The document discusses multi-drug resistance and antibiotic resistance. It provides background on the history of antibiotics and resistance. It then covers the major topics of how antibacterial resistance develops through various mechanisms like mutations, plasmids, efflux pumps, and inactivating enzymes. The document also discusses the Indian scenario of rising drug resistance and the growing problem of NDM-1 enzyme production. It concludes by outlining some strategies to address resistance like developing new antibiotics, prudent antibiotic use, and alternative approaches like phage therapy and quorum sensing inhibition.
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
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
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
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
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.
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
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.
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.
To understand the mechanisms of antimicrobial action and the classification of antimicrobial drugs.
To explain the process of microbial resistance.
To understand the spread of resistant microbes.
Outlines the prevention of microbial resistance.
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.
Antimicrobial resistance is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals, and antifungals) from working against it.
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.
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
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.
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.
To understand the mechanisms of antimicrobial action and the classification of antimicrobial drugs.
To explain the process of microbial resistance.
To understand the spread of resistant microbes.
Outlines the prevention of microbial resistance.
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.
Antimicrobial resistance is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals, and antifungals) from working against it.
Antibiotics Resistance is a new issue in Microbiology-Medicine aspects, taken from Lange Review of Medical Microbiology, this purpose is for education only
Description of the major classes of antimicrobial drug, resistant mechanisms developed by bacteria to combat the action of antimicrobials, and the control measures needed to limit this horizontal gene transfer.
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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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.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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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
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. Objectives
• What is antimicrobial resistance
• Why antibacterial resistance is a concern
• How antibacterials work
• Mechanisms of resistance to antibacterials
• Indian scenario
• NDM-1
• Factors responsible for Resistance
• Alternate & Trending approaches
3. Introduction
• Throughout history there has been a continual
battle between human beings and multitude
of micro-organisms that cause infection and
disease
4. 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, and the
same thing has occasionally happened in the body…
…and by exposing his microbes to non-lethal
quantities of the drug make them resistant.”
History
Nobel Lecture, December 11, 1945
Sir Alexander Fleming
The Nobel Prize in Physiology or Medicine 1945
6. Why resistance is a concern
• Resistant organisms lead to treatment failure
• Increased mortality
• Resistant bacteria may spread in Community
• Low level resistance can go undetected
• Added burden on healthcare costs
• Threatens to return to pre-antibiotic era
• Selection pressure
7. Drug resistance occurs in :
BACTERIA—ANTIBIOTIC RESISTANCE
Endoparasites
Viruses—Resistance to antiviral drugs
Fungi
Cancer cells
Drug Resistance
8. What is Multi Drug Resistance
MDROs are microorganisms,
predominantly bacteria, that are resistant
to one or more classes of antimicrobial
agents
Examples of MDROs
Methicillin-resistant staphylococcus aureus (MRSA)
Vancomycin-intermediate staphylococcus aureus (VISA)
Vancomycin-resistant staphylococus aureus (VRSA)
Vancomycin-resistant enterococcus (VRE)
Streptococcus pneumoniae resistant to penicillin and other broad-
spectrum agents
9. • The concentration of drug at the site of
infection must inhibit the organism and also
remain below the level that is toxic to human
cells.
GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006)
Antibiotic Resistance
10. Antibiotic Resistance
Defined as micro-organisms that are not
inhibited by usually achievable systemic
concentration of an antimicrobial agent with
normal dosage schedule and / or fall in the
minimum inhibitory concentration (MIC)
range.
Antibiotic Resistance (DR)
= MIC / MCC > Toxic Plasma Concentration
13. 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
14. Intrinsic Resistance
1. Lack target :
• No cell wall; innately resistant to penicillin
2. Innate efflux pumps:
• Drug blocked from entering cell or ↑ export
of drug (does not achieve adequate internal
concentration). Eg. E. coli, P. aeruginosa
3. Drug inactivation:
• Cephalosporinase in Klebsiella
It occurs naturally.
15. Acquired resistance
Mutations
• 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
16. Plasmids
• Extra chromosomal genetic elements can replicate
independently and freely in cytoplasm.
• Plasmids which carry genes resistant ( r-genes) are called R-
plasmids.
• These r-genes can be readily transferred from one R-plasmid to
another plasmid or to chromosome.
