Can we save our sickest from superbugs?

Can we save our sickest from superbugs?

Originally published on Newsroom

An almost untreatable superbug from India is fast establishing itself in New Zealand. Can we contain the risk? Eloise Gibson reports.

In 2015, a New Zealand-born woman in her early twenties contracted a superbug called Carbapenemase-producing Enterobacteriaceae (CPE).

She wasn’t the first New Zealander to have it, but she was the first known Kiwi to catch it at her house, not overseas or in hospital.

Since her CPE wasn’t hurting her, the young woman had no reason to suspect she was a carrier when she went to Middlemore Hospital with an injury. She spent 13 days in hospital without anyone noticing she was colonised by an almost untreatable superbug, one which health authorities view as one of the world’s most serious emerging infectious disease threats.

The reason CPE are considered so much more dangerous than other superbugs, including the notorious MRSA, is because they produce an enzyme that destroys carbapenems. Carbapenems are powerful antibiotics that doctors administer as a last resort to save people with multi-drug resistant infections.

As well as trouncing carbapenems, CPE destroy amoxicillin and other, top-shelf antibiotics such as extended-spectrum cephalosporins and quinolones. The only medicines left to treat them are tigecycline and colistin, a 1970s antibiotic that was retired, then dusted off and reintroduced because it worked against superbugs.

But colistin is an average performer, which is why it was retired in the first place. The mortality rate from the first documented CPE outbreak in Australia, in 2012, was 40 percent. It’s only a matter of time before “some of these bugs become resistant to colistin and tigecycline,” says Kurt Krause, a professor specialising in infectious diseases at the University of Otago Medical School. “Then you’re in deep trouble.”

In September 2016, a United States woman died after being infected with a strain of CPE resistant to 26 different antibiotics, including colistin. A recent study in China, where antibiotic overuse is widespread, reported that bacteria resistant to colistin were in the guts of 15 percent of people on average and as high as 33 percent in one province.

While New Zealand doesn't seem to have the colistin-resistant version, in the 11 months to November, the Crown Research Institute ESR counted 71 CPE cases, more than twice as many as in 2017. That included a baby who’d caught it from its mother, and an unexplained cluster of cases around Wellington.

Before Christmas, Juliet Gerrard, the Prime Minister’s Chief Science Adviser, warned New Zealand was in the early stages of a CPE epidemic.

Unfortunately, there are no new treatments on the way anytime soon. According to a 2017 article in the New Zealand Medical Journal, “the prospects of new antibiotics becoming available to treat CPE over the short- to medium-term are poor.”

If antibiotic resistance does as is predicted and kills more people than cancer by 2050, CPE will be among the worst culprits.

Easy to spread

Because CPE is harmless when it stays in the gut, most carriers won’t know they have it.

They can unwittingly take the bacteria into hospitals, where it can reach every category of person most likely to die from it: cancer patients, transplant patients, delicate babies, the very elderly, very sick and anyone with medical tubing inserted.

Hospitals know the risk, and have strict containment policies. But first they need to spot and isolate carriers.

Middlemore Hospital didn’t screen the young woman for CPE in 2015, because she didn’t fit the risk profile. She was hospitalised with an injury, not an infection. She’d never travelled outside New Zealand, and, at the time, all known New Zealand CPE carriers had caught it overseas. Her CPE was found by chance at a rehabilitation centre she went to after hospital. Had she never been injured, she might never have learned of it. 

Happily, no-one else appeared to pick up her bacteria in hospital. According to case notes in the New Zealand Medical Journal, the woman lived with family members who’d travelled to India – the country where CPE first emerged, in 2006. It seems likely that they gave CPE to her, although her housemates were never tested.

This is how superbugs get established. First, a new strain emerges – often in a country where antibiotics are manufactured or used even more liberally than they are here. A few cases appear in New Zealanders who’ve been hospitalised overseas. Then, a few dozen returning travellers who haven’t been hospitalised test positive. Eventually, thousands of people a year are being identified.

CPE seems to be following a similar pattern to ESBL-E, another superbug from the same bacterial family, Enterobacteriaceae. ESBL-E arrived in New Zealand in the 1990s and, at first, like CPE, was found only in people who’d recently been to India or other places with high rates of it.

