Emergence of Colistin and Tigecycline Resistance in Carbapenem-Resistant Hypervirulent During Antibiotics Treatment.

Three carbapenem-resistant (CRKP; strains KP-426, KP-C76, and KP-CT77) were isolated from a patient with severe burns during the treatment of colistin and tigecycline. Single-nucleotide polymorphism typing showed that three ST11 CRKP were clonally related. Three isolates harbored the same set of antimicrobial resistance genes. , , , and genes were located on the same 128,928-bp IncFII/IncR plasmid. (A), , , and genes were located on a plasmid with an unknown Inc-type. , , and were chromosomal genes. An IS and an IS were found in the promoter region of the gene of two colistin-resistant CRKP, KP-C76, and KP-CT77, respectively. A novel amino acid substitution, G300E, was identified in the type 1 Tet(A) variant of KP-CT77 which exhibited high-level tigecycline resistance compared to strains KP-426 and KP-C76 (MIC of 32, 4, and 4mg/l, respectively). Conjugation and cloning experiments confirmed that the mutated Tet(A) resulted in a 4-fold increase in tigecycline minimal inhibitory concentration (MIC) of . Three CRKP belonged to the K64 serotype and possessed a similar IncHI1B/repB virulence plasmid carrying , , and . The survival rates of injected with KP-426, KP-C76, and KP-CT77 were 4.2, 20.8, and 8.3%, respectively. The emergence of colistin and tigecycline resistance in carbapenem-resistant hypervirulent posed a serious threat to clinical anti-infective therapy. The type 1 Tet(A) variant carrying G300E mutation, which conferred significantly elevated tigecycline MIC and was located on a conjugative plasmid, needs attention.