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Management of MDR-TB patients in the hospital: LRS Institute Experience. LRS Institute of TB and Respiratory Diseases Sri Aurobindo Marg, New Delhi. Inflow of patients in LRS Institute. From outside Delhi From Delhi, outside LRS area From LRS DOTS area. Inflow of patients in OPD ….
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Management of MDR-TB patients in the hospital: LRS Institute Experience LRS Institute of TB and Respiratory Diseases Sri Aurobindo Marg, New Delhi
Inflow of patients in LRS Institute • From outside Delhi • From Delhi, outside LRS area • From LRS DOTS area
Inflow of patients in OPD … I Cases from community ( Non- DOTS) - No DST - DST available(a) non- MDR (b) MDR
Inflow of patients in OPD … II Cases from DOT centers: (a) Cat I failure: (i) No DST (ii) Non-MDR (iii) MDR (b) Cat II failure: (a) MDR (b) Non - MDR
Inflow of patients in OPD… III Already taken second line drugs Treatment has to be individualized
Failure to Differentiate • MDR-TB • Treatment Failure • Suspected drug resistance
Aims during Hospitalization • Detailed evaluation of patients • Establish linkage with DOTS plus, if exists • Involve Health education officer, social worker, clinical psychologist • Choose proper regimen • Identify and treat any side effect/ toxicity • Ensure proper follow up after discharge
Sputum smear/ culture/ drug sensitivity studies • Two pre-treatment DST specimens recommended • Conventional methods take 3-4 months • Rapid culture methods: expensive, ? availability • DST for second line drugs not available routinely, standardization/ technical problems
Regimen • STR - Standardized treatment regimen • ITR - Individualized treatment regimen
DOTS-Plus LRSTreatment Regimen • IP : - Kana, Cyclo, Ethio, PZ, Oflox - 6-9 months - 3 consecutive monthly spt culture negative • CP : - Cyclo, Ethio, Oflox - Minimum 18 mth after sputum Conversion
Treatment Regimen at LRS… STR for DOTS Plus patients Duration of IP : Minimum of 6 months or until 3 consecutive months of negative sputum culture whichever is later, upto a maximum of 9 months Admission: at least for one month
STR Regimen at LRS Institute Constraints during IP: Waiting for 3 negative cultures prolongs IP • 39% patients: injections for 6 months • 34% patients: injections for 9 months • Operational problems • Malnourished patient, poor muscle mass: difficult to give injections for 6-9 months
Other Treatment Regimen at LRS… ITR for some patients • IP: 5-6 drugs (aminoglycoside, quinolone, ethionamide, pyrazinamide and 1-2 other drugs) • Continuation phase: 3-4 drugs • Hospitalization: usually prolonged
Toxicity/ Side effects • Severe psychosis: 4/56 patients • Ototoxicity: 6/90 patients • Hypothyroidism: 3/32 patients • Minor: hepatitis, joint pains, nausea
Issues during Hospitalization • STR vs ITR • Second line drugs are expensive • Malnourished patients: 6- 9 months injections difficult • Weight gain during treatment: ? Adjust dosage • Waiting for 3 negative culture, IP is extended
Issues during Hospitalization … • Actions in case of drug intolerance: no defined protocol • Toxic reactions may need referral to other specialties e.g. psychiatrist, endocrinologist, ENT • If one/two drugs not tolerated- limited choice for alternative drugs • Limited experience with alternative drugs e.g. Amox-clauvulanic acid, clofazimine, Clarithromycin
Issues during Hospitalization … • Difficult to calculate requirement for alternative drugs with limited expiry period • Conventional DST take 3-4 months • Too many cultures - adds to load on laboratory • Not sure of DOT after discharge: prolonged hospitalization
Other Issues • Management of MDR-TB with HIV • Management of MDR-TB with co-morbid conditions e.g. liver/ kidney problems • Prolonged hospitalization: social problems, extra-marital relationships, broken marriages, loss of job • Preventive therapy to pediatric/ adult contacts • Preventive measures for spread of MDR-TB in hospitals
DOTS-Plus LRSTime to Conversion Cohort 2002-03 (2 year) n = 26 %
DOTS-Plus LRSTreatment Outcome 2002 Cohortn = 13
DOTS-Plus LRSHospitalization • Minimum one month • Linkage with TBHV in field • Health education & social support • Ascertain tolerability to drugs
DOTS-PLUS LRSAge Distribution Age Group
DOTS-Plus LRSSex Distributionn = 58 Gender Proportion
DOTS-Plus LRSSputum Conversion Cohort 2002-03 (2 year) n = 38
DOTS-Plus LRSTreatment Regimen • Resistance / Toxicity to any drug - replace it with PAS • Capreo replaces Kana • Premature termination - Committee
DOTS-PLUS LRSAge Distribution Age Group
DOTS-Plus LRSSex Distributionn = 58 Gender Proportion
DOTS-Plus LRSTreatment Outcome 2002 Cohortn = 13
Actions during Hospitalization • Detailed history of previous regimen & doses • List the drugs already taken/ not taken • H/o contact with MDR in family/work place • Previous DST if available • Co-morbid conditions e.g. diabetes, liver/ kidney problems, psychiatric illness etc
Discrepant results of DST • Consider laboratory technique (reference laboratory more reliable) • Discuss with laboratory incharge • Review treatment history and assess resistance amplification • Therapy to be based on most resistance antibiogram.
Investigations • Hemogram • Blood Sugar F, PP • LFT, KFT, Serum electrolytes • HIV test with consent and counseling • X-Ray Chest: cavity, extent of lesion • ECG • Other specific tests if required
Initial approach to MDR-TB Management • Suspicious of MDR-TB • Stop failing therapy • Preferably wait for DST studies - but require 3-4 months by conventional methods • If condition very poor, start empiric MDR TB treatment • Prior to empiric MDR TB treatment, at least confirm positive culture • Keep Amplification of Drug Resistance in mind
Initial approach to MDR - TB Treatment (b) Documented MDR – TB • Stop failing therapy • If patient received treatment after last DST, repeat DST before starting treatment • Start MDR - TB treatment
Principals of ITR • Consider past history of drugs, contact, DST • Cost e.g cycloserine is very expensive • Tolerance e.g. cycloserine, thiacetazone, PAS • Cross resistance e. g. quinolones, aminoglycosides • Choose drugs as per efficacy • Start with at least four, preferably five, drugs with one parenteral drug • Adjust to definitive regimen according to DST report later
Principals of STR • Consider regional Epidemiology • Consider cost, tolerance, availability of drugs • Foundation of at least 4, ideally 5, drugs including one parenteral agent
Regimen at LRS Institute Continuation phase Drugs : Ethionamide, Cycloserine, ofloxacin Duration : At least 18 months after sputum conversion
Sputum examination during hospitalization During Intensive Phase • Two sputum specimen smear and culture on consecutive days every month • If sputum positive at 6 months ; continue IP and repeat DST to look for augmentation of drug resistance and review by DOTS plus committee (Recommended is repeat DST every 3 months till sputum is negative)
Sputum examination during continuation phase • Once every two months - two specimens of smear and culture on consecutive days • After initial conversion during CP if one culture is positive, repeat sputum at monthly intervals till 3 cultures are negative
Monitoring of side effects • Identify common side effects • Define protocols for the management of known side effects • Preventive therapy/ investigations for known side effects • Replace drugs, if required and not tolerated as a last resort