Off-label Clinical Applications of Lefamulin for Multidrug-Resistant Tuberculosis and Sexually Transmitted Infections

Lefamulin is a newer pleuromutilin antibiotic approved by the FDA (2019) for the treatment of community-acquired bacterial pneumonia (CAP). In addition, recent studies have shown the off-label use of Lefamulin to treat multidrug-resistant tuberculosis (MDR-TB) and sexually transmitted infections (STIs) caused by Mycoplasma genitalium. Therefore, this study aimed to conduct a literature review evaluating the potential off-label applications of lefamulin. Treatment of MDR-TB is typically complex because of the increased resistance to the standard first-line therapy. In addition, the entry of antibiotics into macrophages is limited by hypoxia, granulomas, and necrosis caused by MDR-TB. Studies have shown that Lefamulin exhibits intense penetration and high intracellular concentrations within macrophages, making it a promising drug for MDR-TB treatment. Furthermore, Lefamulin has shown promise as a possible treatment option for certain STIs, particularly in cases where resistance is becoming a serious problem. Although Lefamulin is not currently included in official STI treatment guidelines, it may offer an alternative for patients whose infections do not respond to standard therapies. This is especially important for multidrug-resistant Mycoplasma genitalium, where resistance to both macrolides and fluoroquinolones is increasingly common.