• Much of the drug resistance encountered in clinical practice is
plasmid mediated
17. Mechanisms of Resistance Gene Transfer
• Transfer of r-genes from one bacterium to
another
Conjugation
Transduction
Transformation
• Transfer of r-genes between plasmids within
the bacterium
By transposons
By Integrons
18. Transfer of r-genes from one bacterium to another
Conjugation : Main mechanism for spread of resistance
The conjugative plasmids make a connecting tube
between the 2 bacteria through which plasmid itself
can pass.
Transduction : Less common method
The plasmid DNA enclosed in a bacteriophage is
transferred to another bacterium of same species.
Seen in Staphylococci , Streptococci
Transformation : least clinical problem.
Free DNA is picked up from the environment (i.e..
From a cell belonging to closely related or same strain.
19. Mechanisms of Resistance Gene Transfer
Transposons
Transposons are sequences of DNA
that can move around different
positions within the genome of single
cell.
The donor plasmid containing the
Transposons, co-integrate with acceptor
plasmid. They can replicate during
cointegration
Both plasmids then separate and each
contains the r-gene carrying the
transposon.
Eg ; Staphylococci,Enterococci
20.
21. Mechanisms of Resistance Gene Transfer
Integrons
Integron is a large mobile DNA
can spread Multidrug resistance
Each Integron is packed with
multiple gene casettes, each
consisting of a resistance gene
attached to a small recognition site.
These genes encode several
bacterial functions including
resistance and virulence.
They cannot promote self transfer
22. Biochemical mechanisms of antibiotic
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
23. Decreased permeability: Porin Loss
Interior of organism
Cell wall
Porin channel
into organism
Antibiotic
Antibiotics normally enter bacterial cells via porin channels
in the cell wall
24. Decreased permeability: Porin Loss
Interior of organism
Cell wall
New porin channel
into organism
Antibiotic
New porin channels in the bacterial cell wall do not allow
antibiotics to enter the cells
25. ATP Binding Cassette
Multidrug and toxic compound exporter
Small multidrug resistance transporters
Resistance-nodulation-division
Major facilitator superfamily
Efflux pumps
• Cytoplasmic membrane transport proteins.
• Major mechanism for resistance in Tetracyclines.
• Some gram -ve bacteria inhibit the plasmid
mediated synthesis of porin channels ,which
obstructs the influx of hydrophilic Penicillins
eg.ampicillin
26. Structurally modified antibiotic target site
Interior of organism
Cell wall
Target siteBinding
Antibiotic
Antibiotics normally bind to specific binding proteins on the
bacterial cell surface
27. Structurally modified antibiotic target site
Interior of organism
Cell wall
Modified target site
Antibiotic
Changed site: blocked binding
Antibiotics are no longer able to bind to modified binding proteins
on the bacterial cell surface
28. Modification/Protection of the Target site
Resistance resulting from altered target sites :
Target sites Resistant Antibiotics
Ribosomal point mutation Tetracyclines,Macrolides
, Clindamycin
Altered DNA gyrase Fluoroquinolones
Modified penicillin binding
proteins (Strepto.pneumonia)
Penicillins
Mutation in DNA dependant
RNA polymerase
(M.tuberculosis)
Rifampicin
30. Antibiotic inactivation
Interior of organism
Cell wall
Antibiotic
Target siteBindingEnzyme
Enzyme
binding
Enzymes bind to antibiotic molecules
31. Antibiotic inactivation
Interior of organism
Cell wall
Antibiotic
Target siteEnzyme
Antibiotic
destroyed
Antibiotic altered,
binding prevented
Enzymes destroy antibiotics or prevent binding to target sites
32. By producing enzymes that inactivates antibiotic
a)Inactivation of b-lactam antibiotics
•S. aureus, N. gonorrohoea, H.influenza, Produce b-
lactamase which cleaves -lactam ring
b)Inactivation of Chloramphenicol
• Inactivated by chloramphenicol acetyltransferase .
• Gram-ve (enzyme present constitutively hence higher
resistance) gram +ve bacteria (enzyme is inducible )
c)Inactivation of Aminoglycosides
• Inactivated by acetyl, phospho & adenylyl transferases
Present in gram +ve and gram –ve .
33. Use of alternative pathways for metabolic / growth
requirements
• Resistance can also occur by alternate
pathway that bypasses the reaction inhibited
by the antibiotic.
