Management of MDR-TB patients Management of MDR-TB patients in the hospital: LRS Institute in the hospital: LRS Institute

ExperienceExperience

LRS Institute of TB and Respiratory DiseasesLRS Institute of TB and Respiratory Diseases

Sri Aurobindo Marg, New DelhiSri Aurobindo Marg, New Delhi

Inflow of patients in LRS Inflow of patients in LRS InstituteInstitute

From outside DelhiFrom outside Delhi

From Delhi, outside LRS areaFrom Delhi, outside LRS area

From LRS DOTS areaFrom LRS DOTS area

Inflow of patients in OPD …Inflow of patients in OPD …

I I Cases from community Cases from community

( Non- DOTS)( Non- DOTS) - No DST- No DST

- DST available- DST available (a) (a)

non- MDRnon- MDR (b) MDR(b) MDR

Inflow of patients in OPD …Inflow of patients in OPD …

II II Cases from DOT centers:Cases from DOT centers:

(a) Cat I failure: (i) No DST (a) Cat I failure: (i) No DST

(ii) Non-MDR(ii) Non-MDR

(iii) MDR(iii) MDR

(b) Cat II failure: (a) MDR(b) Cat II failure: (a) MDR

(b) Non - MDR(b) Non - MDR

Inflow of patients in OPD…Inflow of patients in OPD…

III III Already taken second line drugsAlready taken second line drugs

Treatment has to be individualizedTreatment has to be individualized

Failure to DifferentiateFailure to Differentiate

MDR-TBMDR-TB

Treatment FailureTreatment Failure

Suspected drug resistanceSuspected drug resistance

Aims during HospitalizationAims during Hospitalization

Detailed evaluation of patientsDetailed evaluation of patients Establish linkage with DOTS plus, if existsEstablish linkage with DOTS plus, if exists Involve Health education officer, social Involve Health education officer, social

worker, clinical psychologistworker, clinical psychologist Choose proper regimen Choose proper regimen Identify and treat any side effect/ toxicityIdentify and treat any side effect/ toxicity Ensure proper follow up after dischargeEnsure proper follow up after discharge

Sputum smear/ culture/ drug Sputum smear/ culture/ drug sensitivity studiessensitivity studies

Two pre-treatment DST specimens recommended Two pre-treatment DST specimens recommended Conventional methods take 3-4 monthsConventional methods take 3-4 months Rapid culture methods: expensive, ? availabilityRapid culture methods: expensive, ? availability DST for second line drugs not available routinely, DST for second line drugs not available routinely,

standardization/ technical problemsstandardization/ technical problems

RegimenRegimen

STR - Standardized treatment regimenSTR - Standardized treatment regimen

ITR - Individualized treatment regimenITR - Individualized treatment regimen

DOTS-Plus LRSDOTS-Plus LRS Treatment RegimenTreatment Regimen

IP : - Kana, Cyclo, Ethio, PZ, OfloxIP : - Kana, Cyclo, Ethio, PZ, Oflox

- 6-9 months- 6-9 months

- 3 consecutive monthly spt culture negative- 3 consecutive monthly spt culture negative

CP : - Cyclo, Ethio, OfloxCP : - Cyclo, Ethio, Oflox

- Minimum 18 mth after sputum Conversion- Minimum 18 mth after sputum Conversion

Treatment Regimen at Treatment Regimen at LRS…LRS…

STR for DOTS Plus patientsSTR for DOTS Plus patients

Duration of IPDuration of IP : Minimum of 6 months or until 3 : Minimum of 6 months or until 3 consecutive months of negative sputum culture consecutive months of negative sputum culture whichever is later, upto a maximum of 9 months whichever is later, upto a maximum of 9 months

AdmissionAdmission: at least for one month: at least for one month

STR Regimen at LRS STR Regimen at LRS InstituteInstitute

Constraints during IP:Constraints during IP:

Waiting for 3 negative cultures prolongs IP Waiting for 3 negative cultures prolongs IP

