Antibiotic Resistance PDF

Antibiotic Resistance Dr. ABDULRAHMAN ALSULTAN 18 / 11 / 2024  Learning Objectives 1. The history of antibiotics and resistance 2. How antimicrobial resistance emerge 3. Mechanism of antibiotic resistance [5 important mechanisms] 4. Acquisition “origin” of antibiot...

Antibiotic Resistance Dr. ABDULRAHMAN ALSULTAN 18 / 11 / 2024  Learning Objectives 1. The history of antibiotics and resistance 2. How antimicrobial resistance emerge 3. Mechanism of antibiotic resistance [5 important mechanisms] 4. Acquisition “origin” of antibiotic resistance 5. Threat and consequences of antibiotic resistance 6. Multidrug resistant organisms )MDR) with examples of organisms of concern 7. How antibiotic resistance can be overcome. https://www.pharmamicroresources.com/2019/04/advances-in-antimicrobial-research.html  Introduction The development of modern antibiotics can be traced to a few individuals One of the first is Louis Pasteur who in 1877 noticed that disease causing Anthrax bacteria could be inhibited by Saprophytic bacteria He and his research associates were able to show that Large amounts of Anthrax bacilli did not lead to adverse effects when given to animals when given with Saprophytic bacteria. In 1928, a chance event by Alexander Fleming in the discovery of Penicillin in a London laboratory changed the course of medicine. An agar plate of an invading fungus on which bacteria could not grow  History of antibiotics  The mold/fungus was identified to belong to the Genus Penicillium  He published his findings in 1929, however, he did not live to purify the end product  In 1939 a group of researchers head by Dr. Chain successfully purified Penicillin the extract of mold  In 1940, results from 1st prescription of antibiotics during the 2nd world war on wounded soldiers, penicillin was the drug of choice Fleming, Chain and Florey were awarded the 1945 Nobel price in Medicine and physiology. They published their findings which they called “miracle” in Lancet journal  Question 1 In which of the listed years was penicillin discovered A.1925 B. 1928 C. 1940 D. 1929 The answer B. 1928  History of antibiotics Penicillin was subsequently isolated from other micro-organisms Leading to the term “antibiotics” By the 1940s and 1950s, other antibiotics e.g., Streptomycin, Chloramphenicol, Erythromycin, Vancomycin etc. By the 1950s, the advancements made with Penicillin were threatened β-lactams were produced to prevent this threat But in 1962, the 1st case of Methicillin resistant Staphylococcus aureus [MRSA] was reported in the UK And in 1968, in the USA In 1972, vancomycin was presented to clinicians for the treatment of MRSA However, by 1970s an early 1980, Vancomycin resistant Staphylococci were reported  Intrinsic Resistance  Naturally resistance by some bacteria to antibiotics e.g., Proteus species and colistin antibiotic  Either through the following mechanisms  Absence of cell wall, exhibited by innate [natural without any prior exposure] resistance to penicillins  Mechanism of antimicrobial resistance impermeability changes (1) impermeability changes in the cell membrane of bacteria by the modification of cell wall protein This limits the amount of antimicrobial passage into the bacterium. E.g. Staphylococcus aureus produces a thickened cell wall This makes it difficult for vancomycin to enter bacterium Intrinsic Resistance 2: Enzymatic inactivation  By the inactivation of the antibiotic e.g. [Cephalosporinase in Klebsiella] the mechanism of enzyme production  By which Gram positive bacteria are resistant to β-lactams The bacteria produces enzymes that breaks down the drug Such as in the case of Methicillin resistance Staphylococcus aureus [MRSA]  Mechanism of antimicrobial resistance active efflux 3  By active efflux of the antimicrobial , that is the pumping out of antibiotics by transport proteins e.g., porins or glycoproteins in the bacteria cell like mechanism of resistance to the tetracyclines.  Presence of innate efflux pump; leading to either blockage of antibiotics entering the cells or exporting the antibiotic out of the cell.  Thus, not achieving adequate concentration levels e.g. [Pseudomonas aeruginosa and Escherichia coil]  Mechanism of antimicrobial resistance 4 By permeability The limiting of the uptake of the antimicrobial, e.g., the LPS layer of the Gram-negative bacteria in escherichia coli Which creates a barrier to some molecules also, there is modification of Porins of the cell membrane  Mechanism of antimicrobial resistance 5 by the modification of the target site of the drug e.g., Staphylococcus aureus and penicillin The antibiotic binds to penicillin binding protein [PBPs] which is the target site in the bacteria. Acquisition origin of antibiotic resistance  Threat and the consequences of antibiotic resistance  There is an increase in number of bacteria resistant to antibiotics , 80% of Gonorrhoeal infections are resistant to antibiotics  While about 440,000 new cases of drug resistant bacteria are reported annually Fear of the world returning to “post-antibiotic era”  A simple scratched knee infection could kill the patient Or  A simple hip replacement surgery could lead to 1 in 6 deaths  Also, the cost of treating patients could double  consequences of antibiotic resistance  Infected patients will not be adequately treated  Thus, delays could lead delay in getting the right treatment  prolong hospital stays  Complications  Greater disabilities  and death from very minor infections  Multidrug resistance organism of concern Mycobacterium tuberculosis Resistant to four or more frontline antibiotics, therefore, termed as Extensive Drug resistant [XDR] Of recent, strains totally resistant to all antibiotics [TDR] Vancomycin resistant Enterococci [VRE] Plays a role in hematology-oncology patients Other multidrug resistant [MDR] Gram negative bacteria include Acinetobacter species, Enterobacteria, Pseudomonas aeruginosa  Multidrug resistance organisms of concern Pseudomonas aeruginosa: associated with burn wounds Now a major nosocomial threat of great concern to cystic fibrosis patient with resistance associate with long use of antibiotics in the treatment of these patients Acinetobacter baumannii an opportunistic pathogen that is primarily nosocomial Staphylococcus aureus is a nasal commensal carried by some humans. MRSA has emerged and is a clinical threat to humans Clostridium difficile associated with severe intestinal infections. Infections are usually are as a result of direct antibiotic use.  Can antimicrobial resistance be overcome? What do you think? Four main recommended actions to help fight difficult and deadly infections 1. Prevent the infection [hygienic precautions; vaccinations etc.] 2. Prevent the spread isolate infected patients 3. Track resistant strains by screening for the carriage of resistant strains] 4. Improve the use of antibiotics: stop unnecessary and inappropriate use by promote the production of new antibiotics as well as new diagnostic test for resistant bacteria Thanks