Antibiotics, Misuse of Antibiotics

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Antibiotics, Misuse of Antibiotics

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  • 1.Dr.T.V.Rao MDDr.T.V.Rao MD 1

2. VirusBacteria Common cold Urine infections Diarrhea (99%) Strep Throat Acute Bronchitis Boils/abscesses Influenza (flu) Gangrene Measles Some pneumonia Chicken Pox Ear infections (half) AIDS Sinus infections (< half) Rabies Bubonic Plague Hepatitis Tuberculosis Dr.T.V.Rao MD 2 3. Bacteriaare the cause of the vast majority of deaths due to infection in the United States: sepsis, meningitis, pneumoniaMost viral infections get better all by themselves in 1-3 weeks; no medications are required: colds, flu, stomach virusDr.T.V.Rao MD 3 4. They dont help the patient at all Expense: 75% of outpatient antibiotics areused for respiratory infections Patient expectations: why no better? Side effects: diarrhea, rash, allergy Developmentof resistance: theantibiotic wont work when you really DOneed it for a bacterial infection Dr.T.V.Rao MD 4 5. ANTIMICROBIAL AGENTAny chemical or drugused to treat an infectiousdisease, either byinhibiting or killing the pathogens in vivoDr.T.V.Rao MD 5 6. The discovery ofpenicillin has beenattributed to Scottishscientist AlexanderFleming in 1928 andthe development ofpenicillin for use as amedicine is attributedto the Australian NobelLaureate HowardWalter FloreyDr.T.V.Rao MD 6 7. Dr.T.V.Rao MD 7 8. The term"antibiotic" wascoined by SelmanWaksman in 1942to describe anysubstanceproduced by amicroorganism thatis antagonistic tothe growth of othermicroorganisms inhigh dilution Dr.T.V.Rao MD8 9. Antimicrobialagents that areproducedsynthetically buthave actionsimilar to that ofantibiotics andare defined aschemotherapeutic agents Eg Sulphonamides, Dr.T.V.Rao MD 9Quinolones. 10. Substancesderived from amicroorganismor producedsynthetically,that destroys orlimits the growthof a livingorganismDr.T.V.Rao MD 10 11. Bacteriostatic - Antimicrobial agents that reversibly inhibit growth of bacteria are called as bacteriostic ( Tetracyclnes, Chloramphenicol ) Bactericidal Those with an irreversible lethal action on bacteria are known as bactericidal ( Pencillin, Isoniazid ) Dr.T.V.Rao MD 11 12. Development of anti-infectivesertapenem tigecyclinThe development daptomicin linezolidof anti-infectives telithromicin quinup./dalfop. cefepime ciprofloxacin aztreonam norfloxacin imipenemcefotaxime clavulanic ac.cefuroxime gentamicincefalotinanalidxico ac. ampicillin methicilin vancomicin rifampinchlortetracyclinstreptomycinpencillin G 1920prontosil1930 1940 19501960 197019801990 2000Dr.T.V.Rao MD12 13. Antimicrobial agents are widelyemployed to cure bacterial diseases Definition of Antibiotic Antibioticsare substances that are derived from avarious species of microorganismsand are capable of inhibiting thegrowth of other microorganism evenin small concentrations. Dr.T.V.Rao MD 13 14. ANTIBIOTICS Sources1. Natural a.Fungi penicillin, griseofulvin b.Bacteria Bacillus sp. (polymixin, bacitracin) ; Actinomycetes (tetracycline, chloramphenicol, streptomycin)2. Synthetic Dr.T.V.Rao MD 14 15. ANTIMICROBIAL AGENTIdeal Qualities:1. kill or inhibit the growth of pathogens2. cause no damage to the host3. cause no allergic reaction to the host4. stable when stored in solid or liquid form5. remain in specific tissues in the body long enoughto be effective6. kill the pathogens before they mutate and becomeresistant to it Dr.T.V.Rao MD 15 16. Although a large number of antibiotics exist, they fall intoonly a few classes with an even more limited number oftargets. -lactams (penicillins) cell wall biosynthesis Glycopeptide (vancomycin) cell wall biosynthesis Aminoglycosides (gentamycin) protein synthesis Macrolides (erythromycin) protein synthesis Quinolones (ciprofloxacin) nucleic acid synthesis Sulfonamides (sulfamethoxazole) folic acid metabolismDr.T.V.Rao MD16 17. Is an antibiotic necessary ? What is the most appropriateantibiotic ? What dose, frequency, route andduration ? Is the treatment effective ?Dr.T.V.Rao MD 17 18. Useful only for the treatment of bacterialinfections Not all fevers are due to infection Not all infections are due to bacteria There is no evidence thatantibiotics will preventsecondary bacterial infection inpatients with viral infectionDr.T.V.Rao MD 18 19. Oral vs parenteral Traditional view serious = parenteral previous lack of broad spectrum oral antibiotics with reliable bioavailability Improved oral agents higher and more persistent serum and tissue levels for certain infections as good as parenteralDr.T.V.Rao MD19 20. Eliminates risks ofcomplications associatedwith intravascular lines Shorter duration of hospitalstay Savings in nursing time Savings in overall costs Dr.T.V.Rao MD 20 21. Susceptible BacteriaResistant BacteriaResistance Gene Transfer New Resistant Bacteria Dr.T.V.Rao MD21 22. Decreased entryEfflux pump Altered target site Mechanisms of ResistanceEnzymaticdegradationBypass pathway Dr.T.V.Rao MD22 23. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Antimicrobial Resistance: Key Prevention Strategies Susceptible Pathogen Antimicrobial-Resistant Pathogen PathogenPrevent Prevent Transmission Infection InfectionAntimicrobial ResistanceEffectiveOptimize UseDiagnosis& TreatmentAntimicrobial Use Dr.T.V.Rao MD23 24. Antibiotic resistance isa consequence ofevolution via naturalselection. Theantibiotic action is anenvironmentalpressure; thosebacteria which have amutation allowingthem to survive willlive on to reproduce.They will then pass thistrait to their offspring,which will be a fullyresistant generation.Dr.T.V.Rao MD 24 25. Dr.T.V.Rao MD 25 26. Dr.T.V.Rao MD 26 27. Dr.T.V.Rao MD 27 28. 48% of all antibiotics by weight is added toanimal feeds to promote growth. Results in low,sub therapeutic levels which are thought topromote resistance. Farm families who own chickens feedtetracycline have an increased incidence oftetracycline resistant fecal flora Chickens at Spanish supermarkets have >90% ofcultured campylobacter resistant to quinolones 39% of enterococci in the fecal flora of pigsfrom the Netherlands is resistant to vancomycinvs 0% in Sweden. (Sweden bans antibioticadditives in animal feed)Dr.T.V.Rao MD28 29. Several studies havedemonstrated thatpatterns of antibioticusage greatly affect thenumber of resistantorganisms whichdevelop. Overuse ofbroad-spectrumantibiotics, such assecond- and third-generationCephalosporins,generate resistantstrains. Dr.T.V.Rao MD 29 30. The resistant strains arise either by mutation and selection or by genetic exchange in which sensitive organisms receive the genetic material ( part of DNA) from the resistant organisms and the part of DNA carries with it the information of mode of inducing resistance against one or multiple antimicrobial agents. Dr.T.V.Rao MD 30 31. RESISTANCEACQUISITION OF BACTERIAL RESISTANCEACQUIRED RESISTANCE Species develop ability to resist anantimicrobial drug to which it is as awhole naturally susceptible Two mechanisms: 1. Mutational chromosomal 2. Genetic exchange transformation, transduction,conjugationDr.T.V.Rao MD 31 32. The greatest possibility of evil in self-medication is the use of too small doses sothat instead of clearing up infection, themicrobes are educated to resist penicillinand a host of penicillin-fast organisms isbread out which can be passed to otherindividuals and from them to other untilthey reach someone who gets a septicemiaor a pneumonia which penicillin cannotsave. .Sir AlexanderFlemming Dr.T.V.Rao MD32 33. 1980s ESBL producing GN bacteria 1990 Vancomycin resistant Enterococci emerged2000 VISA (intermediate level resistance)2002-VRSA (high level resistance)2002- Linezolid resistant enterococci and Staphylococci reported Dr.T.V.Rao MD33 34. Evolution of b-LactamasePlasmid-Mediated TEM and SHV EnzymesThird-AmpicillinGenerationCephalosporins19651970s 1980s1987 2000 19831963 TEM-1 TEM-1ESBL >120 ESBLs Reported inESBL in in E coliWorldwide 28 Gram- Europe United S paratyphi NegativeStates Species Dr.T.V.Rao MD 34 35. Resistance to AntibioticsBacteria (and viruses) are very resourceful creatures and they havedeveloped resistance mechanisms to essentially every antibiotic that hasbeen developed.Moreover, increased use of antibiotics results in increased resistance (thparadox of antibiotics).The basic resistance mechanisms are quite simple:1.Modify the antibiotic2.Modify the target of the antibiotic3.Destroy the antibiotic4.Make it more difficult for the antibiotic to get into the cell Dr.T.V.Rao MD 35 36. Plasmid seem to be ubiquitous inbacteria, May encode geneticinformation for properties1 Resistance to Antibiotics2 Bacteriocins production3 Enterotoxin production4 Enhanced pathogen city5 Reduced Sensitivity tomutagens6 Degrade complex organicmolecules Dr.T.V.Rao MD 36 37. Plasmids helps to spread multiple drugresistance Discovered in 1959 Japan Infections caused due to Shigella spreadresistance to following Antibiotics Sulphonamides Streptomycin Choramphenicol, Tetracycline Dr.T.V.Rao MD 37 38. Shigella + E.coliexcreted in thestool resistant toseveral drugs invivo and vitro Plasmid mediated transmitted byConjugation Episomes spreadthe resistance Dr.T.V.Rao MD 38 39. R forms may have evolved as a collection ofTransposons Each carrying Genes that confers resistanceto one or several Antibiotics Seen in Plasmids, Microorganisms AnimalsLaboratory Manipulations are called asGenetic Engineering Dr.T.V.Rao MD39 40. Sulphonamides --- Reduce permeabilityErythromycin---- Modification of ribosomesTetracyclnes ----- Reduced permeabilityChloramphenicol ---- Acetylation of drugStreptomycin----- Adenylation of drugPencillin ----- Hydrolysis of lactum ring Dr.T.V.Rao MD40 41. Therapeutic failures and relapse Facilitates spread in the hospitalunder antibiotic pressure Need to use more costly andtoxic agents The emergence of untreatablepathogens Dr.T.V.Rao MD 41 42. RESISTANCEACQUIRED RESISTANCE EXAMPLES:1. Resistance (R) plasmids Transmitted by conjugation2. mecA gene Codes for a PBP with low affinity for -lacta