39% patients: injections for 6 months39% patients: injections for 6 months

34% patients: injections for 9 months34% patients: injections for 9 months

Operational problemsOperational problems

Malnourished patient, poor muscle mass: difficult to give Malnourished patient, poor muscle mass: difficult to give

injections for 6-9 monthsinjections for 6-9 months

Other Treatment Regimen at Other Treatment Regimen at LRS…LRS…

ITR for some patientsITR for some patients IP: 5-6 drugs (aminoglycoside, quinolone, IP: 5-6 drugs (aminoglycoside, quinolone,

ethionamide, pyrazinamide and 1-2 other drugs)ethionamide, pyrazinamide and 1-2 other drugs) Continuation phase: 3-4 drugsContinuation phase: 3-4 drugs Hospitalization: usually prolongedHospitalization: usually prolonged

Toxicity/ Side effectsToxicity/ Side effects

Severe psychosis: 4/56 patientsSevere psychosis: 4/56 patients

Ototoxicity: 6/90 patientsOtotoxicity: 6/90 patients

Hypothyroidism: 3/32 patientsHypothyroidism: 3/32 patients

Minor: hepatitis, joint pains, nauseaMinor: hepatitis, joint pains, nausea

Issues during HospitalizationIssues during Hospitalization

STR vs ITR STR vs ITR

Second line drugs are expensive Second line drugs are expensive

Malnourished patients: 6- 9 months injections difficultMalnourished patients: 6- 9 months injections difficult

Weight gain during treatment: ? Adjust dosageWeight gain during treatment: ? Adjust dosage

Waiting for 3 negative culture, IP is extendedWaiting for 3 negative culture, IP is extended

Issues during HospitalizationIssues during Hospitalization ……

Actions in case of drug intolerance: no defined protocol Actions in case of drug intolerance: no defined protocol

Toxic reactions may need referral to other specialties e.g. Toxic reactions may need referral to other specialties e.g.

psychiatrist, endocrinologist, ENTpsychiatrist, endocrinologist, ENT

If one/two drugs not tolerated- limited choice for If one/two drugs not tolerated- limited choice for

alternative drugsalternative drugs

Limited experience with alternative drugs e.g. Amox-Limited experience with alternative drugs e.g. Amox-

clauvulanic acid, clofazimine, Clarithromycinclauvulanic acid, clofazimine, Clarithromycin

Issues during HospitalizationIssues during Hospitalization ……

Difficult to calculate requirement for alternative Difficult to calculate requirement for alternative

drugs with limited expiry perioddrugs with limited expiry period

Conventional DST take 3-4 monthsConventional DST take 3-4 months

Too many cultures - adds to load on laboratoryToo many cultures - adds to load on laboratory

Not sure of DOT after discharge: prolonged Not sure of DOT after discharge: prolonged

hospitalization hospitalization

Other IssuesOther Issues

Management of MDR-TB with HIV Management of MDR-TB with HIV

Management of MDR-TB with co-morbid conditions e.g. Management of MDR-TB with co-morbid conditions e.g.

liver/ kidney problemsliver/ kidney problems

Prolonged hospitalization: social problems, extra-marital Prolonged hospitalization: social problems, extra-marital

relationships, broken marriages, loss of jobrelationships, broken marriages, loss of job

Preventive therapy to pediatric/ adult contacts Preventive therapy to pediatric/ adult contacts

Preventive measures for spread of MDR-TB in hospitalsPreventive measures for spread of MDR-TB in hospitals

