A case of MDR-TB

A case of PUO
By
Prof.S.Tito’sUnit

Jayaarthi 26 yr female, married,admitted with c/o fever – 5months,intermittent,low grade with chills and rigors
H/o loss of wt& appettite
H/o Cough with expectoration – 3months,mucoid,non foul smelling, mild to moderate amount not ass with haemoptysis
H/o Breathlessness ,grade-2,no diurnal variation
H/o leucorrhea on and off
NoH/o headache,vomiting,abdominal pain ,loose stools, burning micturition ,jaundice
NoH/o any bleeding tendencies, rec throat infections,
NoH/o jt pain, rec oral ulcers, skin rashes, loss of hair

Past History:
No H/o DM,HT,cardiac illness,
H/o Pul TB diagnosed and treated with ATT –Cat-I, and declared cured
Obstetric History:
No H/o recurrent abortion
H/o full-term normal delivery 6 months before
Family History:
No H/o DM, HT, TB, Connective tissue disorder & malignancy
Menstrual History:
Scanty ,irregular

On examination : pt consc,oriented,febrile,pallor,emaciated
No cyanosis ,no clubbing, no lymphadenopathy,not icteric
no oral ulcers,no pedal edema, no skin rashes, no external markers of TB
Respiratory examination:
Trachea shifted to rtside,apical impulse normal in position ,
movements of chest wall diminished more in the rt side.
B/l coarse crepts
CVS:
S1S2 normaly heard ,No murmur
Abdomen:
soft, No organomegaly
CNS:
No neurological deficit, no meningeal signs

Investigations

CT Chest: Rt Upper lobe bullous lesion ,Rt middle and lower lobe consolidation with ectatic changes lt upper lobe and lower lobe
ECHO: Normal study ,No vegetations
Blood Culture(thrice): Negative for organisms
IgM for brucellosis: Negative
Treatment Given:
Inj.Cefotaxime,chloroquine,Doxy,Metranidazole,Nebulization,
cat-II ATT started

TRC Opinion(30/9/08):
Sputum AFB repeat neg; Sputum C/s for TB taken. Even though pt is sputum AFB negative with symptoms of TB with increasing infiltrates in CXR advice to con ATT-CatII Even after all these treatment measures pt continued with fever but breathlessness,Cough and expectoration subsided.pt advised to continue cat-II ATT until c&sreport arrives.

DIAGNOSIS
INH – resistant pulmonary tuberculosis
Pt referred to Tambaram Sanatorium for further management

On further follow-up
Treatment given
inj.SM 0.75g 3/wk
Cap.Rifampicin 450mg OD daily
T.Ethambutol 800mgOD daily
T.Ciprofloxacin 500mg BD daily
PAS 10g OD daily
Fever subsided, anorexia improved, wt gained

Sputum smear done at the end of 3 and 4th month turned out be POSITIVE
Sputum c&s for ATT at the end of 3rd report awaited.

FINAL DIAGNOSIS
SUSPECTED MDR-TB

NTF Presentations for RNTCP Sensitization First edition 10th Nov 06
Problem of TB in India
Estimated incidence
-75 new smear positive PTB cases/1lakh population per year
Estimated prevalence of TB dise
1.7 million new smear positive cases in 2000
Estimated mortality
Over 1000 deaths a day
2 deaths every 3 minutes
Gopi P et al (TRC), IJMR, Sep 2005

Prevalence of TB infection
40% (~400m) infected with M. tuberculosis (with a 10% lifetime risk of TB disease in the absence of HIV)
Estimated Multi-drug resistant TB
< 3.4% in new cases
12% in re-treatment cases
TB-HIV
10-15% annual risk (60% lifetime risk) of developing active TB disease in PLWHA
Estimated 5% of TB patients are HIV infected

DEFINITIONS OF DRUG RESISTANCE
DR-TB is confirmed through laboratory tests that show that the infecting
isolates of Mycobacterium tuberculosis grow in vitro in the presence of one or
more antituberculosis drugs. Four different categories of drug resistance have been established:
• Mono-resistance: resistance to one antituberculosis drug.
• Poly-resistance: resistance to more than one antituberculosis drug, other
than both isoniazid and rifampicin.
• Multidrug-resistance: resistance to at least isoniazid and rifampicin.
• Extensive drug-resistance: resistance to any fluoroquinolone, and at least
one of three injectable second-line drugs (capreomycin, kanamycin and
amikacin), in addition to multidrug-resistance.

