The document discusses antimicrobial chemotherapy and antibiotic sensitivity testing. It provides definitions of antibiotics and antimicrobial agents, and describes the discovery of penicillin by Alexander Fleming in 1928. It then summarizes various classes of antibiotics including beta-lactams like penicillins and cephalosporins, aminoglycosides, tetracyclines, chloramphenicol, and others. The document also discusses mechanisms of action, resistance, and methods for detecting antibiotic sensitivity and resistance including disk diffusion, dilution, and E-test gradient testing.
Mechanism Antibiotic Resistance
Intrinsic (Natural)
Acquired
Chromosomal
Extra chromosomal
Intrinsic Resistance
Lack target : No cell wall; innately resistant to penicillin
2. Drug inactivation: Cephalosporinase in Klebsiella
3. Innate efflux pumps:
It is an active transport mechanism. It requires ATP.
Eg. E. coli, P. aeruginosa
Altered target sites
PBP alteration
Ribosomal target alteration
Decreased affinity by target modification
Beta-lactamase
Beta-lactamases are enzymes produced by bacteria that provide resistance to β-lactam antibiotics such as penicillins, cephamycins, and carbapenems
Major resistant Pathogen
1. PRSP- Penicillin resistant Streptococcus pneumoniae2. MRSA/ORSA- Methicillin-resistant Staphylococcus Aureus (Super bug)3. VRE -Vancomycin-Resistant Enterococci4. Carbapenem resistant pseudomonas aeruginosa5. Carbapenem resistant Carbapenem resistant 6. Extended spectrum beta-lactamase (ESBL)-producing bacteria
Introduction to bacterial resistance to antibiotics, types of resistance, brief explaining & examples
The lecture was presented at Al-Mahmoudiya General Hospital at Wed, 17th Nov. 2021
Represented & updated as part of the training course for fresh appointed pharmacist at 16/5/2023
The slides explain introduction of antimicrobial chemotherapy and history of chemotherapy. Presented at institute of Biochemistry and Biotechnology, University of Punjab.
Mechanism Antibiotic Resistance
Intrinsic (Natural)
Acquired
Chromosomal
Extra chromosomal
Intrinsic Resistance
Lack target : No cell wall; innately resistant to penicillin
2. Drug inactivation: Cephalosporinase in Klebsiella
3. Innate efflux pumps:
It is an active transport mechanism. It requires ATP.
Eg. E. coli, P. aeruginosa
Altered target sites
PBP alteration
Ribosomal target alteration
Decreased affinity by target modification
Beta-lactamase
Beta-lactamases are enzymes produced by bacteria that provide resistance to β-lactam antibiotics such as penicillins, cephamycins, and carbapenems
Major resistant Pathogen
1. PRSP- Penicillin resistant Streptococcus pneumoniae2. MRSA/ORSA- Methicillin-resistant Staphylococcus Aureus (Super bug)3. VRE -Vancomycin-Resistant Enterococci4. Carbapenem resistant pseudomonas aeruginosa5. Carbapenem resistant Carbapenem resistant 6. Extended spectrum beta-lactamase (ESBL)-producing bacteria
Introduction to bacterial resistance to antibiotics, types of resistance, brief explaining & examples
The lecture was presented at Al-Mahmoudiya General Hospital at Wed, 17th Nov. 2021
Represented & updated as part of the training course for fresh appointed pharmacist at 16/5/2023
The slides explain introduction of antimicrobial chemotherapy and history of chemotherapy. Presented at institute of Biochemistry and Biotechnology, University of Punjab.
this presentation gives informationabout microbial assay of vitamins B2 and B12. it is based upon the guidelines of indian pharmacopoeia. this presentation highlights the principle, process and applications of microbial assay
Dr. Shelley Rankin - One Health Antibiotic Stewardship State of Science - Wha...John Blue
One Health Antibiotic Stewardship State of Science - What Do We Know? What Don't We Know? - Dr. Rick Sibbel, Executive Director, Technical Service, Food Animal Business Team, Merck Animal Health; Dr. Larry Granger, Senior Leader of Antimicrobial Resistance, USDA APHIS; Dr. Shelley Rankin, Associate Professor CE of Microbiology, School of Veterinary Medicine, University of Pennsylvania; Dr. Mark G. Papich, Professor, Clinical Pharmacology, North Carolina State University; Dr. Patrick McDermott, Director, National Antimicrobial Resistance Monitoring System, FDA Center for Veterinary Medicine, from the 2017 NIAA Antibiotic Symposium - Antibiotic Stewardship: Collaborative Strategy for Animal Agriculture and Human Health, October 31 - November 2, 2017, Herndon, Virginia, USA.
