MULTI-DRUG RESISTANTTUBERCULOSIS

&EXTENSIVE D, RESISTANTMDR&XDR

DR/HESHAM BEN ISSA GP,ABUSITTA HOSPITAL

Presentation OutlineDEFINITION

CAUSES EPIDEMIOLOGYPRESENTATIONMANAGEMENT

MONITORINGPREVENTION

CONCLUSION

Drug-Resistant TB: Definitions

DEFINITIONS OF DRUG RESISTANCEMono-resistant: Resistance to a single

drug (e.g INH Only).Poly-resistant(non-MDR): Resistance to more

than one drug, but not the combination of isoniazid and rifampicin.

Multidrug-resistant (MDR): Resistance to at least isoniazid and rifampicin.

Extensively drug-resistant (XDR): MDR plus resistance to fluoroquinolones and at least 1 of the 3 injectable drugs (amikacin, kanamycin, capreomycin).

REPORTING PURPOSES

Primary drug-resistance: “New Cases”Drug resistance in a patient who has never been treated for tuberculosis or received less than one month of therapy

Secondary (acquired) drug-resistance:“Previously Treated Cases”

Drug resistance in a patient who has received at least one month of anti-TB therapy

Causes of DR&/MDR

EPIDEMIOLOGY

Estimated absolute numbers of reported cases with MDR-TB*Notified cases of MDR-TB

Cases of MDR-TB

0–99

100–999

1000–9999

≥10 000

NA

Distribution of MDR-TB among new TB cases, 1994-2010.

0-<3

3-<6

6-<12

12-<18

>18

No data available

Subnational data only

Distribution of MDR-TB among previously treated TB cases, 1994-2010

0-<6

6-<12

12-<30

30-<50

>50

No data available

Subnational data only

Epidemiology

Some of the highest statistics of HIV and multi-drug resistant tuberculosis co-infection are seen in sub-Saharan Africa where HIV/AIDS

prevalence is so high .Currently, world wide MDR-TB mortality rates are at about “40-60% depending on the country of residence and access to immediate care”. These rates are consistent with the rates of untreated tuberculosis

Notifications of MDR-TB increasing

•Notified cases of MDR-TB

•MDR-TB cases treated and estimated numbers

not treated for MDR-TB, among notified TB

patients, 2010

0

10

20

30

40

50

60

2005 2006 2007 2008 2009 2010

Nu

mb

er

of

pa

tie

nts

(th

ou

sa

nd

s)

0

50

100

150

200

250

300

SE Asi

a

W. P

acifi

c

Europe

Africa

EMR

Americ

as

World

Not on treatment

Treated

Why INH and Rifampin

Most potent and bacteriocidalTb can be treated effectively with INH+Rif aloneMono-resistance to one of them can be treated effectively with a regimen containing the other agent with very low failure rate (2.5-5%)Failure rate when INH+Rif resistant is 44% in non-HIV and 70% in HIV patientsDuration required for cure doubles to triples.

PresentationSneezingcoughing

deep cough with bloody sputumchest pain

Chillsunintended weight loss

slight fevernight sweats

loss of appetitepain with breathing

MANAGEMENT

DiagnosisHistory is IMPORTANT

Mantoux tuberculin skin test (TST) chest radiograph

QuantiFERON-TB Gold test (QFT-G)The presence of acid-fast bacilli on a sputum

smear may aid in the diagnosis of tuberculosis, but it is not 100% diagnostic .

The definitive diagnosis is made with a culture of the smear .

susceptibility testing by culture and sensitivity

Predictors of Drug-resistant TB

Assess drug resistance in any patient being started on treatment for tuberculosis

Non-adherence, defaultHistory of prior treatment

Exposure to possible drug-resistant source caseCommunity prevalence of drug resistance

If drug resistance is suspected based on any of the above factors, culture and susceptibility testing should be performed for at least INH and rifampicin

Categories of Anti-TB MDR Drugs: WHO

Group 1 – First-line drugs: Isoniazid , rifampicin , ethambutol , pyrazinamide

Group 2 - Injectable agents: Kanamycin, amikacin, capreomycin, streptomycin

Group 3 - Fluoroquinolones: Levofloxacin, moxifloxacin, ofloxacin

Group 4 - Oral bacteriostatic agents: Ethionamide, cycloserine, para-aminosalicylic acid (PAS), prothionamide, terizadone

