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Antibiotics, Misuse of Antibiotics


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Antibiotics, Misuse of Antibiotics

Antibiotics, Misuse of Antibiotics

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  • 1. Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  • 2. Virus Bacteria 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. Bacteria are 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 virus Dr.T.V.Rao MD 3
  • 4.  They don’t help the patient at all Expense: 75% of outpatient antibiotics are used for respiratory infections Patient expectations: why no better? Side effects: diarrhea, rash, allergy Development of resistance: the antibiotic won’t work when you really DO need it for a bacterial infection Dr.T.V.Rao MD 4
  • 5. ANTIMICROBIAL AGENT •Any chemical or drugused to treat an infectious disease, either by inhibiting or killing the pathogens in vivo Dr.T.V.Rao MD 5
  • 6.  The discovery of penicillin has been attributed to Scottish scientist Alexander Fleming in 1928 and the development of penicillin for use as a medicine is attributed to the Australian Nobel Laureate Howard Walter Florey Dr.T.V.Rao MD 6
  • 7. Dr.T.V.Rao MD 7
  • 8.  The term "antibiotic" was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution Dr.T.V.Rao MD 8
  • 9.  Antimicrobial agents – that are produced synthetically but have action similar to that of antibiotics and are defined as chemotherapeuti c agents Eg Sulphonamides, Dr.T.V.Rao MD 9 Quinolones.
  • 10.  Substances derived from a microorganism or produced synthetically, that destroys or limits the growth of a living organism Dr.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-infectives ertapenem tigecyclinThe development daptomicin linezolid of anti-infectives … telithromicin quinup./dalfop. cefepime ciprofloxacin aztreonam norfloxacin imipenem cefotaxime clavulanic ac. cefuroxime gentamicin cefalotina nalidíxico ac. ampicillin methicilin vancomicin rifampin chlortetracyclin streptomycin pencillin G 1920 prontosil 1930 1940 1950 1960 1970 1980 1990 2000 Dr.T.V.Rao MD 12
  • 13.  Antimicrobial agents are widely employed to cure bacterial diseases Definition of Antibiotic – Antibiotics are substances that are derived from a various species of microorganisms and are capable of inhibiting the growth of other microorganism even in 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 enough to be effective6. kill the pathogens before they mutate and become resistant to it Dr.T.V.Rao MD 15
  • 16.  Although a large number of antibiotics exist, they fall into only a few classes with an even more limited number of targets. –β-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 metabolism Dr.T.V.Rao MD 16
  • 17.  Is an antibiotic necessary ? What is the most appropriate antibiotic ? What dose, frequency, route and duration ? Is the treatment effective ? Dr.T.V.Rao MD 17
  • 18.  Useful only for the treatment of bacterial infections Not all fevers are due to infection Not all infections are due to bacteria There is no evidence that antibiotics will prevent secondary bacterial infection in patients with viral infection Dr.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 parenteral Dr.T.V.Rao MD 19
  • 20.  Eliminates risks of complications associated with intravascular lines Shorter duration of hospital stay 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 MD 21
  • 22. Decreased entryEfflux pump Altered target site Mechanisms of Resistance Enzymatic degradation Bypass pathway Dr.T.V.Rao MD 22
  • 23. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Antimicrobial Resistance: Key Prevention Strategies Susceptible Pathogen Antimicrobial-Resistant Pathogen Pathogen Prevent Prevent Transmission Infection Infection Antimicrobial Resistance EffectiveOptimize Use Diagnosis & Treatment Antimicrobial Use Dr.T.V.Rao MD 23
  • 24.  Antibiotic resistance is a consequence of evolution via natural selection. The antibiotic action is an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce. They will then pass this trait to their offspring, which will be a fully resistant 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 to animal feeds to promote growth. Results in low, sub therapeutic levels which are thought to promote resistance. Farm families who own chickens feed tetracycline have an increased incidence of tetracycline resistant fecal flora Chickens at Spanish supermarkets have >90% of cultured campylobacter resistant to quinolones 39% of enterococci in the fecal flora of pigs from the Netherlands is resistant to vancomycin vs 0% in Sweden. (Sweden bans antibiotic additives in animal feed) Dr.T.V.Rao MD 28
