Healthcare Hygiene magazine November 2019 | Page 9

infection prevention By Wava Truscott, PhD, MBA When Prime Directives Collide: The Survival Wars T he Prime Directive driving all humans is an internal instinct to survive. Throughout the ages, man has struggled and adapted to protect himself, his family, and his tribe. This core drive to survive has advanced weapons for protection, from crushing threats with rocks, to throwing spears, and on to more powerful weapons. To survive weather extremes, man huddled in caves, constructed lean-tos, and moved up to more permanent structures of wood, stone and cement. The same Prime Directive drives microorganisms to adapt or die. However, instead of innovative adaptations requiring thought, bacteria experience genetic mutations that may or may not be helpful. Mutations that protect bacteria enable survival, while mutations that are not sufficiently protective die off with the bacteria. The adaptive capacity of bacteria has been incredibly successful. Most successful mutations are passed on verti- cally from generation to generation in a long looped single chromosome composed of double-stranded DNA residing in the nucleolus of the bacteria. The instructional information is passed primarily during cell division, enabling future progeny to survive in their environment. These traits include such capabilities as biofilm formation for tribe protection, the ability of a small number of bacteria to form one-occupant spores, and the inherited capability that a few bacteria possess to produce small colony variant (SCV) progeny that, in effect, are invisible to the human immune system. Some protective mutations can be transferred horizontally to other bacteria unrelated to the original “mutant.” The genetic instructions are encoded in a much smaller dou- ble-stranded DNA loop, the plasmid. Plasmids can replicate independently producing as many as needed to “share” with other bacteria. Once a bacterium receives a plasmid, it in turn produces replicates to fortify its own protection and potentially to distribute to others. Plasmids are also vertically passed on to progeny during cell division, thus improving the odds of survival for their descendants. Antibiotic resistance genes are very successful muta- tions located on plasmids. The mutations only work on specific antibiotic types and only by specific action modes. There are at least 10 different protection modes that have been successful: Within the bacterial cell itself: 1. Blocks entry of specific antibiotic types trying to enter bacterial cell 2. Flushes the antibiotic out of the bacterial cell before it reaches their targets 3. Produces enzymes that break apart antibiotics before they reach their targets www.healthcarehygienemagazine.com • november 2019 4. Produce antibiotic-modifying enzymes that render the antibiotic ineffective 5. Modify the targets so they cannot be impacted by the antibiotic 6. Make so many clones of the antibiotic targets, that the antibiotic is spent before destroying all the targets Within the group-protective biofilm: 7. Exo-enzymes distributed throughout the biofilm matrix. like land mines in the battlefield, digest specific antibiotic types when contact is made 8. Many bacteria in the center of the biofilm, are altered into persister cells that shut down (hibernate), not allowing anything in – including antibiotics 9. Most biofilm-forming bacteria attract diverse bacte- rial types to increase the odds of biofilm survival through genetically diverse protective adaptations 10. Proximity and purpose of the (a) peripheral bacteria in a biofilm “fortress” makes them the forward perimeter guards. It is there that plasmids for diverse means of protec- tion are most liberally shared. For example, the more means of defeating antibiotics each defender possess, the more effectively broad the antibiotic resistance. Bacteria deeper in the matrix are responsible for (b) harvesting moisture and nutrients, (c) metabolic waste disposal, (d) hibernating as per- sister cells, and (e) transforming into “super surface-grippers.” U.S. Daily Human Cost: Each day, approximately 5,000 Americans acquire a serious antibiotic–resistant infection. Of those, about 63 patients will die and a large percentage of survivors will suffer long term chronic consequences. By 2050, it is projected that untreatable antibiotic infections with overtake cancer as the No. 1 cause of death globally. U.S. Annual Financial Cost: Antibiotic-resistant infections add $20 billion in excess direct healthcare costs and up to $35 billion in additional costs to society for lost productivity. As with any battle, attacking before the enemy can establish a foothold and fortify a reservoir of resistant pathogens is by far the easiest, most effective and least costly means of patient protection. It takes a team to do what’s needed, including infection preventionists, OR and device reprocessing staff, environ- mental services, engineering, and clinicians. Infection preventionists must have help to handle required reports, statistics and trending paperwork so they can be actively on the floors, teaching, advising, admonishing, finding solutions and supporting staff trying to do the right things under pressure. Wava Truscott, PhD, MBA, is principal of Truscott MedSci Associates, LLC. 9