Editorials

Antimicrobial resistance: bacteria on the defence

Resistance stems from misguided efforts to try to sterilise our environment 

Bacterial resistance to multiple antibiotics characterises the present decade. Finding organisms insensitive to over 10 different antibiotics is not unusual. Although most of the hardier organisms are present in hospitals, strains of multidrug resistant bacteria, such as Streptococcus pneumoniae, Mycobacterium tuberculosis, and Escherichia coli, also cause serious community acquired infections. Moreover, resistant bacteria from hospitals can be introduced into the community via the estimated 5% of patients discharged for continued treatment at hometaking with them multidrug resistant Staphylococcus aureus and vancomycin resistant enterococci. Since about half of antibiotic usage in the developed world (and perhaps more in the developing world) is inappropriate, there is a certain optimism that we can reverse the resistance problem if we improve use and thus return to an environment populated with susceptible strains.

To understand resistance, imagine being a bacterium in a world bombarded with antimicrobials. Living in a human, you would face antibiotics being taken for routine infections and for non-threatening conditions like acne. As a susceptible strain you have to acquire a survival mechanism. This is not too difficult, as your resistant counterparts, though less common, are very willing to share their antibiotic fighting strategies with you. Armed with their donated plasmids and transposons, you survive the continuous onslaught of antimicrobials. You may sustain a mutation, rendering the antibiotic target within you resistant. Your progeny bearing the mutation survive along with you, while your sensitive counterparts succumb and diminish or vanish. With any one or more of these new defence mechanisms, you are equipped to survive when introduced to new human hosts.

Should you happen to live in an animal host you face the same onslaught since antibiotics are used heavily in animal husbandry, both as growth enhancers and in treatmentand under this chronic selection pressure you enhance your resistance capabilities. In the United States you may readily become resistant to the ubiquitously used penicillins and tetracyclines. Elsewhere you will probably be confronted with growth promoters unique to the farm, such as avoparcin or virginiamycin.¹ These drugs, though not used in humans, are closely related to human therapeutic drug families, such as vancomycin and streptogramins. You might face fluoroquinolones used to treat animals, a practice which has led to the emergence of quinolone resistance in organisms like E coli, Salmonella spp, and Campylobacter spp. ^{1 2} As you make your way through the food chain back to a human host you carry the trademark of your journey through the animal hostmultidrug resistance.

Or perhaps you have come into the home by way of a food crop. In that environment, too, you have undergone the selective grooming afforded by copious amounts of antimicrobials applied as pesticides. Now in the home, along with the myriad other natural flora found there, you encounter the subtle inhibitory effects exerted by antimicrobials impregnated into soaps, lotions, dishwashing liquids, plastics, and other products.³ These agents, along with disinfectants, exert their own subtle effects to further mould hardy "survivors" into a population that far outnumbers its defenceless predecessors.

You may perhaps find yourself living in yet another hostile environmentthe hospital. Armed with your multidefence mechanisms derived from human, animal, or foodcrop hosts, you are not only well equipped to ward off the attacks of newer and more powerful drugs, but may also share your well developed arsenal with other unarmed, potentially infectious, travelling companions. As such, you have helped create some of today's most resistant and feared pathogens.

The above scenario portrays the multiple and cumulative impacts of antimicrobial agents on the bacterial world. The message is clearwe are using too many antimicrobial drugs for the wrong reasons. Each use can contribute to an altered microbial ecology.

Studies of newly emerging resistance show that resistance in bacteria, as in cancer, arises in steps progressing from low level to high level, unless a plasmid is acquired on which full blown resistance is already present. The initial penicillin resistant pneumococci appeared with slightly decreased susceptibility to the antibiotic but over time evolved high level resistance. Penicillin and tetracycline resistance among gonococci emerged in a similar way. The phenomenon has also been observed with quinolone resistant E coli, where multiple steps are required to reach a clinically relevant level of resistance.⁴ Currently, we are witnessing the same phenomenon with chromosomally mediated resistance to vancomycin in S aureus.⁵ Decreased drug susceptibility should be a warning to change antibiotic use to diminish selection for resistance.

Globally we need to look at how antibiotics are used and where resistant strains reside, since these organisms can move easily between countries. As importantly, we need to look at the ecology in generalthe kinds of resistances in so called reservoirs, the commensal or non-clinical bacteria. They will tell us where the next resistance problem will arise and also where antibiotic selection pressure for resistance is high. Importantly, it may not be the antibiotic itself, but other compounds, that exert the selective force. Heavy metals, disinfectants, antibacterials, and antimicrobialsall can select for different kinds of bacteria, including those resistant to lifesaving antibiotics. ^{3 6}

If a single point can be derived from our understanding of antibiotic resistance, it is the ecological nature of the problem. To this can be added the genetic fluidity of the bacteria. The difficulties we face today derive from misguided efforts to try to sterilise our environment by indiscriminately destroying bacteria when we should reserve our killing capabilities for cases when health is threatened by infectious strains. We should act now to restore and maintain the healthy balanced microbiology of the pre-antibiotic erathat is, one populated by a predominantly susceptible flora.