Old killers resisting arrest

July 19, 1996

Diseases last common in the 19th century have returned with an added danger - the prospect of an antibiotic- resistant super bug. Simon Midgley reports

Until very recently, antibiotics appeared to have all but tamed the most dangerous "Victorian" killer diseases. Tuberculosis, pneumonia, typhoid fever and diptheria, were, many doctors thought, history. Indeed, in 1968 the United States surgeon general, even told Congress: "The time has come to close the book on infectious diseases."

Today that book has been reopened, as many of the old killer diseases return with a vengeance. What has happened? The answer is that bacteria have become increasingly resistant to antibiotics.

The evolution of resistant bacteria began in the early 1940s with the introduction of the first penicillins. It quickened and widened as the pharmaceutical industry kept developing new antibiotics to try to outwit the resistant strains. The growth of antibiotic-resistant bacteria was exacerbated by inappropriate prescribing by doctors, coupled with the overuse of antibiotic agents in agriculture, fisheries and animal husbandry.

Although resistance is a problem in treating gonorrhoea, salmonella and dysentery, it is a real threat when it comes to treating Mycobacterium tuberculosis, the bacterium that cause TB. The latest difficulties are with Streptococcus pneumoniae, which causes several serious and life-threatening diseases including meningitis and pneumonia. According to estimates by the World Health Organisation, around a third of the world's population is infected with the bacteria that causes tuberculosis; each year TB develops in about eight million people, leading to three million deaths.

Since 1985 the incidence of TB has risen in the US. Around ,000 Americans are diagnosed with it each year, of whom 2,000 die. Streptococcus pneumoniae causes around 40,000 deaths. Globally there are three-five million deaths from this clutch of diseases every year. Most at risk are the young and the elderly.

In short, the world has a problem. This past week in London 25 of the world's leading specialists in microbiological disease have been closeted for a four-day conference at the CIBA Foundation to discuss the spread of antibiotic resistance and how it might be contained. They have three problems: the emergence of multiple antibiotic resistance in Mycobacterium tuberculosis, in Streptococcus pneumoniae and in Staphylococcus aureus, a bacterial species that causes serious blood and wound infections in hospital environments.

Staphylococcus aureus has always been the microbe that hospitals fear most. It causes one in five of the infections acquired by patients during treatment because it thrives on the surface of medical devices such as pacemakers and catheters. After penicillin-resistant bacteria started to appear over 40 years ago, doctors started using methicillin to treat such infections. But then methicillin-resistant strains of Staphylococcus aureus - "super staph" - started to emerge.

Brian Spratt, professor of biological sciences at Sussex University, reckons that at any one time more than 50 per cent of large British hospitals have problems with super staph. It is very hard to eradicate, he says, it hangs in the air, lives on people's hands, collects in dust. It is a major problem for hospitals but it is not yet an insoluble problem because the medical service can still deploy what is described as the antibiotic of last resort, vancomycin . But bacterial resistance to vancomycin has emerged in other less virulent bacteria called enterococci, which cause the same kinds of wound and blood infections. Enterococci tend to attack very sick patients, but the fear is that the genes that allowed that bacterium to become vancomycin-resistant could move across and make super staph resistant too.

"One of the major concerns in hospitals," says Spratt, "is that resistance to vancomycin will move across, producing a highly virulent pathogen that we have no proven effective therapy for, which would take us back to the pre-antibiotic era when staphylococcal infections often killed people.

"In the past 20 years or so we have been able to keep alive people who would previously not have survived. This includes a lot of people who are severely immunocompromised, for example patients undergoing cancer chemotherapy and transplant patients whose immune systems have to be suppressed so that they will accept foreign organs, or patients with diseases like Aids that destroy the immune system. These patients tend to get hospital infections so you have to give them a lot of antibiotics. In addition, antibiotics are commonly given to prevent infections following surgery. Consequently hospitals are now awash with antibiotics, providing the perfect environment for the evolution of bacteria resistant to more than one antibiotic."

There have been various rumours of vancomycin-resistant strains of Staphylococcus aureus occurring but none, so far, has been authenticated. While William Noble of the department of microbial diseases at St Thomas' Hospital in London has managed, in the laboratory, to create a vancomycin-resistant strain it is not a methicillin-resistant form and is therefore still susceptible to antibiotics.

What Noble has done does not therefore signify the arrival in the laboratory of the lethal so-called super bug, a microbe that can survive every antibiotic in existence. What Spratt and his fellow specialists fear however is that the emergence of such a bug is only a matter of time.

Vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus (MRSA)tend to be found in the same large American hospitals, so they are likely to meet each other, which gives rise to the possibility that the vancomycin-resistant genes will be transferred from one to the other - a situation Alexander Tomasz of Rockefeller University in New York, one of the world's leading microbiologists, has described as "nothing short of a medical disaster".

"One of the worries if we did get a vancomycin-resistant strain of MRSA," Spratt says "is that I don't think we are ready for it. Worldwide there must be tens of thousands of patients who get serious Staphylococcus aureus hospital infections and many would die if we had no way of treating them.

"I think that what we have is a continual battle with antibiotic resistance and each decade we seem to have increasing problems. We have new bacterial species becoming resistant and we have the percentage of bacteria becoming resistant increasing and we don't have a very good stream of new antibiotics coming along in the future."

Spratt feels that in future we may have to look to combinatorial chemistry to develop new man-made antibiotics that do not originate, as most antibiotics presently do, in organisms from the soil. The theory being that the genes that inactivate antibiotics derive from micro-organisms in the soil from which the antibiotics were originally made.

Another possibility is to invest more in developing vaccines to prevent diseases occurring rather than concentrating on producing new antibiotics to treat the disease once it emerges.

On one thing at least the experts are agreed: the emergence of a growing resistance to antibiotics is potentially very serious. The only problem is that no one, as yet, knows quite what to do about it.

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