Within a few years, dozens of New Zealanders had it. Now ESR’s lab confirms about six thousand ESBL-E infections a year. Some hospitals see ESBL-E daily, wrote Auckland City Hospital microbiologists Matthew Blakiston, Sally Roberts and Joshua Freeman and ESR’s Helen Heffernan, in an article in the New Zealand Medical Journal sounding the alarm on CPE last April. The microbiologists noted that “the current probability of a healthy traveler acquiring ESBL-E. coli when in Southern Asia is 75 percent.”

To these public health experts, the fact that CPE was following ESBL-E’s trend of spread was “alarming, because the consequences of CPE becoming endemic in New Zealand are more serious than for ESBL-E,” they wrote. “CPE have far fewer treatment options, and in some cases no antibiotic treatment options are available.”

They called for “a coordinated national response plan…analogous to response plans developed for other transmissible infectious disease threats such as pandemic influenza and Ebola.”

“While ultimately these measures may only succeed in delaying CPE from becoming endemic in New Zealand, every year free of CPE ensures a safer healthcare system for our patients and buys a little more time for new treatment options and prevention technologies to become available,” they added.

Eighteen months later -- three years after the woman left Middlemore -- the Ministry of Health published CPE guidelines.

A flow chart indicates who should be screened upon entering hospital. The full list is: anyone who’s been hospitalised overseas, travelled within the last year to the Indian subcontinent or South East Asia, been in a New Zealand rest home or hospital known to have CPE, or had contact with someone else known to have CPE.

The young woman didn’t fit any of those categories.

Newsroom raised her case with the Ministry and asked whether it was impossible to catch every patient.

The Ministry replied that “the purpose of testing was to try to catch all cases by focusing on those highest risk patients first.”

“It is important that the history taken on admission includes the travel history of the patient and their family as well as any hospitalisations,” it added.  “There may also be some additional screening carried out in some hospitals.”

As for how hospitals were implementing the guidelines, and what additional screening they might do, the Ministry said those matters were the responsibility of individual District Health Boards.

“DHBs are required to take overall leadership and operational responsibility for preventing, managing and controlling CPE in their region. …each DHB should have in place a CPE response plan that identifies the key triggers for regional action, wider reporting and response escalation,” the Ministry answered.

Keen travellers

It’s very likely that official superbug tallies capture only a fraction of the people who are walking around with drug-resistant bacteria; touching taps, preparing food and wiping down bench-tops.

CPE, for example, can live very quietly in someone’s intestines, never bothering their host. It is only when bacteria get into a wound, lungs, blood, bladder or kidneys that they can cause infections bad enough that the host might require a doctor’s visit. The doctor might send a bacterial sample for testing, and the community lab she sends it to might pass it to ESR for identification, perhaps if the usual antibiotics aren’t working. (Ordinary community labs can’t do the specialised testing required to precisely identify superbugs.)

ESR tallies all the superbugs that are sent to it. But no one counts the healthy carriers, nor people whose infections don't reach ESR's attention. By one estimate, MRSA, the so-called ‘hospital superbug’, has 10-20 additional carriers for every person known to be colonised.

It’s easier than you’d think to encounter these super-strains.

Bacteria have been randomly mutating to gain genes that make them antibiotic-resistant forever – since long before humans found antibiotics. It isn't deliberate, it's just what happens when you reproduce fast and in enormous numbers, as bacteria do. Some errors in DNA copying just happen to make them resistant to being killed by antibiotics -- and when they encounter antibiotics, the weak ones die and the ones with the genes to resist the medicine go on and multiply.

A recent study in New Delhi found CPE was present in street puddles and in 11 percent of newly-admitted hospital patients. Superbugs that used to generate headlines are now considered almost routine. “In the United States now, 50 per cent of people who have staph have (the penicillin-resistant version) MRSA, so do you try to eradicate it?” says Krause. “It’s a tough problem.” In 2014, according to the Royal Society, about one in ten of the S. aureus strains causing infection in New Zealand were MRSA.

