MULTIDRUG-RESISTANT MULTIDRUG-RESISTANT TUBERCULOSIS: What Nurses Should TUBERCULOSIS: What Nurses Should

KnowKnow

Felissa R. Lashley, RN, PhD, FAAN, FACMGFelissa R. Lashley, RN, PhD, FAAN, FACMGProfessor, College of Nursing, andProfessor, College of Nursing, and

Interim Director, Nursing Center for Bioterrorism and Infectious Interim Director, Nursing Center for Bioterrorism and Infectious Disease Preparedness, College of NursingDisease Preparedness, College of Nursing

Rutgers, The State University of New JerseyRutgers, The State University of New Jersey

This module is designed to highlight important information about multidrug resistant This module is designed to highlight important information about multidrug resistant tuberculosis (MDR-TB). MDR-TB is also considered to be a potential agent for bioterrorism tuberculosis (MDR-TB). MDR-TB is also considered to be a potential agent for bioterrorism and is considered as a possible Category C bioterrorism agent by the Centers for Disease and is considered as a possible Category C bioterrorism agent by the Centers for Disease Control and Prevention (CDC). This module was supported in part by USDHHS, HRSA Grant Control and Prevention (CDC). This module was supported in part by USDHHS, HRSA Grant No. T01HP01407. No. T01HP01407.

Multidrug-Resistant Tuberculosis Multidrug-Resistant Tuberculosis (MDR-TB)(MDR-TB)

MDR-TB is considered as a Category-C biological agent MDR-TB is considered as a Category-C biological agent in regard to its potential for use in bioterrorism by the in regard to its potential for use in bioterrorism by the CDC. CDC.

These agents are considered as possible emerging These agents are considered as possible emerging public health threats and are considered as such in the public health threats and are considered as such in the module on Biological Weapons: Essential Information module on Biological Weapons: Essential Information on Category C Agents.on Category C Agents.

XDR-TB (extensively resistant tuberculosis) refers to XDR-TB (extensively resistant tuberculosis) refers to cases of TB that are resistant to isonazid , rifampin, cases of TB that are resistant to isonazid , rifampin, the second line drugs, the fluoroquinolones, and at the second line drugs, the fluoroquinolones, and at least one of three injectable drugs. i.e. amikacin. least one of three injectable drugs. i.e. amikacin.

ObjectivesObjectives

Describe the signs and symptoms Describe the signs and symptoms commonly associated with pulmonary TB.commonly associated with pulmonary TB.

Identify persons at high risk for MDR-TB.Identify persons at high risk for MDR-TB. Describe reasons for development of drug Describe reasons for development of drug

resistance in the treatment of TB.resistance in the treatment of TB. Identify possible clinical outcomes after Identify possible clinical outcomes after

acquisition of acquisition of MycobacteriumMycobacterium tuberculosistuberculosis.. Identify appropriate infection control for Identify appropriate infection control for

persons with MDR-TB.persons with MDR-TB.

DefinitionDefinition

MDR-TB is defined as a case of TB MDR-TB is defined as a case of TB caused by a strain of caused by a strain of M.M. tuberculosistuberculosis that is resistant to two or more that is resistant to two or more antituberculosis drugs. Some define antituberculosis drugs. Some define MDR-TB as a case of TB caused by a MDR-TB as a case of TB caused by a strain of strain of M.M. tuberculosistuberculosis that is that is resistant to isoniazid and rifampin.resistant to isoniazid and rifampin.

EtiologyEtiology Both tuberculosis infection and tuberculosis (TB) Both tuberculosis infection and tuberculosis (TB)

are due to the tubercle bacilli.are due to the tubercle bacilli. The most common in the US is The most common in the US is Mycobacterium Mycobacterium

tuberculosistuberculosis.. M.M. tuberculosistuberculosis is a nonmotile, non-spore forming is a nonmotile, non-spore forming

rod shaped bacillus with no capsule.rod shaped bacillus with no capsule. It does not produce toxin.It does not produce toxin. It is known as acid fast because of staining It is known as acid fast because of staining

characteristics.characteristics. It can survive for long periods under adverse It can survive for long periods under adverse

conditions.conditions.

