Antibiotics: still the best drugs to combat bacterial infections

Consider the difference in size between some of the very tiniest and the very largest creatures on Earth. A small bacterium weighs as little as 0.00000000001 gram. A blue whale weighs about 100,000,00 grams. Yet a bacterium can kill a whale… . Such is the adaptability and versatility of microorganisms as compared with humans and other so-called “higher” organisms, that they will doubtless continue to colonise and alter the face of the Earth long after we and the rest of our cohabitants have left the stage forever. Microbes, not macrobes, rule the world.

BERNARD DIXON

The discovery of penicillin in 1929 by Sir Alexander Fleming had been heralded by the entire scientific community of the world as one of the greatest achievements in the history of man’s fight against diseases caused by bacteria, and the introduction of penicillin for regular treatment in 1940s had indeed proved to be an untold blessing to mankind.

One after another, the dreaded scourges such as pneumonia, meningitis, syphilis, etc, had surrendered with rapidity before the onslaught of this first antibiotic, whose family includes the best drugs of choice for the many infections that still plague humanity. Penicillin was rightly regarded as the king of antibiotics.

The Penicillins are generally cheaper than many of the latest antibiotics. They do not have any serious side-effects and at the same time des­troy any chosen kind of bacteria with accuracy. As Nobel Laureate, Peter Medawar has pointed out Fleming, the discoverer of Penicillin had been feverishly searching since the middle of the First World War for some powerful agent or drug that could destroy bacteria without harming human tissue. . Even though penicillin was the first antibiotic, it had by a stroke of luck satisfied both the above criteria. Most antibiotics are highly toxic inasmuch as they arrest the growth of bacteria by interfering with the metabolic processes of a kind that bacteria have in common with higher organisms. Therefore they are extremely toxic and harmful to human tissue. On the other hand penicillin, unlike other antibiotics, interferes only with the synthetic process peculiar to bacteria, only, namely the synthesis of a distinctive structural element of the bacterial cell wall. The cells in the human body contain only membranes and not cell walls. Hence, they are protected from damage.

But even before doctors could proudly announce that man had finally conquered the microbes, and even as a host of new antibiotics had begun to be invented or synthesised, scientists had started notic­ing that bacteria had begun to quickly marshal their defences. Fleming himself had cautioned other scientists about the appearance of several kinds of resistant bacteria.

In the beginning, scientists had been inclined to attribute this phenomenon to random mutations in the genetic code of bacteria. Physicians had hoped that these resistant bacteria could be destroyed by increasing the dosage of the antibiotic being administered or by developing other specific antibiotics. For a little while it had appeared as though such optimism had been justified.

Towards the end of the last century, the common bacterium found in hospitals staphylococcus aureus (staph) had been 100 per cent susceptible to penicillin. But a few years earlier the Japanese had come across a strain of bacteria (shigella dysenteriae) that could resist four different antibiotics. This kind of bacterial resistance to a drug of choice had begun to be found in various hospitals and clinics all over the world.

In a hospital in Detroit in the United States, one of the officers in charge of control of infectious diseases had noticed that resistant strains of disease-carrying bacteria had begun to find refuge in patients already weakened by illness or by surgery despite various precaution­ary measures taken to keep the walls, floors and bed-sheets of the hospital clean. No amount of scrubbing or boiling could eliminate these bacteria from the hospital wards.

Another development which had caused anxiety was that a number of patients, mainly users of a particular kind of heroin, had begun to get admitted into that hospital. All these patients had been found to be carrying resistant ‘staph’. While doctors had at first been a bit reluctant to establish a direct connection between the source of the heroin and the presence of the dangerous staph, they had begun to suspect that the staph could have entered their systems indirectly.

It would appear that most drug users had also been using antibiotics as a precautionary measure against possible infection from unsterilised needles, and doctors had felt that there was a distinct possibility that such indiscriminate use of antibiotics could have helped to strengthen the bacteria, making them resistant.

The appearance, thus, of bacteria resistant to an antibiotic which had been routinely used in the past to combat that very same strain had been causing concern in medical circles, generating fear that many such well known life-savers would soon become ineffective.

In 1981 about 2700 people in the United States had been afflicted with a new strain of gonorrhoea, resistant to all kinds of penicillin. Leprosy which had originally been treated successfully with a drug called dapsone was being reintroduced in a tenacious form resistant to that drug, by immigrants. Even common diseases such as bacillary dysentery are now proving unyielding to routine antibiotic therapy.

