March 18, 1998

Article at ABC Online

FEATURE | Now the Drugs Don’t Work 

Quantum science series | ABC TV
Companion story to Passing the Bug: The End of Antibiotics? 

Four spherical MRSA bacteria being enveloped and destroyed by human white blood cells

By Wilson da Silva

ROGER PUDNEY can remember the day he was infected with MRSA. A doctor was transplanting a skin graft onto his leg. 

“He was laying the skin,” Pudney told this reporter. “He looked at his watch – I can remember that quite clearly – and he said that he had to go to lunch. Then he returned – no greens, no gloves – and continued to go ahead with what he had previously started.” 

Two weeks later, Pudney went into shock. His temperature skyrocketed. Pathology tests showed he had been infected with a strain of golden staph bacteria that was resistant to just about every antibiotic. It is known as MRSA: Multi-Resistant Staphylococcus Aureus.

He had to be quarantined, lest he transmit the potentially fatal organism to other patients. For nearly six months, doctors threw a slew of antibiotics at him, trying to halt the infection. But Mr Pudney lost the fight. His leg was amputated. 

The Melbourne chiropractor was stunned. He had originally come into hospital with an abscess from a suspected spider bite. “They said that I would stay in for maybe four or five days because the abscess had to be drained and then maybe another week on crutches,” he recalls. 

That was December 27, 1992. Mr Pudney has since had three more amputations, losing his left knee. But the infection will not go away, and Pudney – who was forced to sell his business – is facing another amputation. 

“I’m on an extremely high dose of morphine which I do not want to be on,” he says. “I don’t believe that I have to go through this, seeing it’s been since 1992 that it all started and it’s affected my life and my family absolutely horrendously.” 

Roger Pudney

MRSA IS ONLY one of the more than 30 species of resistant bacteria found in hospitals across Australia. Since the organism was first detected in the late 1970s, is has established a firm foothold in the large metropolitan hospitals of eastern Australia. Slowly but surely, it is making its way west to Adelaide and Perth, and south to Hobart. 

It is also well-established in the United States, where an estimated 130,000 patients are infected annually, and more than 13,000 die, according to the U.S. Centres for Disease Control and Prevention in Atlanta. In the U.S., hospital-acquired infections kill 70,00 people a year; in Britain, 5,000 patients die annually. 

In Australia, the picture is woefully unclear. Hospitals are not required to notify cases of drug-resistant bacterial infections. So most don’t. What is known is that, in eastern Australia, between 0.5 and one per cent of patients in major metropolitan hospitals are infected with MRSA. Microbiologists estimate that, on a national basis, the number of MRSA infections is at least in the tens of thousands. 

“MRSA is a problem organism deeply entrenched in many hospitals in Australia now and becoming more resistant with time,” says Professor John Turnidge, chairman of the National Health and Medical Research Councils Working Party on Antibiotics.

“It’s become established despite the best infection control wishes and all the intensive resources thrown at it. It is ‘part of the furniture’.” 

His laboratory at Adelaide’s Women and Children’s Hospital coordinates a national survey of 30 hospitals and pathology labs. It shows that, in the case of MRSA, the hot spots are Melbourne and Sydney, with between 15 and 25 per cent of golden staph infections being of the super-resistant strain, MRSA. In Brisbane, things are much worse: two of the metropolitan hospitals participating the study reported MRSA rates as high as 45 per cent. No-one seems to keep track of the number of fatalities: again, it is not a notifiable ailment. 

Professor John Turnidge

HOW DO THE BUGS acquire resistance? Bacteria are primitive, unicellular organisms that keep soil fresh, ferment bread, and help things decompose. Only one in every thousand is harmful to humans. 

That one in a thousand can be lethal, and that’s why antibiotics are such a useful invention. As a plus, they don’t harm the human host. But they are a blunt and indiscriminate weapon: antibiotics kill all bacteria, including the billions of good ones in the body. It’s like dealing with a hostage-taker by nuking a whole city. 

Bacteria may be primitive, but they are remarkably flexible. “The evolutionists might tell us that bacteria are a higher living creature,” says Dr Stuart Levy, director of Boston’s Centre for Drug Resistance and a world authority on the issue. “Because they’ve been here a lot longer. They have a resilience. You’re not gonna destroy them. We’re not going to get rid of them. I haven’t heard recently of a bacterium facing extinction.” 

Antibiotics are a powerful weapon. But every now and then, a mutant bacterium will have some genetic quirk that allows it to withstand an antibiotic. With no competition for nutrients, it grows and multiplies. Next time antibiotics are used, there’s a lot more like the resistant ones; and again, their competitors are killed off. It is the paradox of antibiotics that the more you use, the more resistance you breed. 

