“It’s a pretty good test, although certainly not 100%,” says Dr. Shah, who is also an assistant professor of pediatrics and epidemiology at the University of Pennsylvania School of Medicine. “It can be used as an adjunct to skin testing to help exclude or confirm tuberculosis disease, but it should not replace clinical judgment.” Further, it is not clear how reliable the test is in children.
PPD tests are valuable when positive. False positive PPDs are rare; they generally develop from exposure to environmental non-tuberculosis mycobacterial species. A false-positive PPD can result from prior vaccination with the Bacillus Calmette-Guérin (BCG) vaccine used overseas. “Generally speaking, I do not let a patient’s BCG status influence how I interpret their PPD, especially when I am suspecting tuberculosis in the patient,” says Dr. Swanson. “Furthermore, a positive PPD is useful in confirming infection with tuberculosis, but a negative PPD will not definitively exclude TB infection.”
Although molecular diagnostics can verify the presence or absence of the tubercular bacillus, drug susceptibility testing is crucial to determine whether and how the organism should be treated. MDR TB is resistant to at least the first-line drugs rifampin and isoniazid. XDR TB is also resistant to any fluoroquinolone and at least one of three injectable second-line drugs: amikacin, kanamycin, and capreomycin.
Between 1993 and 2006, 49 cases (3% of evaluable MDR TB cases) met the revised case definition for XDR TB from the World Health Organization’s Emergency Global Task Force on XDR TB. Roughly 3% of TB cases in the U.S. are multidrug resistant, says Dr. Shah.
Emergence of drug resistance is more likely in cases of incomplete or intermittent therapy, or when an adequate treatment regimen was not begun after learning the initial two-month treatment phase has been done incompletely, inadequately, or with the incorrect medications.
“I will delay initiation of therapy on a patient so that I can get adequate samples from sputum, gastric aspirates, or tissue for mycobacterial isolation and susceptibility testing. This is because of the recognition that our hospital treats a large population of foreign-born individuals with a higher prevalence of drug resistance,” says Dr. Swanson. “You need to know your susceptibilities before blindly embarking on a treatment regimen.”
In the end, for all the renewed focus on the disease, “[drug resistance with tuberculosis] is not a new phenomenon … it has been flying under the radar,” says Dr. Shah.
Dr. Swanson serves up this analogy: “XDR tuberculosis is like Britney Spears. It gets a lot of attention. But there’s a lot more dysfunction and psychopathology in Hollywood than just Britney Spears, and a lot more disease and debilitation produced by non-XDR tuberculosis.” TH
Andrea Sattinger is a medical writer based in North Carolina.