In the United States bacterial infections are now the fifth leading cause of death; in the hospitals they are directly responsible for forty thousand deaths a year and indirectly for eighty thousand deaths.

How exactly have the microbes developed this strength to combat and defeat man’s most potent weapon in his struggle against disease? Doctors all over the would unanimously agree that misuse of anti­biotics had been the main reason for bringing about this sorry state of affairs.

A teenager who is worried about a few ugly pimples on his face may insist on his doctor giving him a powerful drug. A girl who catches a cold just before going out on a date and a boy who develops a viral fever, just before an examination, may on their own take some antibiotics from the family medical chest even though antibiotics are of no use against a virus.

Similarly, a patient may neglect to complete the prescribed course of an antibiotic, thinking that even half way through he is already feeling better. All theses people are in their own way helping the bacteria in the environment to grow stronger. The problem is made more complicated by the fact that in certain countries where drug control is not rigidly enforced, it is very easy for people to obtain even the most powerful antibiotics across the counter without a prescription.

These then are the major reasons for antibiotics getting pro­gressively weaker and less effective:

 (a) easy access to a wide range of antibiotics;

 (b) prescribing antibiotics for even minor ailments which require either no treatment or could yield to simpler medicines;

(c) failure on the part of patients to complete the entire course of tablets or capsules prescribed for a particular ailment.

As the resistance of bacteria to antibiotics is gradually increasing scientists are simultaneously trying to analyse and understand how different kinds of bacteria have been able to combat successfully the various antibiotics, so that they could develop modified or new types of drugs that could kill those bacteria.

The new generation of antibiotics such as cephalosporins, monobactams and super penicillins swing into action essentially in the same manner as their early predecessors but with certain modifications. Basically they are designed to counter the resistance mechanism developed by the bacteria, thus enabling the chemicals in the antibiotics to do their job effectively.

The new group of antibiotics have also been tested and the first results have shown that they are highly effective against the new diseases such as super staph, super gonorrhoea, super pneumonia and other resistant strains of bacteria that have appeared recently.

But scientists are also aware that no matter how many new types of antibiotics are introduced, the bacteria will always find a way to get stronger, unless human beings give up some of the undesirable habits that enable bacteria to become resistant. A warning in this connection had been given by Nobel Laureate Walter Gilbert of Harvard University when he stated that a time would soon come when almost 80 to 90 per cent of the infections will prove resistant to all known antibiotics.

In their study of the defence mechanism of bacteria scientists have been surprised to discover a wide range of biochemical and physical strategies being adopted by bacteria. Scientists have found that a bacterium is able to produce an enzyme that can pulverise an antibiotic. Another fact that has begun to worry scientists is the manner in which the bacteria have been able to pass their resist­ance on.

Whenever bacteria reproduce, a cell simply divides, giving out a duplicate copy of its own genetic information to each offspring cell. No new characteristics can develop unless a mutation occurs. However, on certain occasions two bacteria indulge in a sort of sexual mating by attaching their thin tubes to each other, thus, exchanging small circular bits of genetic information called plasmids. These plasmids which move outside the bacterial DNA also contain lethal genes that make the germs attach themselves to the intestinal wall, give out toxins and invade tissues.

Until the 1970s scientists had held that all plasmids were very similar in their behaviour, and that they were also limited in the type of host bacterium that would accept them. But later scientists in great Britain and Germany found that certain plasmids contained a sort of jumping gene’ or transposon that could give them the capability to move in random fashion from one strain of bacteria to another.

In other words, the gene itself could circulate and also quickly multiply in the same manner as the host bacterium. In this manner this rebellious gene has the ability to transfer its own antibiotic resistance. It is now becoming increasingly clear that the “jumping gene’ may be responsible for the occurrence of most strains of resistant bacteria.

Almost 90 per cent of all resistant bacteria have plasmids and researchers are inclined to believe that jumping genes show up wherever there are plasmids. The discovery of a plasmid in the syphilis bacterium which till now has been sensitive to antibiotics indicates that it too could in the near future become resistant and pose serious problems to the medical community.

As indicated elsewhere, overuse of antibiotics is one of the major reasons why resistant bacteria have developed.

