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
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
Antibiotic resistance I Mechanism I Types I Contributing factors.kausarneha
Antibiotic resistance in bacteria is a global threat of 21st century. Here is a brief discussion of Antimicrobial resistance or Drug resistance disease. If you want to study via video lecture on this visit on my YouTube channel : Microbiology WISDOM:
Here you can find further more such interesting topics.
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
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
Antibiotic resistance I Mechanism I Types I Contributing factors.kausarneha
Antibiotic resistance in bacteria is a global threat of 21st century. Here is a brief discussion of Antimicrobial resistance or Drug resistance disease. If you want to study via video lecture on this visit on my YouTube channel : Microbiology WISDOM:
Here you can find further more such interesting topics.
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
FLOW OF THE SEMINAR
1. Definition – antibiotic resistance, Multi-resistance, cross-resistance in antibiotics
2. Evolution of resistance
3. Impact of resistance
4. The scenario of resistance: Global, India
5. Factors causing resistance
6. Mechanisms of resistance: Intrinsic and Acquired
7. Acquired mechanism of resistance
8. Quorum sensing
9. Mechanism of resistance in commonly used antibiotics
10. Methods for determining the resistance
11. Strategies to contain resistance
12. Antibiotic stewardship
13. Role of Pharmacologist
14. Initiatives undertaken by India to control resistance
Antibiotic resistance,introduction, cause, mechanism and solution of Antibiot...Dr. Sharad Chand
A illustrative representation of the antibiotic resistance, its introduction, cause, mechanism, examples and possible solutions of the antibiotic resistance. with pictorial illustrations for better understanding.
Resistance to antibiotics is one of the main important facts that most nations are working on. Actually, in USA, it is considered as a health problem to solve. Why it happens? Here is a review to answer this.
Relative or complete lack of effect of antimicrobial agent against a previously susceptible microbe/pathogen.
It is an evolutionary principal that organism adopt genetically to change in their environment.
since the doubling time of bacteria can be as short as 20 mnt, there may be many generations in even a few hours, providing ample opportunity for evolutionary adaptation.
The phenomenon of resistance imposes serious constraints on the options available for the treatment of many bacterial infections.
The resistance to chemotherapeutic agents can also develop in protozoa, in multicellular parasites and in population of malignant cells.
Today there are different strains of S. aureus resistant to almost every form of antibiotic in use.
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
FLOW OF THE SEMINAR
1. Definition – antibiotic resistance, Multi-resistance, cross-resistance in antibiotics
2. Evolution of resistance
3. Impact of resistance
4. The scenario of resistance: Global, India
5. Factors causing resistance
6. Mechanisms of resistance: Intrinsic and Acquired
7. Acquired mechanism of resistance
8. Quorum sensing
9. Mechanism of resistance in commonly used antibiotics
10. Methods for determining the resistance
11. Strategies to contain resistance
12. Antibiotic stewardship
13. Role of Pharmacologist
14. Initiatives undertaken by India to control resistance
Antibiotic resistance,introduction, cause, mechanism and solution of Antibiot...Dr. Sharad Chand
A illustrative representation of the antibiotic resistance, its introduction, cause, mechanism, examples and possible solutions of the antibiotic resistance. with pictorial illustrations for better understanding.
Resistance to antibiotics is one of the main important facts that most nations are working on. Actually, in USA, it is considered as a health problem to solve. Why it happens? Here is a review to answer this.
Relative or complete lack of effect of antimicrobial agent against a previously susceptible microbe/pathogen.
It is an evolutionary principal that organism adopt genetically to change in their environment.
since the doubling time of bacteria can be as short as 20 mnt, there may be many generations in even a few hours, providing ample opportunity for evolutionary adaptation.
The phenomenon of resistance imposes serious constraints on the options available for the treatment of many bacterial infections.
The resistance to chemotherapeutic agents can also develop in protozoa, in multicellular parasites and in population of malignant cells.
Today there are different strains of S. aureus resistant to almost every form of antibiotic in use.
antibiotics in xdr organism,the mechanism of resistance ,cause of resistance ,effect of resistance, levels of resistance, classification, xdr organisms, gram positive and gram negative ,detection and latest idsa guidelines for management.
ambler classification and detection
latest antibiotics and mechanism of action of new antibiotics.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
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.
