multidrug-resistant tuberculosisnid]/09... · multidrug-resistant tuberculosis page 5of 42 8...

Multidrug-resistant Tuberculosis of 42

Multidrug-resistant Tuberculosis

Pennan Barry, MD, MPH

California MDR TB Consult Service

Surveillance and Epidemiology Section

Curry International Tuberculosis Center

Clinical Intensive

September 2019

• Describe the national and global epidemiology of MDR TB

• Recognize who is at higher risk for MDR TB

• Discuss interpretation of molecular tests for drug resistance

• List the general principles of MDR-TB treatment

• Discuss the challenges in managing contacts of MDR TB

• Identify resources for education, training, and expert consultation

Objectives

1


Terminology

• Mono-resistant: resistant to only one drug

• Poly-resistant: resistant to more than one drug, but not the combination of INH and RIF

• Multidrug-resistant (MDR): resistant to at least INH and RIF

• Pre-extensively drug-resistant (Pre-XDR): MDR plus resistance to fluoroquinolone (FQ) or a second-line injectable (Amikacin, Kanamycin, or Capreomycin)

• Extensively drug-resistant (XDR): MDR-TB plus resistance to a FQ and at least one second line injectable

Global MDR Burden

• 2017 Estimate: 558,000 incident cases

– 47% from China, India, and Russia

• Surveillance by country and region

– 2017: Data from 82% (160/194) of countries since 1994

– Continuous surveillance (91) vs epidemiological surveys (69)

– National vs subnational

– National drug resistance surveys ongoing in 12 countries

3WHO Global Tuberculosis Report, 2018


Percentage of New Cases with MDR TBOverall: 3.5%

4WHO, Global Tuberculosis Report, 2018

5WHO, Global Tuberculosis Report, 2018

Percent of Previously Treated Cases with MDR-TBOverall: 18%


XDR-TB

• 127 countries have reported XDR-TB

• 8.5% of MDR-TB cases, increase from 6.2% in 2016

6

0

1

2

3

4

5

6

7

8

9

10

1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016

Isoniazid MDR-TB

7

Primary Anti-TB Drug Resistance, United States, 1993–2016*

* As of June 21, 2017. Note: Based on initial isolates from persons with no prior history of TB; multidrug-resistant TB (MDR-TB) is defined as resistance to at least isoniazid and rifampin.

Re

sist

an

t (%

)

Year


8

Primary Anti-TB Drug Resistance, United States, 1993–2017*

*As of June 1, 2018 Note: Based on initial isolates from persons with no prior history of TB; multidrug-resistant TB (MDR TB) is defined as resistance to at least isoniazid and rifampin.

0

1

2

3

4

5

6

7

8

9

10

1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 2017

Isoniazid MDR TB

Re

sist

ant

(%)

Year

9

Primary Isoniazid Resistance Among U.S.-Born versus Non-U.S.–Born Persons, United States, 1993–2017*

0

2

4

6

8

10

12

14

1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 2017

U.S.-born Non-U.S.–born

Year

Iso

nia

zid

-Re

sist

ant

(%)

* As of June 1, 2018. Note: Based on initial isolates from persons with no prior history of TB.


10

Primary MDR-TB Among U.S.-Born versus Non-U.S.–Born Persons, United States, 1993–2017*

0

1

2

3

1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 2017

U.S.-born Non-U.S.–born

Year

Mu

ltid

rug

-Re

sis

tan

t(%

)

* As of June 1, 2018. Note: Based on initial isolates from persons with no prior history of TB; multidrug-resistant TB (MDR-TB) is defined as resistance to at least isoniazid and rifampin.

11

XDR-TB* Case Count, Defined on Initial DST,†

by Year, 1993–2017§

* XDR-TB , extensively drug-resistant TB.† DST, drug susceptibility test.§ As of June 1, 2018.Note: XDR-TB is defined as resistance to isoniazid and rifampin, plus resistance to any fluoroquinolone and at least one of three injectable second-line anti-TB drugs.

