Saturday 27 April 2019

Antibiotic Resistance of Doom


 
How many microbes can be fitted on a ferret's nostril?
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. 

Lunar Lander

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" 
       
Mrs Saxon on the mend
       
    

5 comments:

  1. Glad she's better. Just a bloody spider!

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    1. Yes. The bite introduced the staph bacteria into the wound. The staph species is a normal part of the flora on skin. Unfortunately, Mrs S has a severe autoimmune condition (RA) requiring drugs which suppress the immune system. Therefore she is exquisitely sensitive to infection and heals poorly. Poor thing has had over 20 operations in 25 years and has had to put with my peculiar brand of madness. Must be love, I suppose. Thanks for your consideration.

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  2. I feel for Mrs S: not on the grounds of who her spouse is (she's got a black country lad - can't get better than that) but on the grounds that since I was 14, I have had psoriasis, and at around 24 or 25 I was diagnosed with psoriatic arthritis. Both are thought to be a problem with the autoimmune system, but luckily my psoriasis is comparitively mild although the arthritis is sometimes a complete aggravation of the anal orifice! Speaking of said orifice I was very recently referred to the local hospital for a full colonoscopy procedure. This filled me with great trepidation, having visions of 1200 feet of firehose being forcibly shoved where the sun don't shine - and the 'clearing laxative' taken the day before can only be descibed as having a nuclear effect. Still, it was nothing like as bad as I feared and I must be one of the few who've observed their own innards (including polyp removal & cauterising) on a large full colour screen while it was happening. Biopsies proved a) the polyps were benign, and b) I am now the proud sufferer from collagenous colitis - thought to possibly yet another autoimmune misbehaviour! Still, being a few months from my 70th I suppose these things are an inevitable part of life's rich tapestry and overall I am not facing anything like the problems your poor SWMBO has to put up with. My body IS a temple - unfortunately it resembles the current state of a Minoan temple...

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  3. Yes Ted, life can be a pile of poo sometimes, but we keep plodding on despite the smell. Sorry to hear about your particular crap pile. I bagged Mrs S on one of my foraging trips to Brumagem. And let us be honest, not much good comes from this hulking shit hole. But now and again, if you are prepared to get your hands dirty, you can find nuggets of gold.

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