• Sulfonamide resistance can occur from
overproduction of PABA
34. Drug Mechanism of resistance
Pencillins &
Cephalosporiins
B Lactamase cleavage of the Blactam ring
Aminoglycosides Modification by phosphorylating, adenylating
and acetylating enzymes
Chloramphenicol Modification by acetylytion
Erythromycin Change in receptor by methylation of r RNA
Tetracycline Reduced uptake / increased export
Sulfonamides
Active export out of the cell & reduced affinity
of enzymes
35. Indian scenario
• Lack of community awareness
• Availability over the counter
• Absence of central monitoring agency
• S. Pneumoniae fully resistant to cotrimoxazole
• Still sensitive to penicillins, macrolides and
fluoroquinolones
37. STD
• Penicillin and fluoroquinolone resistance is
widespread to gonorhhoea
• Alternate drugs like Azithromycin and
cephalosporins should be used
• Syphilis still susceptible to Penicillins
38. Gram positive Cocci
• Streptococci other than S. Pneumoniae
– Resistant to tetracycline and macrolides (40%)
– Still sensitive to penicillins
• Staph Aureus
– Methicillin resistance 50%-100%
– Vancomycin resistance also increasing
39. Mycobacteria
• Multidrug resistance
– Combined resistance to rifampicin and isoniazid
• Extensively drug resistant TB
– Additional acquisition of resistance to a
fluroquinolone and one of the three injectable
second line drugs (capreomycin, kanamycin and
amikacin)
• Steady rise in these patients
40. What is NDM-1?
• NDM-1 stands for New Delhi metallo-beta-
lactamase, an enzyme produced by certain
strains of bacteria that have recently acquired
the genetic ability to make this compound.
• The enzyme is active against other compounds
that beta-lactam ring like penicillins,
cephalosporins, and the carbapenems.
• bacteria that produce NDM-1 are resistant to
all commonly used beta-lactam antibiotics,
including carbapenems.
41. New Delhi metallo-beta-lactamase Why
everyone concerned ?
• There are currently no
new drugs in the research
pipelines that aim to stop
NDM-1.To date, some
strains of E.coli and
Klebseilla pneumoniae
are known carriers of the
gene, but the gene can be
transmitted from one
strain of bacteria to
another through horizontal
gene transfer.
42. Naming the strain as New Delhi creates
controversy
• The gene was named after New Delhi, the capital city
of India, as it was first described by Yong et al. in 2009
in a Swedish national who fell ill with an antibiotic-
resistant bacterial infection that he acquired in India .
The infection was unsuccessfully treated in a New Delhi
hospital and after the patient's repatriation to Sweden,
a carbapenem-resistant Klebsiella pneumoniae strain
bearing the novel gene was identified. The authors
concluded that the new resistance mechanism "clearly
arose in India, but there are few data arising from India
to suggest how widespread it is."
43. Treatment
• Many NDM-1 strains are resistant to all antibiotics
except for colistin.
• Colistin is an older antibiotic that has not been
used much in recent decades, because it is
somewhat more toxic than other antibiotics.
• A few NDM-1 strains have been sensitive to
tigecycline (Tygacil), but this agent should be used
cautiously in serious infections because it does not
achieve high levels in the bloodstream.
• A few strains have also been sensitive to
aztreonam
44. The spread of NDM-1 can be
contained with
• The spread of NDM-1 within health-care
facilities can be curbed through strict
infection-control measures, including patient
isolation and hand washing.
..
45. Strategy to Contain Resistance
• Develop new antibiotics
–Bypass the drug resistance
• Judicious use of the existing
antibiotics:
–Containment of drug resistance
46. New Antibiotic Development
• Only 15 antibiotics of 167 under development
had a new mechanism of action with the
potential to combat of multidrug resistance.
• Lack of incentive for
companies to develop
antibiotics.
47. Phage therapy
• Phage Therapy is the therapeutic use of lytic bacteriophages to
treat pathogenic bacteria infections
• Bacteriophages are viruses that invade bacterial cells and
disrupt bacterial metabolism and cause the bacterium to lyse.
• Bacteriophage therapy is an important alternative to antibiotics
• The success rate was 80–95% with few gastrointestinal or
allergic side effects. British studies also demonstrated significant
efficacy of phages against Escherichia coli, Acinetobacter spp.,
Pseudomonas spp and Staphylococcus aureus.
