Emergence of tigecycline resistance in Escherichia coli co-producing MCR-1 and NDM-5 during tigecycline salvage treatment

OBJECTIVE: Here, we report a case of severe infection caused by Escherichia coli that harbored mcr-1, bla (NDM-5), and acquired resistance to tigecycline during tigecycline salvage therapy. METHODS: Antimicrobial susceptibility testing, Southern blot hybridization, and complete genome sequence of the strains were carried out. The genetic characteristics of the mcr-1 and bla (NDM-5) plasmids were analyzed. The whole genome sequencing of mcr-1-containing plasmid was completed. Finally, putative single nucleotide polymorphisms and deletion mutations in the tigecycline-resistant strain were predicted. RESULTS: Three E. coli isolates were obtained from ascites, pleural effusion, and stool of a patient; they were resistant to almost all the tested antibiotics. The first two strains separated from ascites (E-FQ) and hydrothorax (E-XS) were susceptible to amikacin and tigecycline; however, the third strain from stool (E-DB) was resistant to tigecycline after nearly 3 weeks’ treatment with tigecycline. All three isolates possessed both mcr-1 and bla (NDM-5). The bla (NDM-5) gene was found on the IncX3 plasmid, whereas the mcr-1, fosA3 and bla(CTX-M-14) were located on the IncHI2 plasmid. Mutations in acrB and lon were the reason for the resistance to tigecycline. CONCLUSION: This is the first report of a colistin-, carbapenem-, and tigecycline-resistant E. coli in China. Tigecycline resistance acquired during tigecycline therapy is of great concern for us because tigecycline is a drug of last resort to treat carbapenem-resistant Gram-negative bacterial infections. Furthermore, the transmission of such extensively drug-resistant isolates may pose a great threat to public health.