Antibiotic Resistance

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Antibiotic Resistance

Crystal Anne Burtis

Outline History What are Antibiotics Mechanism of Resistance Antibiotic Resistant Bacteria Public Education The Desperate Need for new Antibiotics

What is an Antibiotic? An antibacterial is acompound orsubstance that killsor slows down thegrowth of bacteria

History• Preantibiotic era• Sulfonamide (sulfa) drug.• Would mimic folic acid, that wouldcomplicate cell multiplication.• Saved millions of lives in WorldWar 2

Great Discovery History of the Discovery of Penicillin?• He observed that a plate culture ofStaphylococcus had been contaminated bya blue-green mold and that colonies ofbacteria adjacent to the mold were beingdissolved.•

What are Antibiotics? Types of Antibiotics- Narrow Spectrum• Antibiotics cause less disruption in the ecologicalbalance of microbes and normal flora.• Limited range• Less antibiotic residence likelihood.- Broad Spectrum• Both Gram + and Gram –• Generally prescribed when seriously ill or when thebacterium has not been identified.• Can kill a large number species of the normal flora• Narrow Spectrum

What are Antibiotics? Mechanisms of Antimicrobial Activity• Interference with the cell wall synthesis○ The antibiotics contains structures (beta-Lactam rings) that interfere with enzymesresponsible for cell wall synthesis.- Penicillin- Cephalosporin

What are Antibiotics? Mechanisms of Antimicrobial Activity• Interferences With Protein Synthesis○ Bacterial ribosomes, sytoplasmic structures onwhich protein synthesis takes place are targets.○ Different then human ribosomes• Prokaryotic 70s vs. Eukaryotic 80s○ Streptomycin- treatment of antibiotic○ Tetracylines○ Choloamphenical- Typhoid Fever• Can cause aplastic anemia- bone barrow can producered blood cells○ Erythromycin

What are Antibiotics? Mechanism of Antimicrobial Activity• Inference with Cell Membrane Function○ Antibiotics bind to and distorts the bacterialcell membrane, resulting in increasedpermeability and leakage of importantmolecules out of the cell.• Polymyxin B

What are Antibiotics? Mechanisms of Antimicrobial Activity• Interference with Nucleic Acid Synthesis○ Quinolones• Inhibit the actions of the enzyme DNA Gyrase○ Block RNA synthesis• Rifapin• Nalidixic acid

What are Antibiotics? Mechanisms of Antibiotics activity. Inference with Metabolic Activity• Antimetabolites are drugs that structurallysimilar to natural compounds involved inmetabolism and competitively bind to theenzymes○ Interference with Metabolic activity○ Molecular Mimicry -captivity bind to enzymes,making them inactive

What are Antibiotics? Acquisition of Antibiotics Resistance• Are bacteria just outsmarting us? No!○ Resistance to antibiotics designed to bring outtheir death• Darwinian process of natural selection○ “survival of the fittest”

What are Antibiotics How do cells develop resistance toantibiotics?• Is based on genetic changes.○ R plasmids○ Mutation of chromosomal DNA or plasmidDNA○ Transponsons

Mechanism of resistance R-plasmid conjugation is a means ofgenetic recombination in bacteria. R-plasmids often contain resistancegenes coding for multiple antibioticresistance, as well as resistancetransfer genes coding for theproduction of a conjugation

Vertical gene transfer The spontaneous mutation frequency forantibiotic resistance is on the order ofabout of about 10 -8 - 10 -9 . Although mutation is a very rare event,the very fast growth rate of bacteria andthe absolute number of cells attainedmeans that it doesn't take long beforeresistance is developed in a population.

Vertical Gene Transfer vertical evolution-The process isstrictly a matter of Darwinian evolutiondriven by principles of natural selection:a spontaneous mutation in the bacterialchromosome imparts resistance to amember of the bacterial population. In the selective environment of theantibiotic, the wild type (non mutants)are killed and the resistant mutant isallowed to grow and flourish

Horizontal Gene transfer process wherebygenetic materialcontained in smallpackets of DNA canbe transferredbetween individualbacteria of the samespecies or evenbetween differentspecies.

