we 077 mdr mdx tb resistant strains

8/6/2019 WE 077 MDR MDX TB Resistant Strains

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*Fredrick M. Abrahamian, DO,

FACEP

Associate Professor of Medicine, David

Geffen School of Medicine at UCLA, Los

Angeles, California; Director of

Education, Department of Emergency

Medicine, Olive View-UCLA MedicalCenter, Los Angeles, California

MDR and MDX: TB Resistant Strains

Tuberculosis is on the rise internationally.

While in the US it seems stable, more and morepeople are immigrating to the United States.

Come and hear about this concern and also the

latest Federal TB Task Force recommendations

to combat extensively drug-resistant

tuberculosis. Do I need to admit this patient, or

can I send them home? HIV and TB are like a

perfect storm. The speaker will discuss what is

new with TB, including MDR and MDX TB,

and what may be on the horizon.

Describe the worldwide and national prevalence

of TB.Illustrate the multi-drug resistance form of TB.

Discuss various treatments for all types of TB.

Discuss strategies of some public health issues

around treatment.

WE-77

9/29/2010

8:00 AM - 8:50 AM

Mandalay Bay Convention Center

*Consultant: Forest Laboratories, Schering-Plough;

Speaker's Bureau-Merck


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MDR & XDR:TB Resistant Strains

Fredrick M. Abrahamian, D.O., FACEPAssociate Professor of Medicine

UCLA School of Medicine

Director of Education

Department of Emergency Medicine

Olive View-UCLA Medical Center

Tuberculosis

#1 cause of death from infectious diseases

in the world

~ 2 million TB-related deaths worldwide

~ 1/3 of worlds population is infected

~ 9 million new cases each year

~ 10-15 million infected in U.S.

MMWR. 2010;59(10):289-294.

MMWR. 2010;59(10):289-294.

TB: U.S., 2009


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MMWR. 2010;59(10):289-294.

High Risk for TB

Medically underserved, low-income

IV drug users

Alcoholics

Homeless

Immigrants from high-risk areas

Underlying medical illness

HIV


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Mycobacterium tuberculosis

Slow-growing, intracellular bacterium

Transmitted by droplet nucleiSmall size

Remains suspended in air

Risk of infection with greater concentrations& longer exposure

Small, poorly ventilated areas

Latent TB Infection

No symptoms

Can not spread TB to others

Positive TB skin test (usually)

Normal CXR & negative sputum

Risk of progressing to active TB

Active TB Disease

Typical symptoms:

Cough, weight loss, fatigue

Hemoptysis, night sweats

Can spread TB to others

Positive TB skin test (usually)

Positive CXR & sputum (usually)


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Extrapulmonary TB

Lymphadenitis

Genitourinary

Sterile pyuria

Musculoskeletal

Potts disease of the spine

Meningitis

Subacute, cranial nerve signs

Lymphocytic pleocytosis

TB & HIV

Greater likelihood of progressing to active TB

8% per year vs. 5-10% over lifetime

Atypical presentations

More extrapulmonary TB

Atypical CXR findings

Often mistaken for PCP or other pneumonia

Multidrug-Resistant (MDR) TB

Resistant to at least INH & rifampin

2008: 107 cases (1.1% of all culture + cases)

~ 8% resistance to INH reported in U.S.High risk:

Prior Hx of TB (risk increases 4 fold)

Known exposure to MDR TB

Immigrant: Asia, Africa, S. America

Homeless

PrisonMMWR. 2010;59(10):289-294.


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MDR TB inHealthcare Workers

PPD conversions in MDR TB outbreak 33% healthcare workers at 1 hospital

50% at another

At least 17 healthcare with active MDR TB

At least 5 healthcare deaths from MDR TB

Extensively Drug-Resistant TB(XDR TB)

Resistance to at least INH & rifampin

Resistance to any fluoroquinolone

Resistance to at least one 2nd-line injectable drug

(e.g., amikacin, capreomycin, or kanamycin)

No cases reported in 2009

4 cases reported in 2006; 2 in 2007; & 4 in 2008

MMWR. 2010;59(10):289-294.


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Number of XDR TB - U.S., 1993-2006

MMWR. 2007;56(11):250-253.

TB Transmission in ED

1983 outbreak: Patient in ED for 4 hours

16 PPD skin test conversions

112 previously negative ED employees

5 developed active TB

3 of 4 physicians involved with patient

converted PPD skin test

TB Infection Control

Early identification of TB patients

Initiate isolation

Initiate effective TB therapy

Use precautions for risky procedures


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TB Isolation &Suspicion of TB in ED

Median time to isolation & therapy (hours)

128 (68-374)

21 (11-111)

Other Dx

12 (9-22)

5 (2-10)

TB Dx

< .001Therapy

< .001Isolation

p

Moran GJ, et al. Ann Emerg Med. 1995;26:290-295.

Predictors of Time to Isolation

6.5 (2-11)No

.008417 (7-132)YesHIV Risk

17 (7-132)No

.00106.5 (2-11)YesX-ray + TB

8 (4-14)No

.00011.5 (1-3)YesTB contact

pMedian Time to

Isolation (hr)PresenceVariable


Isolation Room

Negative pressure

6 air exchanges per hour

Exhaust directly to outside

Need N-95 respirator


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TB Infection Control in U.S. EDs

~ 60% have triage isolation policies

< 20% have AFB isolation rooms< 20% have HEPA filters or UV lights

< 20% use particulate respirator masks

< 20% skin test ED employees q6 months

~ 60% perform sputum induction in ED


Reducing Risk of TB Transmission

Triage protocols to rapidly identify TB patients

Rapid isolation of TB patients

Isolation rooms

HEPA filters

UV lights

Avoid high-risk procedures


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Isolation & Infection Control

