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Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
letter
. 2016 Oct 21;60(11):6994–6995. doi: 10.1128/AAC.00960-16

Plasmid-Mediated mcr-1 Gene in Colistin-Resistant Clinical Isolates of Klebsiella pneumoniae in France and Laos

Jean-Marc Rolain a,, Marie Kempf b, Thongpan Leangapichart a, Selma Chabou a, Abiola Olumuyiwa Olaitan a, Stéphanie Le Page a, Serge Morand c, Didier Raoult a
PMCID: PMC5075128  PMID: 27572402

LETTER

Recently, Yi-Yun Liu et al. reported the emergence of plasmid-mediated colistin resistance involving the mcr-1 gene from Escherichia coli and Klebsiella pneumoniae isolates from animals, food, and humans in China (1). Because of the plasmidic location of this new gene, which encodes a phosphoethanolamine transferase, it is transferable laterally between Gram-negative bacteria (1). We have recently reported the isolation of mcr-1-positive E. coli isolates from animals and humans from Laos (pigs and asymptomatic humans), Thailand (asymptomatic humans), and Algeria (chicken) (2). Although resistance to colistin in humans was believed to be linked only to colistin ingestion in humans, there is evidence of an independent emergence of colistin-resistant bacteria in humans without colistin usage, likely suggesting that such bacteria may preexist in the human gut and be selected upon colistin therapy (3, 4). We have tested by real-time PCR (5) and confirmed by standard PCR and sequencing the possible presence of the mcr-1 gene in 32 colistin-resistant K. pneumoniae isolates previously isolated in Laos (11 isolates), Thailand (14 isolates), France (6 isolates), and Nigeria (1 isolate) (6). We found that 6 isolates, specifically, 4 isolates from humans in Laos and 2 isolates from France (1 from Marseille and 1 from Angers), harbor the mcr-1 gene sequence (Table 1). MICs were determined by the Etest and interpreted with EUCAST guidelines. Interestingly, two of the four isolates from Laos also had either a stop codon (at Cys28 in strain KP LH131) or a mutation (A14S in strain KP LH61) in the mgrB gene sequence; the MICs for them were higher than those for the four other isolates that had only mcr-1, which is consistent with previous findings for colistin MICs for isolates with only mcr-1 (1, 2). These strains were isolated from human stool samples collected in 2012 and 2013 either from healthy individuals (Laos) or from patients at the University Hospital La Timone (Marseille, 4-year-old girl) and the University Hospital Centre (Angers, 83-year-old male) who had never received colistin therapy. Interestingly, although our isolates are resistant to colistin, they remain susceptible to several classes of antibiotics, including cephalosporins and carbapenems (Table 2), but acquisition of additional antibiotic resistance genes within the human gut is a possible scenario (6). To the best of our knowledge, this is the first report of colistin-resistant mcr-1-positive K. pneumoniae clinical isolates in Marseille and Angers, France, and in Laos. Our report clearly demonstrates that plasmid-mediated colistin resistance has already spread all over the world, including Europe. This is probably due to the fact that colistin is extensively used in animal production, including in Europe (3, 4, 7).

TABLE 1.

MICs for and genetic features of Klebsiella pneumoniae clinical isolates positive for mcr-1 by PCRa

Country Isolate Colistin MIC (mg/liter)b ST mgrB feature
Laos KP LH131 32 1319 Stop (at Cys28)
KP LH17 12 37 Intact
KP LH61 24 491 Sub (A14S)
KP LH92 12 39 Intact
France KP FHM128 (Marseille) 4 1310 Intact
KP FHA60 (Angers) 8 8 Intact
a

All strains were mcr-1 positive. ST, sequence type; Intact, intact mgrB gene with no mutation; Stop, mutation leading to insertion of a stop codon; Sub, mutation leading to an amino acid substitution.

b

MICs were determined by the Etest assay.

TABLE 2.

Antibiotic susceptibility testing results for the 6 mcr-1-positive strains

Strain Susceptibility profile for following antibiotic of the indicated classa:
β-Lactams
Aminoglycosides
Quinolones
Cyclins
Sulfamide SXT Nitrofuran NIT FOF
AMX AMC TIM TZP CRO CTX FEP ERT MEM IMP ATM GEN TOB AMK NAL CIP DOX MIN TGC
KP LH17 R S S S S S S S S S S S S S S S S S S S S R
KP LH92 R S S S S S S S S S S S S S S S S S S S S S
KP LH61 R S R S S S S S S S S S S S S S R S S R S S
KP LH131 R R R S S S S S S S S S S S S S R R S S S S
KP FHA60 R S S S S S S S S S S S S S S S R S S R S S
KP FHM128 R S S S S S S S S S S R R S S S R R S R S R
a

AMX, amoxicillin; AMC, amoxicillin-clavulanate; TIM, ticarcillin-clavulanate; TZP, piperacillin-tazobactam; CRO, ceftriaxone; CTX, cefotaxime; FEP, cefepime; ERT, ertapenem; MEM, meropenem; IMP, imipenem; ATM, aztreonam; GEN, gentamicin; TOB, tobramycin; AMK, amikacin; NAL, nalidixic acid; CIP, ciprofloxacin; DOX, doxycycline; MIN, minocycline; TGC, tigecycline; SXT, trimethoprim-sulfamethoxazole; NIT, nitrofurantoin; FOF, fosfomycin; R, resistant; S, susceptible.

Since colistin is now widely used in Europe (Greece and Italy, for example) to treat patients infected with K. pneumoniae carbapenemase producers and also in agriculture production, there is an urgent need to implement a screening strategy for the carriage of colistin-resistant Gram-negative bacteria in hospitalized humans, as has already been done for carbapenemase producers, and to ban the use of colistin in avian and pig production in order to avoid a frightening scenario of the colistin resistance gene spreading to humans, as NDM-1 did 5 years ago.

ACKNOWLEDGMENTS

No funding was received for this work.

We declare that we have no potential conflict of interest or financial interests to report.

REFERENCES

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