Extensively Drug-Resistant Tuberculosis

I n 2006 reports from KwaZulu-Natal, a province in South Africa, described an outbreak of extensively drugresistant tuberculosis (often referred to as XDR TB) in an HIV-infected population. Of 53 people infected, 52 died, most within 30 days of the time their sputum was first collected for culture. According to the Centers for Disease Control and Prevention (CDC), the emergence and transmission of resistant strains of Mycobacterium tuberculosis “highlight the urgency of strengthening national [tuberculosis and HIV–AIDS] control programs worldwide, particularly in settings with high HIV prevalence.” XDR tuberculosis exhibits resistance beyond that of multidrugresistant (MDR) tuberculosis. In the late 1980s and early 1990s, outbreaks of MDR tuberculosis in major U.S. hospitals infected both patients and health care workers. MDR tuberculosis is defined as tuberculosis that is resistant to both isoniazid and rifampin, the two first-line drugs that are the cornerstone of tuberculosis therapy. MDR tuberculosis must be treated with second-line tuberculosis drugs, which are less effective (necessitating longer periods of treatment), more toxic, and more costly than regimens based on isoniazid and rifampin. XDR tuberculosis is resistant not only to isoniazid and rifampin, but also to any fluoroquinolone antibiotic and to at least one of the three injectable second-line drugs for tuberculosis (amikacin, kanamycin, or capreomycin). In a commentary published in the Lancet, Van Rie and Enarson point out that MDR and XDR tuberculosis have the same root cause: “negligent case management and poorly functioning public health services.” They also note that MDR tuberculosis strains can arise from “incorrect prescription of drug regimens, poor drug quality, erratic drug supply, nonadherence by patients, and poor infection control.” Likewise, the inadequate treatment of MDR tuberculosis (using too few drugs, administering drugs for too short a time, or relying on poor-quality secondline drugs) may lead to increases in XDR tuberculosis. The CDC and the World Health Organization (WHO), in a 2006 survey of an international network of tuberculosis reference laboratories, found that 20% of 17,690 isolates from 49 countries were MDR tuberculosis and 2% were XDR tuberculosis. Because tuberculosis laboratories like these are more likely than nonspecialty labs to receive isolates from retreatment cases, treatment failure cases, and other complex tuberculosis cases, their numbers may not present an

I n 2006 reports from KwaZulu-Natal, a province in South Africa, described an outbreak of extensively drugresistant tuberculosis (often referred to as XDR TB) in an HIV-infected population. Of 53 people infected, 52 died, most within 30 days of the time their sputum was first collected for culture. 1 According to the Centers for Disease Control and Prevention (CDC), the emergence and transmission of resistant strains of Mycobacterium tuberculosis "highlight the urgency of strengthening national [tuberculosis and HIV-AIDS] control programs worldwide, particularly in settings with high HIV prevalence." 2 XDR tuberculosis exhibits resistance beyond that of multidrugresistant (MDR) tuberculosis. In the late 1980s and early 1990s, outbreaks of MDR tuberculosis in major U.S. hospitals infected both patients and health care workers. 3 MDR tuberculosis is defined as tuberculosis that is resistant to both isoniazid and rifampin, the two first-line drugs that are the cornerstone of tuberculosis therapy. MDR tuberculosis must be treated with second-line tuberculosis drugs, which are less effective (necessitating longer periods of treatment), more toxic, and more costly than regimens based on isoniazid and rifampin. XDR tuberculosis is resistant not only to isoniazid and rifampin, but also to any fluoroquinolone antibiotic and to at least one of the three injectable second-line drugs for tuberculosis (amikacin, kanamycin, or capreomycin). 2 In a commentary published in the Lancet, Van Rie and Enarson point out that MDR and XDR tuberculosis have the same root cause: "negligent case management and poorly functioning public health services." 4 They also note that MDR tuberculosis strains can arise from "incorrect prescription of drug regimens, poor drug quality, erratic drug supply, nonadherence by patients, and poor infection control." Likewise, the inadequate treat-ment of MDR tuberculosis (using too few drugs, administering drugs for too short a time, or relying on poor-quality secondline drugs) may lead to increases in XDR tuberculosis. 5 The CDC and the World Health Organization (WHO), in a 2006 survey of an international network of tuberculosis reference laboratories, found that 20% of 17,690 isolates from 49 countries were MDR tuberculosis and 2% were XDR tuberculosis. 5 Because tuberculosis laboratories like these are more likely than nonspecialty labs to receive isolates from retreatment cases, treatment failure cases, and other complex tuberculosis cases, their numbers may not present an Betsy Todd is a nurse epidemiologist. She coordinates Emerging Infections: betsy_rising@msn.com.

