Transmitted TB Resistance High In Shanghai

SHANGHAI, China, Feb. 21 -- More than 80% of drug resistance among treated tuberculosis patients here is the result of a new infection with the resistant strain, called reinfection, rather than inadequate therapy, according to researchers here.

The finding, based on a retrospective study of sequential TB isolates from patients in this eastern Chinese city, overturns the accepted wisdom that most resistance among TB patients is acquired, according to Qian Gao, Ph.D., of the Shanghai Medical College of Fudan University.

"The vast majority of drug resistance during therapy was not due to poor response to the initial treatment regimen or to an inadequate treatment regimen but rather to ongoing transmission of drug-resistant strains of M. tuberculosis," Dr. Gao and colleagues reported in the March 15 issue of the Journal of Infectious Diseases.

"It was surprising to find a high rate of primary drug-resistant strains among treated patients," Dr. Gao said. "This overturned the common belief that drug resistance among treated patients is always acquired."

Disturbingly, a quarter of the resistant strains were multidrug resistant (MDR), defined as being resistant to both rifampin (Rifadin) and isoniazid (Nydrazid), two of the main first-line TB drugs, Dr. Gao said.

The finding also comes in the context of the emergence of Extensively Drug Resistant TB (XDR-TB), which combines resistance to rifampin and isoniazid with resistance to at least three of the second-line TB medications.

In the United States, 4% of MDR-TB cases between 2000 and 2004 met the criteria for XDR-TB and other countries have seen higher rates. One outbreak in South Africa was characterized by alarmingly high mortality rates - 52 of 53 patients died within 25 days.

None of the Shanghai cases was XDR-TB, Dr. Gao and colleagues said, but the possibility is "most concerning."

The incidence of pulmonary TB in Shanghai is about 38 per 100,000 population per year, about a third of the average for China as a whole, the researchers said.

Using the records of the Shanghai Centers for Disease Control and Prevention for a five-year period ending in September 2004, the researchers were able to find 100 patients with two discordant TB isolates, as measured by drug-susceptibility testing.

Of those, Dr. Gao and colleagues said, the records included 38 for which genotyping was available for both isolates. They discarded six cases in which the first isolate was more resistant than the second.

Of the remaining 32, Dr. Gao and colleagues found that five had identical genotypes for both isolates, implying that the resistance had been acquired as a result of inadequate treatment or non-adherence to medications.

The remaining 27 (84%) had genotypically different isolates, implying that the second, more-resistant strain was the result of a new infection.

Ten patients had a multi-drug resistant strain, the researchers found, and nine were instances of primary resistance.

The study "suggests that drug-resistant tuberculosis is being transmitted in the facilities and communities in which these patients are being treated, and accelerated efforts to interrupt transmission are needed," the researcher concluded.

The study has limitations because of its retrospective nature and because some patients were excluded because of missing data, the researcher said. A prospective population-based study is under way.