New Zealand still has low rates of antibiotic-resistance compared with other countries. But rates are rising, helped by the fact that we love traveling, and receiving tourists’ money. In the year to April 2018, New Zealanders took 2.9 million overseas trips and received 3.8 million visitor trips. “You can’t ban people from travelling,” says Libby Harrison, the general manager of health and environment at ESR. “If you think about the fact that it’s perfectly natural for bacteria to develop antibiotic resistance and travel is so much easier these days, and you can be back in the country very quickly, we are going to see increasing prevalence.”

“We do have an antimicrobial resistance action plan but I’m not sure whether it’s enough,” she says.

Gut-dwelling microbes like CPE spread particularly easily when people don’t wash their hands properly after using the toilet, potentially leaving bacteria around.

Krause tries to phrase the situation gently. “I don’t know how to say this, but we are all covered in a very fine patina of stool that we pass around to each other.”

“Kids in elementary school and kindergarten do it a little more overtly, but all human beings do. People living in the same house will exchange faecal bacteria in small numbers but that’s actually okay because, for the most part, we’re healthy and just being antibiotic-resistant is not the same as being virulent,” he says.

“We all have E. Coli and we don’t get sick, all of us have Enterococcus, we don’t get sick. If it just so happens you have (antibiotic) resistant Enterococcus, it really doesn’t matter unless you get an infection down the road. But there will be more and more healthy people showing up at hospital with the bacteria who could unwittingly transfer it to someone who might be sick,” says Krause.

“Really you’re trying to make sure the sickest people are not going to be exposed.”

Vulnerable groups

It was the sickest and most vulnerable people Juliet Gerrard chose to highlight in a superbug fact sheet she published late last year. Before writing it, she spoke to the main medical and veterinary people who are leading New Zealand’s efforts to stop superbugs. The picture was fairly daunting. 

Shock-horror news stories about antibiotic resistance sometimes describe how perfectly healthy young adults will be struck down by infection in the prime of life, just as they were before antibiotics. While that certainly looks likely, those stories may not be representative of the burden of death and disease that's coming.

The people most likely to suffer from rising antibiotic resistance are the people who are already most vulnerable to infections. In New Zealand, that includes Māori and Pacifica, poor people, the immune-compromised and the critically ill, says Gerrard. MRSA, for example, is already more prevalent in Pacifica New Zealanders. "People will, increasingly, die from untreatable infections,” says Gerrard’s fact sheet. She added to Newsroom that “any group getting more antibiotics will be more affected, and that includes people in hospital, the very old and the very young.” 

Diseases like childhood pneumonia, rheumatic fever, meningitis, tuberculosis, Strep throat, staph infections, and ear infections are all caused by bacteria. Because New Zealand has higher rates of infectious disease than most other developed countries, we have an outsized group of vulnerable people who will be most threatened by superbugs.

Māori and Pacifica are admitted to hospital for infections two to four times more often than New Zealanders of European or Asian descent. People who live in the poorest neighbourhoods also have a higher risk of going to hospital, especially children under five.

And while significant research is done on the rise of so-called "lifestyle diseases", a 2012 study in the Lancet found hospitalisation for infectious diseases had risen much faster than diseases such as obesity and diabetes. The increase was mostly due to respiratory infections, skin and soft tissue infections and enteric infections. Again, kids under five and adults over 70 were the most at risk. There were alarming rates of skin, respiratory and other infections in Maori, Pacifica people, and poorer people, especially children.

Given those statistics, it is worth recording that Maori have likely contributed least to the rising risk of antibiotic resistance. Despite higher-than-average rates of infections, they consumed 13 percent less antibiotics than European or other ethnic groups in 2006, a gap that increased to 18 percent in 2014.

Evolving response

Like superbugs themselves, New Zealand’s response to the threat posed by antibiotic resistance is still evolving.

Although the World Health Organisation is pushing a global effort to shrink antibiotic use, human efforts seem to move much slower than the microbes. There are still many countries where animals eat antibiotics routinely, even when they aren't sick, and human overuse is widespread, too.

Statistics from ESR show total antibiotic consumption in New Zealand increased by 50 percent from 2006 to 2012, with kids under five and adults over 80 consuming the most per capita.

Our high rates of certain infections partly explain why we have unusually high antibiotic use for developed country, says Gerrard. But that isn’t the whole reason, she says. Seasonal patterns suggest they are still being given for illnesses that are likely viral, achieving nothing apart from increasing the chances of breeding our own native superbug.