DescriptionDescription Infection with Infection with M.M. tuberculosistuberculosis can can be pulmonary or extrapulmonary.be pulmonary or extrapulmonary. Pulmonary TB is the most common Pulmonary TB is the most common form in developed countries.form in developed countries. In extrapulmonary TB, signs and symptoms In extrapulmonary TB, signs and symptoms

depend on the affected organ system as well as depend on the affected organ system as well as systemic symptoms.systemic symptoms.

Major concerns about MDR-TB arose in the early Major concerns about MDR-TB arose in the early 1990s when nosocomial outbreaks occurred.1990s when nosocomial outbreaks occurred.

Concerns about XDR-TB arose in about 2000, and Concerns about XDR-TB arose in about 2000, and appears most prevalent in South Africa, parts of appears most prevalent in South Africa, parts of Asia especially South Korea and Eastern Europe.Asia especially South Korea and Eastern Europe.

EpidemiologyEpidemiology

MDR-TB is particularly common in:MDR-TB is particularly common in:Resource poor areasResource poor areasGlobal "hot spots" such as some areas in Global "hot spots" such as some areas in

the former Soviet Union, India, the the former Soviet Union, India, the Dominican Republic, Ivory Coast, and Dominican Republic, Ivory Coast, and othersothers

Congregate settings such as prisons or Congregate settings such as prisons or long-term care facilitieslong-term care facilities

Epidemiology cont.Epidemiology cont.-2-2

In practice, MDR-TB develops either In practice, MDR-TB develops either because the person is infected because the person is infected initially with a:initially with a:Drug-resistant strain (primary), orDrug-resistant strain (primary), orSusceptible strain that becomes Susceptible strain that becomes

resistant (secondary)resistant (secondary)Primary resistance would be most likely Primary resistance would be most likely

in regard to bioterrorism use.in regard to bioterrorism use.

Epidemiology cont.Epidemiology cont.-3-3

Reasons for secondary resistance are Reasons for secondary resistance are numerous and complex:numerous and complex:Wrong drugs used in an improper wayWrong drugs used in an improper wayFailure to assess drug susceptibility Failure to assess drug susceptibility

patterns of the organismpatterns of the organismA large bacterial load, especially in the A large bacterial load, especially in the

case of cavitationcase of cavitationPoor adherence to the treatment Poor adherence to the treatment

regimenregimen

Epidemiology cont.Epidemiology cont.-4-4

TB (including MDR-TB) and HIV co-infections are TB (including MDR-TB) and HIV co-infections are relatively common globally and each condition relatively common globally and each condition adversely affects the other.adversely affects the other.

In the US in 2007, the overall number of TB cases In the US in 2007, the overall number of TB cases reported in the U.S. was 13, 293.reported in the U.S. was 13, 293.

In the U.S. between 1993 and 2006, 49 cases of In the U.S. between 1993 and 2006, 49 cases of XDR-TB were reported, and in 2006, 116 cases of XDR-TB were reported, and in 2006, 116 cases of MDR-TB were reported.MDR-TB were reported.

The overall case rate was 4.4 cases per 100,000 The overall case rate was 4.4 cases per 100,000 population. U.S. born blacks and foreign born population. U.S. born blacks and foreign born persons account for a disproportionate number of persons account for a disproportionate number of cases.cases.

Epidemiology cont.Epidemiology cont.-5-5

TB remains a major global problem. TB remains a major global problem. Each year about 2 million people die Each year about 2 million people die of TB each year worldwide. In 2006, of TB each year worldwide. In 2006, WHO reported 9.2 million new cases WHO reported 9.2 million new cases of TB.of TB.

In the U.S., 49 cases of XDR-TB were In the U.S., 49 cases of XDR-TB were reported between 1993 and 2006.reported between 1993 and 2006.

