health & science

Fears over rising use of powerful antibiotics

Antibiotics classed as critical to humans have been over-prescribed to cows for years — now Consumer NZ wants regulators to end animal use

Sales of some antibiotics supposed to be kept as a last resort for humans have been rising on farms, prompting Consumer NZ to call for regulators to rethink allowing them to be used in animals.

Drugs that people can typically get only from a hospital pharmacy to treat particularly difficult infections have been used for routine infections in dairy cows since at least 2009, and as a first line of treatment for pets, reports from the Ministry for Primary Industries (MPI) show.

The more often a class of antibiotics is used in animals and people, the greater the risk bacteria will grow resistant to the treatment and the drugs won’t work on seriously ill people when they really need them.

While antibiotic use on New Zealand farms remains low by international standards, an MPI report in October found antibiotics in classes listed as “highest priority critically important” by the World Health Organisation (WHO) had increased significantly in sales for animals.

To keep crucial antibiotics potent for as long as possible, the WHO lists four classes doctors and vets should keep in reserve for treating difficult or multi drug-resistant infections. Sales in two of these classes — macrolides and cephalosporins — rose on New Zealand farms from 2009 to 2014, the period covered by MPI’s 2013 and 2016 Antibiotic Sales Analysis reports.

While sales of most products dipped and rose, ceftiofur, a third generation cephalosporin, grew consistently — up 118 percent between 2009 and 2011 and a further 56 percent between 2012 and 2014. Vets told MPI the drugs were being marketed directly to farmers as cheaper and more convenient than using other, older antibiotic classes, and that farmers wanted them because cows treated for infections took less time to clear the antibiotics from their systems.. Farmers are required to discard milk from cows with antibiotics in their systems so it doesn’t enter the food chain.

The WHO placed third and fourth generation cephalosporins among its four most-critical antibiotics because, it says, they are known to select for cephalosporin-resistant Salmonella and E. coli in animals. “At the same time, third- and fourth-generation cephalosporins are one of few available therapies for serious Salmonella and E. coli infections in humans, particularly in children,” says the WHO on its website. Older, first and second generation cephalosporins are also used in animals but are less important to people.

Use of the drugs as a first port of call in animals seems to contrast with the approach to giving them to people. GPs are advised not to give third and fourth generation cephalosporins to people with routine infections, like chest infections, unless other treatments fail. Humans who need them to clear difficult infections usually have to visit a hospital pharmacy. Last year the Institute of Environmental Science and Research did not include the drugs in its 2006-2014 surveillance report on New Zealanders’ antibiotic consumption because GPs seldom prescribe them to people.

Told of the rising use of ceftiofur in animals, Otago University biochemistry professor Kurt Krause said it raised concerning questions: “I would have some concerns about whether there is a simpler treatment,” he said. “You would want to reserve third and fourth generations more for human use.”

While ceftiofur itself is not used by people, Krause says if bacteria develop resistance to ceftiofur that might cause resistance to other cephalosporins. “If you’re going to use an antibiotic, why not use a simpler one that doesn’t impact human use?” he says.

Global threat

The WHO calls antibiotic resistance “one of the biggest threats to global health, food security, and development today”. Health authorities fear that, unless overuse of antibiotics is curbed and new treatments are developed, bugs will become so immune to treatment that a cut toe could kill and routine operations like hip replacement and caesareans will become too risky.

“A growing number of infections – such as pneumonia, tuberculosis, and gonorrhoea – are becoming harder to treat as the antibiotics used to treat them become less effective. While there are some new antibiotics in development, none of them are expected to be effective against the most dangerous forms of antibiotic-resistant bacteria,” says the WHO in a fact sheet.

Krause, who was until recently the director of Otago’s Webster Centre for Infectious Diseases, saw the impact of antibiotic resistance first-hand when he was working as a doctor in the United States. “In the U.S. I saw a lot of very severe antibiotic resistance because it’s higher there than it is here. I was using some of the drugs of last resort,” he says. “We hadn’t been using these drugs at all and all of a sudden we didn’t have anything else, so I know firsthand what a severe frightening crisis this is,” he says.

Health authorities fear that, unless overuse of antibiotics is curbed and new treatments are developed, bugs will become so immune to treatment that a cut toe could kill and routine operations like hip replacement and caesareans will become too risky.

