REVIEWS
PHARMACEUTICALS Antibiotics alert
Sally Davies, England’s chief medical officer, warned of the ‘catastrophe of antibiotic resistance’ in her 2016 annual report. She emphasised that governments, the World Health Organization (WHO) and the G8 countries need to take the threat seriously. For over 80 years, we have
enjoyed the protection afforded by a multitude of antimicrobial drugs, starting with the synthetic sulfonamides in the mid-1930s, through the naturally derived antibiotics like penicillins, cephalosporins, tetracyclines, aminoglycosides and macrolides, to the synthetic fluoroquinolones and oxazolidinones. These latter two classes were discovered in the 1970s and 1980s and no new classes of antimicrobials have been discovered since. Worryingly, strains of bacteria that are resistant to these antimicrobials are now circulating. In hindsight, there was a clear
inevitability of this disaster occurring. Bacteria have been evolving for around 3.5bn years, and for much of this time in competition with other microorganisms and moulds from which most of our antibiotics have been derived. Bacteria can reproduce every half an hour or so with frequent opportunities for DNA replication errors and consequent rare but ultimately useful mutations. These result in the production of enzymes that destroy antibiotics, produce changes in the architecture of the bacterial cell wall or mechanisms for the expulsion of antibiotics from the cell.
Unwittingly, we have facilitated
the evolution of these resistance mechanisms by over-prescribing antibiotics and using them in excessive amounts in agriculture. In Europe, 3400t/year are used by humans and 8100t for animal production; in the US, 70% of all use is for animal production! So why isn’t the pharmaceutical
industry working frantically to solve the problem? First, there is little profit to be made since patients typically recover within a week of treatment, so there is no need for long-term drug use as with heart
disease or cancer. Secondly, it has proved difficult to identify new targets for drug attack although there is increasing interest in the bacteriophages, which are virus-like and specific for bacterial destruction. There is certainly a need for new
research. The WHO estimated that 96m people were ill with TB in 2014, and 0.5m of these had multiple drug- resistant disease. And, as patients need longer hospital stays during which they are treated with ever more exotic antibiotics, the chances of healthcare-associated infections (HCAI) are increasing. Currently around 40,000 people in Europe and 100,000 in the US die each year from HCAI.
This is not the first book to deal with antibiotic resistance: The coming plague by Laurie Garrrett and my own Life saving drugs both present the science for the general reader. Bowater’s book is both wide-ranging and timely. She sets the scene by reminding us that our reliance on antibiotics has been compromised not only by the emergence of resistant strains of bacteria, but also by the sudden appearance of new bacteria-induced infections like Legionnaire’s disease and the tick- borne Lyme disease. The recent rise of the bacterial pathogen Clostridium difficile in hospital patients, who have been treated with a cocktail of potent antibiotics, is especially worrying. Despite partial success with the drugs vancomycin and metronidazole, around 29,000 patients die each year in North America and a similar number in Western Europe. Early chapters include good
historical reviews of Pasteur’s and Koch’s work in the 19th century, and the discovery of penicillins and cephalsporins and a plethora of antibiotics from Streptomyces moulds in the mid-20th century. A discussion of microbial make-up and the targets for antibiotic attack is particularly good and this leads on to the various mechanisms of resistance and modes of resistance transfer via plasmids, transposons and transduction. The pharmaceutical industry
has strived against these amazingly inventive foes with a combination
The microbes fight back
Author Laura Bowater
Publisher RSC Publishing
Pages 289 Price £21.99
ISBN 978-1-78262- 167-6
Reviewer John Mann is emeritus professor of chemistry at Queen’s University Belfast, UK
of computer modelling-driven drug design and high throughput anti-bacterial screening, but with little to show for a vast effort and the expenditure of billions of dollars. National governments and international agencies like WHO have finally declared a state of international emergency, and former US president Barrack Obama led the way with his National Action Plan in 2014. The pharmaceutical companies will be encouraged to renew their efforts through a mixture of financial incentives and the promise of extended patent lives for new antibacterials. There are a few glimmers of hope. A novel natural product teixobactin has been isolated from a soil bacterium and is displaying exciting antibacterial activity. However, 10,000 soil isolates were studied to reveal this one useful product. A cheaper, totally synthetic product is represented by the drug ridinilazole, which has potency and selectivity against C. difficile and is currently undergoing Phase 3 clinical evaluation. These are but two promising leads, and there is no room for complacency in the fight against bacteria. Bowden’s book does an excellent job of alerting us to this alarming situation.
08 | 2016 39
LEWIS HOUGHTON/SCIENCE PHOTO LIBRARY
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52