Since antibiotics arrived in the 1940s, doctors have prescribed them with glee. And we, too, have grown used to demanding them, even when we had viral infections (for which antibiotics are useless). U.S. research suggests that only one in 10 people who are prescribed antibiotics actually need them. 

Resistant bacteria like MRSA are not necessarily a problem to the healthy. But to a hospital patient who has had major surgery or is immuno-suppressed – such as transplant or chemotherapy patient – it can be fatal. 

Colonies of Multi-Resistant Staphylococcus aureus

In the case of MRSA, at least, there is still one antibiotic that works: Vancomycin. But most frightening of the new resistant bugs is VRE: Vancomycin-Resistant Enterococcus. This is the first bacteria to breach all our defences. 

It arose in Europe in 1988, and within a year was in New York. By 1990, it had spread to 32 New York hospitals and is now endemic throughout the United States. The more doctors used Vancomycin, the more the bacteria prospered. In intensive care units, it can be 60 per cent fatal.

VRE appeared in Australia in 1994 at the Austin Hospital, where a 21-year-old liver transplant patient who died was found with the bacteria in his system. It has since been found in Sydney, Brisbane and Newcastle. There have been 60 cases, six of them fatal. 

“The organism is a major problem for compromised patients,” says Dr Levy. “Patients undergoing chemotherapy, transplant patients in particular – because it is multi-drug resistant, difficult to treat. And if we can’t use Vancomycin, we often have an organism which is virtually untreatable.” 

BUT IT’S NOT JUST over-prescribing to patients that is a problem: antibiotics are also used in animals as growth promotants, saving a few cents each in production costs. Two-thirds of all antibiotics in Australia are used in this way, or about 659 tonnes. Another 132 tonnes are doled out by veterinarians. One of the antibiotics, Avoparcin, is chemically almost identical to Vancomycin, the last line of defence in humans. 

Researchers now believe that VRE may have arisen in animals from the use of antibiotics like Avoparcin, and then been transferred to humans. “There is fairly convincing evidence in Europe that the VRE germ probably developed in animals, pigs and chickens in particular, and this was acquired by the general population through the food chain,” says Associate Professor Peter Collignon, chief microbiologist at Canberra Hospital and a spokesman for the Australian Society for Microbiology, which has called for Avoparcin’s ban. 

“When those people get into hospital, [the bacteria] get amplified by our behaviour in hospital which is to give broad spectrum antibiotics, and to give Vancomycin.” 

Associate Professor Peter Collignon

The evidence was strong enough for the European Union to ban its use in animals last year. Four months ago, the World Health Organisation joined the chorus, recommending that countries ban any antibiotic in animals that is chemically similar to those in humans. But in Australia, it is still in use. 

The National Registration Authority (NRA), a Federal statutory body that regulates such use, does not believe the link is strong enough. “It’s worth noting that the science is very shaky on whether Avoparcin use in animals leads to Vancomycin-resistance in humans,” says Peter Raphael of the NRA.

Scientists disagree. “The resistance gene is identical, that’s really the end of the story,” Dr Ruth Hall, a molecular biologist and antibiotic resistance specialist at the CSIRO’s Division of Molecular Science in Sydney. “So, there is evidence, and there has been good evidence for a very long time ... the difficulty has been to get people to listen to the evidence.” 

Dr Levy, who is also president of the American Society for Microbiology, agrees. “The case I think is very strong to ban the use of Avoparcin as a growth promoter in animals, and in fact, the European Union has done that, following on the footsteps first of Denmark then Germany. The propagation of VRE by the use of a growth promotant is not a risk that warrants whatever benefit this drug would have on the animal.”

Some microbiologists argue that the NRA has a conflict of interest in the case of Avoparcin and other antibiotics: it obtains all of its funding from charging large fees to the drug and chemical companies whose products in animals and agriculture it is meant to supervise. Any ban would mean a corresponding reduction in its own funding. 

VRE: Vancomycin-Resistant Enterococcus

On top of that, the NRA’s principal source of advice on human health matters is Professor Turnidge’s Working Party on Antibiotics. But his committee has just been defunded by the National Health and Medical Research Council. 

Professor Turnidge argues that antibiotics are a precious resource we cannot afford to waste, particularly on animals, where better hygiene and animal husbandry would drastically reduce the need for antibiotics. 

“The politicians must pay attention to the fact that there are major public health issues out there and intervene particularly when it, if you like, crosses portfolios,” he tells Quantum. “This is health and agriculture both with the same problem. We need the political will to rub heads together and make it happen ... ultimately public health issue must prevail.”