High Concentrations of Divalent Cations in Extracellular Environments Reduce in vitro Antibiotic Activity of Tigecycline

Abstract

Tigecycline is known to form a complex with divalent cations such as Mg2+ and Ca2+, which is essential for a mode of action of tigecycline. In this study, we investigated the effects of levels of divalent cations on the in vitro antibacterial activity of tigecycline against two strains each of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. When Mg2+ or Ca2+ was added to be tantamount to criteria levels of severe hypermagnesemia or hypercalcemia in Mueller-Hinton II broth, minimum inhibitory concentrations were increased 2- to 4-fold in all strains. In media containing high concentrations of Mg2+ or Ca2+, bacterial survival rates increased significantly after 24-hour exposure to tigecycline for all strains except one K. pneumoniae strain. Thus, levels of divalent cations in extracellular condition might affect tigecycline activity. While testing on humans is still required, our results suggest that caution should be exercised when using tigecycline to treat infected patients with hypermagnesemia and hypercalcemia.