XDR-TB Turnabout Raises Questions

DENVER, July 4 -- In a surprising turn of events, the tuberculosis that turned Andrew Speaker into an international cause celebre was misdiagnosed, physicians said today.

Instead of an extensively drug-resistant (XDR-TB) infection in 31-year-old Atlanta lawyer's right lung, he has multi-drug resistant TB (MDR-TB). Bad enough, according to Charles Daley, M.D., of National Jewish Medical and Research Center here, but not the most dangerous form of the disease.

The case aroused widespread interest when the CDC in Atlanta -- for the first time in 40 years -- invoked the Public Health Act to quarantine Speaker and announced the details of its actions in a press conference in May.

Now the target of the investigation has become the CDC itself. How did the respected public health agency get it wrong in the first place, and is the new diagnosis firm?

Dr. Daley, the physician in charge of the case since Speaker was moved here, said the finding is "good news," both for Speaker and for anyone who might have been infected during his highly publicized international travels in late May.

"We can treat them with potent antibiotics," he said.

Also the surgery planned for this month to remove the infected part of Speaker's lung is now on hold, Dr. Daley said, adding his doctors will "revisit" the issue as treatment progresses.

Yet Speaker is not out of the woods. His infection remains resistant to the so-called first-line TB drugs, but is susceptible to all the fluoroquinolone drugs -- including levofloxacin (Levaquin) and moxifloxacin (Avelox) -- and the injectable drugs amikacin, kanamycin, and capreomycin.

"The truth is that my condition is just the same as it was back in early May, long before there was a huge health scare," he said. All the samples tested, he said, "show that I do not have nor have I ever had extensively drug-resistant tuberculosis."

He hoped that the news "helps calm the fears" of passengers and crew members of the aircraft who were on several international flights with Speaker as he traveled to Europe and Canada in May.

Although the change in diagnosis is a relief to Speaker and his doctors, it raises questions:

• How did the original diagnosis arise?
• How accurate are the tests and can physicians be sure that even now they have the right result.
• Was the CDC response -- including an international press conference that started several days of intense coverage -- the right one?

The original sample taken from Speaker early this year, via bronchoscopy, was discarded after part of it was cultured, according to Mitchell Cohen, M.D., director of the CDC's Coordinating Center for Infectious Diseases.

But the cultured sample -- tested using the so-called Agar proportions method -- appeared to be susceptible to only two drugs and was classified as XDR, Dr. Cohen said.

But when the CDC and National Jewish tested new samples, they were all susceptible to a wider range of medications.

"I don't know why the first result showed XDR to the CDC and the second result and our results did not," Dr. Daley said, adding that discordant results in TB testing "happen all the time."

"This is a weakness of the diagnostic algorithm of TB -- even in reference labs, the state of the art is such that there is variation in results," he said.

One possible explanation for the discrepancy, Dr. Cohen said, is that by chance the original subculture may have picked up a minority XDR strain, rather than the predominant MDR.

Then, as the culture grew, it would display characteristics of XDR-TB, he said.

But Dr. Daley said he's sure the new results are solid. The CDC repeat test used the Agar proportion method, as did one of the tests run by National Jewish, he said.

But the hospital also uses a quantitative test called MIC determination and "in this case we used a third method," Dr. Daley said.

"Among all the isolates -- doing it three ways -- the results were consistent," Dr. Daley said, "so we're very sure of the results."

Indeed, outside expects said it's highly unlikely that the new diagnosis is also mistaken. One source who's familiar with practice at the hospital said tests that show susceptibility to the flouroquinolones are usually reliable.

On the other hand, he said, the wider susceptibility "doesn't guarantee he won't need surgery."

Speaker acknowledged that sometimes "the government must act to protect the public's welfare, balancing personal liberties with public safety."

But he denounced the "terribly chilling effect" of heavy-handedness. "They can, in a few days, destroy an entire family's reputation, ability to earn a living, and good name," he said.

The CDC's Dr. Cohen, though, said there's very little difference, from the public health point of view, between MDR- and XDR-TB. In both cases, he said, "a person with MDR would be treated the same a person with XDR so the same measures would be indicated."

"The public health interventions would be the same and we would take the same steps," he said.

Dr. Daley said he's optimistic that Speaker will be cured, even though cure rates for MDR-TB are on the order of 70%. He noted most cases of MDR-TB arise as a result of failed therapy among people who are not in good condition in the first place.

Speaker, on the other hand, contracted the disease from someone else and is in top physical shape.

"The cure rates really don't reflect what we expect here," Dr. Daley said.