TransmissionTransmission

Person-to-person through inhalation of droplet Person-to-person through inhalation of droplet nucleiinucleii

Infected person usually coughs or sneezes and Infected person usually coughs or sneezes and projected infected droplet nucleii into the airprojected infected droplet nucleii into the air

Ingestion of contaminated food or water (rare in Ingestion of contaminated food or water (rare in US)US)

Direct inoculation is rare although infection Direct inoculation is rare although infection through transplants has occurred. through transplants has occurred.

Outcomes of Contact with Outcomes of Contact with M.M. tuberculosistuberculosis

Many factors determine outcome Many factors determine outcome such as:such as:Host susceptibilityHost susceptibility, such as genetic , such as genetic

factors and immune statusfactors and immune statusOrganism characteristicsOrganism characteristics, such as , such as

virulencevirulenceEnvironmentEnvironment, such as length of time , such as length of time

and proximity of contact between the and proximity of contact between the susceptible person and the person with susceptible person and the person with TBTB

Sequence of Events in Brief:Sequence of Events in Brief:

After After M.M. tuberculosistuberculosis enters the body, enters the body, possible events include:possible events include:No infectionNo infectionTuberculous infectionTuberculous infection

Remains dormant in latent form (90%)Remains dormant in latent form (90%) Progression to clinical disease (10%)Progression to clinical disease (10%)

Within a year or two (5%)Within a year or two (5%) Years later (5%)Years later (5%)

Thus, persons may have:Thus, persons may have: Latent TB infection in which persons are infected Latent TB infection in which persons are infected

with tubercle bacilli but are not infectious to others with tubercle bacilli but are not infectious to others nor show clinical symptoms but do usually have a nor show clinical symptoms but do usually have a positive reaction to the tuberculin skin test but positive reaction to the tuberculin skin test but usually negative chest radiograph. They may be usually negative chest radiograph. They may be candidates for preventive drug therapy, candidates for preventive drug therapy,

OROR

Active TB in which they are infected with tubercle Active TB in which they are infected with tubercle bacilli, usually have positive sputum smears and bacilli, usually have positive sputum smears and cultures, usually have a positive reaction to the cultures, usually have a positive reaction to the tuberculin skin test, usually have clinical symptoms, tuberculin skin test, usually have clinical symptoms, and may be infectious to others before treatment is and may be infectious to others before treatment is effective.effective.

Clinical ManifestationsClinical Manifestations

MDR-TB are or are not clinically MDR-TB are or are not clinically distinguishable from drug-susceptible distinguishable from drug-susceptible TB at the outset.TB at the outset.

Signs, symptoms, and radiological Signs, symptoms, and radiological findings are similar initially to drug-findings are similar initially to drug-susceptible TB.susceptible TB.

In the non-bioterrorist setting, reasons to In the non-bioterrorist setting, reasons to

suspect drug resistance aresuspect drug resistance are:: A history of previously treated TB in a person A history of previously treated TB in a person

presenting with active TBpresenting with active TB High community rates of drug resistant TBHigh community rates of drug resistant TB Positive HIV statusPositive HIV status High likelihood of exposure to nosocomial, prison High likelihood of exposure to nosocomial, prison

or community sources of MDR-TBor community sources of MDR-TB The infected person is from a country with a high The infected person is from a country with a high

MDR-TB ratesMDR-TB rates Contacts with persons with MDR-TBContacts with persons with MDR-TB Infected person has received inadequate Infected person has received inadequate

treatment regimens for >2 weekstreatment regimens for >2 weeks Smears or cultures remain positive despite 2 Smears or cultures remain positive despite 2

months of treatment for TBmonths of treatment for TB

Symptoms of Pulmonary TB Symptoms of Pulmonary TB include:include:

Cough (usually Cough (usually productive and maybe productive and maybe bloody)bloody)

Low-grade feverLow-grade fever SweatingSweating Chills at nightChills at night FatigueFatigue MalaiseMalaise AnorexiaAnorexia

