Lecture MDR TB

cHRYSós 2 0 2 3
MDR-TB
Dr. nilyn OLIVA-YGNACIO
B3m2
Lecture
OBJECTIVES:
- Define and classify drug resistant TB
- Review updates on the incidence of MDR-TB
- Discuss the diagnostic flow of MDR-TB
- Identify laboratory tools necessary in this disease
- Discuss the treatment regimen of MDR-TB
- Emphasize on the importance of monitoring treatment, evaluation,
and prevention in MDR-TB
GOAL OF TREATMENT:
- Cure
- Minimizing transmission
PATTERNS OF RESISTANCE:
Multidrug resistance (MDR)
- Resistance to at least both isoniazid and rifampicin
Tuberculosis is the top infectious killer in the world:
Extensive drug resistance (XDR) - In 2019, 1.4 million** people died from tb
- Any fluoroquinolone - Including 208,000 people with HIV
- And at least one of three second-line injectable drugs (capreomycin, - TB is the leading killer of people with HIV and a major cause of
kanamycin and amikacin) deaths related to antimicrobial resistance
**The 95% uncertainty intervals are 1.1-1.3 million for TB deaths and 177,000
Pre-XDR TB to 242,000 for TB/HIV deaths
- Resistance to either 1 but not both classes of drugs
Drug-resistant tuberculosis remains a public health crisis:
- In 2019, about 0.5 million people fell ill with drug-resistant TB*
DIAGNOSIS - Only 38% people accessed the treatment
- Of those treated, only 57% were treated successfully
**The 95% uncertainty interval for the incidence of rifampin-resistant TB is
400,000 to 535,000. About 78% of these cases had multi-drug resistant TB
More people reached with quality TB care:

- In 2019, an estimated 10 million people fell ill with TB**
- 7.1 million people reported to have access to TB care up from 6.4
million in 2017
- =2.9million were undiagnosed or not reported
- Better reporting, diagnosis and access to care will close this gap
**The 95% uncertainty interval for TB incidence is 8.9-11.0 million
- Therefore, appropriate treatment with a combination of several

quality-assured TB medicines dramatically diminishes the risk of
selection of resistant strains.
- This is the rationale for using a combination of quality-assured
medicines when treating TB, while ensuring good adherence
PRIMARY DRUG RESISTANCE

- Primary or initial drug resistance means that a person has been
infected with a drug-resistant TB strain
- Transmission of drug-resistant TB occurs exactly in the same way as
transmission of drug susceptible TB
The two strongest risk factors for XDR-TB are:

1. Failure of an MDR-TB treatment regimen, which contains second-line
drugs including an injectable agent and a fluoroquinolone; and
2. Close contact with an individual with documented XDR-TB or with an
individual for whom treatment with a regimen including 2nd-line
drugs is failing or has failed
cHRYSós 2 0 2 3
MDR-TB
B3m2
Lecture
TREATMENT
DIAGNOSTICS:
- Definitive diagnosis of drug-resistant TB requires that
Mycobacterium tuberculosis bacteria be detected and resistance to
anti-TB drugs determined.
o By isolating the bacteria
o By culture, identifying it as belonging to the M.
tuberculosis complex (MTBc), and
o Conducting drug susceptibility testing (DST) using solid
or liquid media or
o By performing a WHO endorsed molecular test to detect
TB DNA and mutations associated with resistance
Drug susceptibility testing:

- Phenotypic
- Genomic
First-line DST
- Most reliable for rifampicin and isoniazid
- Less reliable and reproducible for streptomycin, ethambutol and
pyrazinamide (pyrazinamide testing can only be performed on liquid
media after appropriate pH adjustment)
Second-line DST:
- Has good reliability and reproducibility for 2nd line injectable drugs
(amikacin, kanamycin, capreomycin) and fluoroquinolones
- Data on the reproducibility and reliability of DST for the other 2nd
line drugs are limited, and for several of them methods have not
been established or standardized;
- Data correlating DST results to the clinical outcome are still
insufficient
Ethionamide – has more side effects

Macrolide – did not make any difference in the treatment
cHRYSós 2 0 2 3
MDR-TB
B3m2
Lecture
DURATION OF TREATMENT: Summary:

Intensive phase: - Prevention is better than cure
- Benefits of 5 to 7 months of treatment after conversion were more - Early diagnosis is always the key
pronounced
Continuation phase:
- MDR-TB only - total treatment duration of at least 15 and up to 21
months after culture conversion
- Pre-XDR TB and XDR-TB: total treatment duration of between 15 and
24 months after culture conversion
Correlate clinically:
- Time to conversion was inversely related to duration of treatment
after conversion
MONITORING TREATMENT
Assessment of patients when treatment failure is suspected:

- The treatment card should be reviewed to confirm that the patient
has fully adhered to treatment
- Look for undetected comorbidities
- The bacteriological data should be reviewed
- Review the DST
- Review treatment regimen
INFECTION CONTROL
MANAGEMENT OF CONTACTS (CONTACT TRACING)
Symptomatic adult contacts:
- An evaluation by a physician, including history and physical
examination
- A chest radiograph examination
- Sputum investigations (ideally a rapid diagnostic method such as
Xpert MTB/RIF, or if not available)
- Sputum smear microscopy, culture and drug susceptibility testing
(DST) and
- HIV testing (in areas of high HIV prevalence, or if anyone in the
household is known to be HIV positive)
Symptomatic child contact:

- An evaluation by a physician, including history and physical
examination
- A chest radiograph examination
- Tuberculin skin testing with purified protein derivative
- Sputum investigations (ideally a rapid diagnostic method such as
Xpert MTB/RIF, or if not available,
- Sputum smear microscopy, culture and DST); and
- HIV testing (in areas of high HIV prevalence, or if either parent is
known to be HIV-positive)

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cHRYSós 2 0 2 3

More people reached with quality TB care:

**The 95% uncertainty interval for TB incidence is 8.9-11.0 million

- Therefore, appropriate treatment with a combination of several

PRIMARY DRUG RESISTANCE

The two strongest risk factors for XDR-TB are:

Drug susceptibility testing:

Ethionamide – has more side effects

DURATION OF TREATMENT: Summary:

Assessment of patients when treatment failure is suspected:

Symptomatic child contact:

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