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Defense against infections

Last update 13-6-2009

On the resistance against antimicrobial drugs


The resistance against antimicrobial drugs is a major issue in the defense against infections as this diminishes our ability to aid the natural defense against infections and threatens to eliminate our ability to do so.
This page provides a high level overview of what resistance is and why it has emerged.

The normal situation in the gut

In the gut very large numbers of microorganisms struggle for survival. Some achieve (temporary) residence in the gut while others are more transient. Some species survive by being good at growing fast, others survive by being good at chemical warfare or by being able to live on very little food. Also some survive in areas of the gut that contain oxygen, while others cannot.
The chemical warfare between microorganism species and with the host consists of being able to produce toxins that provide a disadvantage (or even kill) other species as well as being able to ignore or render harmless the toxins produced by other species.
As many microorganisms are able to transfer genetic information between between microorganisms of the same species (each other) and even between species, the ability of microbes to act in chemical warfare can spread rapidly.

What is resistance against antimicrobial drugs?

Anti microbial drugs are substances that are either directly derived from microorganisms, with penicillin as famous example, or modified versions of these substances. The first are therefore taken out of the normal chemical warfare amongst microorganisms. The latter substances are closely related.

How does resistance against antimicrobial drugs develop?

As many microorganisms survive by being able to either ignore or render harmless the many toxins (called defensins elsewhere in this website), it is not surprising that the substances chosen and mass produced by humans as antibiotics can also be ignored or rendered harmless by some or many microorganisms.
As these microorganisms grow, evolve or exchange genetic information more and more microorganisms learn this trick and the antibiotic becomes less and less usable.
Some microorganisms that live in optimal conditions (for example hospitals or high density cattle farms) even manage to become resistant against several antibiotics.

Why is this bad?

Microorganism species come and go in the gut on a daily basis as we come into contact with them through for example our food. Most are not harmful (e.g. potential pathogen), while others cause some discomfort before being eliminated by the defense systems against infections.
However if the defense systems are worn down through treatment with some antibiotics that kill many resident microorganisms, or for example disease or major surgery, potential pathogen microorganisms get the opportunity to develop explosively, translocate into the body in high numbers and thereby cause disease and even death.
During the last decades antibiotics have brought help by killing enough potential pathogens the normal defense against infections could handle the remainder. Now assume the potential pathogen is resistant against the antibiotic given to eliminate it. It still will grow to large numbers. Possibly competing microorganisms are sensitive to the antibiotic and die, thereby providing even more opportunities for the potential pathogen to grow. So the wrong antibiotic substance can even make matters worse.

What makes this situation worse?

In order to limit the development of resistance against antibiotics it is important to kill all potential pathogen microorganisms that might become resistant. This requires sufficiently high antimicrobial doses and for enough days to be sure the potential pathogen microorganisms are killed.
So if the dose is too low or the duration is too short, resistance can more easily develop. Also the more often the antibiotics are given the more opportunities microorganisms have chance to learn to become resistant and to spread this ability.

What can we do about it?

There are several things that can be done:

So do not use low maintenance doses for long durations - the surest way to help microorganisms to become resistant.

Why are there no new antibiotics?

Apparently the pharmaceutical industry has decided it makes more business sense to invest in other drugs that have a longer commercial life and run less risk to be rendered useless by opportunistic or careless use. It appears development on new antibiotics has practically stopped since more than a decade.

Are there any alternatives?

A key purpose of this website is to show how the normal defense against infections in all its complexity works. Our current approach is repeating a trick we learned a few decades ago: participate in the chemical warfare amongst microorganisms. Since then we have largely stopped investigating other options. The last few years food substances with healthy microorganisms have become popular. The good news for the companies that sell them is that in order to work - if they work at all - they need to be ingested daily. The aim is to manipulate the microorganism ecosystem.
Another approach developed decades ago is to teach the adaptive immune system to resist hazardous microorganisms by parenteral inoculation. This would allow the potential pathogenic microorganisms to successfully colonize the gut and start mass translocation into the body. There the adaptive immune system moves in and rapidly kills the invaders.
No attempts are made to structurally manipulate the microbial ecosystem, to strengthen either the innate defense system nor the ideotypic defense system.