Tigecycline in the Era of Antibiotic Resistance: A Current Review

Tigecycline (TIG) is a broad-spectrum antibiotic of the tetracycline class that evades the resistance mechanisms common to first- and second-generation tetracyclines and is effective against Gram-negative and Gram-positive bacteria, as well as intracellular bacteria. TIG is indicated for the treatment of intra-abdominal, skin, and soft tissue infections in adults, as well as community-acquired bacterial pneumonia. The clinical performance of the TIG has been the subject of discussion since its introduction due to variable safety and efficacy outcomes. Concerns have arisen regarding its association with increased mortality when used in ventilator-associated pneumonia. In addition, resistance to TIG has been reported, driven by various mechanisms such as expulsion by efflux via chromosomal pumps, target site modifications, mutations in tet genes, and enzymatic inactivation. The latter, particularly due to the emergence of multiple TetX monooxygenase variants, is of growing concern. The rise of resistance to last-line antibiotics like TIG presents a significant public health challenge, given the limited therapeutic alternatives available. Therefore, this review analyzes the safety and efficacy reports of TIG, third-generation tetracyclines, documented clinical cases of resistance, and the underlying mechanisms contributing to resistance. Keywords: Tigecycline, multidrug resistance, efflux pumps, Tet(X).