Follow us on: Pinterest
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.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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
3. Antibiotic resistance is the ability of bacteria to resist
the effects of an antibiotic – that is, the bacteria are not
killed, and their growth is not stopped
It is a natural phenomenon accelerated by use of
antibiotics. Resistant strains survive and aggregate
4. “The time may come when penicillin can be bought by
anyone in the shops. Then there is the danger that the
ignorant man may easily underdose himself and by
exposing his microbes to non-lethal quantities of the
drug make them resistant.”
- Alexander Fleming
‘Penicillin’ Nobel Lecture, December 11, 1945
7. • Non-susceptibility to at least one agent in
three or more antimicrobial categories
Multidrug- resistant
(MDR) bacteria
• Non-susceptibility to at least one agent
in all but two or fewer antimicrobial
categories
Extensively drug-
resistant (XDR) bacteria
• Non-susceptibility to all agents in all
antimicrobial categories
Pandrug-resistant (PDR)
bacteria
Non-susceptibility refers to either a resistant, intermediate or non-
susceptible result obtained from in vitro antimicrobial susceptibility testing
9. MDR-TB
Beijing strain responsible for majority of cases
Drug resistance acquired through genetic mutations;
cannot be transmitted to other bacteria via plasmids
10. Detection of decreased susceptibility to 3rd generation cephalosporin and
treatment failures
Neisseria gonorrhoeae
12. Antibiotics are given to
food producing animals
and crops
Animals develop drug-
resistant bacteria in their gut
Drug-resistant bacteria reaches
humans through food, the
environment (water, soil, air) or by
direct human-animal contact
Antibiotics are given to patients,
which can result in drug-resistant
bacteria developing in the gut
Patient attends
hospital/clinic
Drug-resistant bacteria spreads
to other patients through poor
hygiene and unclean facilities
Drug-resistant bacteria
spreads to the general
public
17. Why do bacteria become resistant to antibiotics to
which they were earlier susceptible?
Bacteria have to adapt and evolve to survive as the
environmental conditions change
Genetic variability
Antibiotic
resistance
Acquired Resistance
Antimicrobial agents exert strong selective pressures on
bacterial populations, favouring organisms that are capable of
resisting them
20. Point mutations
Spontaneous
Replacement of only one base pair in the DNA structure
Preserved due to “selection pressures” exerted by antibiotics
Resistance is of low level, to a single drug
The trait is passed vertically to daughter cells; termed as
“vertical transfer”; cannot be transferred to other bacterial
species
E.g. Resistance of M. tuberculosis to rifampicin due to
mutation in the rpoB gene which encodes the beta subunit
of the bacteria's RNA polymerase
21. External Acquisition of Genetic elements
Drug resistance acquired by horizontal transfer of resistance
determinant genes from a donor cell
This transfer can occur between bacteria of the same species or of
different species
Mobile genetic
elements
1.Plasmids
1.Bacteriophag
es
Specialized genetic
elements
1.Transposons
1.Integrons
1.Transformati
on
Transduction
Conjugation
GENETIC ELEMENTS PROCESSES
22. Conjugative
plasmids
Extrachromosomal, autonomously replicating agents of
genetic exchange, present in cytoplasm
Consist of covalently closed, circular, double-stranded DNA
molecules
Plasmids that carry resistance genes are called R-plasmids
R-genes are readily transferred from R-plasmid to another
plasmid or chromosome
23. Transposons
Short segments of DNA with their
own recombination enzyme,
transposase
Translocate as a unit from one area
of the bacterial chromosome to
another or plasmid or
bacteriophage DNA
May transpose to nonhomologous
sequences of DNA
Must exist on a replicon (plasmid
or bacteriophage) to be replicated
Integrons
