Therapeutic drug monitoring and the conservative management of chronic tuberculous empyema: case report and review of the literature

Richard Long, James Barrie, Charles A. Peloquin

Chronic tuberculous empyema (CTE) is a rare and unusual, low grade and protracted, infection of the pleural space resulting in marked thickening, even calcification of the visceral and parietal pleura. Historically its management has been extraordinarily challenging. Differential penetration of anti-TB drugs into the pleural space has resulted in acquired drug resistance and surgery to remove the empyema or close a complicating bronchopleural fistula (BPF) has been technically difficult or unacceptably hazardous. On the basis of limited experience, the combination of tube thoracostomy or catheter drainage and high-end dosing of anti-TB drugs has been recommended as an initial approach to these lesions. Herein we report the first well documented case of closure of a BPF and cure of a CTE using this approach. The chances of a favorable outcome are improved, we suggest, by using therapeutic drug monitoring (TDM) to guide high-end drug dosing. An 84 year old male immigrant to Canada from Croatia was diagnosed with a CTE after he developed a BPF. The diagnosis was made 62 years after what was, in retrospect, an episode of tuberculous pleurisy. He was treated with computed tomography-guided catheter drainage and TDM-guided high-end dosed anti-TB drugs (serum and pleural fluid drug concentrations) over a 10 month period. Sustained closure of the BPF and mycobacteriologic cure of the CTE was achieved. Drug concentrations in the present case and all other reported cases are summarized and interpreted. When serum concentrations of the anti-TB drugs isoniazid, pyrazinamide and ethambutol at the high end of the normal range are achieved, pleural fluid concentrations at the low end of the normal range may be anticipated in CTE. Though highly protein bound drugs such as rifampin and moxifloxacin appear to penetrate CTEs less well, their free concentrations in the pleural space may be proportionately higher on account of lower protein concentrations. Interventional radiology and TDM increase the chances that conservative management of CTE will be successful.