During an infection when millions of bacteria invade the human body, there are sure to be one or two transposons present. The bacteria would seek protection by clinging to the transposons in order to survive the onslaught of the antibiotics.

In 1981, a large number of doctors and researchers from twenty- six countries had met in the Dominican Republic and had signed a joint statement calling for international action to prevent global drug abuse. They had also highlighted the need for uniform practice in the prescription and distribution of antibiotics as well as proper and uniform standards in advertising procedures.

Doctors all over the world are unanimous in their condemnation of the indiscriminate use of antibiotics. They are also concerned about the ignorance of the general public regarding the use or abuse of antibiotics. A few years ago, in Boston, a doctor had found that many of his friends had been keeping empty bottles of antibiotics beside the aspirin tablets.

Similarly, the faecal samples of many people, when analysed in one of the hospitals, had been found to contain E. coli (the normal kind of bacteria that are usually found in the human intestines) which were resistant to at least one antibiotic. Scientists fear that these reservoirs of antibiotics resistant E. coli could be exploited by other kinds of bacteria to develop their own strength and resistance.

Such concern was found to be fully justified when a physician in Boston had noticed that some gonorrhoea bacteria had been discovered having the same antibiotics resistance as the E. coli, even though gonorrhoea bacteria do not normally reside in the human gut. This would seem to indicate that some kind of exchanges are in fact already taking place.

Super gonorrhoea is one of the most significant examples of the presence of obstinate antibiotic-resistant bacteria. While in many countries 50 per cent of all gonorrhoea cases are now found to be due to penicillin resistant bacteria, in the United States the figure is still less than 1 per cent.

But even there the figure is gradually beginning to increase. A new antibiotic called spectinomycin seems to be very effective against super gonorrhoea, and doctors are trying their best to restrict its use so as to protect its effectiveness in future.

Another strain of bacteria whose resistance is worrying doctors is the one that causes cystic fibrosis. Almost nine out of ten patients with this ailment die of respiratory failure brought on by pseudomonas aeruginosa. There is no antibiotic now available to counter this, though scientists had identified at least one of its defence mechanism, namely its ability to knock out an antibiotic like tetracycline, thousand times faster than the rate it is pumped in, and in an unchanged form. This ability to remain totally unaffected by a drug such as tetracycline has been acquired by a few strains of E. coli bacteria also.

All these factors have led scientists to plan the development of new antibiotics which they hope would be able to tackle the super germs which have begun to appear. Famous medical companies all over the would are exploring various places on the earth in their search for new kinds of drugs.

One of the famous companies, Squibb Laboratories, New Jersey in the United States, had discovered a new antibiotic after a long search in the Pine Barrens nearby. The antibiotic itself is produced by one kind of bacterium (called chromobacterium violaceum) in order to protect itself against other micro-organisms.

By the addition of new chemical arms to the centre of the molecule, scientists have been able to produce a new series of antibiotics called monobactams. The first of the monobactams which had only recently been synthesised and tested has proved to be an effective cure for refractory lung and urinary infections and even some strains of super gonorrhoea.

The drugs known as cephalosporins seem to be effective against a large number of resistant bacteria even though ineffective against the fatal pseudomonas. But scientists are very optimistic that pseudomonas may be susceptible to a drug called moxalactam which belongs to neither the penicillin family nor the cephalosporin group. The presence of an oxygen atom in the molecule where other antibiotics have a sulphur atom has given this drug its specific quality.

The newly-found corbomycin and the lesser-known complestatin have a never-before-seen way to kill bacteria, which is achieved by blocking the function of the bacterial cell wall. The discovery comes from a family of antibiotics called glycopeptides that are produced by soil bacteria.

The U.S. Food and Drug Administration recently approved Xenleta (lefamulin) to treat adults with community-acquired bacterial pneumonia. Other newly developed antibiotics are Ceftazidime, meropenem-vaborbactam, and plazomicin for various infections

In the final analysis one must conclude that antibiotics are still the most powerful weapon in the scientist’s arsenal in the war against some of the deadliest diseases that afflict the human race. They would continue to retain this pre-eminence, unless man, by his own carelessness and misuse, weakens the hold they have over the tiny microbes, whose potential threat to mankind is, to say the least, totally out of proportion to their dimensions.