ISSN: 2455-5363
Global Journal of Infectious Diseases and Clinical Research
Letter to Editor       Open Access      Peer-Reviewed

Emergent of Colistin Resistant Enterobacteriaceae carrying the mcr-1 gene among clinical isolates from patients in an Argentine hospital: Clinical and microbiological aspects

J Nievas1,2*, D Torres3, F Nicola1, P Bonvehí3, L Scocozza1, W Alcalá3, F Herrera3, S Relloso1 and J Smayevsky1

1Laboratorio de Bacteriología, Micología y Parasitología, CEMIC, Buenos Aires, Argentina
2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
3Sección de infectología y servicio de control de infecciones
*Corresponding author: Jimena Nievas, Laboratorio de Bacteriología, Micología y Parasitología, CEMIC, Buenos Aires, Argentina, E-mail: [email protected]
DOI: 10.17352/2455-5363.000019
Received: 24 December, 2018 | Accepted: 10 December, 2018 | Published: 11 December, 2018

Cite this as

Nievas 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 [7], and mcr-2, identified in Escherichia coli in 2016 in Belgium [8]. 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 [8]. 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 [12]. 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 [13] 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.

Table 1:
Patient Age Isolation date Isolation site Site of adquisition Underlying conditions Recent hospitalization Intensive care unit admission Previous therapy with colistin Isolation MIC Col ph MIC col epsilometer ESBL ST
1 60 January 2016 Soft tissue Health care associated Diabetes mellitus, peripheral vascular diseases No No No E. coli 4 4 POS 69
2 67 February 2016 Urine Hospital adcquired Kidney transplantation Yes Yes Yes E. coli 4 3 NEG 406
3 81 February 2016 Urine Hospital adcquired Chronic heart failure, valvular heart failure Yes Yes Yes E. coli 4 4 NEG 131
4 88 March 2016 Urine Health care associated Valvular heart disease, Breast cancer Yes Yes No E. coli 4 4 NEG 5921
5 69 March 2016 Urine Health care associated Coronary artery disease, Stroke Yes Yes Yes E. coli 4 4 NEG 1485
6 87 March 2016 Urine Hospital adcquired Coronary artery disease, valvular heart disease, chronic renal failure Yes Yes No E. coli 4 8 NEG 1431
7 59 March 2016 Abdomen Hospital adcquired Chronic renal failure Yes Yes No E. coli 8 4 NEG 216
7 59 March 2016 Abdomen Hospital adcquired Chronic renal failure Yes Yes No K.pneumoniae 8 4 NEG 11
8 36 July 2016 Urine Health care associated Chronic renal failure, Kidney transplantation Yes No No E. coli 8 16 NEG 6456
9 39 July 2016 Urine Not Available Not Available Not Available Not Available Not Available E. coli 4 4 NEG 349
10 61 July 2016 Urine Not Available Not Available Not Available Not Available Not Available E. coli 4 3 POS 1148
11 86 August 2016 Urine Hospital adcquired Chronic renal failure, Peripheral vascular disease Yes No No E. coli 4 4 NEG 117
12 8 August 2016 Urine Not Available Not Available Not Available Not Available Not Available K.pneumoniae 4 2 POS 344
13 12 August 2016 Urine Not Available Not Available Not Available Not Available Not Available E. coli 4 4 NEG 227
14 54 September 2016 Urine Hospital adcquired Chronic renal failure, Kidney transplantation Yes Yes No E. coli 4 4 NEG 3223
15 61 September 2016 Urine Health care associated Chronic renal failure No No No E. coli 4 4 NEG 7405
PH:Phoenix; ST:Sequence type; POS: Positive; NEG: Negative; MIC: Minimal inhibitory concentration; ESBL: Extended-spectrum β-lactamase; COL: COLISTIN
         
     

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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© 2018 Nievas J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 

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