Chronic Tuberculous Empyema with Bronchopleural Fistula Resulting in Treatment Failure and Progressive Drug Resistance

doi:10.1378/chest.100.1.124

Chest

Volume 100, Issue 1, July 1991, Pages 124-127

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We treated five patients with a past history of tuberculous pleural infection that led to chronic, quiescent, loculated empyema. Reactivation of TB was associated with formation of BPF and recovery of drug-susceptible Mycobacterium tuberculosis from sputum. All patients had recurrence of positive sputum cultures that yielded tubercle bacilli resistant to drugs they were receiving. The lungs demonstrated gross thickening with calcification of both visceral and parietal pleura. Two patients underwent retreatment chemotherapy followed by decortication-empyemectomy and lung resection surgery; both are now culture-negative for TB. One patient received retreatment chemotherapy but refused surgery; he remains clinically stable with negative sputum cultures. Two other patients’ organisms became drug-resistant and they remain sputum-culture positive. We believe that thick, calcified pleural walls limit penetration of drugs into the infected empyema space, resulting in suboptimal drug concentrations and drug resistance. Intensified chemotherapy and surgical intervention should be considered in these cases.

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Discussion

Exposure of populations of tubercle bacilli to sublethal concentrations of a drug is a proven means to select for mutant bacilli resistant to that drug.² Modern drugs such as isoniazid or rifampin, taken in appropriate doses, generally result in tissue concentrations sufficiently high to kill strains of drug-susceptible tubercle bacilli. We report here five patients who acquired drug resistance despite receiving appropriate drug regimens, presumably through the mechanism of partial exclusion of

References (3)

JC Sibley
A study of 200 cases of tuberculous pleurisy with effusion
Am Rev Tuberc
(1960)

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The organism has a long generation time and a capacity for dormancy, when its low metabolic activity makes it a difficult therapeutic target [5–7]. In addition, M. tuberculosis may be located in pulmonary cavities, empyema pus, or solid caseous material, where penetration of antibiotics is difficult or the pH is sufficiently low to inhibit the activity of most antibiotics [8,9]. Although TB can be cured by an optimized regimen comprising of various first line and second line drugs [10,11], the emergence of MDR-TB and extremely drug resistant TB (XDR-TB, first reported in November 2005 [12]) has created new challenges to control and defeat the disease.
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: Manuscript received July 5; revision accepted November 19.

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Chest

Chronic Tuberculous Empyema with Bronchopleural Fistula Resulting in Treatment Failure and Progressive Drug Resistance

Section snippets

Discussion

A study of 200 cases of tuberculous pleurisy with effusion

Am Rev Tuberc