Hospital and Doctor Caused
Infections Rampant


Note: The longer one stays in hospital the greater the chances of one getting an infection. Well, the dictum seems ironical in that the patient ends up paying, literally and figuratively, to become infected. DR. S. SRINIVASAN analyses the problem.
Even half a century or so after Alexander Fleming's historic discovery of penicillin, the term ``hospital acquired infections'' may sound odd, even unbelievable. But it exists and it speaks volumes of what exactly is the position in even the best hospitals in the most advanced countries. Ironically, the more sophisticated the gadgetry in intensive care, the greater the threat of catching a new infection. And, the longer one stays in hospital with one's bills rising like taxi meter, the more the chances of one getting infected. You virtually end up paying to get infected, and then pay more to get treated for it as well. More on this curious vicious cycle later.
With the advent of powerful, modern antibiotics, a whole new era of what are called `nosocomial infections' has arrived. This term may sound rather strange and seems to indicate an infection of the nose tissue, but is in fact derived from the Greek word ``nosokomeian'', which means a hospital.
To understand ``nosocomial infections'', one needs to understand how medical intervention can cause a problem, in addition to treating it. A parallel expression, ``iatrogenic disease'' is relevant here. ``Iatros'' stands for doctor and ``genic'' indicate cause - ``iatrogenic'' thus stands for anything caused by a doctor. In other words, an iatrogenic disease is a ``doctor- caused'' disease. There are many example. If a doctor prescribes a class of drugs called ``corticosteroids'' for asthama or arthritis, he can create an ``iatrogenic'' peptic ulcer problem in the stomach as a side-effect. If a mental patient is prescribed antipsychotic drugs, one can end up with ``iatrogenic Parkinsonism'' (a disorder of limb movements), again as a side- effect. Similarly, the nosocomial infections can also be classified as iatrogenic diseases.
If doctors are aggressively treating infections all the time, then how can they be also creating new infections? Let us take a fairly straightforward case of, say, severe and extensive burns in a victim caused by an accident in the kitchen. Intensive treatment is started immediately, which means cleaning and dressing the burns, administering intravenous fluids, replacing blood, inserting a catheter in the urinary bladder to drain out urine and providing other supportive measures to sustain vital functions till full recovers. At times, if the patient's condition deteriorates considerably, she may have to be put on a respirator with oxygen too.
All these measures provide an easy path for microbes to invade the body, through the intravenous line, catheter, respirator and so on, especially at a time when the body defences are down due to the stress of burns, blood loss, immobilisation, improper nutrition and other factors. Burns take very, long time to heal, so the hospital stay can extend for several weeks, if not months. To control infection in the burnt area, doctors start a course of antibiotics which kill infecting bacteria alright but soon give way to other types of bacteria resistant to them. So, the patient ends up catching a different type of infection. This goes on and on as long as the burn remains unhealed and thus susceptible to attack by bacteria. In the bargain, the patient becomes a breeding place for difficult-to-treat bacteria which are ``multi- resistant'' to a wide range of antibiotics.
ICU - the ideal place for infections.
Dreaded infections in a hospital find their roots in intensive care units. The reason for this paradoxical phenomenon is easy to understand. To begin with a patient in the ICU is always in a serious condition - he/she is severely injured, has undergone a major operation or has a malfunctioning vital organ. The patient is often unconscious and needs to be sustained on intravenous fluids, has to breathe with the help of a respirator and has tubes and gadgets into him her. He/she can develop bed sores. Coughing out an obstruction in the air-passages, is difficult and getting pneumonia is a certainty. The urinary catheter is a continuous source of infection for the urinary system which can soon affect other parts of the body. There is a depletion of vitamins and minerals essential for the body's defence mechanisms as there are low levels of antibodies. He/she is often treated with corticosteroids which lower the body's defences. The patient is thus ``immuno-compromised'', which means body immunity is below par.
With all this in mind, doctors bombard ICU patients with the best antibiotics. These latest generation antibiotics are known as cephalosporins, fluoro-quinolones, aminoglycosides, and other specific chemical groups and are often administered in combinations to achieve the best results. If the body's defences are satisfactory the bacterium can be tackled using one or more of such drugs. If treatment does not have to be prolonged, the chances of recovery infections are good. If, vice-versa, the patient is in for real trouble.
To understand how bacteria can play tricks on doctors, we can draw a parallel with the cockroach in the kitchen. Even with the best pest control measures, no one can kill all the cockroaches. Some are bound to escape, either because they were inherently resistant to the pesticide or because they did not get sprayed enough. These soon multiply to form a new population resistant to the spray. To tackle this problem, pest control experts are constantly formulating newer pesticides and or using them in combination.
