Nobody seemed too worried about colistin resistance, as it was mainly used in animal medicine and there were basically few resistance issues. We were focussing on cephalosporin and fluoroquinolone resistance. Now that it has started to be used in human medicine as a ‘last resort’ drug, after the carbapenems have failed, it is coming under the microscope.
In an earlier weblog we highlighted the discovery of a new resistance gene associated with colistin, mcr-1, in pigs and chickens in China but this gene could be potentially passed on to human bacteria via a plasmid, especially to human Escherichia coli but also Klebsiella pneumoniae and possibly Pseudomonas aeruginosa, which can cause serious infections in man and are very difficult to treat. The Chinese E. coli isolates were reportedly meropenem sensitive.
Last week it was announced that the Danes have checked over 3000 historic E. coli strains on file and found one human case with this resistance gene and 5 chicken E. coli strains from poultry meat imported from Germany. I suspect other countries are doing/will be doing the same checking now.
We showed in the last weblog that the major users of colistin (>120 tonnes each) in animals was Spain, Germany and Italy (80% of 495 tonnes used in 2013 – ESVAC, 2015). Denmark was a small user at 0.6 tonne, Netherland was 2.0 tonnes, the UK is also a low user <1.0 tonne and sweden 0.1 tonne.>1.0>
I thought I would carry out my own mini-survey. Recent survey results have often included colistin as one of the antibiotics monitored following the EU decision (2013/652/EU). In the UK VMD (2015) reported resistance/reduced sensitivity to 3 isolates of Salmonella from laying hens but none from pigs or broilers.
In Sweden (SVARM, 2015), 3 isolates of Salmonella were resistant to colistin in 2014 but only 1 isolate of E. coli from broiler meat in 2012. All were meropenem sensitive. In Denmark (DANMAP, 2015) 1 isolate of E. coli from imported broiler meat was resistant and 2 isolates of Salmonella from pigs and 1 from pork. Interestingly, in human cases of S. Typhimurium in Denmark, 6 cases were domestic and sporadic, 4 cases were associated with foreign travel. All isolates were meropenem sensitive. In the Netherlands (MARAN, 2015) all E. coli isolates (1127) from broilers, laying hens, pigs, cows and veal calves were susceptible to colistin, as well as meropenem. Salmonella sensitivity to colistin was not reported.
In Germany, a rather different picture was reported (Kaspar, 2012). In E. coli from piglets colistin resistance (>10% of isolates) was observed in 2007 and 2010, in laying hens in 2009, in turkeys in 2009 and 2010 but not in broilers. Whether this is associated with the resistance gene mcr-1 is not reported, it had not been identified at that time but reduced susceptibility/resistance to colistin was relatively commonly found (See table). The susceptibility to meropenem was not reported.
In conclusion, instead of the focus being on the use of cephalosporins and fluoroquinolones in animals and the potential resistance transfer or not to man, this has now switched to colistin following the discovery of the new resistance gene mcr-1 in China and now in Denmark and with a possible link to Germany.
Fortunately, in all of the cases reported, the bacteria have been susceptible to meropenem the main last resort antibiotic in man until recently, so it is not a dual resistance situation/transfer, which must be a great relief to all concerned. Colistin has been used in veterinary medicine for decades, yet resistance is still extremely low, especially in countries where the use is moderate or low. Where its use is especially high, there may be some potential issues but I am sure a lot more surveillance work is going on at the moment to clarify the situation. We will have to await the findings of this work before further decisions are made regarding the use of colistin in veterinary medicine but it might be timely to put colistin on a more restrictive list, where it is used only after antimicrobial sensitivity testing has been carried out and it is indicated.