Transcript The management of multi- drug resistant

Drug resistant tuberculosis
Professor Peter D.O. Davies,
Tuberculosis Research and
Resources Unit, Liverpool.
Warning
• A new plague is sweeping across the planet
•
•
•
Soon multidrug resistant tuberculosis
will kill one person in three
The Constant Gardener
November 2005
Definitions
• Multidrug-resistant tuberculosis (MDRTB)
• Resistance to Isoniazid and Rifampicin
• Extensively (extremely) drug-resistant (XDR-TB)
• MDR-TB plus resistance to a second line
injectable drug such as amykacin plus a
quinolone.
The extent of MDR-TB, 2004.
Zignol M, et al. Global incidence of MDR-TB. JID 2006:194:479-485.
• 424,000 (95%CI 376,000-620,000) 4.3%
of all cases.
• 181,000 (95%CI 135,000-319,000) 43%
previously treated.
• China, India, Russian Fed: 62% of global
burden.
An unfortunate case
• Date
•
•
•
•
Jan 1998
March
April
April
• Sept
• Oct
Smear result
+
Resistance
HRZ
HR
H resistant
HRE
+
HRE resistant
HRZE
• Dec
• Jan
Treatment
SHRE resistant
+
An unfortunate case
• Date
•
•
•
•
Jan 1998
March
April
April
• Sept
• Oct
Smear result
+
Resistance
HRZ
HR
H resistant
HRE
+
HRE resistant
HRZE
• Dec
• Jan
Treatment
SHRE resistant
+
A near miss
Indian male aged 28 with extensive hilar gland enlargement
HRZE
HR resistant and partial E resistant
Action
Stop HR
Increase E and add S and Cipro
ZESCip
Danger
Already E and Z resistant .
May have resistance to S too.
Result
SHRZECipro resistant
Actual
responding to Z Cipro Prothionamide Cyc
Table of drugs used for the treatment of tuberculosis.
First line drugs
Essential
Isoniazid
Rifampicin
Other
Pyrazinamide
Ethambutol
Streptomycin
Second line drugs
Old
Ethionamide
Cycloserine
Capreomycin
Amikacyn
Kanamycin
PAS
Thiocetazone
New
Quinolones
ofloxacin
ciprofloxacin
moxifloxacin
Macrolides
clarithromycin
Clofazimine
Amoxycillin &
Clavulanic acid
New
rifamycins
Rifabutin
Rifapentine
Linezolid
Currently recommended treatment
of fully sensitive tuberculosis
•
•
•
•
•
•
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol/Streptomycin
For 2 months or until sensitivities available
Then
• Isoniazid and Rifampicin for 4 months
•
•
10 months for CNS TB
Use FDCs where possible
Drug resistance - risk factors
•
•
•
•
•
•
•
•
•
•
•
A. Previous treatment especially if prolonged
B. Contact with drug resistant patient
C. Country of origin
East Europe
Former USSR
Middle East
South and SE Asia
Latin America
Africa
D. Age (In MDR area, commoner in children)
E. HIV (Where MDR common)
F. Substance abuse and homelessness
Management of the potentially drug
resistant patient
• 1. History – assess risk factors.
• a. No previous history HRZE
• b. Previous history : HR plus four drugs not taken before.
•
Eg: HRZ: HRE Amik Cipro Eth
•
Eg: SHRZE: HR Amik Cipro Eth Cyclo
• 2. Rifampicin resistance gene
• 3. Fast track bacteriology
• 4. Never add a single drug at a time.
Drug resistant Genes in
M.tuberculosis
• Drug
Gene
• Rifampicin
rpoB
• Streptomycin
rpsL
• Isoniazid
•
•
•
No: base pairs
katG
inhA
Possible regimens according to
patterns of drug resistance
Resistance
Isoniazid
and PZI
Suggested
regimen
Amik,
RIF,E,Mox
Length
Isoniazid
and E
Amik,RIF,
PZI,Mox.
9-12/12
Isoniazid
and RIF
Amik,PZI,
E,Mox.
At least
18/12
Comments
9 months to Anticipate
a year
good
response
Consider
surgery
Possible regimens according to
patterns of drug resistance
Resistance Suggested
regimen
Length
Comments
INH,RIF,
PZI
Amik,E,
18-24/12
Consider
Mox,Eth,Cy After cul-ve surgery
INH,RIF,
PZI,E
Amik,Mox. As above
Eth,Cy,Clar
As above
Assume
Resistance To Strep
Unless
Sensitivity
Other forms of therapy
• Cytokines
•
IL-2
•
Gamma-interferon
• Immunomodulators
•
Mycobacterium vaccae
Infection Control issues
•
•
•
•
•
•
Careful
Evidence free
Negative pressure rooms
Special face masks
Care over transfer of patients
Nursing issues
Management of MDRTB
DON’T
Estonia
•
•
•
•
•
•
Very high rates of MDRTB
Manageable numbers (75-100)
Small country
Single controller
Several treatment supervisors
Monthly progress meetings
England
•
•
•
•
•
•
Low rate
Manageable number (75-100)
Central sensitivity testing
Undesignated experts
No co-ordination of therapy
No central assessment
Proposal for the management of
drug resistant tuberculosis at
national level
•
•
•
•
•
•
•
•
All MDRTB specimens identified by reference lab.
Clinician managing patient informed
Central management co-ordinator informed
Clinician contacted and regimen suggested
Monthly clinical updates from clinician to co-ordinator.
Regular monitoring of bacteriological results
Regular input from central co-ordinator.
Regular meetings convened by co-ordinator
National MDR-TB co-ordination
centre
•
•
•
•
•
Voluntary
Patient data and progress
Outcomes: bacteriological and clinical.
Availability of advice re: management
Development of expert committee.
• [email protected]
Headed MDRTB
MDRTB Useful references
•
The WHO/IUATLD Global project on Anti-tuberculosis Drug Resistance Surveillance,
Antituberculosis drug resistance in the world. Report n. 2. Prevalence and trends.
Geneva:World Health organisation. WHO/CDS/TB/2000.278.
•
http://www.who.int/gtb/publications/drugresistance/infullorpartial.html
•
Iseman M. Treatment of multi-drug resistant tuberculosis. NEJM 1993;329:784-91.
•
Yew WW. Chemotherapy of tuberculosis:present,future and beyond. in Clinical
Tuberculosis, Edit: PDODavies, Arnold 2003,pp 191-210. And other chapters.
•
Davies PDO. Multi-drug resistant tuberculosis. In Tuberculosis, Edit: M Monir
Madkour, Springer 2004, pp809-838.
•
ATS The treatment of tuberculosis MMWR 2003;52:RR 1-77
•
http://www.priory.com/cmol/TBMultid.htm
•
Zignol M, et al. Global incidence of MDR-TB. JID 2006:194:479-485.
Estimated % of new TB cases with MDR, 2000
0 - 0.9
1 - 2.9
3 - 4.9
5 - 6.9
7 or more
No estimate
Source: Dye et al. J.Infect.Dis. 185 (8):1197-1202, 2002
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World
Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or
boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
© WHO 2002
Drug resistance in the UK 2003
HPA DATA http://www.hpa.org.uk/infections/topics_az/tb/epidemiology/table18.htm
Mono
resistance With or
Without
Other
resistance
Isoniazid 273
5.5%
361
7.3%
Rifamp:
23
0.5%
100
2.0%
Any
314
6.3%
404
8.2%
77
1.6%
MDR