Horizontal Gene transfer Conjugation occurs when there is directcell-cell contact between two bacteria(which need not be closely related) andtransfer of small pieces of DNA calledplasmids takes place Most common

Horizontal Gene Transfer Transformation is a process where partsof DNA are taken up by the bacteriafrom the external environment. This DNA is normally present in theexternal environment due to the deathand lysis of another bacterium

Horizontal Gene Transfer Transduction occurs when bacteriaspecificviruses (bacteriophages)transfer DNA between two closelyrelated bacteria.

Antibiotic resistant Bacteria MRSA- Methicillin-resistantStaphylococcus aureus Commonly know as “staph infection” Found in the mucous membranes andthe human skin. One of the first bacteria to becomepenicillin resistant- 1947 just four yearlater.

MRSA continued MRSA is the most frequently identifiedantimicrobial drug-resistant pathogen inUS hospitals MRSA is especially troublesome inhospitals and nursing homes, wherepatients with open wounds, invasivedevices, and weakened immune systemare at greater risk of infection than thegeneral public.

Clostridium difficile nosocomial pathogen that causesdiarrheal disease in hospitals worldwide. Clindamycin-resistant C. difficile wasreported as the causative agent of largeoutbreaks of diarrheal disease inhospitals in New York, Arizona, Floridaand Massachusetts between 1989 and1992

Clostridium difficile Broad spectrum antibiotics are a causefor the resistance Some recent research suggests that theoveruse of antibiotics in the raising oflivestock for meat consumption iscontributing to outbreaks of bacterialinfections such as C. difficile. [16]

Acinetobacter baumannii As a result of its resistance to drugtreatment, some estimates state thedisease is killing tens of thousands ofU.S. hospital patients each year The illness can cause severepneumonia and infections of the urinarytract, bloodstream and other parts of thebody.

Acinetobacter baumannii Acinetobacter enters into the body throughopen wounds, catheters, and breathingtube On November 5, 2004, the CDC reportedan increasing number of Acinetobacterbaumanni bloodstream infections inpatients at military medical facilities inwhich service members injured in the Iraqregion during Operation Iraqi Freedom andin Afghanistan during Operation EnduringFreedom were treated

Antibiotics: Will they work when youreally need them? It is estimated that more than 50% ofantibiotics are unnecessarily prescribedin the office setting for upper respiratoryinfections (URIs), like cough and coldillness, most of which are caused byviruses.

Antibiotics: Will they work whenyou really need them? Up to 50% of antibiotic use in hospitalsis either unnecessary or inappropriate. In children, reactions to antibiotics arethe most common cause of emergencydepartment visits for adverse drugevents.

Public Education on Antibiotics

Get Smart CampaignGoals• promoting adherence to appropriateprescribing guidelines among providers,• decreasing demand for antibiotics for viralupper respiratory infections among healthyadults and parents of young children• increasing adherence to prescribedantibiotics for upper respiratory infections.

Antibiotics Education Center of Disease Control (CDC)• U.S Food and Drug Administration• “Get Smart About Antibiotics”•

Alliance Working for AntibioticResistance EducationAWARE Project Mission Reduce the unnecessary use of antibiotics andreduce the prevalence of antibiotic resistantbacteria in California.AWARE Project Goals Increase appropriate prescribing of antibiotics. Raise consumer awareness andunderstanding regarding the appropriate useof antibiotics. Mobilize the community to reduce theunnecessary use of antibiotics.

Aware Campaign PSA

The Desperate Need for NewAntibiotics. By: Time Magazine In recent years, efforts to combat drugresistantbacteria have focused on theimmediate goal of reducing rates of hospitalacquiredinfections the number of different antibiotics available totreat such infections when they do occur isdwindling because pharmaceutical companieshave neglected to invest in the development ofnew types of drugs.

The Desperate Need for New Antibiotics.By: Time Magazine New antibiotics are desperately needed,but the amount of money being spent onthe research and development of thesedrugs is woefully inadequate. "The issueis quite dreadful," says Elias Mossialos

The Desperate Need for New Antibiotics.By: Time Magazine Why are pharmaceutical companiesinvesting more in antibiotic research?• Antibiotic treatment is typically short• Doctors are more and more prescribing lessantibiotic• when resistance to a certain antibioticinevitably develops, the drug becomeslargely obsolete.

The Desperate Need for NewAntibiotics. By: Time Magazine the scientific challenges are moreworrying than the financial obstacles."Even if we got the incentives right,there's a knowledge gap that needs tobe filled,",8599,1926853,00.html

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