Thank youThank you

DOTS-Plus LRSDOTS-Plus LRS Resistance Pattern of S,Z,EResistance Pattern of S,Z,E

m MDR Patientsm MDR Patients

40 40

24

0

5

10

15

20

25

30

35

40

S E Z

DOTS-Plus LRSDOTS-Plus LRS Resistance PatternResistance Pattern

30

40

24

6

RH

RH+1

RH+2

RH+3

8

50 42

0

10

20

30

40

50

<3 mths 3- 6 mths 7- 9 mths

%

DOTS-Plus LRSDOTS-Plus LRS Time to ConversionTime to Conversion

Cohort 2002-03 (2 year)n = 26

DOTS-Plus LRSDOTS-Plus LRS Treatment OutcomeTreatment Outcome

6215

23

Cured

Default

Died

2002 Cohortn = 13

DOTS-Plus LRSDOTS-Plus LRS HospitalizationHospitalization

Minimum one monthMinimum one month

Linkage with TBHV in fieldLinkage with TBHV in field

Health education & social supportHealth education & social support

Ascertain tolerability to drugsAscertain tolerability to drugs

DOTS-PLUS LRSDOTS-PLUS LRSAge DistributionAge Distribution

4

14

24

86

1 10

5

10

15

20

25

0- 14 25- 34 45- 54 65

and

above

Total

Age Group

DOTS-Plus LRSDOTS-Plus LRSSex DistributionSex Distribution

n = 58n = 58

5050

Male

Female

50

7

54 62

100 100 100

50

93

46 38

0 0 0

0

20

40

60

80

100

120

0-14 15-24 25-34 35-44 45-54 55-64 65 andabove

GenderProportion

68

11

21

Converted

Default

Died

DOTS-Plus LRSDOTS-Plus LRS Sputum Conversion Sputum Conversion

Cohort 2002-03 (2 year)n = 38

DOTS-Plus LRSDOTS-Plus LRS Treatment RegimenTreatment Regimen

Resistance / Toxicity to any drug - Resistance / Toxicity to any drug - replace it with PASreplace it with PAS

Capreo replaces KanaCapreo replaces Kana

Premature termination - Committee Premature termination - Committee

DOTS-PLUS LRSDOTS-PLUS LRSAge DistributionAge Distribution

4

14

24

86

1 10

5

10

15

20

25

0- 14 25- 34 45- 54 65

and

above

Total

Age Group

DOTS-Plus LRSDOTS-Plus LRSSex DistributionSex Distribution

n = 58n = 58

5050

Male

Female

50

7

54 62

100 100 100

50

93

46 38

0 0 0

0

20

40

60

80

100

120

0-14 15-24 25-34 35-44 45-54 55-64 65 andabove

GenderProportion

DOTS-Plus LRSDOTS-Plus LRS Resistance Pattern of S,Z,EResistance Pattern of S,Z,E

m MDR Patientsm MDR Patients

40 40

24

0

5

10

15

20

25

30

35

40

S E Z

DOTS-Plus LRSDOTS-Plus LRS Treatment OutcomeTreatment Outcome

6215

23

Cured

Default

Died

2002 Cohortn = 13

Actions during Actions during HospitalizationHospitalization

Detailed history of previous regimen & dosesDetailed history of previous regimen & doses List the drugs already taken/ not takenList the drugs already taken/ not taken H/o contact with MDR in family/work placeH/o contact with MDR in family/work place Previous DST if available Previous DST if available Co-morbid conditions e.g. diabetes, liver/ kidney Co-morbid conditions e.g. diabetes, liver/ kidney

problems, psychiatric illness etcproblems, psychiatric illness etc

Discrepant results of DSTDiscrepant results of DST

Consider laboratory technique (reference Consider laboratory technique (reference laboratory more reliable) laboratory more reliable)

Discuss with laboratory inchargeDiscuss with laboratory incharge Review treatment history and assess resistance Review treatment history and assess resistance

amplificationamplification Therapy to be based on most resistance Therapy to be based on most resistance

antibiogram.antibiogram.