Health authorities fear that, unless overuse of antibiotics is curbed and new treatments are developed, bugs will become so immune to treatment that a cut toe could kill and routine operations like hip replacement and caesareans will become too risky.

Krause says New Zealand is lucky to have low levels of superbugs compared with many places. “Our levels of resistance are significantly lower than a lot of places,” he says. “Having said that, we have almost all the bad actors, we have MRSA, VRE, the bad E. Coli, a difficult campylobacter…[and] no country can embargo bugs, because people can fly in with them."

In New Zealand, people usually associate the fears of antibiotics overuse with humans, not animals.

Prescriptions of antibiotics to New Zealanders are relatively high by global standards, raising fears that people are taking antibiotics when they don’t need them, like when they have a virus.

An MPI fact sheet notes people who pick up resistant bugs in New Zealand usually catch them in a hospital or community setting, not from animals. Its testing of calf, pig and chicken carcasses in 2009 and 2010 showed lower rates of antibiotic-resistant bugs in animals raised for food than in other countries.

However MPI told Newsroom it has not tested the environment for signs of antibiotic-resistant microbes, for example soil, manure or water close to farms. Overseas studies have found signs of higher antibiotic resistance in microbes from soil where manure from dairy farms is applied as fertiliser. Scientists have raised concerns that manure could introduce bacteria carrying antibiotic resistance genes to the environment — or expose bacteria living in fields and water to residual antibiotics from dairy farms. One study from the U.S., where ceftiofur is widely used, found the drug changed the microbiome of cow dung.

Closing the gates

Consumer NZ’s Jessica Wilson raised alarm about rising farm antibiotic sales in November, citing MPI figures showing the quantity of antibiotics sold rose by 13 percent from 2011 to 2014, to 64,400kg. Cephalosporins (including third generation ones) accounted for 2,300kg of that, and macrolides 8,100kg.

Some of the overall increase in sales may be explained by disease spikes and a change in the make-up of New Zealand’s farm animal population to include more dairy cows and chickens, which use more antibiotics than grazing sheep and beef. Half of all antibiotics sold for animals in New Zealand are fed to pigs and chickens in their food, but often these are low-priority antibiotics for humans like zinc bacitracin, a treatment used to prevent disease in chickens.

Wilson is more concerned about the apparently routine — and rising — use of antibiotics from the WHO’s most-hallowed classes. “This is a trend we don’t want to see,” she says. “When the product contains an antibiotic that we as humans rely on as a last defence, you've got to question why that product would be being advertised for a routine use in agriculture,” she says.

Vets are the gatekeepers for animal antibiotics because farmers need prescriptions to buy products classed as crucial for human medicine. Vets say they are tackling the problem but they will need to work with farmers and others.

The New Zealand Veterinary Association published policies in 2015 and 2016 — after the period covered by the most recent MPI sales figures — saying vets should avoid giving animals the most critical human antibiotics, including cephalosporins, “unless there is a good reason to use them” because of the risk of creating cross resistance. The association’s latest guide to antibiotics in dairying discourages unnecessary use of newer cephalosporins and macrolides.

Dennis Scott, from the association’s antimicrobial resistance group, has called for better surveillance of both vets’ prescribing habits and patterns of antibiotic resistance.

The association’s president, Caroline Robertson, says vets want to keep access to critical antibiotics in case they are needed to treat difficult infections in animals. She says it would be cruel to leave animals untreated if they genuinely need certain classes of drugs.

“There are no quick things we can say that will be perfect answer,” says Robertson. “But I do believe that commoditisation and marketing isn’t the best way for antibiotics when we should be cherishing them and valuing them and making sure we are making the best decisions.”

“Your antibiotic use should be one of the most important decisions you make on your farm every year,” she says. “That’s an education thing of our farmers. We need to make sure they realise the significance of the decision they are making."

The association has set an “aspirational goal” of ending routine use of antibiotics to maintain animal health by 2030. The common concern is when whole groups of farm animals are given antibiotics to prevent infection, rather than reserving them for sick animals. Farmers’ groups like DairyNZ are working on alternatives to mass-antibiotic treatments, such as teat sealing to stop cows getting mastitis during the off-season. Farmers and vets here and overseas are also exploring ways to reduce the need for antibiotics by making animals healthier and less stressed using vaccinations, lower-stress weaning, nutrition and other tactics. Krause would like to see people take a similar approach to their own health, by learning to live with the harmless majority of bacteria rather than always calling on antibiotics and disinfectants.