More presentations at http://www.swinecast.com/2017-niaa-antibiotic-symposium-antibiotic-stewardship
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
2. Uses of Antimicrobial Agents
•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.
11/1/2014 Dr.T.V.Rao MD 2
3. Beginning of Antibiotics with Discovery of Pencillin
•The discovery of penicillinhas been attributed to Scottish scientist Alexander Flemingin 1928 and the development of penicillin for use as a medicine is attributed to the Australian Nobel Laureate Howard Walter Florey.
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6. Chemotherapeutic Agents
•Antimicrobial agents –that are produced synthetically but have action similar to that of antibiotics and are defined as chemotherapeutic agents
•Eg Sulphonamides, Quinolones. 11/1/2014 Dr.T.V.Rao MD 6
7. Definition
•Bacteriostatic-Antimicrobial agents that reversibly inhibit growth of bacteria are called as bacteriostic ( Tetracyclnes, Chloramphenicol )
•Bactericical –Those with an irreversible lethal action on bacteria are known as bactericidal ( Pencillin, Isoniazid )
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8. How Drugs Act
•Drugs differ on their capabilities to act at different sites on bacteria.
•Some drugs have more than one site of action
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9. Major 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.
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10. Pencillin
•Pencillin and cephalosporins act inhibiting Trans peptidases, the enzyme catalyses the final linking step in synthesis of peptidoglycan.
•Due to this reason Pencillin in bactericidal for grwoing bacteria since new peptidoglycan is synthesized at that stage only.
•In nongrwoing cells pencillin is inactive
•An intact beta –lactum is essential for antibacterial activity of pencillins
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11. Classification of Pencillins
•Natural
Benzyl pencillin
Phenoxymethyl pencillin Pencillin v
Semi synthetic and pencillase resistant
1 Methicillin
2 Nafcillin
3 Cloxacillin
4 Oxacillin
5 Floxacillin
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12. Extended spectrum pencillins
Aminopencillins -Ampicillin, Amoxycillin
Carboxypencillins –Carbencillin, Ticarcillin
Ureidopencillin -Piperacillin
Resistance to pencillin is due to pencillinase commonly called as ßlactamase
The enzyme opens Betalactam ring hydrolytically and thus converts the antibiotic to inactive pencillonic acid.
11/1/2014 Dr.T.V.Rao MD 12
13. Inhibitors to Beta lactamase
•Clavulinic acid which is a product of Strept.clavuligerus
•Acts against the Staphylococcal beta ßlactamase.
•And plasmid mediated Betalactamase of Gram negative bacteria.
•Salbactum –this is a semisyntetic sulfone derivative with weak antibacterial activity
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14. •Tazobactam –A penicillonic acid sulfone derivative acts well when combined with piperacillin.
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15. Cephalosporins
•Like pencillin acts similar
•Products of the molds of genus Cephalosporium except cefoxilin
•Divided into 4 generation of cephalosporins depending on the spectrum of activity.
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16. Different Generations of Cephalosporins
•Cephalosporins are grouped into "generations" based on their spectrum of antimicrobial activity. The first cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins.
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17. Major generations of Cephalosporins
•Cephalosporins are divided into 3 generations:
•1st generation: Cephelexin, cefadroxil, cephradine
•2nd generation: Cefuroxime, cefaclor
•3rd generation: cefotaxime, Ceftazidime, cefixime -these give the best CNS penetration
•4thgeneration Cephalosporins are already available
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18. Basis of generations in Cephalosporins
•Cephalosporins are grouped into "generations" based on their spectrum of antimicrobial activity. The first cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins.
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19. Advantages with Newer generations
•Each newer generation of cephalosporins has significantly greater gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against gram-positive organisms. Fourth generation cephalosporins, however, have true broad spectrum activity
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20. Other Beta-lactams include
•Other beta-lactams include:
•Aztreonam: a monocytic beta-lactam, with an antibacterial spectrum which is active only against Gram negative aerobes, including Pseudomonas aeruginosa, Neisseria meningitidisand N. gonorrhoea.
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21. Other drugs
•Imipenem: a carbapenem with a broader spectrum of activity against Gram positive and negative aerobes and anaerobes. Needs to be given with cilastatin to prevent inactivation by the kidney.
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22. Quinolones
•Quinolones are the first wholly synthetic antimicrobials. The commonly used Quinolones.
•Act on the DNA gyrase which prevents DNA polymerase from proceeding at the replication fork and consequently stopping synthesis.
