Antibiotics, big business and super germs
By Robyn Marshall
At a private hospital in Brisbane, two patients were admitted with a bacterial infection that had multiple resistance to antibiotics, in particular, resistance to the last line of defence, Vancomycin. They were placed in the isolation ward, but because it was Christmas, the administration decided to close that ward to cut costs. The two were moved in with other patients in another ward.
As a result, another five patients came down with the Vancomycin-resistant infection, and two patients died. The hospital then spent several thousand dollars cleaning with disinfectants, sterilising everything in the rooms and disposing of equipment, linen and furniture to remove every possible source of the bacterium and its spores.
This is not so much a story of the way privately owned hospitals operate, but of microbes now ruling the world — the revenge of the germs. By 1982, fewer than 10% of infections caused by the bacterium Staphylococcus could be cured by penicillin, as opposed to 100% in 1952.
Staphylococcus achieved this by absorbing the plasmid (a small piece of circular DNA) which contained the beta-lactamase gene (from another bacterium) into its own chromosome and passing it from one generation of bacteria to the next. Bacteria can hold several different plasmids in their cells.
Doctors weren't worried; they moved on to the next antibiotic, methicillin. But by the late 1980s, Staphylococus was resistant to methicillin and its cousin, naficillin. Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA), better known as golden staph, increased in size and frequency worldwide.
In attempts to circumvent MRSA infections, patients in hospitals about to undergo surgery were given pre-operative antibiotics to prevent post-surgical infections. Small children got antibiotics as a matter of routine for all manner of infections, including viral, which antibiotics cannot cure.
This standardised antibiotic treatment only made things worse, producing super strains of Staphylococcus which were resistant to huge numbers of potential drugs.
Australian doctors treated a patient infected with a bacterium that was resistant to cadmium, penicillin, kanamycin, neomycin, streptomycin, tetracyline and trimethoprim. In all, this bacterium was resistant to 31 different drugs. Each resistance capability was carried on a different gene on different plasmids, which could be separately passed from one bacterium to another.
Origin of mutants
Using new genetic fingerprinting techniques, 470 resistant MRSA strains were found to have been derived from one strain that emerged in Cairo in 1961 and spread in 10 years throughout the planet.
By 1993, only one sure-fire Staphylococcus killer remained — Vancomycin, one of the most expensive antibiotics on the market, and totally beyond the reach of the poorer nations.
Staphylococcus isn't the only danger. Every common pathogenic bacterial species has now developed drug resistance.
This now includes gonorrhoea, tuberculosis, cholera and leprosy. Though these originated in huge inner-city hospital complexes, by the 1990s they had reached human beings of all ages, races, social classes and geographic areas.
Streptococcus A, the cause of the common disease scarlet fever, by the 1960s had disappeared from the clinical scene and could be found only in medical textbooks. In 1980 it returned with a vengeance.
Even more serious was the emergence of a virulent strain of Streptococcus pneumoniae or Pneumococcus. In 1990, a third of all ear infections in young children and babies were due to Pneumococcus, and half of these were resistant to penicillins.
Rheumatic fever, which is caused by Streptococcus pyogenes colonising connective tissue, in particular the heart, had disappeared by 1970. In 1985, rheumatic fever broke out in Salt Lake City. The incidence of the disease skyrocketed in three years; increasing numbers of cases are still occurring all over the USA.
In poor countries, management of paediatric disease had to be handled with scarce resources and available antibiotics. The World Health Organisation determined that in 1992, 2 billion children per year suffered acute respiratory tract infections, and 4.3 million died as a result.
WHO concluded that the best policy in the Third World was to assume that all pneumonias were due to bacterial infections, either Streptococcus or Haemophilus influenzae, in the absence of laboratory proof that the infection was viral.
The result was a 36% reduction in child deaths, but village paramedics lacking laboratory support overused the antibiotics. This promoted the emergence of antibiotic-resistant Streptococcus pneumoniae.
Soon, antibiotic-resistant pneumonia strains turned up all over the world. By the 1990s, pneumonia strains had outwitted all aminoglycoside-type antibiotics, chloramphenicol, erythromycin and all penicillin drugs.
