Transcript
MDR TB
DR KHALED HASSANIMO(RESPITARORY MEDICINE)
DMCH
• Multidrug-resistant TB (MDR-TB) is defined as TB resistant to at least the two most potent drugs against TB, isoniazid and rifampicin
• Although its causes are microbial, clinical and programmatic, MDR-TB is essentially a man-made phenomenon
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Definition and causes of MDR-TB
• Multidrug-resistant TB (MDR-TB) is defined as TB resistant to at least the two most potent drugs against TB, isoniazid and rifampicin
• Although its causes are microbial, clinical and programmatic, MDR-TB is essentially a man-made phenomenon
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Definition and causes of MDR-TB
M. tuberculosis ResistanceBasic Concepts
• Natural resistance• Resistance in previously treated patients• Resistance in previously untreated patients• Transient resistance• Poly-resistance
Basic Concepts Resistance of M. Tuberculosis
NATURAL Resistance
M. tuberculosis Resistance Natural Resistance (1)
- When all live species reach a certain number of divisions (in order to perpetuate the specie), they undergo genomic mutations at random, which gives rise to organisms with certain altered functions.
- This always occurs in the successive divisions of each species. It is therefore a dynamic function.
15 million
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M. tuberculosis Resistance Natural Resistance (2)
• Ever since M. tuberculosis has attacked humans, way back in time, it has always presented multiple genomic mutations in its continuous divisions
• Some of these mutations affect the genes in which anti-tuberculous drugs work
• This means that these antibiotics cannot work against M. tuberculosis, and therefore phenotypically, they show resistance to them
M. tuberculosis Resistance Naturally resistant mutants according to bacillary
population
• INH 1 x 105-106 Bacilli• RIF 1 x 107-108 Bacilli• SM 1 x 105-106 Bacilli• EMB 1 x 105-106 Bacilli• PZ 1 x 102-104
Bacilli ?• Quinolones 1 x 105-106
Bacilli ?• Others 1 x 105-106
Bacilli ?
M. tuberculosis Resistance Bacillary population in different TB lesions
• TB Sm+ 107-109 Bacilli• Cavitary 107-109 Bacilli• Infiltrated 104-107 Bacilli• Nodules 104-106 Bacilli• Adenopathies 104-106 Bacilli• Renal TB 107-109 Bacilli• Extrapul. TB 104-106 Bacilli
M. tuberculosis Resistance Selection of resistant mutants
• If Smear positive TB is treated with just ONE drug (H), for each million bacilli, it will kill 999,999, but it will select the resistant mutant (1 individual) that exists.
• If this TB has a minimum of 1,000 million (109) organisms, in 2-8 weeks it will have selected the 1,000 mutant bacilli (1 per million) that are resistant in this population
• These 1,000 bacilli are insufficient to cause clinical symptoms or to be smear +. Good clinical progression!
• The problem is that these 1,000 soon will be 109
Appearance of resistance to INH administered as Monotherapy
Resistant Mutants
Sensitive Bacilli
Months after Start of Treatment No. of viable bacilli
Mitchison DA. En: Heaf F, et al. Churchill, London, 1968
The fall and Rise Mechanism
Organisms in Pansusceptible
new case
Development (cre-ation)
Transmission (spread)
Development and Spread of Drug Resistance
INH,SM:10-5-6 RIF:10-6-7 EMB:10-4-5
New caseswith Primary drug resistance
Drug resistant mutants
Treatment failurewith Acquireddrug resistance
Programmatic Errors
Mismanagement Delay in diagnosis and treat-ment
Modified SJ Kim
M. tuberculosis Resistance PRIMARY or INITIAL Resistance
• If a person is infected by a patient with selected resistant mutants (Acquired R.), he/she may suffer TB with the same resistance pattern PRIMARY RESISTANCE
• Primary resistance is the one presenting in TB patients who have never received treatment (< 1 month)
• Initial R. is the same concept as primary R., but it is a practical term, and includes all patients who state they have never been treated (some do not remember, others lie)
Resistance in “previously untreated patients”
In TB, resistance is always the result of poor
individual or programmatic management of patients
The most Basic Concept in TB Resistance
M. tuberculosis Resistance
Fortunately, of the 4 mechanisms through which antimicrobial
resistance appears (mutation, transduction, transformation
and conjugation), M. TB only uses mutations
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Definitions: Drug Resistance
Resistance Cases
Definition
Mono resistance Resistant to only one Anti TB DrugExm: E or H or S resistance etc.