Integrase - Receptor for resistance
gene cassettes
Promoters - Initiation site for their
transcription
Cannot promote self-transfer
“Hot-spots” for site-specific
recombination events between
nonhomologous sequences of DNA
Located on a transposon or a
conjugative plasmid
24. Conjugation
Common mechanism of resistance transfer among Gr –
ve bacilli present in high density in the gut
Resident nonpathogenic microflora serve as a reservoir
for the resistant genes which can be transferred to other
organisms that invade the host
• Eg. Chloramphenicol resistance of typhoid bacilli
• Streptomycin resistance of E. coli
• Penicillin resistance of Hemophilus and Gonococci
25. Transduction
Plasmid DNA enclosed in a
bacteriophage is transferred to
another bacterium of the same
species
Transformation
Resistant bacterium releases the
resistance carrying DNA into the
medium
Certain bacteria pick up free
homologous DNA from the
environment
New DNA is then incorporated into
the genome of the bacteria which
then becomes resistant
Strains of Staph aureus
Penicillin resistance in Pneumococci and Neisseria
26. Mechanisms of antibiotic resistance
1. Enzymatic modification
2. Decreased Permeability of Bacterial Membranes
3. Promotion of Antibiotic Efflux
4. Altered Target Sites
5. Overproduction of Target
6. Bypass of Antibiotic Inhibition
27. 1. Enzymatic modification
ß-lactamases inactivate β-lactam antibiotics by splitting the
amide bond of the ß-lactam ring
β-lactamase
β-lactamase Bacterial species Hydrolyze
Penicillinase E. coli, S. aureus Penicillin
TEM-1 (Temoniera),
SHV-1
(Sulfhydryl variable-1)
Enterobacteriaceae,
P. aeruginosa, H.
influenzae, and N.
gonorrhoeae
Penicillins and
narrow-spectrum
cephalosporins
28. Extended Spectrum
β-lactamase
Bacterial species Hydrolyze Susceptibility to β-
lactamase inhibitor
TEM-3 Enterobacteriaceae Third-generation
cephalosporins,
aztreonam
Susceptible to
clavulanic acid
CTX-M
(Cefotaxime-M)
E. coli Third-generation
cephalosporins
Susceptible to
tazobactam
OXA
(Oxacillin)
P. aeruginosa Oxymino-β-lactams Poorly inhibited by
clavulanic acid
Carbapenemase K. pneumoniae Carbapenems -
New Delhi metallo-
β-lactamase
K. pneumoniae All β-lactams except
aztreonam
Resistant to
clavulanic acid,
tazobactam and
sulbactam
Aminoglycoside-modifying enzymes confer antibiotic resistance through three
general reactions: N-acetylation , O-nucleotidylation, and O-phosphorylation
29. 2. Decreased Permeability of Bacterial Membranes
Emergence of imipenem resistance during therapy, observed
in up to 25% of P. aeruginosa infections has been ascribed to
mutational loss of its OprD protein aka the D2 porin
30. 3. Promotion of Antibiotic Efflux
Bacteria can overexpress efflux pumps and then expel antibiotics to
which the bacteria would otherwise be susceptibleAntibiotics
Efflux
pumps
Bacterial species Gene designation Resistant against
Streptococcus
pneumoniae
mef (macrolide
efflux)
Macrolides
Staphylococcus
aureus
msr (macrolide
streptogramin
resistance)
Macrolides,
Streptogramins
Enteric Gr-ve
bacteria
Tetracycline-
resistance
determinant (Tet)
Tetracyclines
31. Mechanism of MDR among aerobic and anaerobic Gr +ve bacteria for
macrolides, lincosamides, and streptogramin B (MLSB)
Resistance mediated by methylase enzymes, products of the erm
(erythromycin ribosome methylation) gene → dimethylate adenine
residues on the 23S ribosomal RNA (rRNA) of the 50S subunit of the
prokaryotic ribosome, disrupting the binding of MLSB to the ribosome
4.1. Alteration of ribosomal target sites
4.2. Alteration of target enzymes
Mechanism of resistance in narrow-spectrum penicillin
In S. aureus, methicillin resistance is conferred by the expression of the
mecA gene, which encodes PBP2a, a protein with low affinity for β-
lactam antibiotics, conferring resistance to nafcillin, oxacillin and
methicillin
32. 4.3. Alteration of cell wall precursor targets
Mechanism of resistance to vancomycin and teicoplanin in strains of E.