0

2

4

6

8

10

12

1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 2017

Cas

e c

ou

nt

Year of diagnosis


Multidrug-resistant TB CasesCalifornia, 1995‒2017

47 46 42 36 39 34 31 41 33 37 36 34 28 31 33 23 35 14 26 18 23 29 300

0.5

1

1.5

2

0

5

10

15

20

25

30

35

40

45

501

99

5

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

20

14

20

15

20

16

20

17

Nu

mb

er

of

MD

R c

ase

s

MDR cases Pct MDR

Pe

rce

nt

of

cult

ure

po

sca

ses

12

Who is at higher risk for MDR-TB?

• History of previous TB treatment, particularly if recent

• Known exposure to MDR-TB case

• HIV (+)

Higher incidence of Rifampin mono resistance

• Poor response to standard 4-drug treatment

Culture remains (+) after 2 months treatment


Proportion MDR varies by birthplaceCalifornia, 2011-2018

Credit: Julian Boyce

Proportion MDR varies by birthplaceCalifornia, 2011-2018

Credit: Julian Boyce 2%


Credit: Julian Boyce

MDR more common <4 years after US arrivalCalifornia, 2011-2018

MDRNot MDR

4y

Who is at higher risk for MDR-TB?

• NonUS-born arrived in U.S. within last 4 years• Immigration from or recent extended travel to country with > 2%

MDR among cases from that country diagnosed in California/U.S.• These countries* are:

• Other state or locally identified risk groups, including:– Hmong refugees– Persons of Tibetan origin

*California data from 2014-2018 and U.S. data from 2013-2017

† Current U.S. data are available from the CDC, Division of TB Elimination (DTBE) (www.cdc.gov/tb) 17

India Peru Ethiopia, Eritrea Former Soviet states

Korea Ecuador Nigeria Mongolia

Burma Guatemala Nepal Dominican Republic

Laos


Order Xpert or PSQ for Patients with MDR Risk!

Among 42 smear positive MDR cases with MDR risk, 20 did not get Xpert or PSQ on sputum (California, 2012-2016)

18Lowenthal, Clin Inf Dis 2019

Molecular Testing for Drug Resistance

19


Chapter 3, page 48

Next Generation Sequencing

• Whole genome sequencing

– In use in UK and New York State

– Requires growth of organism (slower)

– CRyPTIC Consortium

• Targeted sequencing

– Under development

– May not require culture growth


Molecular Testing: Drugs/LociAntimicrobial agent Gene/locus

Sensitivity(Sequencing)

Specificity(Sequencing)

Assays

Isoniazid (INH) katG86.0 99.1 Hain, PSQ, MDDR

INH and Ethionamide inhA promoter

INH ahpC promoter 4.5 100 PSQ

INH fabG1 PSQ, MDDR

Rifampin (RIF) rpoB 97.1 97.4 Xpert, Hain, PSQ, MDDR

Ethambutol (EMB) embB 78.8 94.3 Hain, MDDR

Pyrazinamide (PZA) pncA 86.0 95.9 MDDR

Fluoroquinolones gyrA 79.0 99.6 Hain, PSQ, MDDR

Amikacin (AMK) rrs 90.9 98.4 Hain, PSQ, MDDR

Capreomycin (CAP)rrs

55.2 91.0 MDDRtlyA

Lin, et al., Clin Lab Med. 2014 Jun;34(2):297-314. doi: 10.1016/j.cll.2014.02.005

http://www.cdc.gov/tb/topic/Laboratory/MDDRUsersGuide.pdf

Lin, et al., J Clin Micro. 2014;52:475 22

Types of mutations

Silent (synonymous)

• Nucleic acid change

• No amino acid change

• Not associated with drug resistance generally – 514 (TTCTTT) mutation in rpoB

is the most common silent mutation

Missense (nonsynonymous)

• Nucleic acid change

• Amino acid change

• Some are associated with resistance

23


Molecular Testing for Rifampin (rpoB)

