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