Rifampin-resistant TB still rare, but that may change
HIV infection, rifabutin use may be risk factors
While rifampin mono-resistant tuberculosis remains rare in the United States, health officials are concerned that it could become more common in an era of drug-resistant organisms and are unclear about its cause.
A study from the Centers for Disease Control and Prevention (CDC) indicates that risk factors for developing rifampin resistance are prior history of tuberculosis and HIV infection, and that strategies are needed to prevent its emergence.
Rifampin mono-resistance is quite rare; but because health officials rely so heavily on it as the agent that enables short-course chemotherapy, they are concerned anytime there is a threat of resistance," says Renee Rizdon, MD, medical epidemiologist for the CDC and lead author in an article on the risk factors for rifampin mono-resistance, published in the American Journal of Respiratory and Critical Care Medicine.1
In a 1991 survey of susceptibility patterns of TB in the United States, the CDC found that only 0.4% of isolates were resistant to rifampin alone. Most rifampin resistance is seen in association with isoniazid resistance. That rifampin resistance should occur at all is somewhat of a mystery, considering it is never used as a single agent, and most cases have been reported in patients infected with HIV. In efforts to make a more rigorous analysis of risk factors associated with mono-resistant TB, the CDC conducted a multicenter, matched case control study among patients with and without HIV infection.
"From the data we could look at, it appears it is indeed more prevalent in HIV-positive patients," she tells TB Monitor. "The big question is why?"
There probably are multiple factors in its emergence, but one hypothesis is that rifampin mono-resistance is more prevalent than reported but that it shows up more quickly in immunocompromised patients. "It may be a statement of things to come, but we are unable to see it in the general population because it is able to control the infection," she explains.
Another explanation is that many HIV-positive people are being given rifabutin for prophylaxis against mycobacterium avium complex (MAC). Because of the atypical presentation of TB in HIV-positive patients, clinicians unwittingly have prescribed rifabutin for MAC prophylaxis in several co-infected patients who were part of the study, Rizdon says. Also, there are two case reports of patients who apparently developed rifampin mono-resistance while receiving rifabutin prophylaxis.
Recently, another drug in the rifampin family, rifapentine, was studied as a possible treatment for HIV-positive patients infected with TB. The drug was stopped in HIV-positive patients after four of them developed rifampin mono-resistance.
The CDC study, which analyzed 77 cases of rifampin mono-resistance, also found that in addition to rifabutin therapy, prior antifungal therapy and diarrhea were independently associated with rifampin mono-resistance. The exact reasons for these associations are unclear, but the researchers point out that malabsorption of anti-tuberculosis drugs in AIDS patients is not uncommon. Furthermore, the metabolism of those drugs may be altered by drug interactions.
There is growing evidence that clarithromycin and azithromycin can be used effectively for MAC prophylaxis, and thus the use of these alternative therapies may become a viable option for HIV-positive patients at risk for TB infection, she adds.
At the same time, the use of rifabutin for treating TB in HIV-positive patients has increased in the era of protease inhibitors, which are contraindicated for rifampin. Consequently, researchers will want to monitor these patients to see if rifampin mono-resistance increases in this population, Rizdon notes.
Another outcome of the study, which used DNA fingerprint comparisons, was to show that recent transmission of rifampin mono-resistant TB strains accounted for only 13% of those in the study. Laboratory evidence showed that, unlike Strain W, there were multiple strains and not a single clone responsible for large clusters, Rizdon adds. Nine cases came from a cluster in Chicago, and two cases were linked to co-workers who had contact in Alaska, she adds.
Reference
1. Rizdon R, Whitney C, McKenna M, et al. Risk factors for rifampin mono-resistant tuberculosis. Am J Respir Crit Care Med 1998; 157:1,881-1,884.
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