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Antibiotic and antibiotic resistance
- 1. ANTIBIOTICS ANTIMICROBIANS RESISTANCE BY: LESLIE MILLAN ALVAREZ MICROBIOLOGY ONLINE TUTOR Leslie Millan Alvarez Microbiology Tutor 1
- 2. AIMS • THIS MODULE AIMS TO INTRODUCE THE MICROBIOLOGICAL ASPECTS OF ANTIMICROBIAL RESISTANCE. BY THE END OF THE MODULE, YOU WILL BE ABLE TO: • 1. IDENTIFY BACTERIAL ANTIMICROBIAL RESISTANCE MECHANISMS FOR RESISTING ANTIMICROBIAL AGENTS. 2. DISCUSS THE MOLECULAR BASIS FOR BACTERIAL ANTIMICROBIAL RESISTANCE. 3. EXPLAIN LABORATORY METHODS FOR DETECTING AND MEASURING ANTIMICROBIAL RESISTANCE. Leslie Millan Alvarez Microbiology Tutor 2
- 3. CONCEPTS • CHEMOTHERAPY: THE USE OF DRUGS TO TREAT A DISEASE. • ANTIMICROBIAL DRUGS: INTERFERE WITH THE GROWTH OF MICROBES WITHIN A HOST. • ANTIBIOTIC: OF BIOLOGICAL ORIGIN. PRODUCED BY A MICROBE, INHIBITS OTHER MICROBES. • CHEMOTHERAPEUTIC AGENT: SYNTHETIC CHEMICALS • TODAY DISTINCTION BLURRED MANY NEWER "ANTIBIOTICS" ARE BIOLOGICAL PRODUCTS THAT ARE • CHEMICALLY MODIFIED OR • CHEMICALLY SYNTHESIZED Leslie Millan Alvarez Microbiology Tutor 3
- 4. THE HISTORY OF CHEMOTHERAPY PRE ANTIBIOTIC ERA Leslie Millan Alvarez Microbiology Tutor 4
- 5. • IN 1910, EHRLICH DISCOVERED THE ARSENIC- CONTAINING CHEMICAL DYE HE EVENTUALLY NAMED SALVARSAN. IT WAS THE FIRST CHEMICAL COMPOUND SHOWN TO CURE SYPHILIS (SCHWARTZ, THOBURN, WINAU). Naser Tadvi antibiotic resistance ppt Leslie Millan Alvarez Microbiology Tutor 5
- 6. THE GOLDEN AGE OF ANTIBIOTICS AND SYNTHETIC ANTIBACTERIAL DRUGS • IN 1928, THE BRITISH PHYSICIAN-SCIENTIST SIR ALEXANDER FLEMING SERENDIPITOUSLY DISCOVERED THAT THE ANTIBIOTIC SUBSTANCE HE TERMED “PENICILLIN” WAS PRODUCED BY A PENICILLIUM MOLD GROWING ON AGAR PLATES IMPREGNATED WITH STAPHYLOCOCCI. • 1930’S SULFONAMIDE BY GEHARD DOMARGK SULFA DRUGS (SULFANILAMIDE) DISCOVERED IN 1932 AGAINST GRAM+ BACTERIA • 1928: FLEMING DISCOVERED PENICILLIN • 1940: HOWARD FLOREY AND ERNST CHAIN PERFORMED FIRST CLINICAL TRIALS OF PENICILLIN. Leslie Millan Alvarez Microbiology Tutor 6
- 7. ANTIBIOTICS ARE DRUGS USED FOR TREATING INFECTIONS CAUSED BY BACTERIA. ALSO KNOWN AS ANTIMICROBIAL DRUGS, ANTIBIOTICS HAVE SAVED COUNTLESS LIVES. • HTTPS://MICROBIOLOGYSOCIETY.ORG/MEMBERS-OUTREACH- RESOURCES/OUTREACH-RESOURCES/ANTIBIOTICS- UNEARTHED/ANTIBIOTICS-AND-ANTIBIOTIC- RESISTANCE/WHAT-ARE-ANTIBIOTICS-AND-HOW-DO-THEY- WORK.HTML Leslie Millan Alvarez Microbiology Tutor 7
- 8. SELECTIVE TOXICITY • AN IDEAL ANTIMICROBIAL DRUG IS THE ONE THAT DO NOT PRODUCE ANY HARM TO THE HOST. • NOT ALWAYS LIKE THAT • MOST ANTIBIOTICS PRODUCE NON OR LES HARM TO THE CELLS Leslie Millan Alvarez Microbiology Tutor 8
- 9. ANTIBIOTIC ACTION ANTIBACTERIAL DRUGS • BACTERIOSTATIC • BACTERICIDAL Leslie Millan Alvarez Microbiology Tutor 9
