Drug Resistant TB - Definition of Drug Resistant

Definition

The worldwide emergence of extensively drug-resistant tuberculosis (XDR-TB) and a provisional definition for this form of TB were first reported in November 2005. XDR-TB was then provisionally defined as cases in persons with TB whose isolates were resistant to isoniazid and rifampin and at least three of the six main classes of SLDs (aminoglycosides, polypeptides, fluoroquinolones, thioamides, cycloserine, and para-aminosalicyclic acid).

In October 2006, the World Health Organization convened an Emergency Global Task Force on XDR-TB, which revised the case definition to specify resistance to at least isoniazid and rifampin among first-line anti- TB drugs, resistance to any fluoroquinolone, and resistance to at least one second-line injectable drug (amikacin, capreomycin, or kanamycin).

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Incidence & Prevalence

During 2000-2004, the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) surveyed the WHO/International Union Against Tuberculosis and Lung Disease Global Supranational TB Reference Laboratory (SRL) Network to assess the frequency and distribution of XDR-TB cases. The survey determined that of 17,690 TB isolates, 20% were MDR and 2% were XDR (Table 5).

In addition, population-based data on drug susceptibility of TB isolates were obtained from the United States (for 1993-2004), Latvia (for 2000-2002), and South Korea (for 2004), where 4%, 19%, and 15% of MDR TB cases, respectively, were XDR.

U.S. National TB Surveillance System (NTSS) data were analyzed for reported XDR-TB cases during 1993-2006; a total of 49 cases (3% of evaluable multidrug-resistant [MDR] TB cases) met the revised case definition for XDR-TB. Of these, 17 (35%) were reported during 2000-2006. Compared with 1993-1999, cases from 2000-2006 were more likely to be in persons who were foreign born and less likely to be in persons with human immunodeficiency virus ( HIV) infection.

XDR- TB has now been identified in all regions of the world but is most prevalent in Asia and in Eastern Europe. According to India's Health Ministry records, over 3% of the fresh cases suffering from XDR-TB while over 12% of old cases undergoing treatment have developed this strain.

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Etiology

Drug-susceptible TB and XDR-TB are spread the same way. People who are ill with pulmonary TB are often infectious and can spread the disease by coughing, or sneezing, or simply talking, as this propels TB bacteria into the air. A person needs only to breathe in a small number of these germs to become infected. Sometimes the bacteria are already drug resistant if they come from a person who already has drug-resistant TB.

A second way of developing XDR- TB is when a patient's own TB develops resistance. This can occur when anti-TB drugs are misused or mismanaged. This happens when TB control programmes are poorly managed, for example when patients are not properly supported to complete their full course of treatment; when health-care providers prescribe the wrong treatment, or the wrong dose, or for too short a period of time; when the supply of drugs to the clinics dispensing drugs is erratic; or when the drugs are of poor quality.

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Clinical Presentation

Symptoms of XDR-TB are no different from ordinary or drug-susceptible TB:

• A cough with thick, cloudy mucus (or sputum), sometimes with blood, for more than 2 weeks
• Fever
• Chills and night sweats
• Fatigue and muscle weakness
• Weight loss
• In some cases shortness of breath and chest pain

Management

Several countries with good TB control programmes have shown that cure is possible for up to 50-60% of affected people. But successful outcomes also depend greatly on the extent of the drug resistance, the severity of the disease and whether the patient's immune system is compromised. It is vital that clinicians caring for TB patients are aware of the possibility of drug resistance and have access to laboratories that can provide early and accurate diagnosis so that effective treatment is provided as soon as possible. Effective treatment requires that all six classes of second-line drugs are available to clinicians who have special expertise in treating such cases.