Infections
By Betsy Todd, MPH, RN, CIC

Factors that Increase the Likelihood that a New Tuberculosis Infection Was Caused by a Resistant Strain
The chance that a person is infected with a resistant form of tuberculosis increases when that person has been exposed to someone with active tuberculosis who • is known to be infected with drug-resistant tuberculosis.
• had prior treatment (that is, treatment that failed or disease that is relapsing) and whose current susceptibility pattern is unknown. • is from an area in which there is a high prevalence of drugresistant tuberculosis. • has sputum that still tests positive for acid-fast bacilli (AFB+ sputum) after two months of combination therapy.
Traveling to an area that has a high prevalence of drug-resistant tuberculosis also increases the risk of acquiring multidrug-resistant or extensively drug-resistant tuberculosis.
culosis here since 1993. 6 More foreign-born than U.S.-born residents had MDR tuberculosis, probably reflecting exposure to tuberculosis in countries where prevention and control are poor and, therefore, where MDR tuberculosis infection rates are higher. 6 In the United States, 49 cases of XDR tuberculosis were identified between 1993 and 2006, which represent 3% of evaluable MDR tuberculosis cases. (Evaluable refers to cases with available culture and sensitivity results. Cultures aren't available in about 20% of reported tuberculosis cases, making prompt recognition of MDR or XDR tuberculosis impossible.) Patients identified from 2000 to 2006 were more likely than those from 1993 to 1999 to be foreign born and less likely to have HIV. 7 Because a growing number of XDR tuberculosis cases will seriously hamper tuberculosis control worldwide, the WHO has formed a global task force on XDR tuberculosis. At its first meeting in October 2006 in Geneva, the task force outlined accurate picture of worldwide resistance. Still, the CDC-WHO findings clearly document the wide geographic distribution of XDR tuberculosis (including in the United States) as well as its worse treatment outcomes. 5 The greater the proportion of MDR tuberculosis cases in any population, the greater the likelihood that XDR strains will develop and spread. In  Rapid testing of isolates for rifampin resistance facilitates the early detection and effective treatment of MDR tuberculosis. 8 Likewise, it is essential to test all MDR tuberculosis isolates for susceptibility to second-line tuberculosis drugs to rapidly detect and treat XDR tuberculosis. Not all laboratories have the capacity to test for second-line drug resistance; it may be necessary to consult a state or local health department or the CDC. When antibiotic susceptibility testing does identify a case of MDR or XDR tuberculosis, the patient is best managed in close consultation with tuberculosis experts. (Usually, these are clinicians from tuberculosis control programs within city or state departments of health.) Enhanced laboratory capacity also facilitates surveillance for XDR tuberculosis, which is essential for both a greater understanding of this resistance pattern and the deployment of resources to halt its transmission.
The WHO document also emphasizes the need for better infection control and protection of health care workers, especially in settings where HIV prevalence is high (allowing both sensitive and resistant strains of tuberculosis to be transmitted more easily). The report suggests that good infection control practices be "repackaged" in both health care and other important settings (for example, prisons) in order to "make them more attractive and relevant to those responsible for their implementation." 8 Because most transmission of tuberculosis occurs outside of health care settings, good infection control also requires intensified case finding, good contact tracing, expanded preventive treatment for latent tuberculosis infection, and better design of public buildings (including heating, air-conditioning, and ventilation systems and all design aspects that affect air flow) to minimize opportunities for tuberculosis transmission. M the measures necessary to halt the proliferation of XDR tuberculosis, including better access to rapid testing for rifampin resistance, increased availability of high-quality second-line tuberculosis drugs, and better access to HIV testing and treatment. The task force also pledged to mobilize technical assistance teams to help with tuberculosis prevention and control efforts, especially in countries where there are clusters of XDR tuberculosis cases. 8 Tuberculosis control in all countries needs immediate strengthening. The resurgence of tuberculosis in the United States during the 1980s and 1990s (including a significant increase in the proportion of MDR cases) followed a period of complacency about tuberculosis prevention and control. Funding had been redirected to other areas and programs were cut. The dramatic surge in cases in New York City at that time, and the city's equally impressive containment of the outbreak, provide a reminder that tuberculosis control programs decrease incidence and transmission, improve treatment outcomes, and are cost-effective. 9 Expert management of suspected cases of XDR tuberculosis is critical not only to the health of the infected individual, but also to containing the spread of resistant strains in any community. Effective management of The root cause is 'negligent case management and poorly functioning public health services.'