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Clinical Trial
. 2017 Apr 24;17(1):299.
doi: 10.1186/s12879-017-2335-7.

Predictors of delayed culture conversion among Ugandan patients

Daniel Atwine  1   2   3 , Patrick Orikiriza  4   5 , Ivan Taremwa  4 , Arnold Ayebare  4 , Suzan Logoose  4 , Juliet Mwanga-Amumpaire  4   5 , Amina Jindani  6 , Maryline Bonnet  4   7
Affiliations
Clinical Trial

Predictors of delayed culture conversion among Ugandan patients

Daniel Atwine et al. BMC Infect Dis. .

Abstract

Background: Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda.

Methods: Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion.

Results: Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion.

Conclusion: The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2.

Trial registration: ISRCTN ISRCTN55670677 . Registered 09th November 2010. Retrospectively registered.

Keywords: Delayed culture conversion; Efficacy; HIV-negative TB patients; Time-to-detection; Treatment failure.

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References

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