Cite this asNievas J, Torres D, Nicola F, Bonvehí P, Scocozza L, et al. (2018) Emergent of Colistin Resistant Enterobacteriaceae carrying the mcr-1 gene among clinical isolates from patients in an Argentine hospital: Clinical and microbiological aspects. Glob J Infect Dis Clin Res 4(1): 010-012 DOI: 10.17352/2455-5363.000019
The recent emergence of multidrug-resistant (MDR) or extremely drug-resistant (XDR) Gram-negative bacteria has renewed interest in colistin (Polymyxins, a family of cationic polypeptide antibiotics) as a last-resort in the treatment of severe bacterial infections [1,2], despite being a drug with potential serious adverse events (mainly high risk of nephrotoxicity) [3,4]. Acquired resistance to polymyxins is generally associated with chromosomal mutations [5,6]. However, increasing use of this antibiotic in clinical and veterinary practice has led to the emergence of mobile colistin resistance genes, including mcr-1, which was first reported in Escherichia coli in 2015 in China , and mcr-2, identified in Escherichia coli in 2016 in Belgium . Recently, three further plasmid mediated colistin resistance genes, mcr-3, mcr-4 and mcr-5, were identified, with Enterobacteriaceae being the predominant hosts (particularly Escherichia coli and Salmonella spp). Mcr-1 and mcr-2 are the most frequent variants found in human clinical isolates. [7-11].
In this report, we describe the detection of mcr-1 gene in clinical isolates of colistin-resistant Enterobacteriaceae from a University Hospital from Buenos Aires, Argentina. Clinical and microbiological findings were also collected.
Forty clinical isolates of colistin-resistant Enterobacteriaceae were evaluated from August 2014 to November 2016. Twenty-two Escherichia coli and 18 Klebsiella pneumoniae were isolated from urine (25), blood culture (3), soft tissue (1), abdominal fluid (3) and rectal swabs . MALDI-TOF (BD-BrukerDaltonics) was used for identification. Minimal inhibitory concentrations (MICs) were determined by Phoenix method (Becton, Dickinson) and epsilometer method according to the guidelines of the CLSI and EUCAST joint subcommittee . Results were interpreted using EUCAST breakpoint as updated in 2018 (www.eucast.org). All isolates were screened by PCR for the presence of mcr-1 and mcr-2 genes as previously described [7,8]. Multilocus Sequence Type (MLST) was carried out as described previously  and PCR amplicons were purified with QIAquik PCR Purification Kit (QIAGEN) and were sequenced by the Sanger method Unit of Genomics Institute of Biotechnology CICVyA CNIA INTA.
The mcr-1 gene was detected in 16 isolates, 14 Escherichia coli and 2 Klebsiella pneumoniae strains, all with MICs at colistin greater than 4 μg/ml. One patient had polymicrobial infection. Escherichia coli isolates did not show significant antibiotic resistance; only 2 were ESBL (extended-spectrum β-lactamase) producers. One isolate of Klebsiella pneumoniae was multidrug-resistant (KPC positive), being sensitive only to amikacin. Of the isolates that were not positive for the mcr-1 gene (n = 24), 16 were Klebsiella pneumoniae (13 KPC +) and 8 Escherichia coli (4 ESBL +) recovered from urine (13), rectal swabs (8), blood cultures (2), and abdominal fluid (1). The mcr-2 gene was not found in any isolate. In this study the resistance mechanism to colistin of those mcr-1 and mcr-2 gene non-carrier strains were not evaluated.
Sixteen strains from 15 patients (13 adults and 2 pediatrics) were detected. The median age was 61 years (p25-75: 46.5-69). No clinical data were obtained from four patients.
All had multiple comorbidities (chronic renal failure, heart disease, renal transplantation, peripheral vascular disease, neoplasia or diabetes mellitus). The site of acquisition was nosocomial in six patients, and five patients had health care-associated infections (three with recent hospitalization, one had outpatient surgery and the other had frequent contact with the health system). Nine patients had previously received antibiotics, only three were treated with colistin. The clinical source was urinary (13 patients), cutaneous (one) and abdominal (one). Ten received appropriate antibiotic treatment according to microbiological findings.
The mcr-1-positive isolates belonged to several different sequence types (STs) (Table 1), some of which have not been previously associated with mcr-1.
Plasmid-mediated colistin resistance is now emerging. In our hospital during two years (2014-2016), we detected the presence of the mcr-1 gene mainly in Escherichia coli and Klebsiella pneumoniae strains. All isolates were genetically unrelated. The occurrence of mcr-1 in clinical isolates of Enterobacteriaceae is alarming. The detection of these strains is of great importance, since it allows implementing corresponding actions. In hospitals, we recommended the application of contact precautions to avoid their dissemination to other patients and their transfer to other species. Moreover, we need antimicrobial stewardship programs to use these drugs responsibly, only when other options are not available. Beside this, global industrial and veterinary use of colistin should be limited to reduce the appearance of this resistance mechanism and to prevent the potential transmission from farm to humans.
This study was supported by René Baron Fundation
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