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LB-2112-24 Diagnostic accuracy, clinical impact and antimicrobial resistance consequences of using trial-of-antibiotics for tuberculosis diagnosis: a randomised controlled trial in Malawi (ACT-TB study)

Divala, T, Corbett, E, French, N, Kandulu, C, MacPherson, Peter ORCID:, Moyo, B, Nliwasa, M, Chiume, L, Ndaferankhande, J and Fielding, K (2020) 'LB-2112-24 Diagnostic accuracy, clinical impact and antimicrobial resistance consequences of using trial-of-antibiotics for tuberculosis diagnosis: a randomised controlled trial in Malawi (ACT-TB study)' in THE 51ST UNION WORLD CONFERENCE ON LUNG HEALTH, Online, 20-24th October 2020.

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Background: Tuberculosis (TB) diagnostic algorithms often include ‘trial-of-antibiotics’— empirical antibiotics for mycobacteriology-negative individuals to treat infectious causes other than tuberculosis, as a ‘rule- out’ diagnostic test for tuberculosis. We investigated the effect of trial-of-antibiotics among adults being investigated for TB on diagnostic accuracy, clinical outcomes, and antimicrobial resistance (AMR). Methods: We randomised (1:1:1) Malawian adults (≥18 years) attending primary care for illness ≥2 weeks in- cluding cough not previously treated with antibiotics to receive: azithromycin (500mg once daily, 3 days), amoxi- cillin (1g three times/day, 5 days), or standard-of-care (SOC, no immediate antibiotic). Sputum taken at enrol- ment and day 8 was tested using mycobacteriology (mi- croscopy, Xpert MTB/RIF, and TB culture). Nasopha- ryngeal swabs at enrolment and day 29 were cultured onto blood agar. Primary outcomes were specificity, de- fined as proportion reporting symptom improvement on audio computer-assisted self-interview at day 8 among those with negative mycobacteriology, and proportion with composite day 29 endpoint of death, hospitalisa- tion or missed tuberculosis diagnosis (clinical impact). The secondary outcome was the proportion with newly resistant nasopharyngeal Streptococcus pneumoniae on day 29. (NCT03545373).
Results: Between 02/2019-03/2020, we screened 2452 adults with cough and randomised 1583 (40% male, median age 32 years, 11.9% HIV-positive) to SOC (530), azithromycin (527), or amoxicillin (526). Overall 3.79% (60/1583) had positive mycobacteriology by day 8. Com- pared to SOC (79.1%), trial-of-antibiotics improved specificity of TB diagnosis: azithromycin vs. SOC (dif- ference +7.40% [3.6%-11.2%]); amoxicillin vs. SOC (difference +6.70% [2.8%-10.6%]). Proportions with day 29 poor clinical outcomes (SOC 1.13%) or new AMR (SOC 5.28%) were similar (Table) including when antibiotic arms were combined.
Conclusions: Immediate trial-of-antibiotic during TB diagnosis investigations resulted in modestly increased but still suboptimal specificity, with no impact on early clinical outcomes or AMR generation. National pro- grams can consider omitting routine trial-of-antibiotics from diagnostic algorithms, but more effective strategies to minimise unnecessary TB treatment are needed.

Item Type: Conference or Workshop Item (Speech)
Additional Information: Published in The International Journal of Tuberculosis and Lung Disease, 'The Abstract Book', Vol 24 No 10 October 2020 Supplement 2
Subjects: QV Pharmacology > QV 38 Drug action.
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
WF Respiratory System > Lungs > WF 600 Lungs
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Related URLs:
Depositing User: Stacy Murtagh
Date Deposited: 27 Oct 2020 15:20
Last Modified: 11 Nov 2020 12:50


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