Weight lossWeight loss Dull, aching chest pain Dull, aching chest pain

or tightnessor tightness

Symptoms of Symptoms of extrapulmonary TB extrapulmonary TB depend on the organ depend on the organ system involved but system involved but may include systemic may include systemic symptoms such as symptoms such as malaisemalaise

Diagnosis generally consists of:Diagnosis generally consists of:

Medical history,Medical history, Clinical signs and symptoms,Clinical signs and symptoms, Chest x-ray for pulmonary TB,Chest x-ray for pulmonary TB, Sputum smear and/or culture for Sputum smear and/or culture for

acid-fast bacilli, and possibly acid-fast bacilli, and possibly A tuberculin skin test.A tuberculin skin test.

Diagnosis notesDiagnosis notes Tuberculin skin test with purified protein Tuberculin skin test with purified protein

derivative as screen; anergy may be seen in derivative as screen; anergy may be seen in elderly and the immunosuppressed.elderly and the immunosuppressed.

Chest x-ray or radiograph of extrapulmonary site Chest x-ray or radiograph of extrapulmonary site shows characteristic findings of abnormalities in shows characteristic findings of abnormalities in apical or posterior segments of upper lobe or apical or posterior segments of upper lobe or superior segments of lower lobe but is not used to superior segments of lower lobe but is not used to confirm diagnosis of pulmonary TB.confirm diagnosis of pulmonary TB. Appearance may be unusual in HIV-positive personsAppearance may be unusual in HIV-positive persons

Sputum smears and cultures for tubercle bacilli.Sputum smears and cultures for tubercle bacilli.

TreatmentTreatment

Initial non-MDR-TB therapy in drug-Initial non-MDR-TB therapy in drug-susceptible disease calls for 8 weeks susceptible disease calls for 8 weeks of therapy with isoniazid, rifampin, of therapy with isoniazid, rifampin, pyrazinamide, and ethambutol pyrazinamide, and ethambutol followed by a continuation regimen followed by a continuation regimen of isoniazid and rifampin for 18 more of isoniazid and rifampin for 18 more weeks as the most frequent option.weeks as the most frequent option.

Aggressive treatment is suggested.Aggressive treatment is suggested.

Treatment cont.Treatment cont.-2-2

Usually the initial regimen for MDR-Usually the initial regimen for MDR-TB will consist of at least 3 TB drugs TB will consist of at least 3 TB drugs the patient has not used before (a the patient has not used before (a single drug should never be added) single drug should never be added) and as many as 6 drugs.and as many as 6 drugs.

There are detailed dosages and There are detailed dosages and possible options available depending possible options available depending on many factors. Newer guidelines on many factors. Newer guidelines should always be consulted. should always be consulted.

Treatment cont.Treatment cont.-3-3

MDR-TB treatment depends on the MDR-TB treatment depends on the drug resistance pattern present:drug resistance pattern present:It may include directly observed therapyIt may include directly observed therapyOccasionally, surgical resection may be Occasionally, surgical resection may be

used in treatmentused in treatmentDetailed information about management Detailed information about management

options are given in the references (see options are given in the references (see CDC reference in particular)CDC reference in particular)

PreventionPrevention

MDR-TB may be prevented by MDR-TB may be prevented by clinicians:clinicians:Choosing the appropriate therapeutic Choosing the appropriate therapeutic

regimen based on clinical, regimen based on clinical, microbiological, pathological, microbiological, pathological, radiological and epidemiological radiological and epidemiological information, andinformation, and

Assuring a regimen with the highest Assuring a regimen with the highest likelihood of adherence to therapy.likelihood of adherence to therapy.

Management, including Infection Management, including Infection ControlControl

Teaching the patient and family about Teaching the patient and family about preventing transmission, especially preventing transmission, especially etiquette and hygiene, use of masks etiquette and hygiene, use of masks where indicated, and handwashing.where indicated, and handwashing.

Isolation precautions are usually needed Isolation precautions are usually needed until there have been 3 negative sputum until there have been 3 negative sputum cultures.cultures.