- 10. THE USE OF ANTIBIOTICS ANTIBIOTICS USED TO TREAT INFECTIONS ARE AN INVALUABLE TOOL, AND THEIR INTRODUCTION REVOLUTIONIZED THE TREATMENT OF INFECTIOUS DISEASE. OTHER APPLICATIONS. IN THE UNITED STATES, ROUGHLY HALF ARE USED IN NON- HUMAN APPLICATIONS. LARGE AMOUNTS ARE EMPLOYED IN BOTH PLANT AND ANIMAL FARMING. IN ANIMALS, ANTIBIOTICS ARE USED TO PREVENT INFECTION AS WELL AS TO TREAT DISEASE. SMALLER DOSES ARE ADDED TO ANIMAL FEED TO PROMOTE GROWTH. ANTIBIOTICS, CHIEFLY STREPTOMYCIN AND OXYTETRACYCLINE, ARE USED TO CONTROL BACTERIAL INFECTIONS OF FRUITS AND VEGETABLES. BECAUSE OF THEIR WIDE-SPREAD USE, IT IS NOT SURPRISING THAT ANTIBIOTICS HAVE BEEN FOUND IN LIQUID WASTE AT ANIMAL FEEDLOTS, AND HAVE SPREAD INTO MANY SURFACE AND GROUND WATER SUPPLIES Leslie Millan Alvarez Microbiology Tutor 10
- 11. ANTIBIOTICS GENERAL CHARACTERISTICS OF ANTIMICROBIAL DRUGS • SELECTIVE TOXICITY – AGENT MUST KILL OR INHIBIT MICROBE WHILE DAMAGING THE HOST ASLITTLE AS POSSIBLE • RANGE OF EFFECTIVENESS |LEVELS OF ACTIVITY OF AN ANTIMICROBIAL DRUG IS MEASURE BY A. VALUES EXPRESSED AS: • 1. MIC (MINIMAL INHIBITORY CONCENTRATION) - LOWEST CONCENTRATION OF DRUG THAT PREVENTS GROWTH • 2. MLC (MINIMAL LETHAL CONCENTRATION) - LOWEST CONCENTRATION OF DRUG THAT KILLS MICROBE B. TESTS FOR DETERMINING ANTIMICROBIAL ACTIVITY • 1. DILUTION SUSCEPTIBILITY TEST - DILUTE ANTIBIOTIC IN 2-FOLD INTERVALS AND TEST FOR MIC • 2. DISK DIFFUSION TEST Leslie Millan Alvarez Microbiology Tutor 11
- 12. Leslie Millan Alvarez Microbiology Tutor 12
- 13. https://apua.org/science-of-resistance Leslie Millan Alvarez Microbiology Tutor 13
- 14. ANTIBACTERIAL RESISTANCE AND THE ENVIRONMENT • BEFORE THE WIDE-SPREAD USE OF ANTIBIOTICS, RESISTANT STRAINS WERE A SMALL FRACTION OF THE MICROORGANISM ECOSYSTEM. SIGNIFICANT CHANGE HAS OCCURRED WITH THE LARGE SCALE HUMAN USES OF ANTIBIOTICS BECAUSE THESE SUBSTANCES, KILL OFF ANTIBIOTIC SUSCEPTIBLE BACTERIA, AND THUS CREATE FAVORABLE ENVIRONMENTS FOR THE OVERGROWTH OF RESISTANT STRAINS. Leslie Millan Alvarez Microbiology Tutor 14
- 15. SUPERBUGS • HARMLESS BACTERIA WITH RESISTANCE GENES CAN TRANSFER THESE GENES TO PATHOGENIC BACTERIA THAT ENTER THE SAME ENVIRONMENT. THE GENETIC ELEMENTS THAT ARE TRANSFERRED OFTEN CARRY FACTORS THAT IMPART RESISTANCE TO MORE THAN ONE TYPE OF ANTIBIOTIC. WHEN SUCH GENETIC ELEMENTS ARE TRANSFERRED, THEY CREATE "SUPERBUGS" THAT ARE RESISTANT TO MANY DISTINCT ANTIBIOTICS. Leslie Millan Alvarez Microbiology Tutor 15
- 16. Image source: http://file.scirp.org/Html/19-8202738_43142.htm https://amrls.umn.edu/microbiology Leslie Millan Alvarez Microbiology Tutor 16
- 17. Leslie Millan Alvarez Microbiology Tutor 17
- 18. MECHANISMS GENETIC RESISTANCE TRANSFERING FROM ONE BACTERIA TO ANOTHER • CONJUGATION • TRANSFORMATION • TRANSDUCTION FROM PLASMIDS WITHIN THE BACTERIA • TRANPOSONS • INTEGRONS Leslie Millan Alvarez Microbiology Tutor 18