• Rifampin cornerstone of TB treatment

– Resistance requires a longer duration of therapy

– Rif resistance without INH resistance rare

Rif resistance ≈ MDR

Xpert Probes: Coverage of rpoB

427

428

429

430

431

432

433

434

435

436

437

438

439

440

441

442

443

444

445

446

447

448

449

450

451

452

Codon#

Most common silent mutation

(433 TTT)

Most common resistance mutation

(450 TTG)

Location of silent mutation Location of missense mutation


Xpert Probe B mutation might be silent

• ~20% of all mutations detected in the rpoB core

region are Silent!(In California and other low MDR areas)

• Most common is 433TTT

• Mutations detectable by probe B:

– 70% is this silent mutation

– Disputed mutation: 435TAC, 435TTC,

– RIF-R mutations: 435GTC, 432AAA, GAA, etc.

26

Xpert interpretatiom-Curry Center-9/26/18

Xpert Performance Rifampin Resistance

• Pooled median sensitivity:

– 95% (95% CrI: 90, 97)

• Pooled median specificity:

– 98% (95% CrI: 97, 99)

Steingart 2014 Cochrane Review (http://tbevidence.org/wp-content/uploads/2014/01/Steingart-Cochrane-Library-Updated-Xpert-SR.pdf)

27


Number and Proportion MDR TB by Country/Region of Origin, CA 2014–2018

Countries with >30 cases tested for MDR 28

Country/Region No. %Former Soviet Republics 6 14.0

Peru 5 13.2

Laos 12 10.0

Burma 2 3.3

Nepal 1 2.9

Philippines 32 2.0

India 9 2.0

Ethiopia 1 1.9

Vietnam 16 1.8

China 9 1.4

Guatemala 2 1.2

United States 13 0.9

Mexico 8 0.4

Number and Proportion MDR TB by Country/Region of Origin, CA 2014–2018

Countries with >20 cases tested for MDR 29

Country/Region No. %PPV

(99% spec)PPV

(98% spec)

Former Soviet Republics 6 14.0 94% 89%

Peru 5 13.2 94% 88%

Laos 12 10.0 91% 84%

Burma 2 3.3 76% 62%

Nepal 1 2.9 74% 59%

Philippines 32 2.0 66% 50%

India 9 2.0 66% 50%

Ethiopia 1 1.9 65% 48%

Vietnam 16 1.8 64% 47%

China 9 1.4 57% 40%

Guatemala 2 1.2 54% 37%

United States 13 0.9 46% 30%

Mexico 8 0.4 28% 16%


MDR-TB Cases by Country/Region of Origin and Years in the US, CA 2014–2018

Country/Region

TotalMDR TB

cases

≤ 4 years in US

No. (%)>4 years in US

No. (%)

All Countries (excl U.S.)

106 48 (3.6) 56 (1.1)

30

How to interpret results of molecular tests for resistance

31


Case 1

• 70 yo asymptomatic man from India with abnormal preimmigration CXR, no TB history

• Domestic CXR with multifocal infiltrates

• Sputum smear positive x 3

• Xpert positive: rifampin resistant

What do you do next?

• Start MDR treatment

• Order pyrosequencing or MDDR

• Start RIPE

• Repeat Xpert on another specimen

• Start treatment for monoRif resistance

32

Case 1

• Treatment held; PSQ available within 2 days and clinically stable

• Pyrosequencing:– katG mutation: INH R

– rpoB 531TTG mutation: RIF R

– gyrA (FQ): no mutations

– rrs (amikacin): no mutations



• Order MDDR

• Start RIPE


• Order second line DSTs

• Cancel DSTs (already have molecular results)

33


Case 2

• 70 yo man from Mexico in US x 25 years with 4 weeks of cough, no TB history

• CXR with multifocal infiltrates

• Sputum smear positive x 3

• Xpert positive, rifampin resistant



• Order pyrosequencing or MDDR

• Start RIPE


• Start treatment for monoRif resistance

34

Case 2

• RIPE started

• PSQ:

– katG/inhA: no mutationINH Sens

– rpoB: 514TTT silent mutation: RIF Sens

35


How to interpret molecular test for resistance

• Put into clinical and epidemiologic context!