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23. Aminoglycosides
•Aminoglycosides are group of antibiotics in which amino sugars liked by glycoside bonds
•Eg Streptomycin,
•Act at the level of Ribosome's and inhibits protein synthesis
•Other Aminoglycosides –
Gentamycin, neomycins,paromomycins,tobramycins Kanamycins and spectinomycins
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24. Tetracycline's
•Broad spectrum antibiotic produced by Streptomyces species
•1. Oxytetracycle, chlortetracycle and tetracycline
•Tetracyclnes are bacteriostatic drugs inhibits rapidly multiplying organisms
•Resistance develops slowly and attributed to alterations in cell membrane permeability to enzymatic inactivation of the drug
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25. Choramphenicol
•Choramphenicol is bacteriostatic drug
•Can produce bone marrow depression
•Chloramphenicol interferes with protein synthesis.
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26. Macrolides,Azalides,Ketolides
•Contain macro cyclic lactone ring Erythromycin. Is popularly used drug
•Other drugs Roxithromycin,Azithromycin
•Inhibits the protein synthesis.
•Used as alternative to pencillin allergy patients.
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27. Other Antimicrobial agents
•Lincomycins
Clindamycin resembles Macrolides in biting site and antimicrobial activity.
Streptogramins
Quinpristin / dalfopristin
useful in gram postive bacteria
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28. Antibiotics in Anaerobes
•Major anaerobes –Anaerobic cocci, clostridia and Bacteroides are susceptible to Benzyl pencillin
•Bact.fragilis as well as many other anaerobes are treatable with Erythromycin,Lincomycin, tetracycline and Chloramphenicol
•Clindamycin is effective against many strains of Bacteroides
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29. Metronidazole in Anaerobic Infections
•Since the discovery of Metronidazole in 1973 since then it was identified as leading agent anaerobes.
•But also useful in treating parasitic infections
Trichomonas, Amoebiasis and other protozoan infections.
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32. Antibiotic resistance
•Antibiotic resistanceis the ability of a micro organism to withstand the effects of antibiotics. It is a specific type of drug resistance. Antibiotic resistance evolves naturally via natural selectionacting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population. Once such a geneis generated, bacteria can then transfer the genetic information in a horizontal fashion (between individuals) by plasmidexchange.
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35. •Diffusion method
–Put a filter disc, or a porous cup/a bottomless cylinder containing measured quantity of drugs on the a solid medium that has been seeded with test bacteria
•Dilution method
–vary amount of antimicrobial substances incorporated into liquid or solidmedia
–followed by inoculation of test bacteria Dr.T.V.Rao MD 35
Antimicrobial Susceptibility Testing
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36. Susceptibility Testing MethodsInnoculateMH platePlace diskson agar plateIncubate plate18-24 hr, 35 CMeasure and record zone of inhibition around each disk 11/1/2014 Dr.T.V.Rao MD 36
37. Antimicrobial susceptibility tests
Minimum inhibitory concentration [MIC]
–The smallest concentration of antibiotic that inhibits the growth of organism
Liquid media (dilution) allows MIC estimation
Solid media (diffusion)
–Disk diffusion (Kirby-Bauer)
–E-tests
–Allows MIC estimation
Beta lactamase production: quick screening method 11/1/2014 Dr.T.V.Rao MD 37
38. Disk Diffusion Susceptibility Testing
Improper agar & disk placement
Mueller Hinton agar &
good disk placement
Use Mueller Hinton agar
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40. Dilution in liquid broth
•Tubes containing increasing antibiotic concentrations
•Incubation during 18 hr at 37°C
•Tedious
0 (Control) 0,25 0,50 1 2 4 8mg/l
MIC
Bacterial growth
Inhibition
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41. Kirby-Bauer disc testing
Antibiotic-impregnated discs placed on an agar plate at the
interface between test organism and susceptible control organism
Resulting zones of inhibition compared, use of controls
Susceptibility is inferred (standard tables)
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43. Dr.T.V.Rao MD 43
E test –MIC Reports are helpful in Critical management decisions
•Quantitative MIC data is a prerequisite for the management of critical infections, including sepsis, especially among critical care patients. Etestis
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44. E-test
Plastic strips with a predefined
gradient of
– One antibiotic
– One antifungal
Only one manufacturer
One strip per antibiotic
Wide range of antibiotics
Easy to use
Storage at -20°C
Short shelf life, expensive
47. Choose the Appropriate Antibiotic
Think before prescribing Are we using Right drug for the Right bug ?
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48. •Program created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing world
•Email.
•doctortvrao@gmail.com
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