- 19. CAUSES OF ANTIBIOTIC RESISTANCE • MISUSE OF ANTIBIOTICS SELECTS FOR RESISTANCE MUTANTS. MISUSE INCLUDES • USING OUTDATED OR WEAKENED ANTIBIOTICS • USING ANTIBIOTICS FOR THE COMMON COLD AND OTHER INAPPROPRIATE CONDITIONS • USING ANTIBIOTICS IN ANIMAL FEED • FAILING COMPLETE THE PRESCRIBED REGIMEN • USING SOMEONE ELSE'S LEFTOVER PRESCRIPTION Leslie Millan Alvarez Microbiology Tutor 19
- 20. 20 Leslie Millan Alvarez Microbiology Tutor • HETEROGENEOUS RESISTANT GROWTH OF THE THE SAME BACTERIA • CROSS RESISTANCE • MUTATIONS OTHER FAILURES IN ANTIBIOTIC TREATMENT ARE DUE TO
- 21. ORIGEN OF ANTIBIOTIC RESISTANCE • NON GENETIC: INTRINSIC CHARACTERISTICS OF BACTERIAS TO SURVIVE IN THE ENVIROMENT THEY ARE IN. SPORES FORMATIONS, CAVERNS, CYSTS. THOSE MECHANISMS ALLOW BACTERIAS TO SURVIVE THE IMMUNE SYSTEM REACTION AND STAY LATENT UNTIL CONDITIONS ARE FAVORABLE TO GROW. • GENETIC • CHROMOSOMAL: SPONTANEOUS MUTATIONS THAT PROVOKE INHIBITION OF THE MICROBIOTA AND INDUCE BACTERIAL GROWTH • EXTRACHROMOSOMAL: PLASMIDS Leslie Millan Alvarez Microbiology Tutor 21
- 22. CLINICAL IMPLICATIONS OF DRUG RESISTANCE • N. gonorrheae IS RESISTANT TO SULFONAMIDES, TETRACYCLINE, PENICILLIN(STILL SUSCEPTIBLE SOME STRAINS), QUINOLONES. • N. meningococcic IS RESISTANT TO SULFONAMIDES AND RIFAMPICIN • Staphylococcus aureus IS RESISTANT TO PENICILLIN (MRSA) METICILLIN RESISTANT IS CALLED. NOW THERE IS AN EMERGENCY DUE TO RESISTANT STRAINS TO VANCOMYCIN (VRSA) AND LINEZOLID. • S. pneumoniae IS RESISTANT TO PENICILLIN, TRIMETHROPRIM/SULFAMETHOXAZOLE, ERITHROMYCIN, TETRACYCLINE, QUINOLONES. Leslie Millan Alvarez Microbiology Tutor 22
- 23. MECHANISM OF ANTIBIOTIC THERAPY • ANTIMICROBIAL SYNERGISM CAN OCCUR IN SEVERAL TYPES OF SITUATIONS. SYNERGISTIC DRUG COMBINATIONS MUST BE SELECTED BY COMPLEX LABORATORY PROCEDURES. TWO DRUGS MAY SEQUENTIALLY BLOCK A MICROBIAL METABOLIC PATHWAY. • ANTIMICROBIAL ANTAGONISM IT OCCURRED WHEN A BACTERIOSTATIC DRUG (WHICH INHIBITED PROTEIN SYNTHESIS IN BACTERIA) SUCH AS CHLORAMPHENICOL OR TETRACYCLINE WAS GIVEN WITH A BACTERICIDAL DRUG SUCH AS A PENICILLIN OR AN AMINOGLYCOSIDE. ANTAGONISM OCCURRED MAINLY IF THE BACTERIOSTATIC DRUG REACHED THE SITE OF INFECTION BEFORE THE BACTERICIDAL DRUG, IF THE KILLING OF BACTERIA WAS ESSENTIAL FOR CURE, AND IF ONLY MINIMAL EFFECTIVE DOSES OF EITHER DRUG IN THE PAIR WERE PRESENT. Leslie Millan Alvarez Microbiology Tutor 23
- 24. REFERENC ES • HTTP://FILE.SCIRP.ORG/HTML/19- 8202738_43142.HTM • HTTPS://AMRLS.UMN.EDU/MICROBIOLOGY • HTTPS://MEDLINEPLUS.GOV/ANTIBIOTICS.HTML • HTTPS://WWW.BRITANNICA.COM/SCIENCE/ANTIBI OTIC Leslie Millan Alvarez Microbiology Tutor 24
Editor's Notes
- An ideal antimicrobial agent exhibits selective toxicity, which means that the drug is harmful to a pathogen without being harmful to the host. Oft en, selective toxicity is relative rather than absolute; this implies that a drug in a concentration tolerated by the host may damage an infecting microorganism. Selective toxicity may be a function of a specifi c receptor required for drug attachment, or it may depend on the inhibition of biochemical events essential to the pathogen but not to the host.