• Confirm non-sequencing tests (e.g., Xpert) with sequencing test

• Consider Rif resistance on Xpert to be MDR (not just rifampin monoresistant)

• Can usually treat based on sequencing test results; follow the growth based DST results

36

Limitations / Areas for Caution

• Molecular tests vs. DST discordance

– Undescribed mutations outside of loci in current molecular tests resistance

– Emerging resistance in mixed populations may not be detected

– “Disputed” mutations

• DSTs show susceptible but associated with clinical treatment failure

37


Experts on Xpert: A Laboratorian and a Clinician Discuss Interpretation of Xpert MTB/RIF ResultsThis 90-minute webinar discussed the principles of Xpert MTB/RIF testing, highlighting it as an important tool for the rapid diagnosis of TB and how to best utilize the tool. A laboratorian and a clinician reviewed the rules set by the manufacturer, presented cases that addressed pitfalls in interpretation of test results, and offered expert opinion on how to proceed. The training was created for physicians who diagnose and treat patients with TB. The webinar may also be of interest to microbiologists. The webinar content is more advanced, and does not spend time on the basics.

38https://www.currytbcenter.ucsf.edu/trainings/experts-xpert-laboratorian-and-clinician-discuss-interpretation-xpert-mtbrif-results

MDR TB Treatment

39


Ask for help!MDR TB Needs Expert Consultation

Patients …[with]MDR are at high risk for treatment failure and further acquired resistance; they must be referred immediately to a specialist or consultation obtained from specialized treatment centers.

— CDC, ATS, IDSA Treatment Guidelines, 2003

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm

Evolving recommendationsChoosing a regimen

2016 CITC/CA DPH “Survival Guide” 3rd edition

2015 WHO CompanionHandbook 2016 WHO DR-TB Guidelines


WHO announces landmark changes in MDR-TB treatment regimens — 17 AUGUST 2018, GENEVA

42https://www.who.int/tb/features_archive/new_MDR_regimens/en/

First ever U.S. DR-TB Guidelines – in progress……. expected late 2019

How many drugs for MDR?Initial phase

Goal: 4-6 likely effective drugs optimally at least 5

• WHO Guidelines 2019: at least 4

• Studies suggest better outcomes with at least 5 drugs

• Expert input: • Consider more if extensive disease and/or resistance

• Four may be sufficient with limited disease and/or limited resistance

• Also depends on which drugs (e.g., NIX-TB had 3 drugs; BDQ,LZD,Pa)


WHO Reclassified MDR Medications

44Adapted from: WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update. [Pre-final text]

Group A:Include all three

Levofloxacin ORMoxifloxacin

Lfx , Mfx

Bedaquiline Bdq

Linezolid Lzd

Group B:Add one or both

Clofazimine Cfz

Cycloserine Cs

Group C:Add to complete the regimen (ranked by relative balance of benefit to harm)

Ethambutol E

Delamanid Dlm

Pyrazinamide Z

Imipenem-cilastatin OR

Meropenem (PLUS clavulanate)

Ipm-Cln

Mpm

Amikacin (OR Streptomycin) Am (S)Ethionamide Eto

p-aminosalicylic acid PAS

WHO Reclassified MDR Medications

45Adapted from: WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update. [Pre-final text]

Group A:Include all three

Levofloxacin ORMoxifloxacin

Lfx , Mfx

Bedaquiline Bdq

Linezolid Lzd

Group B:Add one or both

Clofazimine Cfz

Cycloserine Cs

Group C:Add to complete the regimen (ranked by relative balance of benefit to harm)

Ethambutol E

Delamanid Dlm

Pyrazinamide Z

Imipenem-cilastatin OR

Meropenem (PLUS clavulanate)

Ipm-Cln

Mpm

Amikacin (OR Streptomycin) Am (S)Ethionamide Eto

p-aminosalicylic acid PAS

First line drugs demoted

First line drugs demoted

BDQ and LZD for all cases(BDQ for age 6y+)

No injectable for most!!(No capreomycin for any)

Need to address access!