Robertson says lowering antibiotic use could be a marketing opportunity for New Zealand: “New Zealand is one of the lowest users of antibiotics in the world so we are starting in a great position,” she says. “Antibiotic resistance is going to affect all of us. It’s you getting injured by the garden fork and … you will die of that, just like you did in the old days. The way we live our lives is going to be greatly changed if we don’t try and control antibiotic resistance.”

Right now, New Zealand's rates of mastitis and other infections are comparatively low because of our less-intense, pasture-based farming system — an advantage Fonterra highlights on its website. But a report by PwC for the vets’ association found the government’s goal of increasing agricultural exports may encourage farmers to increase productivity with more animals, more crowding and more production per animal. That might increase the risk of infectious diseases and the pressure to use antibiotics.

Wilson believes tighter regulation is needed. “It is good they (vets) have taken a stance,” she says. “[But] for us the fundamental question has to be, should these [drugs] be in the mix when vets are deciding what to prescribe, or should we make the decision that these antibiotics should not be used for animals because they are so important to human health?”

Repeated warnings

All antibiotics for animals must be registered and approved for use by MPI’s Agricultural Compounds and Veterinary Medicines Group.

MPI papers show alarm was raised about cephalosporins in 2006, when an expert review panel told the ministry that third generation cephalosporins should only be available for animals with “life-threatening conditions” and “where bacterial culture and sensitivity testing provides evidence of unique clinical value.” The panel recommended the ministry stop allowing farmers to buy the drugs as an injectable intra-mammary treatment, according to MPI’s 2013 sales report.

In 2011 the then-Ministry of Agriculture and Fisheries (now part of MPI) took stock of antimicrobial resistance on farms. However it determined the biggest threat was from in-feed and in-water oral antibiotics used in food animals. It concluded injected treatments for cows were unlikely to create superbugs in humans because of the types of drugs used and the ways farmers managed the milk. Still, MAF said it would review current registrations for ceftiofur to ensure it was dealt with “according to the rules that apply to all third and fourth generation cephalosporins.”

By 2013, when MPI first collected and published data on antibiotic sales, the ministry sounded more concerned: “Veterinarians report that with more intensive farming practices becoming more prevalent in New Zealand, and growing farms having less time and fewer skilled labourers available for individual animal management, longer-acting injectable products are becoming the preferred method of treatment for infectious disease,” the sales report said. “This, compounded by short withholding times … and direct marketing to farmers based on convenience, has driven a demand for veterinarians to supply more antibiotics critical to human health despite the presence of prudent use warnings,” it said.

Pets seemed to be worsening the problem, with vets telling the ministry third and fourth generation cephalosporins were being marketed to vets as more convenient options for pet owners, even though using older antibiotics would be more appropriate.

The report gave the impression the ministry was reconsidering its rules: “Based on the trends noted in the sales data and the feedback from industry, a review of the use of cephalosporins in companion animal and dairy medicine appears to be necessary to determine the best way forward … more restrictive controls … may be required,” it said.

But by last October the issue had grown. MPI’s October 2016 Antibiotic Sales Analysis showed a 28 percent increase in sales of third and fourth generation cephalosporins injections between 2011 and 2014, mostly because of rising ceftiofur sales for cows. Vets told MPI the drugs were being favoured during periods of high milk return because they cleared so quickly that farmers didn’t have to throw away milk. This time, MPI said it would consider the trend when it reviewed its antibiotic controls and developed its antimicrobial resistance work programme.

Newsroom asked MPI about the work programme, and how it was responding to rising use of cephalosporins and other critical antibiotics. The ministry said it could not answer questions because its subject matter expert was out of the country. It declined to share publicly the latest version of the draft work programme on antibiotic resistance, though it says the draft has been sent to vets’, farmers’ and industry groups. A version released online from a year ago says controls and labelling on antibiotics will be reviewed as a “higher priority activity.” Fonterra did not respond to queries by phone.

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