Group 5 – Unclear role: Clofazamine, linezolid, amoxicillin/clavulanate, Imipenem/cilastatin, thioacetazone, high-dose isoniazid, clarithromycin

Empiric Regimens for Drug-resistant TBPredicted

Resistance Pattern

PREDICTEDRESISTANCE PATTERN

INH INH, EMB

RIF

RIF, EMB

Empiric Regimen

(minimum duration)

EMPIRIC REGIMINMINIMUM DURATION

• RIF, EMB, PZA (6-9 mo)• RIF, PZA, Fluoroquinolone +

Injectable (9-12 mo)• INH, EMB + PZA (18 mo

minimum)• INH, Fluoroquinolone,

PZA + Injectable (18-month minimum)

“I have been treated several times over the past five years and I’m still coughing and can’t gain weight”!

Empiric Regimens for MDR-TBPREDICTED RESISTANCE PATTERN

INH, RIF INH, RIF, EMB

INH, RIF, PZA

INH, RIF, PZA, EMB

EMPIRIC REGIMIN

• Fluoroquinolone, PZA, EMB, Injectable Fluoroquinolone, PZA, Injectable, CS, + PAS or ETH

• Fluoroquinolone, EMB, Injectable, CS, + PAS or ETH

• Fluoroquinolone, Injectable, CS, PAS or ETH, + one more drug

Common Adverse Effects• G.I. complaints

• Hepatotoxicity(early symptoms are anorexia and

malaise, then abdominal pain, vomiting, jaundice)

• Ethionamide CycloserinePAS Fluoroquinolones Clofazimine Rifabutin

• INH Rifampicin/rifabutin Ethionamide PZA PAS Fluoroquinolones

Common Adverse Effects

PERIPHERAL NEUROPDATHY

RASH

HEADACHE

SEIZURES

• INH • Ethionamide • Cycloserine • Linezolid• Ethambutol• All• Fluoroquinolones • Isoniazid • Cycloserine • Ethionamide • Ethambutol• Cycloserine

Common Adverse Effects

• HypothyroidismHEARING LOSS&VESTIBULAR TOXICITY

BEHAVIORAL CHANGES

VISUAL CHANGES

RENAL F• HYPOKALEMIA

• Ethionamide, PAS• Aminoglycosides,

Capreomycin• Cycloserine,

Ethionamide, Isoniazid, Fluoroquinolones

• Ethambutol, Rifabutin, Isoniazid, Linezolid

• Aminoglycosides, Capreomycin

MDR/XDR-TB: MonitoringCLINICALLY

SIGNS OF TREATMENT FAILUREPERSISTANT OR NEW WT LOSS

PERSISTANT OR DEVELOPING NEW TB SYM ASFEVER ,COUGH,

PERSISTANT SPUTUM POSITIVE RESULT OR POS CULTURE SMEAR.

MDR/XDR-TB: MonitoringLAB

CBC UREA,E,C

LFT AST,ALT,BILIRUBINPREGNANCY TEST FOR WOMEN

TSH AT SECOND MONTH FOR EARLY DETECTION OF HYPOTHYRODISM

How is MDRTB prevented?MDRTB is a condition that can be prevented by following the international TB control strategy called DOTS, which stands for Directly Observed Treatment, Short-course.

Health care providers should always adhere to the National Tuberculosis Program Guidelines and use only the recommended anti-TB treatment regiments, drug combinations and drug dosages.Anti-TB drugs, preferably Fixed Dose Combinations of high quality should be

available in regular and sufficient quantities .

Adherence to anti-TB treatment must be ensured with support, encouragement and monitoring of adherence by a relative, community volunteer, or a clinic nurse.

XDR-TB

CAUSES OF DEATH AMONG MDR &XDR

RESPIRATORY ARRESTADVERSE DRUG REACTIONSSEPTIC SHOCKPROGRESSION OF HIV DISEASEMASSIVE HAEMOPTYSISARF

Conclusion

MDR-TB is a problem!As PAs we must follow our appropriate procedures for diagnosing, reporting, and treatingWe can be effective globally with our time, education, supporting research for vaccines, etc.

THANKS