The ‘Golden Age’ of antibiotic use has passed. Alas, the ‘sweet spot’ lasted but 30 years before the problem of antibiotic resistant bacteria began to manifest. Antibiotic resistance is a wonderful example of evolution in action. Bacteria have the ability to multiply rapidly and a single cell can become a billion within a relatively short period. A mutation in a single cell that confers immunity to an antibiotic is all that is required to render the antibiotic ineffective. The myriad of non-resistant bacteria will succumb but the single resistant bacterium will thrive and prosper producing billions of antibiotic resistant offspring. And this process can occur sequentially. Thus, bacteria can become immune to a succession of antibiotic drugs resulting in ‘superbugs’. Imprudent dispensing of antibiotics and the addition of antibiotics to animal feed has exacerbated the problem enabling disease causing bacterial species to become multi-resistant within a relatively short period.
The discovery of penicillin in the 1920s was hailed as a wonder drug, and indeed, antibiotics have saved millions of lives. Prior to 1928, there was little in the way of effective treatment for bacterial infections and a patient’s survival was mainly dependant on how their immune system responded to a microbial insult. Often a person’s immune system was overwhelmed by an infection considered trivial by today’s standards. Between 1935 and 1960 20 new classes of antibiotics were introduced however, in the past 60 years only 6 new antibiotic drugs have been added to the therapeutic repertoire. Our ingenuity in producing new drugs has been exhausted, at least for now. Unfortunately, bacteria are capable of evolving faster than our ability to produce new effective drugs; we are truly entering a post-antibiotic era.
A world without effective antibiotics is going to be a scary place, or is it? Although the scenario appears grim there are viable alternatives. The vaccination of populations against bacterial disease is one possible prophylactic option. As is the case with viral vaccination, an attenuated non-viable form of the pathogenic microbe is given. The patient then develops antibodies which will effectively deal with the bacterial disease if encountered thereafter. Sounds like a plan but there are limitations with this approach. Some bacterial diseases cannot be cultured in the laboratory setting, a necessary precursor to vaccine development. Other species exhibit antigenic variability making an all-encompassing vaccine bothersome or impossible. Another problem concerns the action of the immune system in dealing with bacterial infections. Invariably there is a delay in action allowing initial bacterial growth with the concomitant production of toxins. These toxins may result in organ damage even after the disease organism is contained.
Another approach utilises a specific type of virus called, bacteriophages. Bacteriophages prey on bacteria and have several attractive advantages as an anti-bacterial therapy. Bacteriophages are highly species-specific and therefore other bacterial species are spared including the ‘good’ bacteria normally present in the human body. Conventional antibiotics are not so selective and cause a bacterial wasteland in the body resulting in negative consequences not related to the invading pathogen. Unlike some antibiotics, phage therapy is non-toxic and does not cause the development of life-threatening allergies. A downside to this form of therapy is that bacterial species have evolved mechanisms to mitigate phage infection by the development of an immune system of their own. Interestingly, one of the defence systems (CRSIPR) is being developed by geneticists in the controversial area of genetic engineering. I have posted on this very topic recently. You may want to read about this exciting and potentially troublesome technology, here. One way around the problem may be in the use of bacteriophage derived enzymes rather than the use of the viral particle itself.
There are a number of plant extracts with known antimicrobial properties. They are particularly effective when applied directly to a wound; consider the use of honey in preventing bacterial growth. Currently, the antibacterial properties of essential oils are utilised in a diverse range of commercial products including pesticides, food preservatives, and cosmetics. A mixture of thymol/cinnamaldehyde exerts anti-bacterial properties against disease causing bacteria such as E.coli but spares beneficial bacteria present in the gut of the host animal.
Although our current crop of agents will eventually become ineffective this should not prevent research into the elucidation of novel antibiotic compounds. Reverse genetic engineering of bacterial genomes may help in the identification of vulnerable and essential metabolic pathways to be exploited by designing antagonistic molecules. To be fair, antibiotics are a tough act to follow and it unlikely there will be a single agent or strategy to fully replace antibiotic therapy. A multi-disciplinary approach will be essential, utilising prophylaxis, asepsis, disinfection and the judicious application of biological and manufactured agencies. Or failing this……….. don’t become infected. This brings me swiftly to my own story. Recently, Mrs Saxon received a spider’s bite while attending to the roses. Within a couple of days, my wife developed a life-threatening infection and sepsis necessitating a week in hospital on an antibiotic drip. Initially, the antibiotics used were ineffective and eventually a cocktail of drugs had to be employed to keep the staph infection at bay. Once released from the hospital, a further month of mega antibiotic therapy was required. The infection caused an ulcer requiring surgery to remove skin and bone with subsequent immobilisation of the limb in a cast. All this mayhem caused by an organism a million times smaller than a ferret’s nostril.
"Both the great and the humble are laid low by fever's cold caress"