- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- ICU - the ideal place for infections.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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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