Bloodstream infection by mcr-1-harboring Escherichia coli in a cancer patient in southern Brazil

The rapid spread of plasmid-mediated mcr-1 gene has become a worldwide concern since it confers resistance to polymyxins considered as a last resource for treatment of infections caused by multidrug-resistant Gram-negative bacilli.¹ Despite its low frequency in Brazil, the mcr-1 gene has been reported in Escherichia coli² and Klebsiella pneumoniae³ clinical isolates. In this study, we report a case of bloodstream infection by mcr-1-harboring E. coli in southern Brazil.

The presence of mcr-1 gene was investigated in 340 polymyxin-resistant Gram-negative bacilli clinical isolates (Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa) collected between August 2015 and January 2018 in a university hospital located in Santa Maria, Rio Grande do Sul, Brazil. Among clinical isolates, one E. coli harbored the mcr-1 gene isolated from blood cultures in September 2017. The patient was a 59-year-old woman with malignant neoplasm of middle third of esophagus and intrahepatic cholangiocarcinoma admitted to the hospital for a transthoracic esophagectomy. Four days after the procedure, the patient was transferred to the Adult Intensive Care Unit (ICU) due to hemodynamic instability and ventilatory discomfort. Empirical treatment with ceftriaxone (1 g 12/12 h) and metronidazole (1.5 mg/day) was initiated. Laboratory tests revealed leukocytosis (27,115 ± 7684.20/mm³) with left shift (8997.75 ± 1619.14/mm³ immature leukocytes) and increased C-reactive protein (>25 mg/dL; reference value: <0.3 mg/dL). E. coli isolate was recovered in two blood cultures from different peripheral sites and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) isolate in a rectal swab culture for epidemiological surveillance. Based on antimicrobial susceptibility testing (Table 1) by the VITEK^®2 system (bioMérieux, Marcy-l’Étoile, France), the antibiotic regimen was switched to amikacin (250 mg 12/12 h) and meropenem (1 g 8/8 h). Nine days after transthoracic esophagectomy, the patient had complications such as septic shock, peritonitis, surgical wound dehiscence and died.

Table 1
Antimicrobial susceptibility profile of KPC-Kp, E. coli harboring mcr-1, transconjugant and E. coli J53.

Antimicrobial agent	MIC range (µg/mL)	KPC-Kp	E. coli harboring mcr-1	Transconjugant	E. coli J53
Amikacin	2-64	4	≤2	≤2	≤2
Cefepime	1-64	≥64	≥64	32	≤1
Ceftazidime	1-64	16	≥64	16	≤1
Ceftriaxone	1-64	≥64	≥64	32	≤1
Ciprofloxacin	0.25-128	64	32	≤0.25	≤0.25
Colistin	0.25-128	≥128	64	4	≤0.25
Ertapenem	0.5-8	≥8	≤0.5	≤0.5	≤0.5
Gentamicin	1-16	≥16	≤1	≤1	≤1
Imipenem	0.25-16	8	≤0.25	≤0.25	≤0.25
Meropenem	0.25-16	≥16	≤0.25	≤0.25	≤0.25
Piperacillin/tazobactam	4-128	≥128	≤4	≤4	≤4
Tigecycline	0.5-8	2	≤0.5	≤0.5	≤0.5

Resistance to colistin was verified by broth microdilution according to EUCAST (http://www.eucast.org) and confirmed by polymyxin-NP test.⁴ Presence of the mcr-1 gene was verified by conventional PCR using specific primers⁵ and detected only in the E. coli isolate, being confirmed by Sanger sequencing. Species identification of the mcr-1-positive isolate was confirmed using MALDI-TOF MS system (Bruker Daltonics, Germany). To assess the transfer ability of the mcr-1 gene, conjugation experiment with azide-resistant E. coli J53 was performed. We were able to obtain one tranconjugant carrying mcr-1 gene and it was selected on Luria-Bertani agar supplemented with 150 µg/mL sodium azide and 2 µg/mL colistin. The transconjugant presented elevated MIC for colistin in comparison with E. coli J53.

This study reports the first detection of mcr-1 gene in Santa Maria, RS, Brazil and emphasizes the need to strengthen hospital infection prevention and control measures to prevent its spreads.

• Financial support
  None reported.

Acknowledgements

The authors would like to thank Silvana Silveira Coelho and Roberta Filipini Rampelotto for technical support.

REFERENCES

• ¹ Poirel L, Jayol A, Normdann P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev. 2017;30:557-96.
• ² Dalmolin TV, Castro L, Mayer FQ, et al. Co-occurrence of mcr-1 and blaKPC-2 in a clinical isolate of Escherichia coli in Brazil. J Antimicrob Chemother. 2017;72:2404-6.
• ³ Aires CAM, da Conceição-Neto OC, Oliveira TRTE, et al. Emergence of plasmid-mediated mcr-1 gene in clinical KPC-2-producing Klebsiella pneumoniae ST392 in Brazil. Antimicrob Agents Chemother. 2017;61, e00317–17.
• ⁴ Nordmann P, Jayol A, Poirel L. Rapid detection of polymyxin resistance in Enterobacteriaceae. Emerg Infect Dis. 2016;22:1038-43.
• ⁵ Liu YY, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16:161-8.

Publication Dates

• Publication in this collection
  Jul-Aug 2018

History

• Received
  29 May 2018
• Published
  07 Aug 2018