Data for recommendations from meta-analysis (not RCTs)

• Individual patient data metaanalysis, n=13,104

• Propensity score matched (attempt to control for differences)

• Drugs analyzed only when susceptible

46The Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment Lancet 2018; 392: 821–34

Use these drugs

47

https://www.who.int/tb/publications/2019/consolidated-guidelines-drug-resistant-TB-treatment/en/

< 1.0 is good


Don’t use these drugs

48https://www.who.int/tb/publications/2019/consolidated-guidelines-drug-resistant-TB-treatment/en/

49

Medicine(ranked by

relative balance of benefit to harm)


50

We are using Bedaquiline moreBDQ use by year, MDR Service

3 0 0 2 7 200%

20%

40%

60%

80%

100%

0

5

10

15

20

2013 2014 2015 2016 2017 2018

% o

f C

on

sult

s

Pat

ien

ts o

n B

DQ

51


Choosing to use all-oral regimens in California

Status-quo• Very good TB

outcomes with prior regimens (88% success)

• Can routinely provide appropriate monitoring(audiogram, electrolytes, creatinine, vestibular)

52

All-oral

• We do see (and worry about) hearing loss/tinnitus

• PICC / IM injections carry risk or pain

• Injectable administration is inconvenient and expensive

• We have other options

We are using injectables lessInjectable use by year, MDR Service

53

0%

20%

40%

60%

80%

100%

2015 2016 2017 2018

% P

atie

nts

on

In

ject

able


2019: MDR Regimen Questions

• When (if ever) to use injectable?

• Use Clofazimine in all?

– Difficult to get

– FQ, BDQ, CFZ all prolong QTc

• How long to use BDQ? >6months?

• What will ATS/CDC/IDSA/ERS MDR Guidelines say?

54

“Bangladesh Regimen”Short course treatment for MDR

• Recommended by WHO 2016

• Observational data impressive (85-90% cure)

• RCT noninferior

• Contraindications: resistance to any drug in regimen, extrapulmonary disease, pregnancy

• Should this be used in the U.S.?

WHO, 2016. http://who.int/tb/Short_MDR_regimen_factsheet.pdf 55


Short(er) Course Regimen for MDR-TB

Isoniazid*

Moxifloxacin*

Pyrazinamide

Ethambutol

0 1 2 3 4 5 6 7 8 9+

months

Clofazimine

Prothionamide

Kanamycin

Initial Phase (7 drugs) Continuation Phase (4 drugs)

*High dose

Barriers to Implementing

• Clofazimine availability

• Contains injectable

• Few qualify by strict criteria (15% in California)

• How to substitute for adverse events or resistance?


Pretomanid

• FDA approved August 14, 2019 (not available yet)

• Nitroimidizole (same class as delamanid)

• Approved for:

– use with LZD 1200mg and BDQ (NIX-TB study)

– XDR TB

– MDR TB in patients “intolerant or nonresponsive” to treatment

• Several other ongoing trials (ZeNIX, SimpliciTB)

58

Beyond susceptibility results, consider:

• Cross-resistance

– low level INH-R (inhA, ahpC, fabG) Ethionamide R)

– Moxifloxacin Levofloxacin

– Clofazimine ↔ Bedaquiline

• Side effect profile

• Avoid drugs used previously


Medication Fact Sheets

• Drug class/trade name• Activity against TB• Cross-resistance• Dose (adult, peds, renal)• Route of administration• Preparation/storage• Pharmacokinetics• Oral absorbtion/metabolism• CSF penetration• Special circumstances• Adverse

reactions/contraindications• Monitoring• Costs/patient education

Treatment Duration(Longer regimens)

• WHO 2019 Guideline:

– Total duration at least 18 months AND at least 15 months after culture conversion

– Intensive phase (injectable only) 6-7 months

• Survival Guide – Expert consensus for U.S. Setting: – Use culture conversion to guide minimum duration – Intensive phase: at least 6 mo beyond culture conversion for

use of injectable agent– Total duration: at least 18 months beyond culture conversion

• ATS/CDC/IDSA/ERS Guideline pending

• Future: NIX, ZeNIX, others studying shorter regimens


Surgery?

