We might feel like we are on the winning side of the battle against multi-resistant organisms but surely are on the verge of losing this war!
Worldwide, antibacterial resistance has increased drastically over the past few years and is currently acknowledged as a major medical challenge in most healthcare settings.
Throughout history, there has been a continual battle between humans and the multitude of microorganisms that cause infection and diseases.
Antimicrobial resistance
The resistance of a microorganism to an antimicrobial medicine to which it was originally sensitive to. Resistant organisms (including bacteria, fungi, viruses, parasites etc.) are able to withstand attack by antimicrobial medicine such as antibiotics, antifungals, antivirals and antimalarials.
Multi drug resistance (MDR)
Having acquired non susceptibility (resistance) to at least one agent in three or more antimicrobial categories.
Origin of resistance
Bacterial resistance to antimicrobial agents may be intrinsic or acquired.
Intrinsic resistance
The type of resistance which is naturally coded and expressed by all (or almost all) strains of that particular bacterial species. An example of intrinsic resistance is the natural resistance of anaerobics to aminoglycosides and gram negative bacteria against Vancomycin. Another example is the resistance of Mycoplasma species to B-lactams antibiotics, due to their lack of cell wall and pleomorphic characters.
Acquired resistance
Acquired resistance is said to occur when a particular microorganism obtains the ability to resist the activity of a particular antimicrobial agent to which it had previous susceptibility to.
Types of mutation
- Point mutation (change in single base pair in the DNA)
- Substitution (replacement of an original base pair or sequence of base pair by another, may be transition or transversion)
- Deletion
- Insertion
- Silent mutation.
Major biological mechanisms of antimicrobial resistance
Whichever way a gene is transferred to a bacterium, the development of antibiotic resistance occurs when the gene is able to express itself and produce a tangible biological effect resulting in the loss of activity of the antibiotic.
- Decreased uptake (impermeability) and increased efflux of drug from the microbial cell.
- Expression of resistant genes that code for an altered version of the substrate to which the antimicrobial agent binds
- Covalent modification of the antimicrobial drug molecule which inactivates its antimicrobial activity
- Increase production of competitive inhibitors
- Drug tolerance of metabolically inactive persisters
- Biofilm
- Swarming
Factors that promote bacterial resistance
- Suboptimal use of antimicrobials for prophylaxis and treatment of infection.
- Noncompliance with infection control practices
- Prolonged hospitalization, increased number and duration of intensive care unit stays, multiple comorbidities in hospitalized patient
- Increased use of invasive devices and catheters
Overcoming Bacterial Resistance: Nanotechnology as a therapeutic tool to combat microbial resistance
Consequently, there is a desperate need of developing new therapeutic methodologies. Nanotechnology offers opportunities to re-explore the biological effects of already known antimicrobial compounds, such as antibiotics, by manipulating their size to change their effect. We must aim to consider the antimicrobial resistance as a serious global health threat, clarify microbial drug resistance mechanisms and present evidence on how nanotechnology should be considered a tool against this concern.
A broad range of nano-platforms have been designed to overcome the unfavorable physicochemical properties and the deficient local bioavailability of several existing antibiotics, thereby eventually improving their therapeutic features along with decelerating the emergence of drug resistance. Additionally, overcoming antibiotic resistance has also been achieved by co-encapsulating therapeutic combinations in a single nanocarrier formulation, in which a synergistic antimicrobial effect has strengthened therapeutic efficacy.
Nevertheless, despite these favorable preclinical results, sundry challenges remain for clinical exploitation of nanocarrier-based antibiotic delivery strategies. The safety of nanomaterials in the human body is a major bulwark to the clinical use of these dosage forms.
On the whole, with the continual advances in drug delivery and antibiotic discovery, we could expect that the nanocarrier-based antibiotic formulation would be misused as a common therapeutic practice subsequently, delivering consequential contributions for fighting bacterial infection.
Antimicrobial resistance, being one of the greatest threats to global health, warrants continued attempts in antibiotic drug discovery which play a pivotal role. These solutions alone probably would not be enough to get the seal on the required level of infection control in the future. New strategies and innovative models are needed to preserve the effectiveness of antimicrobials. Through optimized access of antibiotics to their sites of action, nanocarriers can unlock the full potential of the antibiotic cargoes, extend the antimicrobial spectrum, and take the edge off the required dose of antibiotics while preserving efficacy.
Efforts to create laboratory infrastructure is paramount to addressing the colossal and universal burden of AMR, by improving the management of individual patients and the quality of data in local and global AMR surveillance and bolstering national AMR plans of action. Enhanced infrastructure would also expand AMR research in the future to access the indirect effects of AMR, such as the effect of AMR on perioperative prophylaxis or prophylaxis of infections in transplant recipients, the effects of AMR on transmission, the impact and prevalence of specific variants evaluated through genotypic epidemiology and more. Identifying strategies that work to reduce the burden of bacterial AMR—either across a wide range of settings or those that are specifically tailored to the resources available and leading pathogen–drug combinations in a particular setting—is an urgent priority.