Ascertaining likelihood of adherence and Ascertaining likelihood of adherence and using measures to enhance adherence.using measures to enhance adherence.

Promptly isolate persons suspected or Promptly isolate persons suspected or known to have TB.known to have TB.

Use appropriate infection control.Use appropriate infection control.

MDR-TBMDR-TBFor sputum positive pulmonary MDR-TB, appropriate For sputum positive pulmonary MDR-TB, appropriate

infection control includes: infection controlinfection control includes: infection control

Special airborne precautions, including isolation in Special airborne precautions, including isolation in a negative pressure isolation room, and a negative pressure isolation room, and appropriate air handling. appropriate air handling.

Staff should wear appropriate personal protection Staff should wear appropriate personal protection devices, and close door behind them. devices, and close door behind them.

Staff should remove personal protection devices Staff should remove personal protection devices before exiting anteroom and sanitize hands after before exiting anteroom and sanitize hands after leaving room. See infection control module details, leaving room. See infection control module details, and CDC, (2005). Guidelines for preventing the and CDC, (2005). Guidelines for preventing the transmission of My cobacterium, 2005. transmission of My cobacterium, 2005.

Murphy, R.A. (2008) The emerging crisis of drug-resistant tuberculosis in Murphy, R.A. (2008) The emerging crisis of drug-resistant tuberculosis in South Africa: Lessons from New York City. Clinical Infectious Diseases 46, South Africa: Lessons from New York City. Clinical Infectious Diseases 46, 1729-17321729-1732

For sputum positive pulmonary MDR-TB, For sputum positive pulmonary MDR-TB, appropriate infection control includes:appropriate infection control includes:

Special airborne precautions, including Special airborne precautions, including isolation in a negative pressure isolation isolation in a negative pressure isolation room.room.

Staff should wear powered-air purifying Staff should wear powered-air purifying respirators (PAPRs), and close door behind respirators (PAPRs), and close door behind them.them.

Staff should remove PAPR before exiting Staff should remove PAPR before exiting anteroom and sanitize hands after leaving anteroom and sanitize hands after leaving room. See infection control module for room. See infection control module for details or CDC (2005).details or CDC (2005).

MDR-TB ReferencesMDR-TB References CDC. (2003). Treatment of TB. American Thoracic Society, CDC. (2003). Treatment of TB. American Thoracic Society,

Centers for Disease Control and Prevention, and Infectious Centers for Disease Control and Prevention, and Infectious Disease Society of America. Disease Society of America. MMWR, 52 (RR-11)MMWR, 52 (RR-11),1-88. ,1-88.

Lashley, F.R., & Durham, J.D. (Eds.). (2007). Lashley, F.R., & Durham, J.D. (Eds.). (2007). Emerging infectious Emerging infectious diseases: Trends and issues.diseases: Trends and issues. 2 2ndnd edition. New York: Springer edition. New York: Springer Publishing Co. Publishing Co.

Mukherjee, J.S., Rich, M.L., Socci, A. R. et al. (2004). Programers Mukherjee, J.S., Rich, M.L., Socci, A. R. et al. (2004). Programers and principles in treatment of multidrug- resistant tuberculosis. and principles in treatment of multidrug- resistant tuberculosis. Lancet, 363Lancet, 363, 474-481. , 474-481.

CDC (2008). Trends in tuberculosis- United States, 2007. CDC (2008). Trends in tuberculosis- United States, 2007. MMWR MMWR 5757, 281-285. , 281-285.

CDC (2005) Guidelines for preventing the transmission of CDC (2005) Guidelines for preventing the transmission of tuberculosis; healthcare settings, 2005. tuberculosis; healthcare settings, 2005. MMWR,54MMWR,54,1-141.,1-141.

Yew, W.W. and Leung, C.C. (2008) Management of multidrug-Yew, W.W. and Leung, C.C. (2008) Management of multidrug-resistant tuberculosis: Update 2007. resistant tuberculosis: Update 2007. Respirology, 13Respirology, 13, 21-46. , 21-46.