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Multidrug-Resistant Tuberculosis (MDR TB)

Multidrug-resistant tuberculosis (MDR TB) is a form of tuberculosis that is resistant to two or more of the primary drugs (isoniazid and rifampin) used for the treatment of tuberculosis.  Extensively drug-resistant TB (XDR TB) is TB resistant to at least isoniazid and rifampin among the first-line anti-TB drugs and among second-line drugs, is resistant to any fluoroquinolone and at least one of three injectable drugs. Resistance to one or several forms of treatment occurs when the bacteria develops the ability to withstand antibiotic attack and relay that ability to newly produced bacteria.  Since that entire strain of bacteria inherits this capacity to resist the effects of the various treatments, resistance can spread from one person to another.  On an individual basis, however, inadequate treatment or improper use of the anti-tuberculosis medications remains an important cause of drug-resistant tuberculosis. Drug-resistant TB is difficult and costly to treat and can be fatal.

  • In 2005, the CDC reported that 7.8 percent of tuberculosis cases in the U.S. were resistant to isoniazid, the first line drug used to treat TB.
  • The CDC also reported that 1.2 percent of tuberculosis cases in the U.S. were resistant to both isoniazid and rifampin.  Rifampin is the drug most commonly used with isoniazid.
  • Overall, 124 cases of MDR-TB cases were reported in 2005, which remained constant from the previous year.
  • Only 27 percent of primary MDR-TB cases were in U.S. born persons. The percentage of U.S. born persons with MDR-TB has remained stable at approximately 0.6 percent since 2000.  The proportion of MDR-TB cases continued to disproportionately affect foreign-born persons in the United States. Among this group, MDR-TB cases has increased from 26 percent in 1993 to 81.5 percent of cases in 2005.
  • The World Health Organization estimates that up to 50 million persons worldwide may be infected with drug resistant strains of TB. Also, 300,000 new cases of MDR-TB are diagnosed around the world each year and 79 percent of the MDR-TB cases now show resistance to three or more drugs.
  • A strain of MDR TB originally develops when a case of drug-susceptible tuberculosis is improperly or incompletely treated.  This occurs when a physician does not prescribe proper treatment regimens or when a patient is unable to adhere to therapy.  Improper treatment allows individual TB bacilli that have natural resistance to a drug to multiply.  Eventually the majority of bacilli in the body are resistant.
  • Once a strain of MDR TB develops it can be transmitted to others just like a normal drug-susceptible strain.  Airborne transmission has been the cause of several well-publicized cases of nosocomial (hospital-based) outbreaks of MDR TB in New York City and Florida.  These outbreaks were responsible for the deaths of several patients and health care workers, a majority of whom were coinfected with HIV.
  • MDR-TB has been a particular concern among HIV-infected persons.  Some of the factors that have contributed to the number of cases of MDR-TB, both in general and among HIV-infected individuals are:
    • Delayed diagnosis and delayed determination of drug susceptibility, which may take several weeks
    • Susceptibility of immunosuppressed individuals for not only acquiring MDR-TB but for rapid disease progression, which may result in rapid transmission of the disease to other immunosuppressed patients
    • Inadequate respiratory isolation procedures and other environmental safety conditions, especially in confined areas such as prisons
    • Noncompliance or intermittent compliance with antituberculotic drug therapy.
  • MDR-TB is more difficult to treat than drug-susceptible strains of TB.  The success of treatment depends upon how quickly a case of TB is identified as drug resistant and whether an effective drug therapy is available.  The second-line drugs used in cases of MDR-TB are often less effective and more likely to cause side effects.
  • Tests to determine the resistance of a particular strain to various drugs usually take several weeks to complete.  During the delay the patient may be treated with a drug regimen that is ineffective.  Once a strain’s drug resistance is known, an effective drug regimen must be identified and begun.  Some strains of MDR-TB are resistant to seven or more drugs, making the identification of effective drugs difficult.  To deal with this problem, it is recommended that newly discovered cases of TB in populations at high risk for MDR-TB be treated with four drugs rather than the standard three as part of initial treatment.
  • Treatment for MDR-TB involves drug therapy over many months or years. Despite the longer course of treatment, the cure rate decreases from over 90 percent for nonresistant strains of TB to 50 percent or less for MDR-TB.
  • Because it is difficult for some people to successfully complete their tuberculosis treatment, several innovations have been developed. One of these is the use of incentives and enablers, which may be transportation, tokens or food coupons that are given to patients each time they appear at the clinic or doctor’s office for treatment. Incentives and enablers are combined with the use of directly observed therapy (DOT). DOT is a system of treatment in which the patient is administered his or her medication by a nurse or other health worker and observed taking the medication.
  • FDA has approved Rifater, a medication that combines the three main drugs (isoniazid, rifampin, and pyrazinamide) used to treat tuberculosis into one pill.  This reduces the number of pills a patient has to take each day and makes it impossible for the patient to take only one of the three medications, a common path to the development of MDR-TB.
  • In June 1998, the U.S. Food and Drug Administration approved the first new drug for pulmonary tuberculosis in 25 years. The drug, rifapentine (Priftin), has been approved for use with other drugs to fight TB. One potential advantage of rifapentine is that it can be taken less often in the final four months of treatment—once a week compared with twice a week for the standard regimen.
  • In 2006, a study in Africa revealed the presence not only of multidrug-resistant (MDR) tuberculosis but also what is now known as extensively drug-resistant (XDR) tuberculosis in patients infected with HIV. The Centers for Disease Control and Prevention and the World Health Organization reported the existence of XDR-TB in 17 countries including 4 percent of cases here in the United States.

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