{Reference Type}: Meta-Analysis
{Title}: Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: A systematic review and meta-analysis.
{Author}: Gray AT;Macpherson L;Carlin F;Sossen B;Richards AS;Kik SV;Houben RMGJ;MacPherson P;Quartagno M;Rogozińska E;Esmail H;
{Journal}: PLoS One
{Volume}: 18
{Issue}: 11
{Year}: 2023
{Factor}: 3.752
{DOI}: 10.1371/journal.pone.0293535
{Abstract}: <B>BACKGROUND: </B>People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease.<BR><B>METHODS: </B>We conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486).<BR><B>RESULTS: </B>We included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002).<BR><B>CONCLUSIONS: </B>Multi-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach.