Bacterial Resistance to Antibiotics

As multiresistant bacteria continue to multiply and develop, the medical community finds itself faced with more and more potentially untreatable diseases. Part of the blame for this phenomenon is to be placed on the medical community itself. Over-prescription of and misuse of antibiotics-attempting to treat viral infections with antibiotic drugs for example-continues to contribute to the development of increasingly virulent bacteria.

Bacterial resistance

Even during the early stages of antibiotic development, it was clear that some bacteria could survive and multiply in the presence of antibiotics. These bacteria had acquired resistance to the effects of those antibiotics.

In an interview with The New York Times in 1945, Alexander Fleming warned that the misuse of penicillin could lead to the selection and multiplication of mutant forms of resistant bacteria. He also predicted that this problem of resistance would worsen if penicillin was made available in oral form, if inadequate doses were given, if a course of treatment was not completed, or if people were given too long a course of penicillin. Just how serious is this antibiotic-resistance problem, though?

In the early 1980s, a number of hospitals in Melbourne were plagued with infections that were resistant to almost all known antibiotics. The organism causing the problem, which resulted in the deaths of a number of hospital patients, was Staphylococcus aureus. This situation represents the gravest of resistance problems. It raised such fears among hospital workers that many of them wore masks at work. The bacteria were resistant not only to antibiotics but also to antiseptics, making them virtually impossible to kill. Only one antibiotic remained effective-vancomycin, a drug that is both expensive and toxic. Doctors had no alternative but to use it. In this way, the hospital infections were eventually brought under control.

That was in the 1980s. Today, vancomycin resistance is indeed a reality, but it occurs in a different group of bacteria-Enterococci. We know, however, that these bacteria are able to transfer their resistance to Staphylococcus aureus, the organism that causes hospital-based infections. This means it is only a question of time until resistance to vancomycin occurs in Staphylococcus. Then, hospital infections, such as those in Melbourne, really will be impossible to treat with antibiotics.

So it is clear that we are facing a potentially disastrous situation. An infection that is untreatable by present means is now a real possibility. It is only a matter of months, or a year or two at most, according to some microbiologists.

Why do bacteria develop resistance?

The problem of widespread bacterial resistance is one that we have brought upon ourselves. Bacteria's reasons for developing resistance are simply a matter of the organisms' drive to survive. However, through our excessive use of antibiotics, we have exacerbated the need of the bacteria to fight for life to the point that the existence of bacterial resistance has become worrisome.

Bacterial resistance to antibiotics is not a new phenomenon; it has been around for as long as bacteria themselves, but at a very low level. We can see this in soil, for example, where fungi and bacteria coexist. This coexistence is not entirely peaceful, though. In fact, fungi and bacteria battle with each other for space and resources in the soil. Fungi compete with bacteria in the soil by producing antibiotics. (You may remember that many antibiotics were originally isolated from soil samples containing fungi.) In order to survive, bacteria devised a means of protecting themselves against these natural antibiotics; they developed resistance. So resistance is a natural survival mechanism.

But if resistance to antibiotics has always existed, why has it now become so widespread? And why is it such a danger? The answers to these questions lie in the way we have approached the use of commercial antibiotics. We have overused them in some instances and underused them in others. We have used them inappropriately in still other circumstances. In general, we have grossly misused them, and through this misuse, we have encouraged the never-ending development of resistance in bacteria.

It is not only doctors and patients who are at fault when it comes to over-prescribing antibiotics; pharmacists and governments are too. In many developing countries, antibiotics are freely available without a prescription. This leads to their misuse, thereby encouraging the development of resistance.

Antibiotics have been used in animal feeds for quite a long time. Livestock-cattle and pigs in particular-are given large amounts of antibiotics as growth enhancers and to treat specific infections. These animals (and their products) end up as food in our supermarkets, either as meat or as dairy products, like cheese and milk.

The bacteria in these animals tend to be multiresistant-that is, they have resistance to many antibiotics at the same time. This multiresistance can be passed on to humans through direct contact with the animals, through contaminated food, or via the soil (the feces of these animals form part of the soil). Interactions between humans and animals can alter the bacterial flora of each group. Flora is the bacterial population that lines the skin and cavities of the body, including the respiratory and digestive tracts. Resistant bacteria can spread from the animal to the human via feeding or handling.

Over-the-counter sales of antibiotics for the farming -community must be stopped. All antibiotics should be administered by a veterinary surgeon and, as with humans, should be used as a last resort only. There are many excellent homeopathic remedies available for animals.

It is known that small amounts of penicillin and tetracycline can enhance the growth of livestock. Consequently, far greater amounts of antibiotics are given to commercial livestock to enhance growth than are used to actually treat infections. Administering even small amounts of antibiotics on a continuous basis can encourage bacterial resistance, as the bacteria develop their own means of overcoming the effects of the antibiotic instead of being killed by it. Using penicillin and tetracycline as growth enhancers has been stopped in Europe for the most part, but not in the United States and other parts of the world. This is clearly an issue that must be addressed globally.

Antibiotics are even used in our pets' food. One study has shown that 70 percent of dogs have in their feces a strain of multiresistant E. coli, a bacterium that is a normal constituent of the bowel in most animals, including humans. Some of the bacteria in the bowels of these dogs are resistant to two or more antibiotics. This may well be due to the fact that antibiotics are added to commercial dog foods as growth enhancers. And, even small amounts of antibiotics will encourage bacterial resistance.

Bacteria have the ability to develop resistance to almost any drug to which they are exposed. This resistance is now threatening our ability to treat infections, not only in humans, but also in animals. Using antibiotics in animal feeds to enhance the growth of livestock contributes greatly to the continuation and spread of resistance. The bacteria in the bowels of commercial animals (cattle, sheep, pigs), as well as in pets (cats, dogs), are resistant not just to one or two antibiotics but to many.

Antibiotic resistance is a worldwide problem that needs the cooperation of governments, doctors, pharmacists, veterinary surgeons, and farmers alike, as well as the education of the general public.

Multiresistant bacteria

In the late 1950s in a hospital in Japan, a very startling thing happened, alarming the whole scientific community-the birth of multiple drug resistance. In this hospital, a number of patients were suffering from Shigella dysentery. The bacteria causing this infection were resistant to tetracycline, the sulphonamides, streptomycin, and chloramphenicol. Multiple drug resistance was unknown prior to this. Now it suddenly sent shock waves across the world.

By 1966, a number of countries had reported multiple drug resistance. In one South African hospital, 50 percent of the E. coli bacteria isolated from the feces and urine of patients showed resistance to one or more antibiotics. Resistance information was carried by the plasmids (units of DNA that replicate within the cell independently of the chromosomal DNA) within the bacterial cell. These plasmids were transferred to other bacteria, making them multiresistant as well. In other words, the resistant bacteria share their ability to defeat antibiotics with other bacteria.

Drug resistance has truly become a worldwide problem. Today, virtually the whole planet has a problem, to a greater or lesser extent, with antibiotic-resistant infections. This problem is not specific to the developing or developed parts of the world; it affects us all and, in a way, unites us.

How do bacteria develop resistance?

The mechanism by which bacteria overcome antibiotics, so-called "magic bullets," is fascinating. One can only be in awe of these changeable and resilient organisms and the ways in which they are able to overcome our efforts to kill them.

Our limited thinking and our lack of awareness of nature are now forcing us to view things differently. We must accept that even pathogenic (disease-causing) bacteria have a positive and important role to play in nature. We don't have to understand what this role is; we need only respect it. Respect is the key to solving the problem of antibiotic resistance.

The health-care practitioners in underdeveloped countries seem to employ this respect. Many seem to have an understanding of the interconnectedness of all living things, and so are always attempting to work with nature by obeying its laws. They do not see themselves as different from, or better than, the rest of nature. Western civilizations, on the other hand, tend to see humans as all-important, as separate in some way and, therefore, able to rise above nature and control it. Simple single-celled organisms called bacteria have taught us the folly of our ways. Not only can they evade our magic bullets, but their ability to do so can also teach us a very valuable lesson. We all need to learn this lesson and to the shift our thinking away from control-control of nature, control of people, control of land-towards living in harmony with nature.

Are bacteria able to fight back?

Bacteria have been able to survive over the centuries through a process known as spontaneous mutation. Every so often, genetic material mutates, or changes, and produces a gene that can help the bacteria to survive in the face of any toxic material in its environment, including antibiotics. At low levels of antibiotic usage, this is all that is necessary for survival. The presence of an antibiotic kills off the bacteria that are susceptible to it. This leaves behind those bacteria that possess genetic material which has mutated in such a way as to make them impervious to the antibiotic. These impervious bacteria, then, are left alive to reproduce. The gene for antibiotic resistance is passed on from one generation of antibiotic-resistant bacteria to the next. As those bacteria that are sensitive to antibiotic die, they leave behind a bacterial population that is composed of nothing but the initially rare antibiotic-resistant bacteria.
In the 1940s, Sir Alexander Fleming, a Scottish biologist, noticed such mutants in his experiments and warned of them. He predicted that the more widespread the use of antibiotics, the more widespread and more numerous these mutant forms would be. Through spontaneous mutation, the genes of bacteria can adapt, enabling them to survive in a hostile environment. This is quite amazing. It shows how a change in the environment can cause unseen changes in the world of bacteria.

Ubiquitous use of antibiotics has led to bacteria becoming even more adaptable. They developed new, improved survival mechanisms in the form of plasmids.
Plasmids are self-duplicating mini-chromosomes, or extra bits of genetic material, that exist in a bacterial cell. They are independent of the chromosomes. Sometimes a plasmid mutates spontaneously, and it is from this mutation that an antibiotic-resistant gene arises. The plasmids containing the mutated gene now carry new information about how to survive in the presence of a previously deadly substance. In this way, they are able to help bacteria to adapt faster than ever to the changes going on around them. While we were making antibiotics widely available and patting ourselves on the backs for our wonderful scientific advances, bacteria were busy developing more efficient means of protecting themselves. Plasmids are in a constant state of change. They are continually losing genes that are no longer of use to the survival of the cell and, at the same time, acquiring new genes. The environment dictates and selects which genes are of value and need to be retained, and which cells are no longer necessary for the cell's survival.
Through our misuse of antibiotics, we have ensured the development of plasmids and their continued importance. The main function of plasmids is to prevent bacteria from being killed by antibiotics. Plasmids were unknown until the 1970s, when resistance became a major problem. They began to ring the death knell for penicillin and warned of what was to come.
A unique characteristic of plasmids is that they can be transferred from one bacterial cell to another and from one species of bacterium to another. This allows bacteria to become resistant to a drug very quickly.

There seems to be no limit to what bacteria will do in their war against antibiotics. If producing plasmids was not enough, bacteria have now developed transposons that transfer such properties as antibiotic resistance between genetic materials. Transposons are even smaller pieces of DNA (or genetic material) than plasmids. As the name suggests, they are able to jump from one piece of genetic material to another (transposition). They can jump from a plasmid to a chromosome or vice versa. Each transfer rearranges the DNA of the cell that the transposon comes to rest in. In this way, they can easily transfer resistance genes within a bacterial cell or from one bacterial cell to another. This is an even faster and more efficient way of spreading resistance genes among a population of bacteria. Spontaneous mutations, the production of plasmids, and the development of transposons are the main methods bacteria employ to survive in the presence of antibiotics. These are the mechanisms that have led to the epidemics of bacterial resistance that currently plague many modern hospitals.

Did we create antibiotic resistance?

To answer this question, we must visit the more remote peoples of this planet and see if they, too, carry bacteria that have antibiotic-resistant genes.

Studies have been performed on the Bushmen tribes of southern Africa. These people have little contact with the Western world and would never have taken antibiotics. The bacteria in stool samples from these people show very low, but detectable, numbers of resistant bacteria. The same result has been found in other studies of remote tribes in different parts of the world.

Among the Kalahari Bushmen, approximately one in fifty bacteria carry a resistance gene, whereas in European people, twenty-five out of fifty bacteria carry a resistance gene.

So, we did not create bacterial resistance. What we have done is encourage the development of resistant and multiresistant bacteria. In fact, we have unwittingly allowed these bacteria to flourish and prosper.

The effects of resistance

Bacterial resistance affects us all. However, the results of its existence are not entirely bad.

As with all situations in life, we can choose to view things negatively or positively. The negative way of viewing resistance is evident in the media. The problem of resistance is portrayed as a plague that can wipe out the whole of humanity in a short space of time. This may not be untrue, but if we created the problem, we can surely solve it too.

The more positive way of viewing resistance is to see it as a blessing in disguise. It is a blessing because it makes us stop and think. It makes us become more responsible for our actions (for example, not using an antibiotic as a quick fix if you have a cough or a cold). It is forcing all of us to educate ourselves not just about antibiotics but about the harmful effects of all drugs. It is asking us to make choices about our lifestyles. In more subtle ways, this problem of resistance is challenging our view of ourselves and our world, since we are finding it harder to view ourselves as superior to single-celled bacteria or as separate from them. It challenges our concept of control not just of nature but of many things in our lives.

Resistance to antibiotics is a major public health problem. It is threatening our ability to fight even common infections like tonsillitis, ear infections, and urinary tract infections. Because it is such a massive problem, global in its dimensions and not well understood by the public, an organization called the Alliance for the Prudent Use of Antibiotics has been established in the United States to address the issue. The main aims of this organization are to encourage people to take a more responsible approach to the use of antibiotics and to promote the improved use of antibiotics through communication of research information from different countries around the world. It also seeks to educate people: doctors, patients, veterinary surgeons, farmers, pharmacists, pharmaceutical companies, and lay people alike. This kind of international cooperation involving all those interested in the use of antibiotics is absolutely necessary.

Can bacterial resistance be overcome?

Plasmids and transposons allow those bacteria that contain them to survive in the presence of an antibiotic; hence, survival of the fittest is clearly at work. But if a bacterial cell contains one or more plasmids (and / or transposons), this is disadvantageous to its survival in two ways. First, carrying this extra genetic material consumes a lot of the bacterial cell's energy, so less energy is available for its growth or reproduction. Second, the bacterial cell is less virulent with these passengers.

So carrying resistance genes has both advantages and disadvantages for a bacterial cell. We are constantly pressuring bacteria to carry resistance genes through our misuse of antibiotics. If this pressure is removed by not using an antibiotic at all for a period of time, bacteria start to lose their plasmids / transposons and return to their original state.

In one hospital in Southern Africa, the doctors had a problem with bacterial resistance to an antibiotic called gentamicin. The doctors stopped prescribing gentamicin for a time, substituting a less common antibiotic instead. After a period of five years, the particular bacteria whose antibiotic resistance had been troubling them (Klebsiella pneumonia, which can cause lung infections) lost its resistance genes and once again became sensitive to gentamicin. Gentamicin, therefore, became useful again.

This suggests that a more prudent approach to the use of antibiotics will indeed result in bacterial changes. These changes will lead to reduced bacterial resistance and a return to their natural state of susceptibility to antibiotics. This is a beautiful example of the balances that work within nature.