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A plasmid-mediated transferable colistin resistance gene, mcr-1, was recently described in China (1) and was rapidly reported in several other countries (2). The spread of the mcr-1 gene was not only reported in Escherichia coli but also associated with other Enterobacteriaceae species isolated from human clinical samples, farm animals, and travelers (2, 3). However, whether or not the mcr-1 gene is acquired during the Hajj (the Muslim pilgrimage to Mecca) remains unknown.
We conducted two cohort studies of pilgrims traveling to Mecca in 2013 (22 September to 23 October) (4, 5) and in 2014 (19 September to 12 October) (6). A total of 440 rectal swab samples were collected from pilgrims (in 2013, 129 pilgrims [before and after their pilgrimage]; in 2014, 92 pilgrims before and 90 pilgrims after their pilgrimage) and were then screened for the presence of the mcr-1 gene by real-time PCR and results confirmed by standard PCR and sequencing as described previously (7). All PCR-positive samples were then tested in an attempt to isolate mcr-1-resistant strains by culture on Cepacia agar (bioMérieux, Marcy-l'Étoile, France). Different colonies were tested by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF), antibiotic susceptibility testing (EUCAST), Etest (MIC susceptibility, ≤2 mg/liter), PCR, sequencing of the mcr-1 and extended-spectrum-beta-lactamase (ESBL) genes (blaCTX-M, blaTEM, and blaSHV) (5), and multilocus sequence typing (MLST) analysis (http://mlst.warwick.ac.uk/mlst/dbs/Ecoli/ and http://bigsdb.web.pasteur.fr/klebsiella/klebsiella.html). All mcr-1 and ESBL gene sequencing results were then analyzed with NCBI database.
The prevalences of mcr-1-positive isolates determined by PCR in rectal swabs of pilgrims were similar in 2013 and 2014, and the prevalence was significantly higher upon return (in 2013, 1.55% [2/129] before the pilgrimage versus 8.53% [11/129] after the pilgrimage [P = 0.0104]; in 2014, 1.02% [1/92] before the pilgrimage versus 9.18% [9/90] after the pilgrimage [P = 0.0091]). Ten E. coli isolates and 1 K. pneumoniae isolate from 23 pilgrims who were mcr-1 positive by PCR were successfully identified by culture (Table 1). The sequence of the detected mcr-1 gene showed 100% identity with the published sequence (1). Our colistin-resistant isolates were not resistant to all antibiotics (Table 1). MICs of colistin ranged from 3 to 4 mg/liter. Two unrelated pilgrims (no. 95 and 96) carried the common sequence type of E. coli, ST10, likely suggesting that the isolates from those two pilgrims represented the same clone. Also, two other unrelated pilgrims (no. 6 and 117) carried the same sequence type of E. coli, ST648. Conversely, two Moroccan pilgrims (no. 134 and 143) who formed a pair (wife/husband) carried different E. coli sequence types (ST602 and ST1300).
Overcrowded conditions, especially during the Hajj, are a major risk for dissemination of antibiotic resistance (AR) bacteria. Moreover, taking antibiotics during travel may play a major role in selecting AR bacteria (8). However, without colistin selection in pilgrims during the Hajj, mcr-1-resistant strains can disseminate among pilgrims, demonstrating a low transmission fitness cost. Additionally, some of the pilgrims who did not take any antibiotics during the Hajj were colonized by a mcr-1 strain. In our study, we could not determine the sources and modes of transmission of this AR bacterium. The mcr-1 gene has been reported to occur worldwide in many different sources, including foods, environments, animals, and humans (2, 9). Possible transmission of colistin-resistant bacteria between human and animals has been also reported (10, 11). Different types of sequence strains identified in pilgrims, including in the couple whose results indicated the acquisition of mcr-1, may come from multiple sources, including by direct and indirect transmission. Plasmids carrying the mcr-1 gene may circulate in our cohorts and may spread when pilgrims return to their home countries. Our study results clearly demonstrate that mcr-1 plasmid-mediated colistin resistance has already spread worldwide and that screening of stool samples from travelers is urgently needed.
We thank Linda Hadjadj for her experimental assistance. We thank TradOnLine for the English corrections.
This work was supported by the Centre National de la Researche Scientific (France) and IHU Méditerranée Infection.
We declare that we have no competing financial interests.