faecium and E. faecalis
vanA gene on the plasmid encodes an inducible protein that is related to
the d-ala-d-ala ligases involved in cell wall synthesis
Synthesizes peptidoglycan precursors that have a depsipeptide terminus
(d-alanine d-lactate) instead of the usual d-ala-d-ala
Modified peptidoglycan binds glycopeptide antibiotics with reduced
affinity, conferring resistance
33. 5. Overproduction of target
Sulfonamides compete with para-
aminobenzoic acid to bind the
enzyme DHPS and halt the
generation of pteridines and nucleic
acids
Sulfonamide resistance is mediated
by the gene felP by the
overproduction of the synthetic
enzyme DHPS
Excess DHPS can overwhelm sulfa
inhibition
6. Bypass of antibiotic inhibition
Auxotrophs are mutants that require
substrates normally synthesized by the
target enzymes
But if the substrates are present in the
environment, the organisms are able to
grow despite inhibition of the synthetic
enzyme
Enterococci can be folate auxotrophs
requiring environmental acquisition of
folic acid for growth
They become intrinsically resistant to
the folic acid inhibitors (sulfa drugs or
trimethoprim) in the process
34. Cross resistance
Acquisition of resistance to one antibiotic conferring resistance to another
antibiotic, to which the bacteria has not been exposed
More common between chemically related drugs
Complete
Resistance to one tetracycline
means insensitivity to others
Partial
Gentamicin-resistant strains may
respond to amikacin
Two-way
Erythromycin and clindamycin
and vice versa
One-way
Enterobacteriaceae resistant to
neomycin will be resistant to
streptomycin, but many other
bacteria resistant to streptomycin
remain susceptible to neomycin
35. Constitutive resistance vs. Inducible resistance
Resistant strains of Gr+ve and Gr-ve bacteria inactivate chloramphenicol
by producing chloramphenicol acetyltransferase
Gr-ve bacteria exhibit five-fold higher resistance compared to Gr+ve
bacteria
In Gr-ve bacteria , the enzyme is present constitutively, i.e. available
even when the substrate drug is absent
In Gr+ve bacteria this enzyme is inducible, synthesized only when the
drug is present even in sub-therapeutic concentrations
The r-genes, usually present on plasmids, are
disposed of when bacteria are in antibiotic-free
media
In presence of repeated environmental antibiotic
exposure, eg. In hospitals and ICUs
37. Measures to combat antibiotic resistance
1. Public awareness and education
2. Antibiotic Stewardship Program
3. Rapid point-of-care diagnostic tests
4. WASH and IPC
5. Development of new antibiotics/Alternatives
39. Antibiotic Stewardship Program: Goals
Optimal treatment with antibiotics
Prevent antimicrobial overuse, misuse, and abuse
Minimize the development of resistance
Secondary goal: Reduce healthcare costs without adversely impacting
quality of care
1.
2.
3.
Right antibiotic
Right dose
Right route
Right time
Right duration
41. Antimicrobial Stewardship Strategies:
Multidisciplinary
Individual instruction by an antibiotic-utilization expert appears to be the
most successful educational strategy, whereas utilization review is less
useful
Continuous reinforcement is necessary
Limiting the availability of agents on formulary - most direct method to
influence antimicrobial utilization
Simple way to prohibit the use of newer, more expensive antibiotics in
favor of older, equally effective drugs
1. Education
2. Antimicrobial Formulary Restriction
42. Certain antibiotic classes or agents have a lower intrinsic risk of
selecting for antimicrobial resistance
Antimicrobial “cycling” ensures homogenous antimicrobial use delaying
emergence of resistance
Justification by prescribers and approval by infectious diseases
physicians to limit the use of systemic antimicrobial agents
Prospective audit of antimicrobial prescribing (usually accomplished by
daily review of prescriptions of targeted antimicrobials), coupled with
feedback to physicians to improve antimicrobial use
Resistance in Pseudomonas spp. was more difficult to achieve with
meropenem than with imipenem because two mutations were required
rather than one
3. Prior Approval and Justification
4. Prospective Audit and Feedback
43. Clinic Hospital
Does the patient have a
bacterial infection?
