Aggressive Surgery Improves Outcomes in MDR-TB

KEYSTONE, COLO. — Aggressive resectional surgery has led to markedly improved microbiologic and clinical success in treating multidrug-resistant pulmonary tuberculosis, according to experience with patients at the National Jewish Medical and Research Center in Denver.

The use of surgery to treat MDR-TB patients is associated with a greater than fourfold increased likelihood of an initial favorable response to treatment. Fluoroquinolone therapy also is predictive of an initial favorable response, but only in patients older than 40 years.

“Surgery has become a very significant part of our practice at National Jewish,” said Dr. Charles L. Daley, head of the division of mycobacterial and respiratory infections at the center. “We think that in selected patients, surgical resection is really important to consider.”

The goal of the surgery is to remove cavitary lesions and sections of destroyed lung with a high bacillary burden. The operation is most likely to be successful in patients with focal disease and adequate pulmonary function, said Dr. Daley at a meeting on allergy and respiratory disease sponsored by the National Jewish Medical and Research Center.

Good surgical candidates are patients with MDR-TB who remain culture positive after 4–6 months of drug therapy, as well as patients with extensively drug-resistant TB (XDR-TB). The World Health Organization's revised definition of XDR-TB, issued in late 2006, describes it as MDR—that is, resistance to at least isoniazid and rifampin—plus resistance to any fluoroquinolone and one of the second-line injectable drugs, namely amikacin, capreomycin, or kanamycin.

The success of the surgical strategy was shown by a retrospective study published in 2004. The study reviewed outcomes in 205 patients with MDR-TB treated at National Jewish during 1984–1998, and compared the outcomes with those of 171 other MDR patients treated there during 1973–1983. All the MDR patients in the review were severely resistant to a median of six TB drugs and treated with a median of six agents while at National Jewish.

Treatment outcomes were better in the more recent cohort. Analysis identified two reasons why: resectional surgery and fluoroquinolone therapy, the novel elements of MDR-TB management introduced at the center after 1983. Each was an independent predictor of good outcome, said Dr. Daley, who also is a professor of medicine at the University of Colorado, Denver.

The initial favorable response rate, defined as at least three consecutive negative sputum cultures over at least 3 months, was 65% in the 1973–1983 cohort, compared with 85% in those treated during 1984–1998. The overall cure rate improved from 56% in 1973–1983 to 75% afterward. Moreover, the TB death rate fell from 22% to 12%.

In a multivariate analysis, surgery was associated with a 4.6-fold increased likelihood of an initial favorable response. Fluoroquinolone therapy, introduced in the 1980s, also was predictive of an initial favorable response, but only in patients more than 40 years old.

There was a trend toward improved survival in patients who underwent resection. It didn't reach significance, perhaps because of the relatively small sample size (Am. J. Respir. Crit. Care Med. 2004;169:1103–9).

The use of surgical resection climbed steadily at National Jewish as physicians came to recognize that it resulted in improved outcomes and had a low complication rate. Just 4% of patients treated for MDR-TB in 1973–1983 underwent one or more resectional procedures, compared with 44% discharged in 1984–1988, 63% in 1989–1993, and 83% in 1994–1998.

“We used to use a thoracotomy but are now turning to VATS [video-assisted thoracoscopic surgical] resection whenever possible,” Dr. Daley said.

Predictors of therapeutic failure in patients with MDR-TB include a low body mass index, comorbid HIV, previous therapy, and poor adherence, according to Dr. Daley.