Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment

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.

Time to sputum culture conversion and its predictors among patients with multidrug resistant tuberculosis in Hangzhou, China: a retrospective cohort study

“…Third, the median time to initial SCC in our study was 85 days, which is relatively high when compared with the median 58-91.5 days reported in earlier studies (7,8,11,12,18,19). This may due to multiple reasons, for example unknown second-line drug (SLD) susceptibility, treatment regimens, lost to follow-up rates and laboratory tests.…”

Counting Pyrazinamide in Regimens for Multidrug-Resistant Tuberculosis

“…Among regimens of exactly five likely effective drugs of which none was PZA (group C), those including PZA (and by definition not likely to be effective) were associated with higher mortality than those that did not include PZA. This observation may be a chance (8)(9)(10). Some regimens corresponding to this category included pyrazinamide (PZA), which was not likely effective.…”

“…Several recent studies have examined the effect of an "aggressive" regimen (i.e., one containing at least five likely effective TB drugs, including an injectable agent during the intensive phase) on different treatment endpoints. In Peru, individuals who received aggressive regimens experienced lower rates of mortality (8) and recurrent TB (9) and faster rates of sputum conversion (10). In Russia, patients who received aggressive regimens also had significantly reduced rates of death and treatment failure (11).…”

Evaluation of community‐based treatment for drug‐resistant tuberculosis in Bangladesh

“…The vast majority of patients saw their healthcare providers as scheduled and were visited daily by their DOT providers. Sputum culture conversion at 6 months has been shown to be a good predictor of treatment outcome, [11] and in wellperforming programmes, this has been reported in 81-87% of patients [11][12][13]. In this cohort, 88% of patients with initially positive sputum cultures converted their cultures before the sixth month, suggesting very good response to treatment.…”