Coexistence of MCR-1 and NDM-1 in Clinical Escherichia coli Isolates

To the Editor—Infections caused by New Delhi metallo-β lactamase 1 (NDM-1)–producing Enterobacteriaceae are reported to have a significantly higher likelihood of in-hospital mortality [1]. Previous evidence showed that NDM-producing bacteria are often susceptible to colistin, which has become the last resort for the treatment of infections due to NDM-producing bacteria [2]. However, the plasmid-mediated colistin resistance (MCR-1) gene, was first identified in Enterobacteriaceae recently [3]. Therefore, patients ultimately might receive only extremely limited drug options [4]. Here, we characterize for the first time 2 clonally unrelated Escherichia coli strains co-producing MCR-1 and NDM-1, which were recovered from 2 patients with bloodstream infection.

Patient 1 was a 10-day-old male infant who was admitted to the Affiliated Hospital of Jining Medical University, China, due to fever and difficulty breathing. Blood culture demonstrated growth of E. coli strain EC1002. He was diagnosed with neonatal sepsis and treated with levofloxacin and amoxicillin-clavulanic acid. Patient 2 was a 56-year-old man who suffered a traffic accident and was admitted to the Anhui Provincial Hospital, China. An E. coli strain EC2474 was recovered from the blood culture. Both patients showed clinical improvement after antibiotic therapy and were discharged after lengthy hospital stays.

Antimicrobial susceptibility revealed that EC1002 had a high-level resistance to carbapenems, cephalosporins, and aminoglycosides, but was susceptible to quinolones and tigecycline. Meanwhile, EC2474 was resistant to all antibiotics tested, except tigecycline (Table 1). Clonal diversity was assessed by pulsed-field gel electrophoresis (PFGE), which demonstrated that both isolates were clonally unrelated (Supplementary Data). Multilocus sequence typing indicated that EC1002 belonged to sequence type (ST) 2373 and EC2474 was ST131. Polymerase chain reaction and sequencing identified both isolates encoding the MCR-1, bla_NDM-1, and bla_CTX-M-15 genes. EC1002 also positive for aac(6′)-Ib and bla_TEM-1, and EC2474 was positive for bla_CTX-M-55 and rmtB (Table 1).

The analysis of S1-PFGE demonstrated that plasmid profiles were diverse; EC1002 contained 4 plasmids, whereas EC2474 contained 3 plasmids, which ranged from 80 kb to 250 kb (Supplementary Data). Southern blotting confirmed that the MCR-1 gene was located on an approximately 80 kb plasmid in EC1002 and an approximately 250 kb plasmid in EC2474, whereas bla_NDM-1 was located on an approximately 125 kb plasmid in EC1002 and an approximately 110 kb plasmid in EC2474 (Supplementary Data). The plasmids harboring the bla_NDM-1 and MCR-1 genes were transferable to E. coli J53, which indicated that bla_NDM-1 and MCR-1 were located on self-conjugative plasmids (Table 1).

Epidemic clone E. coli ST131 was associated with the global spread of bla_CTX-M-15 [5]. In China, ST131 was the most common ST associated with extended-spectrum (ESBL)–producing E. coli [6]. The co-production of MCR-1 with NDM-5 or NDM-9 in Enterobacteriaceae has been reported very recently [7, 8]. Of particular concern is that our data further demonstrate the co-location of MCR-1 along with NDM-1 and ESBLs from clinical isolates. Interestingly, we found that both strains were still susceptible to tigecycline. However, tigecycline resistance in Enterobacteriaceae has been detected increasingly during treatment with this agent [9, 10]. This raises a concern that the pan-resistant E. coli may spread to clinical settings with ST131. Our study was limited by the relatively small number of patients with MCR-1– and NDM-1–producing E. coli. Thus, the close monitoring of colistin- and carbapenem-resistant Enterobacteriaceae from clinical isolates is warranted.

_supplementary Data

Supplementary materials are available at http://cid.oxfordjournals.org. Consisting of data provided by the author to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the author, so questions or comments should be addressed to the author.

Notes

Acknowledgments. The authors thank the microbiology staff at both the Affiliated Hospital of Jining Medical University and Anhui Provincial Hospital. We also thank Dr Yunbo Chen, Miss Jinru Ji, and Miss Chaoqun Ying for their technical support in laboratory investigation.

Financial support. This work was supported by the National Basic Research Program of China (973 program, number 2015CB554201) and the National Natural Science Foundation of China (81361138021 and 81301461).

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

Author notes