• No hard and fast rules; WHO: Surgery “may be used”

• Metaanalysis suggests success

• Consider if:

Very extensive resistance

Residual large cavity

Predominantly one-sided disease

Previous MDR treatment failure

Marrone MT, et al. Surgical interventions for drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis 2013;17(1):6-16.

MDR-TB Clinical Case Management

• Seek consultation with MDR-TB expert as soon as multidrug resistance known

• Use daily DOT throughout entire treatment course

– No intermittent therapy for drug resistance!!

• Use case management tools (drug-o-gram) to follow serial changes in drugs, bacteriology, CXR, toxicities

• Optimize management of underlying medical conditions and nutritional status (i.e. diabetes)


Therapeutic Drug Monitoring

• Cycloserine:

– absorption variable

– therapeutic and toxic levels are very close

– drug levels are highly recommended

– Draw 2 hours after dose

• AK, PAS, FQ, ETA, Linezolid (esp low dose)

– Some experts use routinely for all

Common Side EffectsG.I. symptoms Ethionamide, PAS, Quinolones, Clofazimine,

Rifabutin, Linezolid

Hearing loss, vestibular toxicity Injectables

Renal insufficiency/Electrolyte Injectables

Hepatotoxicity PZA, PAS, Rifabutin, Ethionamide, Quinolones

Peripheral neuropathy Linezolid, INH, Quinolones, Ethionamide, Cycloserine

Neuropsychiatric: depression, agitation, psychosis, difficulty concentrating, insomnia

Cycloserine, Quinolones, Ethionamide

QTc prolongation Bedaquiline, Clofazimine, Quinolones

Rash All

Visual changes EMB, Rifabutin, Linezolid

Hypothyroidism Ethionamide, PAS

Headache Quinolones, Cycloserine, Ethionamide, EMB

Chapter 9


QTc Prolongation

• Use Fredericia formula (most ECG machines use Bazett)

• QTc has substantial diurnal variation (up to 75ms)– Longest in AM

• Prolonged QTcF: >470 for females; >450 for men– Repeat ECG after 30 minutes to confirm

– QTcF >500ms is more concerning; requires action

• Think about/address other prolonging drugs and conditions (in addition to TB meds)

Challenge TB 2018 QTc Guide: https://www.challengetb.org/publications/tools/pmdt/Guidance_on_ECG_monitoring_in_NDR_v2.pdf 70

Monitor MDR-TB patients for treatment response

• Collect sputum monthly throughout

• End-of-treatment sputum for smear and culture

• CXR quarterly and at end of treatment

• Monitor for 2 years after treatment

– Quarterly: first year, Q6 months: second year)


88% of MDR cases have good outcomesCalifornia 2009–2018

Off Treatment191

On Treatment50

Moved23

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

All MDR Casesn=267

*Includes 1 patient with relapse 8 years later with matching genotype but nonMDR DSTs

72

Cure/Complete169

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Off Treatmentn=191

Death=9 (5%)Default/LTFU=7Failure(ADR)=5*Failure(micro)=1

Died before Rx=3

Prevention

• Preventing acquired drug resistance

– DOT and daily therapy as appropriate

• Preventing transmission of MDR-TB to contacts

– Effective treatment, Isolation until noninfectious

• Preventing progression to active disease in infected MDR-TB contacts

– MDR LTBI treatment and monitoring


Pulmonary MDR-TB considered infectious until: CDPH/CTCA Guidelines

• Effective MDR regimen tolerated for 2 weeks AND

• Favorable clinical response AND

• 3 consecutive sputum smears are AFB negativeAND

If high risk setting: (congregate, vulnerable contacts)