- As antibiotics become more widely used, resistant strains of both harmful and harmless bacteria are replacing antibiotic susceptible bacteria. Furthermore, resistant bacteria in one environment may not be confined to that specific environment, but can be carried thousands of miles away by wind, water, animals, food, or people. And, most importantly, antibiotic resistant organisms that develop in animals, fruits, or vegetables can be passed to humans through the food chain and environment. All of these factors have had the effect of changing the balance between antibiotic susceptible and the antibiotic resistant bacteria in our ecosystem, locally and globally.
- Over the past few decades, the use of antibiotics has enabled us to control many serious infectious diseases. However, as resistant strains become more widespread due to natural and inevitable evolutionary adjustments, antibiotics will cease to be the effective tool they have been for physicians and patients to control infectious diseases.
- A few examples will illustrate the impact of the emergence of drug-resistant organisms and their selection by the widespread use of antimicrobial drugs.
- Two drugs may sequentially block a microbial metabolic pathway. Sulfonamides inhibit the use of extracellular PABA by some microbes for the synthesis of folic acid. Trimethoprim or pyrimethamine inhibits the next metabolic step, the reduction of dihydro- to tetrahydrofolic acid. The simultaneous use of a sulfonamide plus trimethoprim is effective in some bacterial (shigellosis, salmonellosis, Serratia species) and some other infections (pneumocystosis, malaria). Pyrimethamine plus a sulfonamide or clindamycin is used in toxoplasmosis. drug such as a cell wall inhibitor (a penicillin or cephalosporin) may enhance the entry of an aminoglycoside into bacteria and thus produce synergistic effects. Penicillins enhance the uptake of gentamicin or streptomycin by enterococci. Thus, ampicillin plus gentamicin may be essential for the eradication of Enterococcus faecalis, particularly in endocarditis. Similarly, piperacillin plus tobramycin may be synergistic against some strains of Pseudomonas species. 3. One drug may affect the cell membrane and facilitate the entry of the second drug. The combined effect may then be greater than the sum of its parts. For example, amphotericin has been synergistic with flucytosine against certain fungi (eg, Cryptococcus, Candida species). 4. One drug may prevent the inactivation of a second drug by microbial enzymes. Thus, inhibitors of β-lactamase (eg, clavulanic acid, sulbactam, tazobactam) can protect amoxicillin, ticarcillin, or piperacillin from inactivation by β-lactamases. In such circumstances, a form of synergism takes place.