Misuse of-antibiotics
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Question was in my mind how the bacteria learn the biochemical mechanisms of defense against antibiotics , l know it should have gens that produce defense ways , but how they have thes gens , how antibiotics produce resistance in bacteria for them self and another's ? All that I tried to answer in this seminar and how can be treated or minimized .
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Misuse of-antibiotics
- 1. MISUSE OF ANTIBIOTICS Presented & prepared By Ali Al _samawy
- 2. OBJECTIVES : What are antibiotics ? What are the antibiotic resistance ? How the bacteria become resistant to antibiotics ? What the mech. Of that resistance ? What are the misuse of antibiotics ? How we minimize misuse of antibiotics ? Are we overuse antibiotics with example of misuse in Iraq and right use in USA .
- 3. ANTIBIOTICS Antibiotics, also called antibacterials, are a type of antimicrobial drug used in the treatment and prevention of bacterial infection. Chemical Antibiotic: produced by a microorganism that kills or inhibits the growth of another microorganism . .
- 4. MECHANISMS OF ANTIMICROBIAL DRUGS 1 Inhibition of cell wall synthesis 2 Inhibition of cell membrane function 3 Inhibition of protein synthesis inhibition of translation and transcription of genetic material) 4 Inhibition of nucleic acid synthesis.
- 5. the Right Antibiotic for Bacterial Infections Does the prescribed antibiotic kill the bacterium or merely stop it from dividing? What type of bacteria does it target? Which parts of the bacteria does it target? How is the antibiotic applied? How long should the antibiotic be used?
- 6. ANTIBIOTIC RESISTANCE Antibiotic resistance is a specific type of drug resistance when a microorganism has the ability of withstanding the effects of antibiotics. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population. Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion(between individuals) by conjugation, transduction, or transformation.
- 7. RESISTANCE AND SUSCEPTIBILITYDetermined by in vitro activity, pharmacologic characteristics, and clinical evaluation. The minimal inhibitory concentration(MIC) can be comfortably exceeded by doses tolerated by the patient. Susceptible implies their MIC is at a concentration attainable in the blood or other body fluid at the recommended dose. Resistant MIC is not exceeded by normally attainable levels
- 8. ANTIBIOTIC RESISTANCE Some microorganisms may'born' resistant, some achieve' resistance by mutation or some have resistance"thrust upon them" by plasmids “Some are born great, some achieve greatness or some have greatness thrust upon them”
- 9. MECHANISMS OF DRUG RESISTANCE
- 10. ORIGIN OF DRUG RESISTANT STRAINS The resistant strains arise either by 1.mutation and selection It refers to the change in DNA structure of the gene. Occurs at a frequency of one per ten million cells. Eg. Mycobacterium tuberculosis,Mycobacterium lepra MRSA. Often mutants have reduced susceptibility
- 11. ORIGIN OF DRUG RESISTANT STRAINS 2 . genetic exchange in which sensitive organisms receive the genetic material ( part of DNA) from the resistant organisms the part of DNA carries with it information of mode of inducing resistance against one or multiple antimicrobial agents.
- 12. Selective pressure The influence exerted by some factor (such as an antibiotic) on natural selection to promote one group of organisms over another. In the case of antibiotic resistance, antibiotics cause a selective pressure by killing susceptible bacteria, allowing antibiotic-resistant bacteria to survive and multiply.
- 13. Sir Alexander Fleming In his 1945 Nobel Prize lecture Fleming himself warned of the danger of resistance "It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, the same thing has occasionally happened in the body... and by exposing his microbes to non-lethal quantities of the drug make them resistant.“ Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistance .
- 14. Sub-MIC selection Selection of resistance at non-lethal antibiotic concentrations 1.Growth rate 2.tolerance thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission Since the fitness cost and not the level of resistance is the most influential parameter for selection of resistant cells at low levels of antibiotics, de novo selected mutants enriched at sub-MIC are expected to have very low fitness costs. since selection for high fitness is strong at sub-MIC levels of antibiotics it is less likely that the resulting resistance is reversed in the absence of antibiotic, either by mutation or by competition with more fit susceptible bacteria the rate with which resistance mutations will arise is expected to be higher at low concentrations of antibiotics
- 15. BIOCHEMICAL MECHANISMS OF DRUG RESISTANCE Prevention of drug accumulation in the bacterium Modification/protection of the target site Use of alternative pathways for metabolic growth requirements By producing an enzyme that inactivates the antibiotic
- 17. Practices Contributing to Misuse of AntibioticsInappropriate specimen selection and collection Failure to use stains/smears Failure to use cultures and susceptibility tests Use of antibiotics with no clinical indication(eg, for viral infections) Use of broad spectrum antibiotics when not indicated inappropriate choice of empiric antibiotics Drug
- 19. 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
- 20. People can help tackle resistance by People can help tackle resistance by: using antibiotics only when prescribed by a doctor; completing the full prescription, even if they feel better; never sharing antibiotics with others or using leftover prescriptions.