All these resistant bacteria can be traced to a single clone of one transformed bacterium.
Wherever one looked, the basic principle held true: the overuse of antibiotics in small children and hospitalised patients had prompted the emergence of resistant bacteria.
Third World
The worst toll has been amongst children, particularly in the Third World, because of the lack of good nutrition, clean water and sewage treatment.
During the 1960s, Shigella dysenteriae became the first bacterium causing diarrhoea to become resistant to penicillins. Half of all Shigella infections were caused by bacteria that were resistant to four or more antibiotics.
In Burundi, where the government couldn't afford alternative drugs from the multinational pharmaceutical companies, thousands of people died from dysentery. This was repeated throughout Africa.
In response, some of the poorest Third World governments decided to develop their own pharmaceutical industry. They made up a list of the 100 most essential drugs, which they decided could be produced because they were no longer patented and were easy to manufacture, and set out to make the products.
The US-based Pharmaceutical Manufacturers Association, representing 65 US companies and 35 foreign multinationals, blocked the purchase of raw materials required for drug manufacture by the Third World.
Vancomycin resistance
In 1988, one of the most disturbing but inevitable events occurred. A Vancomycin-resistant bacterium, Enterococcus faecium, emerged.
There was enormous concern that soon Enterococcal bacteria would share their resistance genes with other untreatable microbes. This has now happened; hence the two deaths in the Brisbane hospital.
Such a bacterial strain possesses not only drug-resistant genes but also those for heightened virulence. The pharmaceutical companies report that there is nothing on the shelf or in the pipeline to fight these infections; they have run out of ideas.
Having lost Vancomycin, we will be back to the 1930s, helpless in the face of Staphylococcus and Streptococcus infections.
Vancomycin-resistant strains have usually emerged in hospitals. In 20 different hospitals in New York, 42 patients of 100 with the infection died between 1989 and 1991.
The bacterial infection patients can pick up in a hospital are far worse than they will ever get at home — tenacious bacteria that can live on chlorine, in detergent or on a bar of soap.
Livestock practices
Another practice has contributed greatly to the emergence of super bugs. A radical change in veterinary and livestock practices took place with the discovery of antibiotics. Expensive livestock lived longer if they were treated with antibiotics. Preventive treatment seemed even better.
So billions of cows, chickens, pigs, ducks and other livestock underwent treatment with antibiotics, more than doubling the global selective pressure on bacterial populations.
It is useless to regulate humans' use of antibiotics while allowing unregulated sales of the drugs to the agricultural industry. But the European Community and the US Food and Drug Administration refuse to take action so as not to impinge on the competitiveness of their agricultural producers.
One of the most troubling examples of animal-human transmission is that of Esherichia coli. This bacterium is normally found in the intestines of all humans and many other mammals, where it aids the digestion of food.
But in 1982, something new turned up, E. coli 0157:H7. This mutant is capable of causing haemorrhages of the colon and kidneys of people of all ages. All known cases of infection came from contaminated meat.
Because of widespread agricultural use of antibiotics, all kinds of E. coli strains have acquired a broad range of resistance and greater virulence. These mutant bacteria are resistant to ampicillin and tetracycline, and have acquired the ability to produce Shigella-like toxins that are lethal.
In 1993, 500 people in Washington state became ill after eating hamburgers at fast-food outlets; four children died.
This is similar to the case in Adelaide, in which a small girl died after eating a salami.
Also in 1993, 35,000 residents in New York City had to switch to boiled water when E. coli 0157:H7 made its way into the water supply.
Epidemiologist Mark Lappe warned in 1980: "We have organisms now proliferating that never existed in nature. We have selected them, and they are now causing 30% of diseases. We have changed the whole face of the earth by the use of antibiotics." We should brace ourselves for the coming plagues.
[Material for this article has been taken from the book The Coming Plague: Newly Emerging Diseases in a World out of Balance by Laurie Garrett. Published by Penguin, 1994.]