First Detection of the mcr-1 Colistin Resistance Gene in Escherichia coli in Italy

Abstract

P olymyxins are old antibiotics that have recently regained popularity for treatment of severe infections caused by extensively drug-resistant (XDR) Gram-negative bacterial strains (1). As a likely consequence, emergence of polymyxin resistance is being increasingly reported in the clinical setting, especially among carbapenem-resistant Klebsiella pneumoniae isolates (2, 3). Acquired resistance to polymyxins is generally associated with chromosomal mutations (4, 5), but a new plasmid-mediated transferable resistance determinant, the mcr-1 gene, encoding a phosphoethanolamine transferase, has been described recently (6). The mcr-1 gene was originally detected in Enterobacteriaceae (mostly Escherichia coli) of animal and human origin in China (6) and subsequently also elsewhere (7-15), suggesting a broader distribution. In this communication, we report on the first detection of mcr-1 in colistin-resistant (COL-R) E. coli isolates from Italy. A retrospective analysis of the laboratory databases from the clinical microbiology laboratories of two Italian hospitals (Florence, central Italy; Lecco, northern Italy) revealed overall stable and low rates of colistin resistance among E. coli clinical isolates in the period 2012 to 2015 (Table 1). In both laboratories, routine susceptibility testing had been performed with the Vitek 2 system (bioMérieux, Marcy l'Etoile, France), and interpretation had been performed according to the EUCAST breakpoints (www.eucast .org). Eleven isolates that had been reported as colistin resistant (COL-R) were available for investigation, and nine of them were confirmed to be COL-R by reference broth microdilution (16). The COL MIC was 8 g/ml in all cases. The presence of mcr-1 was screened for by PCR and sequencing as previously described (6), using also an additional pair of primers (CLR5-F1, 5=-ATGATGCAGCATACTTCTGTGTGG; CLR5-R1, 5=-TCAGCGGATGAATGCGGTGC) targeting the extremities of the mcr-1 gene. Multilocus sequence typing (MLST) was carried out as described previously (17). Eight of the nine COL-R E. coli isolates were positive for the mcr-1 gene. In the sequenced region (positions 25 to 1576), with reference to the mcr-1 coding sequence (accession no. KP347127), the nucleotide sequences from all isolates were identical to that previously reported (6). Isolates positive for mcr-1 were detected from both centers, from inpatients in different wards, and also from two outpatients. Two mcr-1-positive isolates (LC-902/14

Frequency of MCR-1-mediated colistin resistance among Escherichia coli clinical isolates obtained from patients in Canadian hospitals (CANWARD 2008-2015)

“…23,25 In addition, clinical isolates that contain the mcr-1 gene have been reported in Vietnam, China, Taiwan, Thailand, Laos, Cambodia, the Netherlands, Sweden, the UK, Germany, Denmark, Switzerland, Italy, South Africa, Egypt, Argentina and the United States. 23,[25][26][27][28][29][30] Of interest, Shen and colleagues 31 showed the presence of mcr-1 in 3 E. coli isolates of chicken origin from China dating back to the 1980s, which supports the view that this is not a new resistance mechanism despite its recent recognition. The mcr-1 gene has been found most commonly in E. coli but has also been detected in Salmonella spp.…”

Travelers Can Import Colistin-Resistant Enterobacteriaceae, Including Those Possessing the Plasmid-Mediated mcr-1 Gene

“…We should note that such strains have been previously observed in humans and animals (8,9,28) and that they are Col-R, probably due to chromosomal mutations (10,29). Notably, the stool samples from three of the travelers mentioned above were negative for Col-R Ent at the 3-and 6-month follow-up screenings.…”

“…These strains (especially Escherichia coli) have been isolated worldwide from humans (1,(3)(4)(5)(6)(7)(8)(9)(10), food-producing animals (4,6,(11)(12)(13)(14), the food chain (7,10,(15)(16)(17), and the environment (4,15). However, most of these studies searched for mcr-1 in previously stored extended-spectrum cephalosporinresistant Enterobacteriaceae (ESC-R-Ent) (8,12,13,15,17).…”

mcr-1.2 , a New mcr Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512

“…The gene has often been reported in strains susceptible to other antibiotics, but occasionally also in multidrug-resistant (MDR) strains (3)(4)(5)(6)(7)(8), including members of highrisk epidemic lineages spreading in the clinical setting (9,10). Thus far, however, it had never been found in Klebsiella pneumoniae strains of clonal group 258 (CG258), which is the lineage mainly responsible for the dissemination of KPC-type carbapenemases on the global scale (11,12).…”

“…The transfer frequency was expressed as the number of transconjugants per recipients (t/r). Transfer of mcr to transconjugants was confirmed by PCR targeting the mcr gene (10).…”