- 21. Health workers and pharmacists can help tackle resistance by: Optimize patient evaluation Adopt judicious antibiotic Immunize patients enhancing infection prevention and control; prescribing and dispensing the right antibiotic(s) to treat the illness. Optimize consultations with other clinicians Educate others about judicious use of antibiotics
- 22. Are we over use antibiotics Rx Cetriaxone Suprax itraconazole fluconazole miconazole Clotrimazozol Other
- 23. 9 HOURS IN EMERGANCY UNIT IN USA
Editor's Notes
- quotation
- Mutation Mutations result from damage to DNA which is not repaired, errors in the process of replication, or from the insertion or deletion of segments of DNA by mobile genetic elements. Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements. Insertions in the coding region of a gene may alter splicing of the mRNA(splice site mutation), or cause a shift in the reading frame(frameshift), both of which can significantly alter the gene product. Insertions can be reversed by excision of the transposable element. Deletions remove one or more nucleotides from the DNA. . Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes. transposable element (TE or transposon) is a DNA sequencethat can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genome size. Chromosomal inversions: reversing the orientation of a chromosomal segment. Causes::::::::::::::: (1) spontaneous mutations (molecular decay), (2) mutations due to error-prone replication bypass of naturally occurring DNA damage (also called error-prone translesion synthesis), (3) errors introduced during DNA repair, and (4) induced mutations caused by mutagens. mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level By effect on function 1_loss-of-function mutations, also called inactivating mutations, result in the gene product having less or no function (being partially or wholly inactivated). 2_Gain-of-function mutations, also called activating mutations, change the gene product such that its effect gets stronger (enhanced activation) or even is superseded by a different and abnormal function. 3_Dominant negative mutations (also called antimorphicmutations) have an altered gene product that acts antagonistically to the wild-type allele 4_Lethal mutations are mutations that lead to the death of the organisms that carry the mutations effect on fitness :: 1_A harmful, or deleterious, mutation decreases the fitness of the organism. 2_beneficial, or advantageous mutation increases the fitness of the organism. Mutations that promotes traits that are desirable, are also called beneficial 3_ neutral mutation has no harmful or beneficial effect on the organism. Chat Conversation End
- Horizontal gene transfer (HGT) refers to the transfer of genesbetween organisms in a manner other than traditional reproduction. Lateral gene transfer is a type of horizontal gene transfer which occurs between eukaryotic organisms. (LGT), it contrasts with vertical transfer, the transmission of genes from the parental generation to offspring via sexual or asexual reproduction. HGT has been shown to be an important factor in the evolution of many organisms. [1] Mech Transformation, the genetic alteration of a cell resulting from the introduction, uptake and expression of foreign genetic material (DNA or RNA).[27] This process is relatively common in bacteria, but less so in eukaryotes.[28] Transformation is often used in laboratories to insert novel genes into bacteria for experiments or for industrial or medical applications. See alsomolecular biology and biotechnology. Transduction, the process in which bacterial DNA is moved from one bacterium to another by a virus (a bacteriophage, orphage).[27] Bacterial conjugation, a process that involves the transfer of DNA via a plasmid from a donor cell to a recombinant recipient cell during cell-to-cell contact.[27] Gene transfer agents, virus-like elements encoded by the host that are found in the alphaproteobacteria orderRhodobacterales.[29] A transposon (jumping gene) is a mobile segment of DNA that can sometimes pick up a resistance gene and insert it into a plasmid or chromosome, thereby inducing horizontal gene transfer of antibiotic resistance.[27]
- Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth .rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic Recent studies have shown that resistant bacteria can be selected at concentrations severahundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant The underlying mechanisms of resistance development have been studied extensively in particular pathogen–antibiotic combinations. However, the broader questions of the driving forces behind where and how resistance arises and is selected and how resistance genes spread between different bacteria and different environments are complex and still not completely understood It is intuitive that for most kinds of antibiotics a bacterium will still experience a reduction in growth even at concentrations just below the MIC even if growth is not completely prevented minimum selective concentration (MSC) as the lowest concentration of an antibiotic that still selects for a given resistance mutation. The fact that antibiotic levels several hundred-fold below the MIC of the susceptible strains can select resistant bacteria means that the sub-MIC selective window is much larger than the traditional selective window. In effect this means that concentrations of antibiotics commonly found in sewage water in European countries and the USA (see (9,14,15) and references therein) are high enough to enrich for resistant bacteria is thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission. Since the fitness cost and not the level of resistance is the most influential parameter for selection of resistant cells at low levels of antibiotics, de novo selected mutants enriched at sub-MIC are expected to have very low fitness costs. It is therefore unlikely that the one-step high-level resistant mutants with relatively high fitness costs commonly found when high-level selection is performed will be selected (17). Instead, accumulation of mutations giving increasing resistance levels but having very low fitness costs is predicted to occur First, since selection for high fitness is strong at sub-MIC levels of antibiotics it is less likely that the resulting resistance is reversed in the absence of antibiotic, either by mutation or by competition with more fit susceptible bacteria
- gene duplication and amplification (GDA) constitutes an important adaptive mechanism in bacteria. For example, resistance to sulphonamide, trimethoprim and beta-lactams can be conferred by increased gene dosage through GDA of antibiotic hydrolytic enzymes, target enzymes or efflux pumps. Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density.
- Although it is still not completely understood why and how antibiotics increase the growth rate of pigs, possibilities include metabolic effects, disease control effects, and nutritional effects