Fosfomycin to Control Contamination in M. tuberculosis Culture in BACTEC MGIT 960 System

The BACTEC MGIT 960 system is widely used for recovery of Mycobacterium tuberculosis, but high contamination rates compromise its diagnostic performance. Efforts to control contamination must balance elimination of contaminating organisms while preserving growth of tuberculous bacilli. Fosfomycin has activity against many bacteria responsible for culture contamination yet is inactive against Mycobacterium tuberculosis. Therefore, it holds potential as a selection agent for the culture of M. tuberculosis clinical samples with the MGIT system. In this study, we assess the ability of fosfomycin supplement to MGIT cultures of clinical sputum specimens. Sputum specimens collected at 62 diagnosis and treatment monitoring visits during a randomized controlled trial of high-dose rifampin (ClinicalTrials.gov NCT01408914) were split: one-half was treated as conventional and the other half was treated with 1mg of fosfomycin. The frequencies of contamination and of recovery of M. tuberculosis were compared using McNemar and Wilcoxon signed-rank test, respectively, with a=0.05. In the fosfomycin-treated samples, 2/62 (3.2%) yielded contaminated cultures while 12/62 (19.4%) of untreated cultures were contaminated (p<0.001, McNemar Test). Detection of M. tuberculosis was not significantly altered by the addition of fosfomycin (Time to positivity, p=0.576, Student’s T Test; log colony forming units), nor the Colony Forming Unit Counts (Wilcoxon signed-rank test p=0.671). These results suggest that the use of fosfomycin to control contamination does not affect the natural growth of MTB. Its use could result in a significant improvement in recovery of M. tuberculosis in MGIT