Download XDR-TB

XDR-TB
Presented by: :Mona Ahmed Sherif
Supervised by: DR . SEHAM HAFEZ
What is XDR-TB?
XDR-TB (Extensive /Extreme Drug Resistant TB)
is MDR-TB that is also resistant to three or more
of second-line drugs.
OR
MDR-TB that is resistant as well to any one of the
fluoroquinolones and to at least one of three
injectable second-line drugs
(Amikacin, Capreomycin or Kanamycin).
Causes for drug resistance to tuberculosis
Although its causes are microbial, clinical and
programmatic, DR-TB is essentially a man-made
phenomenon.
From a microbiological perspective, resistance is
caused by a genetic mutation that makes a drug
ineffective against the mutant bacilli.
From a clinical and programmatic perspective, it is
an inadequate or poorly administered treatment
regimen that allows a drug-resistant strain to
become the dominant strain in a patient infected
with TB.
Causes for drug resistance to
tuberculosis
Health-care providers
Patients:
Inadequate regimens
Inappropriate guidelines
Noncompliance / Absence
of guidelines
Poor training
No treatment monitoring
Poorly organized or funded
TB control programmes .
Inadequate drug intake
Poor adherence
Lack of information,
money, transportation
Adverse effects
Social barriers
Malabsorption
Coinfection with HIV
Drugs:
Inadequate supply or quality
Poor quality
Poor storage conditions
Wrong dose or combination
Risk factors for XDR-TB
The two strongest risk factors for XDR-TB are:
(i) Failure of an anti-TB regimen that contains
second-line drugs including an injectable agent
and a fluoroquinolone.
(ii) Close contact with an individual with documented
MDR-TB or with an individual for whom treatment
with a regimen including second-line drugs has failed.
Assessment of patients at risk for
treatment failure
Patients who do not show signs of improvement
after 4 months of treatment are at risk for
treatment failure.
All patients who show clinical, radiographical or
bacteriological evidence of progressive active
disease, or reappearance of disease after
month 4 of treatment, should be considered as
being at high risk for treatment failure.
Recommendation for patients at risk for
treatment failure :
XDR-TB poses a severe public health threat, especially in populations with high rates of
HIV .
Recommendations (acc to the WHO Guidelines ) for Prevention of XDR-TB include:
The treatment card should be reviewed to confirm that the patient has adhered to
treatment.

Ensure prompt diagnosis and treatment of drug resistant cases to cure existing cases
and prevent further transmission.

The treatment regimen should be reviewed in relation to medical history contacts and
all DST reports. If the regimen is inadequate, a new regimen should be designed.

The bacteriological data should be reviewed (the smear and culture data are the
strongest evidence that a patient is not responding to therapy).

The health-care worker should confirm that the patient has taken all the prescribed
medicines.

Other illnesses that may decrease absorption of medicines (e.g. chronic diarrhoea) or
may result in immune suppression (e.g. HIV infection) should be excluded.

Apply infection-control measures to avoid MDR-TB and XDRTB transmission to
protect patients, health workers, others working in broader community, especially in
high HIV prevalence settings.

If surgical resection is feasible, it should be considered.
Diagnosis
DR-TB must be diagnosed correctly before it
can be treated effectively. Case-finding
strategies may vary depending on the
epidemiological situation and local
capacity.
Practically
All suspects of DR-TB should have DST of
isoniazid and rifampicin, the second-line
injectable agents and a fluoroquinolone.
For people living with HIV who are at risk of
XDR-TB, given the high and rapid risk of
death, DST of first- and second-line drugs
is recommended.
XDR-TB
• While drug-susceptible TB can be cured within 6 months,
forms of DR-TB require extensive chemotherapy for up
to 2 years.
• It has proven that treatment of XDR-TB is much more
difficult to than treating MDR-TB and is extremely difficult
to treat in HIV-positive patients.
• Treatment outcomes are significantly worse in XDR-TB
patients than in MDR-TB patients.
• While for HIV positive patients being promptly diagnosed
with XDR-TB and placed on an adequate regimen have
been shown to have cure rates that exceed 50% .
Management guidelines for patients with XDR-TB
1.
2.
Use any oral First line agents that may be effective.
Use an injectable agent (kanamycin , amikacin ,capreomycin,streptomycin ) to
which the strain is susceptible and consider an extended duration of use (12
months). If resistant to all injectable agents, it is recommended to use one that
patient has never used before.
3.
4.
6.
7.
8.
Use a later-generation fluoroquinolone such as moxifloxacin.
Use all Group 4 agents (Oral bacteriostatic second-line antituberculosis drugs)
ethionamide ,protionamide ,cycloserine ,terizidone ,p-aminosalicylic acid
that have not been used extensively in a previous regimen .
Use 2 or more agents from Group 5 (Antituberculosis drugs with unclear
efficacy or unclear role in MDR-TB treatment (not recommended by WHO for
routine use in MDR-TB patients) clofazimine,linezolid ,amoxicillin/clavulanate
,thioacetazone, clarithromycin, imipenem
Consider high-dose isoniazid treatment if low-level resistance is documented.
Consider adjuvant surgery if there is localized disease.
Ensure strong infection control measures.
9.
10.
Treat HIV .
Provide comprehensive monitoring and full adherence support .
5.
Conclusion
Programmatic management of DR-TB is a
complex health intervention, and
no one strategy will fit all situations.
Programe managers need to consider
the epidemiological, financial and
operational factors when deciding which
strategy to use.
DR-TB and HIV co-infection
HIV infection is a significant challenge for the prevention,
diagnosis and treatment of DR-TB, especially in the case
of MDR-TB and XDR-TB.
The diagnosis of TB (including MDR-TB and XDR-TB) in
HIV-infected people is more difficult and may be
confused with other pulmonary or systemic infections.
The presentation is more likely to be extrapulmonary or
sputum smear-negative than in HIV-uninfected TB
patients, especially as immunosuppression advances .
This can result in misdiagnosis or delays in diagnosis, and
in turn, higher morbidity and mortality.
Reports have shown high mortality rates among HIVinfected patients with DR-TB.
Mangment of DR-TB and HIV Coinfection
• Use mycobacterial cultures and newer more rapid methods of
diagnosis.
• Perform DST at the start of antituberculosis therapy.
• Determine the extent (or prevalence) of TB drug resistance in
patients with HIV.
• Introduce ART (AntiRetrovial Therapy )rapidly in DR-TB/HIV
patients.
• Consider empirical therapy with second-line antituberculosis drugs.
• Provide CPT (co-trimoxazole preventive therapy) for patients with
active TB and HIV.
• Arrange treatment follow-up by a specialized team.
• Implement additional nutritional and socioeconomic support.
• Ensure effective infection control.
Concomitant treatment of DR-TB and HIV
The treatment of DR-TB in patients with HIV is very similar to that in patients
without HIV , with the following exceptions:
•
ART plays a vital role, as mortality in MDR-TB/HIV patients without the use
of ART is extremely high (91–100% ) .
•
The use of ART in HIV-infected patients with TB improves survival for both
drug-resistant and susceptible disease.
•
Adverse effects are more common in patients with HIV, due to multiple
medicines involved in DR-TB with recognized high toxicity risks, often
combined with ART, results in a high incidence of adverse effects. Some
toxicities are common to both antituberculosis treatment and ART, which
may result in added rates of adverse events.
•
Monitoring needs to be more intense for both response to therapy and
adverse effects.
•
IRIS (immune reconstitution inflammatory syndrome) may complicate
therapy.
Supportive care for patients in whom all the
possibilities
of XDR-TB treatment have failed
A number of supportive measures can be
used once the therapy has been
suspended.
It is very important that medical visits
continue and that the patient
is not abandoned.
These supportive measures are :
 Pain control and symptom relief. Paracetamol, or codeine with paracetamol,gives
relief from moderate pain. Codeine also helps control cough.Other cough
suppressants can be added. If possible, stronger analgesics,including morphine,
could be used when appropriate to keep the patient adequately comfortable.
 Relief of respiratory insufficiency. Oxygen can be used to alleviate shortness of
breath. Morphine also provides significant relief from respiratory insufficiency and
should be offered if available.
 Nutritional support. Small and frequent meals are often best for a person at the end
of life. It should be accepted that the intake will reduce as the patient’s condition
deteriorates and during end-of-life care. Nausea and vomiting or any other conditions
that interfere with nutritional support should be treated.
 Regular medical visits. When therapy stops, regular visits by the treating physician
and support team should not be discontinued.
 Continuation of supplementary medicines. All necessary additional medications
should be continued as needed. Depression and anxiety, if present, should be
addressed.
 Hospitalization or nursing home care.
 Preventive measures. Oral care, prevention of bedsores, bathing and prevention of
muscle contractions are indicated in all patients. Regular scheduled movement of the
bedridden patient is very important.
 Infection control measures. The patient who is taken off antituberculosis treatment
because of failure often remains infectious for long periods of time. Infection control
measures should be continued.