Abstract
Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs.
Highlights
Sputum cultures are an important tool in monitoring the response to tuberculosis (TB) treatment, especially in multidrugresistant TB (MDR-TB)
Eighty-one patients were excluded: two because they had already received an individualized regimen for MDR-TB, two for incomplete treatment regimen data and 77 because they did not have a positive culture prior to the initiation of the individualized MDR
We found that patients treated for MDR-TB had higher rates of sputum culture conversion if they received an aggressive regimen for MDR-TB for the 14 preceding consecutive days compared to those who did not
Summary
Sputum cultures are an important tool in monitoring the response to tuberculosis (TB) treatment, especially in multidrugresistant TB (MDR-TB). Sputum culture conversion—the transition in sputum culture results from a positive sample growing Mycobacterium tuberculosis to two consecutive negative cultures separated by at least 30 days —is a key clinical milestone signifying that the patient is responding to therapy [2,3]. It is known that culture conversion can be delayed in the treatment of MDR-TB compared to drug-susceptible disease [4]. Risk factors for delayed culture conversion during MDR-TB therapy include markers of advanced pulmonary disease, smear positivity [5,6] and the presence of cavitary lung lesions [7]. Culture conversion has been shown to occur more slowly in patients with resistance to second line anti-TB drugs [8,9]. Co-morbidities like low body weight [10] and smoking [11] have been linked to delayed conversion
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