Many unnecessary admissions to isolation

On average, only ~ 68% of TB patients are isolated

Instrument to predict which patients do NOT have TB No TB Hx. or previous positive TB skin test result

Non-immigrant

Not homeless

Not recently incarcerated

No recent weight loss

No apical infiltrate or cavitary lesion on CXR


Testing for TB Disease & Infection

Indications for PPD Testing

Suggestive symptoms or CXR

Contact with active TBHIV

Diabetes, renal failure, immunosuppressed

Exposure Risk: Immigrants, homeless,

prison, long-term care facility, healthcare

workers


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Administering the TuberculinSkin Test

Inject intradermally 0.1 ml of 5 TU PPD

tuberculin

Produce wheal 6 mm to

10 mm in diameter

Anergy skin testing no

longer routinely recommended

Reading the Tuberculin Skin Test

Read reaction 48-72 hours after injection

Measure only induration

Record reaction in millimeters

Tuberculin Reaction

5 mm is classified as positive in:

HIV+ Recent close contact

Persons with fibrotic changes on CXR

consistent with old healed TB

Immunosuppressed (e.g., > 15 mg/day

of prednisone for 1 month or longer)


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Tuberculin Reaction


Immigrants from high-prevalence countries

Injection drug users Individual at high-risk congregate settings

Mycobacteriology laboratory personnel

High risk conditions (DM, CA, renal failure)

Children < 4 years of age

Children exposed to adults in high-risk

categories

Tuberculin Reaction


Persons with no known risk factors

for TB

Bacille Calmette-Guerin (BCG)

Most commonly used TB vaccine

Used in many countries with high TB risk

Provides only partial protection

BCG history does not change interpretation

of PPD results:

Given in areas at risk for TB

BCG usually causes reaction < 10 mm

Reaction wanes with time


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Chest Radiograph

Abnormalities often seen in apical or

posterior segments of upper lobe orsuperior segments of lower lobe

May have unusual appearance in HIV+

persons

Can not confirm diagnosis of TB

CXR: AIDS & TB

35%No infiltrate

6%Typical TB findings

12%No abnormality

18%Upper lobe infiltrate

29%Middle / lower lung infiltrate

59%Hilar / mediastinal adenopathy


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Specimen Collection

Obtain 3 sputum specimens for

smear examination & culture

Persons unable to cough up sputum,

induce sputum, bronchoscopy or

gastric aspiration

Follow infection control precautions

during specimen collection

AFB Smear

AFB (shown in red) are tubercle bacilli

Colonies of

M. tuberculosis

growing on media

Use to confirm diagnosis

Culture all specimens, even if smear negative

Results in 4 to 14 days when liquid medium

systems used

Cultures


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TB Preventive Treatment

To reduce likelihood of progression to activedisease

Consider risk of TB vs. toxicity of therapy

INH x 9 months for most

If INH resistance likely: Rifampin + PZA

Positive PPD: Indications for Rx

Any new converter

HIV+

Recent contact with infectious TB

Old TB on CXR

Increase risk of active TB:

DM, CA, steroids, renal failure

Age < 35

? older patients: Monitor for hepatotoxicity

Treatment of Active TB

Requires multiple drugs

Start with 4 drugs, then reduce to 2 drugsbased on susceptibility

Culture & susceptibility takes ~ 8 wks

Compliance important

Directly Observed Therapy (DOT) when

possible


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1st Line TB Drugs

Adult dose

Isoniazid 300 mg/d

Rifampin 600 mg/d

Pyrazinamide 25 mg/kg/d (max 2.5 gm)

Ethambutol 15-25 mg/kg/d

Streptomycin 15 mg/kg/d

2nd Line TB Drugs

Capreomycin

Ciprofloxacin

Clofazimine

Cycloserine

Ethionamide

Kanamycin

Amikacin

Levofloxacin

Ofloxacin

Aminosalicylic acid

Rifabutin

Rifapentine

3rd Line TB Drugs

Linezolid

Imipenem

Amoxicillin/clavulanate

Macrolides

Schecter GF, et al. Clin Infect Dis. 2010;50:49-55.


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Treatment of Active TB

Common regimen:

INH, Rifampin, PZA, Ethambutol daily x 8 wks

Then INH + Rifampin for 18 weeks

(assuming organism is susceptible)

Longer duration of therapy for TB meningitis,

miliary TB, or bone/joint TB infection

Dexamethasone beneficial with TB meningitis

Prasad K, et al. Cochrane Database Syst Rev. 2008.Thwaites GE, et al. N Engl J Med. 2004;351:1741-1751

Treatment of MDR & XDR TB

Treatment must be individualized

Requires combination of 2nd or 3rd

line agents

Expert consultation

Directly Observed Therapy

Response to Treatment

Requires monthly bacteriologic assessment until

cultures convert to negative

After 3 months of therapy, if cultures are + or Sxs

not resolved, reevaluate for:

Potential drug-resistant disease

Non-adherence to drug regimen

If cultures do not convert to negative despite 3

months of therapy, DOT needs to be initiated


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Period of Infectivity

TB patients are considered no longer

infectious if:

On adequate therapy

Significant clinical response to therapy

3 consecutive negative sputum smears

Fitzwater SP, et al. Clin Infect Dis. 2010;51:371-378.

Take Home Points

Initial treatment of active TB with 4 drugs:

INH, RIF, PZA, ETB

Treatment of MDR & XDR TB:

Requires combination of various agents

Treatment of latent infection:

INH (optimal therapy: 9 months)

Tuberculin skin test reaction:

Induration 5 mm considered + in a patient

taking > 15 mg/day of prednisone for 1 month

we 077 mdr mdx tb resistant strains

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