Resistant bacteria are ``selected'' in a similar manner whenever an antibiotic is given. While many die off, some remain and multiply to yield a whole new colony of resistant bugs. Of course, the probability of such a thing happening can be predicted reasonably by what is called ``in vitro'' (literal meaning, in glass, that is laboratory test tube sensitivity testing, in which a culture of the bacterium isolated from the body is exposed to the antibiotic to be given, in the laboratory under controlled conditions. If the bacterium is inhibited or killed, it is called ``sensitive'' to the antibiotic, and if not, it is deemed ``resistant''. But even if ``in vitro'' testing shows sensitivity, there is no guarantee that all bacteria will die. So, the danger of some inherently resistant ones multiplying to yield resistant bugs is always there.
When it comes to cunning, bacteria can even outsmart the best defences. For instance, not only do they learn to develop resistance to a strong antibiotic even as treatment is on, but they can also quickly transmit the resistance to other bacteria in the process, with devastating consequences. Research is intense so that counteractive measures can be taken on a war footing. But somehow, the bugs manage to stay a step ahead.
Resistance to antibiotics is acquired by bacteria through changes in genetic make-up, which results in changes in bio-chemistry, which in turn evades the killing action of the antibiotic. For instance, a bacterium can learn to prevent the entry of the antibiotic inside itself or can learn to chemically destroy the antibiotic after it acts. Powerful enzymes are brought to operation in order to achieve this.
One such enzyme is ``beta-lactamase'' which can destroy even modern antibiotics of the ``beta lactam group'' known as ``cephalosporins''. Researchers try to overcome this by discovering newer generations of ``cephalosporins'' which can be stable to attack by ``beta-lactamses''. The bacteria, in turn, try to overcome this by designing newer and newer types of ``beta-lactamases'' and bringing them into operation. And so the ding-dong battle continues.
Transmissible resistance is one in which the resistance is offered by loosely occurring genetic material called ``plasmids'' which can be passed on from one bacterium to another. The passing on is done through ``conjugation'' which is a sort of marriage between the bacteria which then separate and transmit the resistance to others through a chain of conjugations.
To find out how bacteria behave under ICU conditions in major hospitals, a study was undertaken in Europe a few years ago. On April 29, 1992, 10,038 patients from ICUs of 17 countries in Western Europe were surveyed for possible infection. Popularly known as the EPIIC study (European Prevalence of Infection in Intensive Care) this study came up with some very interesting results.
Of those surveyed, 45 per cent had some infection on that very day. Of these, nearly half the number of infections originated in the ICU. It was noted that those who were at special risk were those with in-dwelling urinary catheters meant for draining out their urinary bladder, those with central venous catheters meant for intravenous fluid administration and measuring central venous pressure, those who were put on assisted ventilation with a respirator and those who had stayed in the ICU for 14 days or more for whatever reason. Pneumonia was the commonest type of infection followed by bronchitis, urinary tract infection, wide- spread infection all over the body (``septicemia'') and infection of surgical wounds.
Not only are infections more common in absolute terms in ICU patients, but it also turns out that the types of bacterial causing these infections are changing over the years, thanks to the widespread use of advanced, broad spectrum antibiotics. Decades ago, when catheters and other invasive devices were not common, bacteria of the ``Gram negative bacilli'' category were predominant in hospitals. These rod-shaped bacteria, that look pink after staining, originate in the intestines of the patient. Today, ``Gram positive cocci'', which originate from invasive devices, tend to cause a number of infections. Then there are old organisms which have learnt new tricks. Examples of these are Pseudomonas, Enterococci, Enterobacter, Citrobacter and Serratia. Once again, to tackle Gram positive as well as Gram negative infections in difficult ICU settings, doctors have to resort to therapy with combinations of ultramodern antibiotics like fourth generation cephalosporins and glycopeptides.
All this war - like imagens may remind one of missile technology. It is anybody's guess where this will all end, if it ends at all. Already, scientists have started looking at totally different modes of infection control in which the emphasis will be not on killing the invading bacterium but on boosting the body's defences through ``immunomodulation''. This approach, also known as ``biological response modification'' reminds one of our changing strategy towards mosquito control, in which we have started relying equally, if not more, on mosquito repellants rather than on killing the mosquitoes.
If microbes are going to be forever hoodwinking modern drugs, then it is perhaps not a wise idea to go after newer and newer antibiotics, but instead look for more ingenious ways of dealing with them.

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