• 2 consecutive negative sputum cultures

Guidelines for the Assessment of Tuberculosis Patient Infectiousness and Placement into High and Lower Risk Settings, 2017: https://ctca.org/wp-content/uploads/2018/11/InfectiousnessOctober2017.pdf

Preventing Progression to Active TB

• Some published data on LTBI treatment for MDR-TB contacts; No randomized trials reported

• CDC guidance last in 1992

• Contact investigation and management principles same as drug susceptible:

– Drug resistant TB is not more infectious, but consequences of transmission are greater

– Consider infectiousness of index case, duration/intensity of contact, immune status of contact, LTBI test results

– Rule out active disease prior to starting LTBI treatment


Fluoroquinolones for MDR Contacts

• Published data from 2 MDR outbreaks in Chuuk:

– 104 of 119 received LTBI treatment x 12 months

• Adults: MFX + EMB (n=24) or MFX/LFX alone (n=51)

• Children: LFX + EMB (N=17) or LFX + Ethionamide (n=12)

– 11 stopped early; 6 received >6 mos

– 0 cases in treated vs 3 among 15 refused (36 mo f/u)

76Bamrah et al, Int J Tuberculosis Lung Dis 2014

Treatment Regimens for MDR-TB Contacts

• FQ monotherapy

• FQ + EMB

• Monitor for 2 years only – acceptable

• FQ + PZA – very poorly tolerated

• PZA + EMB

• Other combinations? Duration?

– BDQ, LZD, ETA, CS, PAS


Resources

78

Resources: COEs• Curry International Tuberculosis Center

1-877-390-NOTB or 1-877-390-6682 www.currytbcenter.ucsf.edu

• Heartland National Tuberculosis Center1-800-TEX-LUNG or 1-800-839-5864www.heartlandntbc.org

• New Jersey Medical School Global Tuberculosis Institute1-800-4TB-DOCS or 1-800-482-3627www.umdnj.edu/globaltb

• Southeastern National Tuberculosis Center1-800-4TB-INFO or 1-800-482-4636http://sntc.medicine.ufl.edu

• Mayo Clinic Center for Tuberculosis 855-360-1466http://centerfortuberculosis.mayo.edu/


MDR Resources

• Curry Survival Guide v3 (2016)– https://www.currytbcenter.ucsf.edu/products/cover-pages/drug-resistant-tuberculosis-

survival-guide-clinicians-3rd-edition

• Partners in Health Guide (2013) – http://www.pih.org/library/pih-guide-to-the-medical-management-of-multidrug-resistant-tuberculosis-

2nd

• WHO MDR Guides– Companion Guide (2014)

http://apps.who.int/iris/bitstream/10665/130918/1/9789241548809_eng.pdf

– Guideline (2019)https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?ua=1

• International Union Guide (2018)– http://origin.theunion.org/what-we-do/publications/technical/english/TheUnion_DR-TB-Guide.pdf

80

California Resources

• MDR-TB Service

Provides clinical consultation, case management, CI assistance – 510-620-3000

• CA Microbial Diseases Lab

pyrosequencing for drug resistance

phenotypic DST for first-line drugs and amikacin, moxifloxacin, capreomycin, and ethionamide


Acknowledgments

• Lisa True

• Lisa Chen

• Neha Shah

• Grace Lin

• Gisela Schecter

• Janice Westenhouse

• Marya Husary

• Julian Boyce

• Adam Readhead

[email protected]

Pennan Barry(MD)

Kristen Wendorf

(MD)

MaryaHusary(Project

Specialist)

Lisa True(RN)

Phil Lowenthal

(epi)

Shereen Katrak

(MD)

Neha Shah

(ret.)

Leslie Henry

(RN)

multidrug-resistant tuberculosisnid]/09... · multidrug-resistant tuberculosis page 5of 42 8...

Documents