No
No
antibiotics
Conduct proper microbiological diagnosis
Yes
Interpret results; evaluate AST data
Does the patient have a
bacterial infection?
Initiate prompt empiric
antibiotic therapy
Prescribe/ de-escalate the empiric therapy to a
narrow spectrum antibiotic
Appropriate antibiotic therapy with shortest duration
Is the patient prone to
a bacterial infection?
Optimal antibiotic
for short duration:
Bactericidal
Non-toxic
Inexpensive
Active against
typical pathogens
Prefer monotherapy over combination
Prefer oral dosing over intravenous
administration
Bacteriostatic vs. bactericidal antibiotic
Host factors
Supervise for potential contraindications like
allergies and toxicity
Reassess within 48 hours and adjust antibiotic
if necessary or stop antibiotic if indicated
Ensure patient adherence
46. Infection Prevention & Control
Hand hygiene compliance
Surveillance of infections due to MDROs and surveillance
cultures for asymptomatic MDROs colonization
Contact precautions: gowns, gloves, PPE
Patient isolation: patient cohorting or single room isolation
Environmental cleaning
Multimodal IPC strategies
47. The US National Institutes of Health (NIH), the world’s
largest single funder of health research, allocated just
1.2 percent of its grant funding to AMR-related
research between 2009 and 2014, compared to 18.6
percent (more than five billion USD annually) to cancer
research
Lack of investment in R & D
48.
49. Quorum Sensing Inhibitors (QSIs)
Bacteria communicate with each other and exchange chemical signal
molecules called autoinducers
This process termed as quorum sensing allows bacteria to co-ordinate
gene expression for resistance
Occurs only when the population of bacterial cells reach a critical
density (quorum) with a minimal threshold stimulatory concentration
of an autoinducer
Bacteria Autoinducer
Gr+ve Acylhomoserine lactone (AHL)
Gr-ve Autoinducing peptide (AIP)
Gr+ve and Gr-ve Autoinducer-2 (AI-2)
Synthetic furanones
50. Phage Therapy
Therapeutic use of bacteriophages to treat pathogenic bacterial
infections
Bacteriophages are very specific, targeting only one or a few strains of
bacteria
Harmless to the gut flora, reducing the chances of opportunistic
infections
Especially successful in case of a biofilm covered by a polysaccharide
layer, which antibiotics typically cannot penetrate
Phages currently being used therapeutically to treat bacterial infections
that do not respond to conventional antibiotics in Russia, Georgia and
Poland
In 2007, a Phase 1/2 clinical trial was completed at the Royal National
Throat, Nose and Ear Hospital, London, for P. aeruginosa infections
(chronic otitis)
Phase 1 clinical trial completed in the Southwest Regional Wound
Care Center, Lubbock, Texas for an approved cocktail of phages
against bacteria, including P. aeruginosa, S. aureus and E. coli.
(chronic venous leg ulcers)
51. “Some experts say we are moving back to the pre-
antibiotic era. No. This will be a post-antibiotic era. In
terms of new replacement antibiotics, the pipeline is
virtually dry. A post-antibiotic era means, in effect, an
end to modern medicine as we know it. Things as
common as strep throat or a child's scratched knee
could once again kill.”
- Margaret Chan
Former Director-General, WHO
52. References
Opal SM, Pop-Vicas A. Molecular Mechanisms of Antibiotic Resistance in
Bacteria. In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and
Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia.
Saunders; 2015.
Gumbo T. General Principles of Antimicrobial Therapy. In: Brunton LL, Hilal-
Dandan R, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological
Basis of Therapeutics. 13th ed. New York. The McGraw-Hill Companies, Inc.;
2018.
Satoskar RS, Rege NN, Bhandarkar SD. Pharmacology and
Pharmacotherapeutics. 25th ed. Mumbai: Popular Prakashan Private Limited;
2013. Chapter 51, General Principles of Chemotherapy of Infections; p.718-28.
Tripathi KD. Essentials of Medical Pharmacology. 7th Ed. New Delhi: Jaypee
Brothers Medical Publishers (P) Ltd; 2013. Chapter 49, Antimicrobial Drugs:
General Considerations; p.688-703.