Poly resistance Resistant to more than one Anti TB Drug other than both H and R
Exm: HE or ES or SRE- resistance etc.
MDR-TB Resistant to at least both most potent Anti TB Drug, H and R
XDR-TB(Extensive
Drug –resistance)
Resistance to any fluoroquinolone, and at least one of three injectable second line drugs (Capreomycin, Kanamycin and
Amikacin), in addition to MDR-TB
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Definitions: Diagnostic Cat IV
Cases DefinitionConfirmed MDR-
TBTB resistant to at least both most potent Anti TB Drug, H and R
Suspected MDR-TB
Patient may be entered in Cat-IV register and can be started on Cat-IV treatment before MDR-TB is confirmed only the relevant health authority recommends
RR-TB Rifampicin Resistant detected by Gene Xpert
Definitions: As per Site
Cases DefinitionPulmonary TB Involving only the lung parenchyma
Extra Pulmonary TB
TB of organs other than the lungs
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Definitions: According to previous Anti TB Drug historyCases Definition
DR-TB New patients Patients who have never received anti-TB treatment, or who have
received anti-TB treatment for < 1 month.
DR-TB patients previously treated with only first-line drugs.
Patients who have been treated for 1 or > 1 month with only first-line
drugs. DR-TB patients previously treated with second-line drugs.
Patients who have been treated for 1 or > 1 month with one or more
second-line drugs, with or without first-line drugs.
Suspects of DR-TB1. Failures of Category I (remain positive Month 5 or starts Category I
as smear negative and becomes smear positive at month 2);2. Failures of Category II (remain positive Month 5 or 8); 3. Non-converters of Category I (remain positive at month 3);4. Non-converters of Category II (remain positive at month 4);5. All relapses (Category I and Category II); 6. All return after default (Category I and Category II); 7. Close contacts of MDR-TB patients with symptoms;8. All TB/HIV infected patients at the start of TB therapy;9. Others (Specify):………………………..
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Factors of inadequate anti-TB treatmentHealth care providers:inadequate regimens
Drugs:inadequate supply/quality
Patients:inadequate drug intake
Noncompliance with guidelinesPoor trainingNo monitoring of treatmentPoorly organized or funded TB control programme
Poor quality Unavailability of certain drugs (stock-outs or delivery disruptions)Poor storage conditionsWrong dose or combination
Poor adherenceLack of information Lack of money Lack of transportationAdverse effectsSocial barriersMalabsorptionSubstance dependency disorders
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Summary table of bacteriological examination
Test Sensitivity Time Additional time for DST
location
microscopy >5000 2h N/A NTRL,RTRL,DOTS centre
LJ (Solid culture) 100 cfu/ml 4 wk 6 wk NTRL,RTRL
MGIT(Lequid culture)
10 cfu/ml 10-12 days 12 days NTRL
Xpert 10 cfu/ml 2h N/A NTRL,RTRL,DOTS centre
LPA Only on smear positive
3 days N/A NTRL
Regimen• 8(km,Z,Ofx/Lfx,Eto,Cs)-Intensive Phase
• 12(Z,Ofx/Lfx,Eto,Cs)-Continuation Phase
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Hospitalization
• All patient should be hospitalized- where facility is designed for MDR TB
Reasons-
• To have an intensive time for patient education
• To document that patient is tolerating the drugs
• To make patient smear negative and less infectious
Re-admission
• Very sick,clinicaly and physically unfit to receive treatment at home
• Adherence problem• Severe adverse effect• Immobility
Discharge criteria
• Smear negative ( 2 sample one week apart)• Clinically improving• patient is tolerating the drugs• At least 4 wks of hospitalization• OPD is trained and ready to give
community/home based DOT
Laboratory monitoring scheduleBaseline Follow up
Sputum Smear microscopy Weekly until Smear negative ( 2 sample one week apart)Then monthly
culture Monthly-intensive phaseQuarterly- continuation phase
DST Any culture positive at or beyond 4 months
RFT Monthly-intensive phase
LFT 3 Monthly Who are at risk (alcoholics,HBV,HCV)
TSH 6 Monthly if getting PAS,ETO,PTO
Laboratory monitoring scheduleBaseline Follow up
CD4 6 Monthly
CBC As required
Audiometry Monthly-intensive phase
Weight Monthly
CXR 6 Monthly
Specific infectious control measures
• Implement NTP• Educate all health care provider• Restrict attendants presence a minimum• Separate Smear positive in ward• Separate HIV pt from MDR TB pt• Isolate treatment failure cases, XDR cases
Treatment of MDR TB in special situation
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