Juliet Gerrard has echoed the microbiologists' 2017 call for an urgent national response to CPE. “New Zealand is in the early stages of an epidemic of…CPE that requires a coordinated infection control response at the national level across the entire New Zealand health sector,” says last year's fact sheet. 

She has also pointed out some serious gaps in New Zealand's response to the problem so far.

New Zealand has a superbug-prevention group, the Antimicrobial Resistance Action Plan Governance Group, which includes representatives from the Ministries of Health and Primary Industries. The group has a list of priority actions -- from public education to improving diagnostics -- that it released in 2017. But Gerrard notes it “is largely holding a watching brief” and lacks the money for active containment.

Gerrard discussed antibiotic resistance with Prime Minister Jacinda Ardern before Christmas, but told Newsroom the governance group – not her – would be the ones to request any extra money they needed in May's Budget.

The other gaps in New Zealand's response are holes in our surveillance – both of antibiotic resistant bugs and antibiotic use. “We do not have the surveillance data to help monitor and contain antimicrobial resistance,” says Gerrard, citing “incomplete information” on antibiotic use and the need for better monitoring of superbugs in the environment. 

One gap encountered by Newsroom is that the Ministry of Health doesn’t hold figures on hospitals' antibiotics prescriptions.  Hospitals often prescribe the most critical medicines that we can least afford to lose if microbes gain resistance, but ESR's antibiotics survey only captures GPs' prescriptions. The Ministry said it didn’t hold the data and referred our enquiry to PHARMAC, which is still working on the request two months later, citing workload constraints.

Another shortfall in monitoring concerns bacteria in our waterways and the wider environment. In the right circumstances, bacteria can share DNA with each other just by hanging around together -- a process called horizontal gene transfer. One fear is that CPE will share its carbapenems-fighting powers with other bacteria. That might potentially happen if CPE is, say, released in hospital wastewater and mingles with other bacteria outside, as has happened in Britain.

There’s also potential for resistant bacteria to end up in water or soil via animal faeces, although surveys so far show New Zealand’s animals have low levels of antibiotic resistance. The comprehensive data on what’s in our animals and waterways is mostly more than a decade old. ESR wants to repeat a survey it helped do 15 years ago on microbes in freshwater, especially in places where people like to swim. Farming has intensified since then, and microbes have been changing, too. But: “it comes down to funding,” says Harrison.

Krause agrees that a water survey is needed: “If you’re giving antibiotics in animal feed and they are doing what they do and stuff is getting washed out to rivers, it would be interesting to know the antibiotic-resistance level in our rivers,” he said.

Then there is the need to monitor animal antibiotic use. MPI tracks antibiotic purchases by farmers, but the figures are more than two years out of date by the time they’re published. A vet and researcher who’s published more recent snapshots in veterinary journals has offered to collect and share more recent data to go into the surveillance system, but nothing has yet come of it. 

Gerrard’s list of urgent needs for New Zealand are summarised below. Superbug watchers will learn in May whether the Budget allocates more money for finding, testing and containing bugs. If so, it might save more money later -- medical reports on CPE, for example, all note the very high cost of trying to manage people in hospital with the bug.  

As for the average person at home, perhaps the best thing anyone can do right now is go and wash their hands thoroughly, to remove that fine patina. Do it twice if you're heading to hospital.

What New Zealand needs urgently to fight superbugs, according to the office of the Prime Minister’s Chief Science Adviser:

- A detailed assessment of current use of antibiotics, appropriateness of use, and the extent of antibiotic resistance in humans and animals.

- Laboratory-based surveillance in both humans and animals to identify emerging and persisting patterns of antibiotic resistance.

- Comprehensive use of recording systems for prescribing and dispensing statistics;

- Data on environmental isolates (bacteria in the environment).

- Research on the best ways to contain the crisis.

- A widespread and continuing education programme to healthcare professionals, trainees, the public, and in schools on the dangers of inappropriate prescribing.

- Response systems and pathways to investigate and respond to significant changes over time in antibiotic resistance in both humans and animals.

- A nationally coordinated infection prevention and response plan to address epidemic transmissible antibiotic resistance threats such as CPE in healthcare facilities. This must include surveillance and response systems and pathways for responding to outbreaks and increases in incidence.

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