Sharma HL, Sharma KK. Sharma’s & Sharma’s Principles of Pharmacology. 3rd
Ed. New Delhi: Paras Medical Publisher; 2017. Chapter 52, Introduction to
Chemotherapy; p.699-713.
MacDougall C. Antimicrobial Stewardship. In: Bennett JE, Dolin R, Blaser MJ,
editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious
Diseases. 8th ed. Philadelphia. Saunders; 2015.
53. References
Magiorakos AP et al. Multidrug-resistant, extensively drug-resistant and
pandrug-resistant bacteria: an international expert proposal for interim standard
definitions for acquired resistance. Clin Microbiol Infect. 2012 Mar;18(3):268-81.
Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial
pathogens: no ESKAPE. J Infect Dis. 2008 Apr 15;197(8):1079-81.
Singhal N, Kumar M, Kanaujia PK, Virdi JS. MALDI-TOF mass spectrometry: an
emerging technology for microbial identification and diagnosis. Front Microbiol.
2015 Aug 5;6:791.
Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A,
Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen
DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K. A
newantibiotic kills pathogens without detectable resistance. Nature. 2015 Jan
22;517(7535):455-9.
https://www.Nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf
Discovered the world's first antibiotic substance benzylpenicillin (Penicillin G) from the mould Penicillium notatum in 1928, for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain
(i.e. bacterial isolates remain susceptible to only one or two categories)
(i.e. no agents tested as susceptible for that organism)
MDROs
ESKAPE pathogen (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), a group of pathogens with a high rate of antibiotic resistance that are responsible for the majority of nosocomial infections
Methicillin
Vancomycin
Carbapenem
Colistin
Clostridium difficile
Neisseria gonorrhoeae
WHO
Treatment of MDR-TB requires second-line drugs (i.e., Fluoroquinolones, IV aminoglycosides – amikacin, kanamycin, capreomycin
), which in general are less effective, more toxic and much more expensive than first-line drugs. Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over $100,000 USD
Global Surveillance Report 2014 on AMR by WHO
Elevated MIC: Cefixime - 0.25 mcg/L Ceftriaxone – 0.125 mcg/L
UK Prime Minister commissioned the Review on
Antimicrobial Resistance in 2015 David Cameron
They lack the metabolic process or the target site which is affected by the particular drug
Bacteria are divided into two groups, Grampositive and Gram-negative, based on their cell wall formation and staining properties. Penicillin is effective only against Gram-positive bacteria because Gram negative bacteria have a lipopolysaccharide and protein layer that surrounds the peptidoglygan layer of the cell wall, preventing penicillin from attacking.
This type of resistance does not pose a significant clinical problem
Genetic variability is an evolutionary phenomenon which may occur by a variety of mechanisms – mutations, whole-scale rearrangements of large segments of DNA or acquisition of foreign DNA
When a microbial species is subjected to an existential threat, chemical or otherwise, that pressure will select for random mutations in the species’ genome that permit survival. Pathogens will evolve to develop resistance to the chemical warfare to which we subject them
Any sensitive population of a bacteria contains a few mutant cells which require higher concentration of the antibiotic for inhibition. These are selectively preserved and get a chance to proliferate when the sensitive cells are eliminated by the antibiotic. Thus, in time it would appear that a sensitive strain has been replaced by a resistant one. E.g. Rifampicin resistance
a mutation in the rpoB gene, which encodes the beta subunit of the bacteria's RNA polymerase. In non-resistant TB, rifampin binds the beta subunit of RNA polymerase and disrupt transcription elongation. Mutation in the rpoB gene changes the sequence of amino acids and eventual conformation of the beta subunit. In this case rifampin can no longer bind or prevent transcription, and the bacteria is resistant
here are many mutations that confer resistance to isoniazid (INH), including in the genes katG, inhA, ahpC and others. Amino acid replacements in the NADH binding site of InhA apparently result in INH resistance by preventing the inhibition of mycolic acid biosynthesis, which the bacterium uses in its cell wall. Mutations in the katG gene make the enzyme catalase peroxidase unable to convert INH to its biologically active form
Most common method
Gene cassettes have been identified for all antibiotics except for fluoroquinolones.
