Title: Surface evaluation of curing potentials of homodium bromide, acridine orange, thioridaxine, elevated temperature, ascorbic acid and plant products (Garlic, Apple cider vinegar) on selected multidrug resistant bacterial pathogens
Microbial infections are presently posing major health threats worldwide and this may be because a number of infections such as urinary tract infections, pneumonia, tuberculosis, gonorrhea, meningitis, pharyngitis, salmonellosis etc are becoming more difficult to treat largely owing to antimicrobial (antibiotic) resistance (AMR). The phenomenon of AMR is not new as antibiotic resistance genes (ARGs) have evolved over millions of years. Epidemiological studies have suggested that ARGs emerge in microbial populations within 5years of the therapeutic introduction of an antibiotic.Causes of AMR include global trade, foods, medical tourism, unregulated use of antibiotics in animal feeds, drug under dosage, self-medication, administration of expired drugs etc. Increased rates of morbidity/mortality, longer treatment duration and higher hospitalization costs are some of the effects of AMR. Multidrug resistant bacterial pathogens resist antibiotics by means of antimicrobial resistance genes (ARGs) which they carry on mobile genetic elements (MGEs) such as plasmids, transposons, integrons, phages etc and the mechanism of transfer is by spontaneous mutation or horizontal gene transfer.One technique used to control antimicrobial resistance is through the removal of MGEs (especially plasmids) from the genome of MDR pathogens. The removal of plasmids from the genomes of antimicrobial resistant pathogens is called CURING. Curing is used to describe the process of removing ARGs from bacterial populations and the compounds used to achieve this are called CURING AGENTS. Based on the fact that most ARGs and virulence factors are located on plasmids, the term “Curing” has been associated with the removal of plasmids. Notable curing agents include detergents, ethidium bromide, acridine orange, acriflavine etc.We have used Homodium bromide dilutions of 0.35, 0.45, 0.75, 0.85 and 0.95µgml to enhance antibiotic sensitivity of a multidrug resistant strain of Escherichia coli to some commonly used antibiotics. In the report, each of the dilutions, reduced the MIC of gentamicin by 4-fold, 2-fold, 2-fold, 4-fold, 4-fold, respectively. In the study, only 0.35, 0.45 0.85 and 0.95µgml dilutions recorded significant (P?0.05) resistance losses of 171.7%, 138.9%, 57.4% and 50.8% respectively. In a related study, we have used 0.35, 0.55, 0.75 and 0.95µgml dilutions of acridine orange to induce 60.0%, 52.2% and 52.7% sensitivity enhancement of a Staphylococcus aureus strain respectively to erythromycin. Doses of thioridaxine have been used also to enhance antibiotic sensitivity in a multidrug resistant (MDR) Escherichia coli uropathogen. After treatment with 2000-2240µg/ml dilutions of thioridaxine, ≤50.0% resistance loss was recorded for 2040 µgml, 2160 µgml and 2240µgml dilutions. Moreover, we have used increasing (or elevated) temperatures of 30oC, 35oC, 40oC and 45oC to remove plasmids of Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus pathogens at Nutrient broth dilutions of 10-5, 10-6 and 10-7 each of the pathogens were subjected to each temperature for 18hr. Ascorbic acid (AA) or vitamin C curing potential has been tested on fifteen uropathogen strains of Escherichia coli of which 100-1000µg/ml ascorbic acid dilutions were tested on the uropathogen. We have also tested the curing potential of Ginger (Allium sativum) on a multidrug resistant strain of Klebsiella spp isolated from midstream urine of a UTI patient. And we have tested the curing potential of apple cider vinegar on three urine pathogens (ie Escherichia coli, Pseudomonas aeruginosa and Klebsiella spp) using Apple cider vinegar dilutions of 50-600µg/ml. Patients diagnosed with MDR bacterial infections may be administered sterile scaled up dilutions (of the various agents stated) standard human doses synergistically with any of the selected antibiotics used in the various studies to eliminate drug resistance genes or plasmids thus enhancing treatment outcome. The safety of the stated dilutions (apart from ascorbic acid, ginger and apple cider vinegar) that recorded significant resistance losses should however be ascertained first by carrying out cytotoxicity and toxicological tests on them.
Audience Take Away Notes :
1.Drug abuse (use of drugs without a Doctor’s prescription) can cause antimicrobial (antibiotic) resistance (AMR).
2.Need to insist on having a treatment (antibiotic) prescription based on an antibiotic sensitivity testing (AST) or antibiogram report of a diagnostic test you carried out.
3.Need to complete a full dose of any prescribed antibiotic treatment plan. Under dosage can cause AMR.
4 Self-medication (also, a form of drug abuse) can cause AMR.
5.Administration or in-take of expired drugs can cause AMR. Therefore this need to purchase antibiotics or any other drug(s) from Government approved health facilities.
6.Owners of pharmaceutical companies in the audience can explore and scale up curing agents dilutions (doses) highlighted in the various studies that recorded significant (P?0.05) and very significant (P?0.01) sensitivity improvements or resistance losses after their use or treatment on the MDR pathogens stated. They can develop (formulate) a technique of combining any of these agents (particularly the non-toxic agents and plant products) into the formulation of old drugs like gentamicin, the floroquinolones (eg ciprofloxacin, ofloxacin), some cephalosporins such as ceftazidime, chloramphenicol, the macrolide-erythromycin, urinary antiseptic-nitrofurantoin etc.It is our projection that with a drug formulation containing sub-lethal, non-toxic concentrations of such curing agents combined with the active ingredient of the antibiotic, when taken orally, whereas the agent will remove plasmid (partially or wholly), the antibiotic will inhibit (if bacteriostatic) or kill (if bacteriocidal) the pathogen by selectively destroying the target site (eg chloramphenicol kills bacterial pathogens by attacking their ribosomes thereby stopping protein synthesis in them. That way, the stated antibiotic(s) may work faster and more potently. It is also our projection that as a result, most of the commonly used antibiotics (which had lost their effectiveness and potency) can be RECLAIMED