  • 29.  Several studies have demonstrated that patterns of antibiotic usage greatly affect the number of resistant organisms which develop. Overuse of broad-spectrum antibiotics, such as second- and third- generation Cephalosporins, generate resistant strains. 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 an antimicrobial drug to which it is as a whole naturally susceptible  Two mechanisms: 1. Mutational – chromosomal 2. Genetic exchange – transformation, transduction, conjugation Dr.T.V.Rao MD 31
  • 32.  The greatest possibility of evil in self- medication is the use of too small doses so that instead of clearing up infection, the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save. . Sir AlexanderFlemming Dr.T.V.Rao MD 32
  • 33. 1980s –ESBL producing GN bacteria 1990 Vancomycin resistant Enterococci emerged 2000 VISA (intermediate level resistance) 2002-VRSA (high level resistance) 2002- Linezolid resistant enterococci and Staphylococci reported Dr.T.V.Rao MD 33
  • 34. Evolution of b-Lactamase Plasmid-Mediated TEM and SHV Enzymes Third-Ampicillin Generation Cephalosporins 1965 1970s 1980s 1987 2000 1983 1963 TEM-1 TEM-1 ESBL >120 ESBLs Reported in ESBL in in E coli Worldwide 28 Gram- Europe United S paratyphi Negative States Species Dr.T.V.Rao MD 34
  • 35. Resistance to Antibiotics•Bacteria (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 in bacteria, May encode genetic information for properties 1 Resistance to Antibiotics 2 Bacteriocins production 3 Enterotoxin production 4 Enhanced pathogen city 5 Reduced Sensitivity to mutagens 6 Degrade complex organic molecules Dr.T.V.Rao MD 36
  • 37.  Plasmids – helps to spread multiple drug resistance Discovered in 1959 Japan Infections caused due to Shigella spread resistance to following Antibiotics Sulphonamides Streptomycin Choramphenicol, Tetracycline Dr.T.V.Rao MD 37
  • 38.  Shigella + E.coli excreted in the stool resistant to several drugs in vivo and vitro Plasmid mediated – transmitted by Conjugation Episomes spread the resistance Dr.T.V.Rao MD 38
  • 39.  R forms may have evolved as a collection of Transposons Each carrying Genes that confers resistance to one or several Antibiotics Seen in Plasmids, Microorganisms AnimalsLaboratory Manipulations are called as Genetic Engineering Dr.T.V.Rao MD 39
  • 40. Sulphonamides --- Reduce permeabilityErythromycin ---- Modification of ribosomesTetracyclnes ----- Reduced permeabilityChloramphenicol ---- Acetylation of drugStreptomycin ----- Adenylation of drugPencillin ----- Hydrolysis of lactum ring Dr.T.V.Rao MD 40
  • 41.  Therapeutic failures and relapse Facilitates spread in the hospital under “antibiotic pressure” Need to use more costly and toxic agents The emergence of untreatable pathogens Dr.T.V.Rao MD 41
  • 42. RESISTANCEACQUIRED RESISTANCE – EXAMPLES: 1. Resistance (R) plasmids  Transmitted by conjugation 2. mecA gene  Codes for a PBP with low affinity for -lactam antibiotics  Methicillin-resistant S. aureus Dr.T.V.Rao MD 42
  • 43. RESISTANCEORIGIN OF DRUG RESISTANCENON-GENETIC 1. Metabolically inactive organisms may be phenotypically resistant to drugs – M. tuberculosis 2. Loss of specific target structure for a drug for several generations 3. Organism infects host at sites where antimicrobials are excluded or are not active – aminoglycosides (e.g. Gentamicin) vs. Salmonella enteric fevers (intracellular) Dr.T.V.Rao MD 43
  • 44. RESISTANCEGENETIC 1. Chromosomal  Occurs at a frequency of 10-12 to 10-7  20 to spontaneous mutation in a locus that controls susceptibility to a given drug  due to mutation in gene that codes for either: a. drug target b. transport system in the membrane that controls drug uptake Dr.T.V.Rao MD 44
  • 45. RESISTANCEGENETIC2. Extrachromosomal a. Plasmid-mediated  Occurs in many different species, esp. gram (-) rods  Mediate resistance to multiple drugs  Can replicate independently of bacterial chromosome  many copies  Can be transferred not only to cells of the same species but also to other species and genera Dr.T.V.Rao MD 45
  • 46. Pathogens Resistant to Antibiotics (%) 100 90 MRSA = methicillin-resistant Staphylococcus 80 aureus 70 VRE = vancomycin-resistant enterococci 60 GISA = glycopeptide-intermediate S aureus 50 VRSA = vancomycin-resistant S aureus MRSA1 40 30 20 10 VRE2 GISA3 VRSA4 1975 1980 1985 1990 1995 2000 1996 2002 Year1SmithTL et al. N Engl J Med. 1999;340:493-501. 2Martone WJ. Infect Control Hosp Epidemiol. 1998;19:539-545.3Hiramatsu K et al. J Antimicrob Chemother. 1997;40:135-136. 4CDC. MMWR Morb Mortal Wkly Rep. 2002;51:565-567. Dr.T.V.Rao MD 46
  • 47. Practices Contributing to Misuse of Antibiotics< Inappropriate specimen selection and collection< Inappropriate clinical tests< Failure to use stains/smears< Failure to use cultures and susceptibility tests Dr.T.V.Rao MD 47