Direct physical mating between bacteria
Chromosomal or extrachromosomal conjugative plasmids containing r-genes , make a connecting tube (sex pili) between the two bacteria through which the plasmid itself can pass
Eg. Chloramphenicol resistance of typhoid bacilli, Streptomycin resistance of E. coli, penicillin resistance of Hemophilus and gonococci
(i.e., from a cell belonging to closely related or the same strain)
β-Lactamases can be classified according to their amino-acid structure into four molecular classes, A through D (Table 18-2), as first suggested by Ambler
Aminoglycoside-modifying enzymes confer antibiotic resistance through three general reactions: N-acetylation , O-nucleotidylation, and O-phosphorylation.
The outer membrane in Gr –ve bacteria is made of lipopolysaccharide is made up of tightly bound hydrocarbon molecules that impede the entry of hydrophobic antibiotics, such as nafcillin or erythromycin
The passage of hydrophilic antibiotics through this outer membrane is facilitated by the presence of porins, proteins that are arranged so as to form water-filled diffusion channels through which antibiotics may traverse.
Resistance to nalidixic acid and other quinolones in P. aeruginosa – mutational
Plasmid-mediated chloramphenicol resistance in E. coli
DNA gyrase is necessary for the supercoiling of chromosomal DNA in Gr –ve enteric bacteria to have efficient cell division
Alteration in DNA gyrase due to spontaneous mutations in gyrA gene that code of the two B subunits of the enzyme confer resistance to fluoroquinolones
IDSA – Infectious Diseases Society of America
SHEA – Society for Healthcare Epidemiology of America
alternating the predominant antimicrobial used for empirical therapy for all patients in a particular patient care area in a regular pattern over time
as bacteria in an intensive care unit (ICU) or hospital acquire new resistance genes directed against a predominant antibiotic, a new antibiotic to which the organism is susceptible will be introduced into the environment and will eradicate the emerging pathogens that are resistant to the prior antibiotics
Computer-assisted Stewardship Program affords a unique opportunity for instantaneous feedback, education, and alteration in prescription patterns
Common cold and flu
Investigate for potential focus of infection
targeting the most likely pathogen based on site of infection, age or prior antibiotic usage
For bacteria, dilution tests employ antibiotics in serially diluted concentra
tions
on solid agar or in broth medium that contains a culture of the test
microorganism. The lowest concentration of the agent that prevents visible
growth after 18–24 h of incubation is known as the minimum inhibitory
concentration (MIC).
Recently, nucleic acid amplification–based reactions of specific bacte
rial
genes have been used in the clinic for rapid diagnosis of drug resis
tance.
The genes targeted are those encoding known drug resistance
proteins or processes. For example, rifampin resistance in Mycobacterium
tuberculosis has been difficult to ascertain in a timely fashion: The bacteria
take 2 to 3 weeks to grow in order to identify them as a cause of disease,
and then a similar amount of time is needed to form some version of the
broth dilution tests. Small PCR reactors at points of care can purify and
concentrate a patient’s fluid sample, perform nucleic acid amplification of
a target gene, identify mutations, and provide a result in less than 2 h. In
other bacteria, MALDI-TOF MS is being used for identification of resis
tance
to drugs such as vancomycin in Staphylococcus aureus and is being
extended to many other compounds and bacterial species.
India, Indonesia, Nigeria and Brazil
Guidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities. Geneva: World Health Organization; 2017
WHO Guidelines on hand hygiene in health care should be implemented
Phages have been investigated as a potential means to eliminate pathogens like Campylobacter in raw food[23] and Listeria in fresh food or to reduce food spoilage bacteria
George Eliava Institute, Tbilsi, Georgia
Despite the limited effectiveness of colistin at 1 curing infection,
1
the risk of deteriorating renal function, and the fact that it has little activity against
2
Serratia spp., Providencia spp., and Proteus mirabilis [36, 37], in centres with
3
endemic carbapenem resistance, empiric therapy decisions now may likely dictate the
4
use of colistin over other agents
Keynote address at the conference on Combating antimicrobial resistance: time for action Copenhagen, Denmark 14 March 2012