ITR STR

Efficacy Maximum Moderate-High

Cost – Initial - Long term

High Lower

Moderate- Higher

Risk of Amplification of resistance

Very Low Low to Moderate

Data on Local epidemiology of resistance

Not required

Required

Technical capacity required High Moderate

Drug Toxicity Same Same

InvestigationsInvestigations

HemogramHemogram Blood Sugar F, PPBlood Sugar F, PP LFT, KFT, Serum electrolytesLFT, KFT, Serum electrolytes HIV test with consent and counselingHIV test with consent and counseling X-Ray Chest: cavity, extent of lesionX-Ray Chest: cavity, extent of lesion ECGECG Other specific tests if requiredOther specific tests if required

Initial approach to MDR-TB Initial approach to MDR-TB ManagementManagement

(a)(a) Suspicious of MDR-TBSuspicious of MDR-TB Stop failing therapyStop failing therapy Preferably wait for DST studies - but require 3-4 Preferably wait for DST studies - but require 3-4

months by conventional methodsmonths by conventional methods If condition very poor, start empiric MDR TB If condition very poor, start empiric MDR TB

treatmenttreatment Prior to empiric MDR TB treatment, at least Prior to empiric MDR TB treatment, at least

confirm positive cultureconfirm positive culture Keep Amplification of Drug Resistance in mindKeep Amplification of Drug Resistance in mind

Initial approach to MDR - Initial approach to MDR - TB TreatmentTB Treatment

(b) (b) Documented MDR – TBDocumented MDR – TB

Stop failing therapyStop failing therapy If patient received treatment after last DST, If patient received treatment after last DST,

repeat DST before starting treatmentrepeat DST before starting treatment Start MDR - TB treatment Start MDR - TB treatment

Principals of ITRPrincipals of ITR

Consider past history of drugs, contact, DSTConsider past history of drugs, contact, DST

Cost e.g cycloserine is very expensiveCost e.g cycloserine is very expensive

Tolerance e.g. cycloserine, thiacetazone, PASTolerance e.g. cycloserine, thiacetazone, PAS

Cross resistance e. g. quinolones, aminoglycosidesCross resistance e. g. quinolones, aminoglycosides

Choose drugs as per efficacyChoose drugs as per efficacy

Start with at least four, preferably five, drugs with one Start with at least four, preferably five, drugs with one

parenteral drugparenteral drug

Adjust to definitive regimen according to DST report laterAdjust to definitive regimen according to DST report later

Principals of STRPrincipals of STR

Consider regional Epidemiology Consider regional Epidemiology Consider cost, tolerance, availability of drugsConsider cost, tolerance, availability of drugs Foundation of at least 4, ideally 5, drugs Foundation of at least 4, ideally 5, drugs

including one parenteral agentincluding one parenteral agent

Regimen at LRS InstituteRegimen at LRS Institute

Continuation phaseContinuation phase

Drugs : Ethionamide, Cycloserine, ofloxacinDrugs : Ethionamide, Cycloserine, ofloxacin

Duration : At least 18 months after sputum Duration : At least 18 months after sputum conversionconversion

Sputum examination Sputum examination during hospitalizationduring hospitalization

During Intensive PhaseDuring Intensive Phase Two sputum specimen smear and culture on consecutive Two sputum specimen smear and culture on consecutive

days every monthdays every month If sputum positive at 6 months ; continue IP and repeat If sputum positive at 6 months ; continue IP and repeat

DST to look for augmentation of drug resistance and DST to look for augmentation of drug resistance and review by DOTS plus committeereview by DOTS plus committee

(Recommended is repeat DST every 3 months till sputum (Recommended is repeat DST every 3 months till sputum is negative)is negative)

Sputum examination Sputum examination during continuation phaseduring continuation phase

Once every two months - two specimens of Once every two months - two specimens of smear and culture on consecutive dayssmear and culture on consecutive days

After initial conversion during CP if one After initial conversion during CP if one culture is positive, repeat sputum at culture is positive, repeat sputum at monthly intervals till 3 cultures are negativemonthly intervals till 3 cultures are negative

Monitoring of side effectsMonitoring of side effects

Identify common side effectsIdentify common side effects Define protocols for the management of Define protocols for the management of

known side effectsknown side effects Preventive therapy/ investigations for known Preventive therapy/ investigations for known

side effectsside effects Replace drugs, if required and not tolerated as Replace drugs, if required and not tolerated as

a last resorta last resort