training Modules 2009
Drug-induced HepatotoxicityHepatotoxic reactions: Transaminase elevation age-dependent
with INH Transaminase elevation dose-dependent
with PZA Cholestasis (increase in bilirubin and
alkaline phosphatase) with RIF Symptoms imply significant hepatotoxicity (Mild transaminase elevation may not be
clinically significant)
ISTC TB Training Modules 2009
Managing Hepatotoxicity
Management Hold all medications and follow liver
enzymes for significant hepatotoxicity Re-challenge depends on circumstances
and severity of liver dysfunction In general, patients should be restarted
with EMB (the least hepatotoxic drug) and RIF, usually followed in several days by INH if there is no worsening of liver function
ISTC TB Training Modules 2009
A written record of all medications given, bacteriologic response, and adverse reactions should be maintained for all patients
Standard 13: Monitoring Record
ISTC TB Training Modules 2009
Standard 21: Reporting Cases
All providers must report both new and retreatment tuberculosis cases and their treatment outcomes to local public health authorities, in conformance with applicable legal requirements and policies.
ISTC Training Modules 2008
ISTC TB Training Modules 2009
Summary: Appropriate treatment and assessment of
adherence to treatment is an important public health issue.
The use of internationally accepted first-line treatment regimens is associated with a high cure rate and a low risk of acquired drug resistance.
Initial Treatment of Tuberculosis
ISTC TB Training Modules 2009
Summary (cont.): Pulmonary and extrapulmonary TB are
generally treated with the same regimens. (Exception: extended duration in meningeal and bone/joint disease.)
Treatment includes assessment and services for co-morbid conditions that may effect tuberculosis treatment outcomes
Monitoring for both response to treatment and for potential adverse events is essential.
Initial Treatment of Tuberculosis
ISTC TB Training Modules 2009
Summary: ISTC Standards Covered*
Standard 7: Practitioners assume an important public health responsibility in ensuring both appropriate treatment regimens and assessment of treatment adherence for their patients.
* Abbreviated versions
ISTC TB Training Modules 2009
Summary: ISTC Standards Covered*
Standard 8: All patients (including those with HIV infection) who have not been previously treated should receive an internationally accepted treatment regimen of known bioavailability:• Initial phase: 2 months INH, RIF, PZA, and
EMB• Continuation phase: 4 months INH and RIF
The doses of anti-TB drugs used should conform to international recommendations. Fixed-dose combinations are highly recommended.
* Abbreviated versions
ISTC TB Training Modules 2009
Standard 10: Response to therapy in patients with pulmonary TB should be monitored by follow-up 2 sputum smears at the end of the initial phase, and if positive, repeated at the end of 3 months (if positive at 3 months, obtain culture and DST). In extrapulmonary TB and in children, the response to treatment is best assessed clinically.
Summary: ISTC Standards Covered*
* Abbreviated versions
ISTC TB Training Modules 2009
Standard 13: A written record of all medications given, bacteriologic responses, and adverse reactions should be maintained for all patients.
Standard 17: All providers should conduct a thorough assessment and provide services or referrals for co-morbid conditions with particular attention to those known to effect treatment outcome
* Abbreviated versions
Summary: ISTC Standards Covered*
ISTC TB Training Modules 2009
Standard 21:
All providers must report both new and retreatment TB cases and their treatment outcomes to local public health authorities
* Abbreviated versions
Summary: ISTC Standards Covered*
ISTC TB Training Modules 2009
Alternate Slides
ISTC TB Training Modules 2009
Purpose of ISTC
ISTC TB Training Modules 2009
ISTC: Key Points
21 Standards (revised/renumbered in 2009) Differ from existing guidelines: standards
present what should be done, whereas, guidelines describe how the action is to be accomplished
Evidence-based, living document Developed in tandem with Patients’ Charter
for Tuberculosis Care Handbook for using the International
Standards for Tuberculosis Care
ISTC TB Training Modules 2009
Audience: all health care practitioners, public and private
Scope: diagnosis, treatment, and public health responsibilities; intended to complement local and national guidelines
Rationale: sound tuberculosis control requires the effective engagement of all providers in providing high quality care and in collaborating with TB control programs
ISTC: Key Points
ISTC TB Training Modules 2009
Questions
ISTC TB Training Modules 2009
Initial Treatment of Tuberculosis
1. A 28 year-old woman taking standard four-drug treatment for TB for five weeks now complains of nausea, vomiting, and right upper-quadrant discomfort. When seen in clinic she is noted to have scleral icterus and right upper-quadrant tenderness. Her urine is dark colored. What is the appropriate action to take at this time?
A. Stop all drugs
B. Stop isoniazid
C. Give pyridoxine (vitamin B6)
D. Replace pyrazinamide with streptomycin
ISTC TB Training Modules 2009
Initial Treatment of Tuberculosis
2. A 68 year-old woman with smear-positive TB needs to start treatment. She lives too far to be given directly-observed treatment (DOT) by your office. Which treatment regimen is preferred for this patient?
A. Isoniazid and ethambutol for twelve months
B. Isoniazid/rifampicin/ethambutol for the first two months, followed by isoniazid/rifampicin for an additional four months
C. Fixed-dose combination of isoniazid/rifampicin/pyrazinamide for nine months
D. Fixed-dose combinations of isoniazid/rifampicin/ethambutol/pyrazinamide for the first two months, followed by isoniazid/rifampicin for an additional four months
ISTC TB Training Modules 2009
Initial Treatment of Tuberculosis3. In considering treatment for extrapulmonary
disease, all of the following statements are correct except:
A. Extrapulmonary disease is a sign of disseminated disease, and therefore always requires a longer duration of treatment
B. Most presentations of extrapulmonary TB can be treated with the same standard six month regimens used for pulmonary TB
C. Extending the duration of therapy is recommended by many experts for central nervous system (CNS) and bone/joint extrapulmonary TB
D. Corticosteroids are sometimes recommended for pericardial and central nervous system (CNS) extrapulmonary TB