Inappropriate use of antibiotics promotes the emergence of multidrug-resistant pathogens, such as Vancomycin-resistant Enterococci (VRE), Methicillin-resistant Staphylococcus aureus (MRSA), and Multidrug-resistant (MDR) Enterobacteriaceae, which justifies the search for alternative clinical approaches. Indeed, increasing antibiotic resistance (AR) is partly an economic problem and is considered one of the most important threats to human health according to the World Health Organization. Noticeably, dangers of AR are highlighted by a recently study that has reported a new strain of Escherichia coli (“superbug”) that is resistant to the antibiotic colistin, the antibiotic of last resort. “Although in the past there were other reports of this particular case of AR, this is the first appearance of what is called plasma-mediated colistin resistance by which a gene called mcr-1 that enables bacteria to be resistant to colistin is carried on a piece of DNA called a plasmid that can be rapidly exchanged between organisms”, said Sarh Fortune, professor of immunology and infectious diseases at Harvard Chan School.
A recent study, led by Dr. Paul E. Turner from the Department of Ecology and Evolutionary Biology at Yale University, New Haven (USA), has found that phage therapy may constitute a useful antibacterial strategy that can reduce the incidence of antibiotic resistant infections. The researchers have found that a lytic bacteriophage – called OMKO1 and from the family Myoviridae – could be used in conjunction with antibiotics in treating infection with Pseudomonas aeruginosa, a common multi-drug resistant bacterial pathogen that can lethally infect people with a compromised immune system. The virus acts by attaching to the cell membrane where bacteria pump out antibiotics, a system involved in AR. As a result, this pumping mechanism becomes less efficient and bacteria are more susceptible to antibiotics. “This virus could help preserve our limited antibiotic arsenal in combating deadly bacteria”, said Dr. Turner.
Replacement of depleted microbes through probiotics to fight antibiotic-resistant bacteria is an emerging field. In another recent review, Dr. Eric G. Pamer highlighted that next-generation probiotics from gut commensals are being developed to re-establish or enhance resistance against colonization and invasion by pathogens and thus would help fight AR. Bacterial species that constitute a small fraction of the commensal microbiota have been recently characterized and can provide colonization resistance against many of the most threatening antibiotic-resistant pathogens. Although it is an exciting novel strategy, currently the researchers are only in the discovery phase and clinical studies of safety and effectiveness are needed so the U.S. Food and Drug Administration (FDA) can regulate their progression to the clinic (health claims related to treating or preventing a disease).
It is not clear to what extent probiotics directly reduce the spread of AR, but maintaining a balanced gut microbiota during antibiotic treatment is considered a useful tool for preventing AR. According to Ouwehand and colleagues, the role of probiotics in reducing AR is based on the fact that probiotics are specifically selected to not carry transferable AR; they have been observed to reduce the risk of certain infectious diseases (such as antibiotic-associated diarrhoea) and thus may reduce the need of antibiotics for secondary infections that are (paradoxically) associated with antibiotic treatment.
In conclusion, current antibiotic use puts patients at risk for various disease states. Several potential strategies are at various states of clinical development, which in the future will allow novel approaches to substitute or complement antibiotic therapies. Further research is needed in order to assess the impact of such strategies in clinical practice.
Chan BK, Sistrom M, Wertz JE, Kortright KE, Narayan D, Turner PE. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci Rep. 2016. doi:10.1038/srep26717.
Ouwehand AC, Forssten S, Hibberd AA, Lyra A, Stahl B. Probiotic approach to prevent antibiotic resistance. Ann Med. 2016; 48(4):246-55. doi:10.3109/07853890.2016.1161232.
McGann P, Snesrud E, Maybank R, Corey B. Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First report of mcr-1 in the USA. Antimicrobial Agents and Chemotherapy. 2016; doi: 10.1128/AAC.01103-16
Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science. 2016; 352(6285):535-8. doi:10.1126/science.aad9382.
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