Resistance incidence
INH resistance 18%
RIFAMPICIN resistance 2%
Failure rate even after complete trt under cat1 &cat2 tretment are 2% and 6% respectively.
New cases 1-3%
Previously treated cases 12-17%

WHEN TO SUSPECT MDR-TB
1.cat1/cat3 treatment failure
2.Even after 4 months of cat2 treatment sputum smear is positive
3.Source of contact is MDR-TB
Exclusion: 1.<15 years of age
2.Having had >1month treatment with any secondline drug

Common treatment strategies for DR-TB
Representative DRS data in well-defined patient populations are used to design the regimen. All patients in a patient group or category receive the same regimen.
Standardized treatment
Initially, all patients in a certain group receive the same regimen based on DST survey data from representative populations. The regimen is adjusted when DST results become available (often DST is only done to a limited number of
drugs).
Standardized treatment followed by individualized
treatment
Each regimen is individually designed on the basis of patient history and then adjusted when DST results become available (often the DST is done of both first- and second-line drugs)
Empirical treatment followed by individualized treatment

HOW TO BUILD A TREATMENT REGIMEN FOR MDR-TB

Guidelines for the programmatic management of drug-resistant tuberculosis
Emergency update 2008 WHO– page60

CATEGORY IV Regimen
• Confirmed MDR-TB.
• Suspected MDR-TB –pt may be started on Category IV treatment before MDR-TB is confirmed only if representative DST surveys or other epidemiologic data indicate a very high probability of MDR-TB
• Poly-resistant TB. Some cases of poly-resistant TB will require Category IV treatments. These patients require prolonged treatment (18 months or more) with first-line drugs combined with two or more second-line drugs .
Category –II Failure Cases

Culture and DST results and further action

RNTCP Grouping Drugs
Group 1: First-line oral anti-TB agents Isoniazid (H); Rifampicin (R); Ethambutol (E); Pyrazinamide (Z)
Group 2: Injectable anti-TB agents Streptomycin (S); Kanamycin (Km); Amikacin (Am); Capreomycin (Cm); Viomycin (Vm).
Group 3: Fluoroquinolones Ciprofloxacin (Cfx); Ofloxacin (Ofx); Levofloxacin (Lvx); Moxifloxacin (Mfx); Gatifloxacin (Gfx)
Group 4: Oral second-line anti-TB agents Ethionamide (Eto); Prothionamide (Pto); Cycloserine (Cs); Terizadone (Trd); paraaminosalycilic acid (PAS); Thiacetazone (T)

RNTCP CATEGORY IV REGIMEN(DOTS+ strategy)
6 (9) Km OfxEto Cs Z E / 18 OfxEto Cs E

Follow up
Sputum smear to be done monthly during IP and every three months during CP
Sputum culture to be done at the end of the months 3, 6,12, 18 and 24. If any of the cultures in the last three quarters becomes positive monthly culture to be done.

conversion
Patients will be considered culture converted after having two consecutive negative cultures taken at least one month apart.
Similarly patients will be considered smear converted after having two consecutive negative smears taken at least one month apart.

MDR-TB requiring surgery
Absence of clinical or bacteriological response to chemotherapy despite six to nine months of treatment with effective antituberculosis drugs;
High risk of failure or relapse due to high degree of resistance or extensive parenchymal involvement;
Morbid complications of parenchymal disease e.g. haemoptysis, bronchiectasis, bronchopleural fistula, or empyema;
Recurrence of positive culture status during course of treatment;
Relapse after completion of anti-tuberculosis treatment.
If surgical option is under consideration at least six to nine months of chemotherapy is recommended prior to surgery

X-DR 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 multidrug-resistance.

XDR-TB IN INDIA
Extreme drug-resistant TB (XDR-TB) It is known as the worlds most untreatable form of tuberculosis
Study at Hinduja hospital Mumbai showed 32% suffered from multiple drug resistance (MDR-TB), and 8% of them were XDR-TB cases.
Mortality rate of XDR-TB patients in the study is known to be 42%. "XDR-TB is a growing problem in India affecting mostly young, working-age people .

MANAGEMENT GUIDELINES FOR PATIENTS WITH DOCUMENTED XDR-TB
1. Use any Group 1 agents that may be effective.
2. Use an injectable agent to which the strain is susceptible and consider an extended duration of use (12 months or possibly the whole treatment). If resistant to all injectable agents, it is recommended to use one the patient has never used before.
3. Use a later-generation fluoroquinolone such as moxifoxacin.
4. Use all Group 4 agents that have not been used extensively in a previous regimen or any that are likely to be effective.
5. Use two or more agents from Group 5.
6. Consider high-dose isoniazid treatment if low-level resistance is documented.
7. Consider adjuvant surgery if there is localized disease.
8. Ensure strong infection control measures.
9. Treat HIV

Initiating ART (Anti-Retroviral Therapy) in patients with MDR- TB

A case of MDR-TB

by Stanley Medical College, Department of Medicine on Dec 30, 2009

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