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The Cancer Journal - Volume 6, Number 2 (March-April 1993)


How to diminish microbial resistance to antibiotics ?

Drug-resistant microbes pose a new threat to our society. Infectious diseases that were prevalent in the Thirties, e.g., pneumonia, meningitis, and typhoid, and virtually disappeared after the discovery of antibiotics, are gradually returning. More and more microbes become resistant to antibiotics. While in 1942 virtually all strains of Staphylococcus aureus worldwide were susceptible to penicillin G, today more than 95% of Staphylococcus aureus worldwide are resistant to penicillin, ampicillin, and anti-pseudomonas penicillins (1). Multi-drug resistance is most pronounced in the recently emerging tubercle bacillus (2). This alarming development was recently reviewed in "Science" (1-5).

Resistance may be acquired in several ways, e.g., chromosomal mutation, inductive expression of a latent chromosomal gene, exchange of genetic material through transformation, and conjugation with plasmid transfer of DNA (1). As the pharmaceutical industry continues developing new antibiotics, more and more microbes become resistant to a variety of drugs (4). After analyzing the biochemical and epidemiological aspects of the problem, experts turn to the medical community with the following advice: physicians should prescribe antimicrobials more selectively, should be taught to prescribe the right antibiotics for a disease, and finish treatment only when microbes were wiped out. Some companies advise "combination therapy", using more than one drug, which may breed more drug-resistant microbes (5). All this may be of no avail since massive doses of antimicrobials are given to livestock.

"Bacteria are cleverer than men!" exclaims one expert (1), highlighting the conceptual bankruptcy of modern microbiology. Nothing in their advice can avert the danger. At best they hope to postpone it. Experts agree that "the solution requires more than scientific breakthroughs" (3), but have little to suggest. They hope to solve the issue by technology, disregarding its biological implications. Microbes may be smarter than microbiologists but have never outsmarted the human organism which learned how to resist them long before microbiology was conceived. True, before the antibiotic era many had died from infectious diseases. On the other hand, many more had survived them.

An infectious disease results from an interaction between microbes and host defense e.g., inflammation or immunity (6). Defense strategies evolved throughout the ages and from generation to generation became more efficient. According to Darwin's theory, today's organisms are equipped with the best strategies to deal with microbes, otherwise they would not have survived. The organism and microbes maintain a delicate balance that is disturbed during infection. Most antibiotics restore the balance by assisting strategies of the organism, and when these fail, e.g., during agranulocytosis or agamma-globulinemia, antibiotics are of no avail. This important aspect of health was forgotten in the wake of the antibiotic era and is regarded as insignificant. A negligence that bred multi-drug resistant microorganisms.

Darwin's law applies also to microbes that continuously improve their defense strategies for dealing with antimicrobial agents. The heavier the selection pressure, the more resistant they get Microbial resistance is an ecological problem that may be averted only by reducing the use of antibiotics. Antibiotics should be reserved only for humans and their administration to livestock, prohibited or at least restricted drastically.

Contrary to the claim of microbiology, bacteria were not created in order to destroy us. Of the 200,000 species of microbes on Earth only 400 are pathogenic. Bacteria are deeply intertwined in the global food chain and it appears that without their active participation in it, life on Earth would not be possible (7). The indiscriminate administration of anhbiotics may threaten also this important task, in the same way as toxic waste does to our environment. In view of their importance to life, we should not wage a war against microorganisms, as the expert suggests (3), but attempt to co-exist with them without endangering our health.

A normal human being hosts about 1.2 kilograms of bacteria (8). The bulk are in the gut lumen, and the rest in the skin, oro-pharynx, and genitalia. Some are potential killers and yet they thrive without harming us. How do we protect ourselves against our own flora and how could medicine apply this protection against more dangerous pathogens? What is the secret of human carriers of pathogens who remain unharmed? Our flora might even protect us against dangerous microbes, e.g., hospital strains, by preventing their colonization in our body. After all, in order to infect us an antibiotic-resistant microbe has to enter a niche in our body that might be already occupied by our own "protective" flora. Such ideas should be explored and considered during antibiotic treatment.

The phenomenon of anti-microbial resistance to chemotherapy is also relevant to cancer chemotherapy. It is assumed that cancer cells will ultimately respond to chemotherapy in the same way as microbes do. Unfortunately each treatment breeds resistant cancer cells, exactly as in bacteria. Oncology should therefore turn its attention to the role of the organism in cancer and stop its indiscriminate prescription of chemical drugs.o

G. Zajicek
e-mail: Gershom@md2.huji.ac.il


1. Neu HC. The crisis in antibiotic resistance. Science 257, 1064-1072, 1992.
2. Bloom BR, Murray CJL. Tuberculosis: Commentary on a re-emerging killer. Science 257, 1056-1063,1992.
3. Koshland Jr. DE. The microbial wars. Science 257, 1021,1992.
4. Cohen ML. Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 257, 1050-1055,1992.
5. Gibbons A. Exploring new strategies to fight drug-resistant microbes. Science 257, 1036-1038,1992.
6. Zajicek G. What is a disease? The Cancer J 4, 296,1991.
7. From Gaia to Selfish Genes. Barlow C. Editor The MIT Press Cambridge MA, 1991.
8. Bocci V. The neglected organ: bacterial flora has a crucial immunostimulatory role. Persp Biol Med 35, 251-260, 1992.