In The Era Of Antibiotics Resistance; Victory or War For Microbes?

Antimicrobial resistance (AMR) is a top global health threat, directly causing roughly 1.27 million deaths and contributing to 4.95 million deaths annually as of 2019. By 2050, deaths are projected to rise to 10 million annually. In the U.S., over 2.8 million resistant infections occur each year according to World Health Organization 

Antibiotic resistance is the ability of a micro-organism to survive and multiply in the presence of antibiotics that will normally inhibit or kill them. 

All antibiotics are not targeted at killing the organism causing illness but some can stop the spread allowing your immune system to fight and protect the body 

Bacteria, Not People, Develop Resistance: It's important to note that antibiotic resistance refers to bacteria, not individuals. When bacteria are exposed to antibiotics, some may survive due to natural mutations. These surviving bacteria can then reproduce, leading to a population that is resistant to the antibiotic. "People don’t develop it, bacteria evolve it."

Agricultural Contribution To Antibiotic Resistance 

Agricultural antibiotic resistance is a major, accelerating global health crisis driven by the overuse of antimicrobials in livestock and crops. It is estimated that 5 million human deaths were associated with bacterial antimicrobial resistance (AMR) worldwide in 2019, with a significant portion linked to agricultural practices.

Global antimicrobial consumption in livestock is estimated to be between 63,000 and over 100,000 tons annually and Global livestock antibiotic consumption is predicted to increase by 8% to 15% by 2030.

China, Brazil, India, the USA, and Australia accounted for 58% of global veterinary antimicrobial use in 2020 and the average annual consumption is estimated at 172 mg/kg for pigs, 148 mg/kg for chicken, and 45 mg/kg for cattle.

“If bacteria keep eventually developing resistance to antibiotics, will there come a point in time when we are completely unable to treat an illness? Or, will we continue to tweak antibiotics so they kill the evolved bacteria, then tweak them again so they kill the next endlessly ? I read someone say that evolution always has a cost to it, in that sense it is possible that eventually bacteria evolution loops back to old antibiotics being useful again?”

A fundamental question that rise in the mind of the people…the questions are sprouting more than the planting of the solution 

Sources of Antibiotics 

Though antibiotics are classified to be 

• Natural 
• Semisynthetic 
• Synthetic 

These classification is base on how they extract and manufacture the antibiotics 

Natural antibiotics: they are produced from micro-organism directly; example 

-Streptomyces grieus produces streptomycin 

-Amycolatopsis orientalis (formerly Streptomyces orientalis): Source of Vancomycin

-Micromonospora purpurea: Source of Gentamicin.

Semi-synthetic Antibiotics: They are chemically modified natural antibiotics… Here, it’s just about adding or removing a core substance to enhance its effectiveness. Example;Amoxicillin, Methicillin and Ampicillin. 

Synthetic Antibiotics: these classes of antibiotics are completely made in the laboratory outside plant and microbial origin.Examples include sulfonamide, fluoroquinolones. 

Primary Sources of Antibiotic Resistance

The sources of antibiotics resistance have been traced to some animals such as 

Pigs and Poultry (Highest Risk): 

These animals are the primary drivers of AMR in human infections. Research indicates they act as reservoirs for high-consequence bacteria like Salmonella and E. coli. Colistin Resistance: The spread of mcr gene which confers resistance to colistin—a "last-resort" human antibiotic—has been traced from pigs and calves to humans.

Tetracycline/Beta-lactam Resistance: High volumes of these antibiotics are used in pig/poultry feed, resulting in widespread multidrug resistance.

Cattle: 

Cattle, particularly in dairy, are significant sources of E. coli and Salmonella that carry resistance genes to third-generation cephalosporins.

Companion Animals (Pets): 

Dogs and cats are emerging as significant sources of AMR pathogens in households, such as Staphylococcus pseudintermedius (MRSP) and ESBL-producing E. coli, which can be transferred through close contact

Mechanism of resistance in human 

⁠Biofilms: 

Organisms can become resistant to antibiotics by forming biofilms, which are protective matrices that shield them from the effects of antibiotics 

Biofilms are highly structured, cooperative communities of microorganisms (including bacteria, fungi, algae, and protozoa) that attach to living or non-living surfaces and enclose themselves within a self-produced matrix of Extracellular Polymeric Substances (EPS)… just organisms forming colonies on a surface posing threat to human death.

According to science direct; between 59% and 100% of microbial isolates from infant catheters are capable of forming biofilms and up to 87% of these isolates are classified as "strong" biofilm producers, particularly Pseudomonas aeruginosa and Klebsiella pneumoniae the rate of colonization is approximately 17.9% to 47% of intravenous catheters (IVCs) in neonates show microbial colonization

Quite a significant number of organism resists antibiotics through this mechanism 

Alteration of the target site 

Alteration of the target site is a common antibiotic resistance mechanism where bacteria modify the target molecule—often through genetic mutation or enzymatic changes—to prevent the drug from binding effectively. This structural alteration significantly reduces the antibiotic's affinity for the target, allowing the bacteria to survive while maintaining normal cellular function. 

Reduced permeability

Organism uses a component of their wall to prevent the entrance of antibiotics and this is classical of certain organism such as Escherichia coli and staphylococcus aureus

Efflux pump

Efflux pumps are a major mechanism of multi-drug resistance (MDR) in pathogenic bacteria, with approximately 5% - 10% of all bacterial genes involved in transport, including those encoding pumps. These systems, particularly in Gram-negative bacteria, contribute to resistance by over 70% against multiple antibiotic classes according to Oxford academic

Alternatives and Solutions

• ⁠Phage Therapy: Bacteriophages, viruses that infect and kill bacteria, are a promising alternative. They can evolve alongside bacteria, potentially overcoming resistance. "Phages can evolve and adapt to overcome bacterial resistance; antibacterial drugs cannot.

• ⁠New Antibiotics: Developing new antibiotics is crucial, but the pipeline has been drying up due to lack of profitability and investment. "We haven’t been able to make a new antibiotic for deca

• ⁠Combination Therapies: Using multiple antibiotics or combining them with other drugs that inhibit resistance mechanisms can be effective. "You can use antibiotics combined with drugs that inhibit enzymes that degrade the antibiotic.

⁠Improved Hygiene and Infection Control: Simple measures like handwashing, using protective equipment, and maintaining clean environments can reduce the spread of resistant bacteria. "Clean water, soap, sunshine, and safe distances do a lot to keep bacteria away when medicine is not available.

Insight…

Antibiotic-resistant bacterial infections could take the lives of more than 39 million people by 2050 unless action is taken to improve healthcare quality, prevent infections, reduce inappropriate antibiotic use, and develop new antibiotics, according to a landmark new study published this week in The Lancet.

What’s next?…