  • 48. RESISTANCELIMITATION OF DRUG RESISTANCE1. Maintain sufficiently high levels of the drug in the tissues  inhibit original population and first-step mutants.2. Simultaneous administration of two drugs that do not give cross-resistance  delay emergence of mutants resistant to the drug (e.g. INH + Rifampicin)3. Limit the use of a valuable drug  avoid exposure of the organism to the drug Dr.T.V.Rao MD 48
  • 49. What Is Antimicrobial Stewardship?• A combination of infection control and antimicrobialmanagement• Mandatory infection control compliance• Selection of antimicrobials from each class of drugsthat doesthe least collateral damage• Collateral damage issues include– MRSA– ESBLs– C difficile– Stable derepression– MBLs and other carbapenemases– VRE• Appropriate de-escalation when culture results areavailable Dr.T.V.Rao MD 49
  • 50. IDSA Guidelines – Definition of Antimicrobial Stewardship•Antimicrobial stewardship is anactivity that promotes– The appropriate selection ofantimicrobials– The appropriate dosing ofantimicrobials– The appropriate route and durationof antimicrobial therapy Dr.T.V.Rao MD 50
  • 51. The Primary Goal of Antimicrobial Stewardship• The primary goal of antimicrobial stewardship is to– Optimize clinical outcomes while minimizing unintendedconsequences of antimicrobial use• Unintended consequences include the following– Toxicity– The selection of pathogenic organisms, such as C difficile– The emergence of resistant pathogens Dr.T.V.Rao MD 51
  • 52. The Primary Goal of Antimicrobial Stewardship• The primary goal of antimicrobial stewardship is to– Optimize clinical outcomes while minimizing unintendedconsequences of antimicrobial use• Unintended consequences include the following– Toxicity– The selection of pathogenic organisms, such as C difficile– The emergence of resistant pathogens Dr.T.V.Rao MD 52
  • 53. Practices Contributing to Misuse of Antibiotics< Inappropriate specimen selection and collection< Inappropriate clinical tests< Failure to use stains/smears< Failure to use cultures and susceptibility tests Dr.T.V.Rao MD 53
  • 54. Inappropriate Antibiotic Use Use of antibiotics with no clinical indication (eg, for viral infections) Use of broad spectrum antibiotics when not indicated Inappropriate choice of empiric antibiotics Dr.T.V.Rao MD 54
  • 55. Inappropriate Drug Regimen Inappropriate dose - ineffective concentration of antibiotics at site of infection Inappropriate route - ineffective concentration of antibiotics at site of infection Inappropriate duration Dr.T.V.Rao MD 55
  • 56.  If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug. The term antimicrobial resistance is sometimes use to explicitly encompass organisms other than bacteria Dr.T.V.Rao MD 56
  • 57.  Antibiotic resistance has become a serious problem in both developed and underdeveloped nations. By 1984 half of those with active tuberculosis in the United States had a strain that resisted at least one antibiotic.In certain settings, such as hospitals and some childcare location Dr.T.V.Rao MD 57
  • 58. Dr.T.V.Rao MD 58
  • 59. Fischbach MA and Walsh CT Science 2009 Dr.T.V.Rao MD 59
  • 60. Other cliniciansPatientsOptimize patient evaluation Optimize consultations withAdopt judicious antibiotic other cliniciansprescribing practices Use infection control measuresImmunize patients Educate others about judicious use of antibiotics Dr.T.V.Rao MD 60
  • 61.  Bacteria evolve resistance to antibiotics in response to environmental pressure exerted by the use of antibiotics. Many of these bacteria are significant pathogens. Our responsibility to our community is to use antibiotics prudently, for appropriate indications. Dr.T.V.Rao MD 61
  • 62. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings 12 Steps to Prevent Antimicrobial Resistance Prevent Transmission 12 Break the chain 11 Isolate the pathogen Use Antimicrobials Wisely 10 Stop treatment when cured 9 Know when to say “no” to vanco 8 Treat infection, not colonization 7 Treat infection, not contamination 6 Use local data Diagnose & Treat 5 Practice antimicrobial control Effectively 4 Access the experts 3 Target the pathogen 2 Get the catheters out Prevent Infections1 Vaccinate Dr.T.V.Rao MD 62
  • 63.  Antibiotic resistance is a major problem world-wide Resistance is inevitable with use No new class of antibiotic introduced over the last two decades Appropriate use is the only way of prolonging the useful life of an antibiotic Dr.T.V.Rao MD 63
  • 64. Dr.T.V.Rao MD 64
  • 65.  Surveillance Prevention and Agency for Control Health Care Research and Quality Department of Defense Research Health Care Department of Product Financing Agriculture Administration Development Environmental Protection Agency Department of Veterans Affairs Health Resources and Services Dr.T.V.Rao MD Administration 65
  • 66. Think beforeprescribing Arewe using Rightdrug for theRight bug ? Dr.T.V.Rao MD 66
  • 67.  Createdby Dr.T.V.Rao MD for Medical Professionals in the Developing World Email Dr.T.V.Rao MD 67