Alternate Approaches
48. Quorum sensing
• Microbes communicate with each other and
exchange signaling chemicals (Autoinducers)
• These autoinducers allow bacterial population
to coordinate gene expression for virulence,
conjugation, apoptosis, mobility and
resistance
49. Why named quorum sensing
• Single autoinducer from single microbe is
incapable of inducing any such change
• But when its colony reaches a critical density
(quorum), threshold of autoinduction is
reached and gene expression starts
• QS signal molecules AHL, AIP, AI-2 & AI-3 have
been identified in Gm-ve bacteria
• AI-2 QS –system is shared by GM+ve bacteria
also
50. WHY INHIBIT QUORUM SENSING
Proved to be very potent method for bacterial virulence
inhibition.
Several QS inhibitors molecules has been synthesized which
include AHL, AIP, and AI-2 analogues
QS inhibitors have been synthesized and have been isolated
from several natural extracts such as garlic extract.
QS inhibitors have shown to be potent virulence inhibitor
both in in-vitro and in-vivo,using infection animal models.
51. Factors of Antibiotic Resistance
Environmental
Factors
Drug Related
Factors
Patient Related
Factors
Prescriber
Related Factors
Antibiotic
Resistance
52. • Huge populations and overcrowding
• Rapid spread by better transport facility
• Poor sanitation
• Increases community acquired resistance
• Ineffective infection control program
• Widespread use of antibiotics in animal husbandry
and agriculture and as medicated cleansing products
1. Environmental Factors
53. • Over the counter availability of antimicrobials
• Counterfeit and substandard drug causing sub-
optimal blood concentration
• Irrational fixed dose combination of
antimicrobials
• Soaring use of antibiotics
2. Drug Related
Policy
Decision at
Higher level
54. • Poor adherence of dosage Regimens
• Poverty
• Lack of sanitation concept
• Lack of education
• Self-medication
• Misconception
3. Patient Related
Patient
Counseling,
Awareness
Program
55. Prescriber Related
• Inappropriate use of available drugs
• Increased empiric poly-antimicrobial use
• Overuse of antimicrobials
• Inadequate dosing
• Lack of current knowledge and training
56. Poor Clinical Practice
• Poor clinical practice that fail to incorporate
the pharmacological properties of
antimicrobials amplify the speed of
development of drug resistance.
Bubonic plague, TB , Malaria, hiv have affected significant number of hyman beings and caused mortality and morbidity
Adult humans contains 1014 cells, only 10% are human – the rest are bacteria
Antibiotic use promotes Darwinian selection of resistant bacterial species
Bacteria have efficient mechanisms of genetic transfer – this spreads resistance
Bacteria double every 20 minutes, humans every 30 years
Development of new antibiotics has slowed – resistant microorganisms are increasing
Antimicrobial agents were viewed as miracle cure when introduced into clinical practice. However it became evident rather soon after the discovery of penicillin that resistance develops quickly terminating the miracle. This serious development is ever present with each new antimicrobial agents and threatens end of antimicrobial area. Today even major class of antibiotics are resistant
If this can be achieved, the microorganism is considered susceptible to the antibiotic.
If an inhibitory or bactericidal concentration exceeds that which can be achieved safely in vivo, then the microorganism is considered resistant to that drug.
Antibiotic resistance refers to unresponsiveness of microorganism to antimicrobial agents.
Susceptible
MIC is at a concentration attainable in blood or other appropriate body fluid using usually recommended dosages
Resistant
MIC is higher than normally attainable levels in body fluids
Intermediate (moderately sensitive, moderately resistant)
MIC is between sensitive and resistant levels, may be able to treat with increased dosage
Presence of few mutants not sufficient to produce resistance
Single step : E.coli & staph to Rifampicin
Multistep : erythromycin, tetracyclines, chloramphenicol
The new DNA is then incorporated into the genome of the bacteria which becomes resistant.
They have insertion sequence at end of gene.
They are commonly associates with Transposons.
Commonly operate in
E.coli,P.aeruginosa,S.typhi,Staph.aureus,N.gonorroea.
It remains to be seen if widespread use of antibiotics in syndromic control of LRTI chanfes pattern overtime
Shigella
superbugsgene transfer.
Some antibiotics like aminoglycosides and fluoroquinolones do not contain beta-lactam rings. Unfortunately, the bacteria that have acquired NDM-1 have also acquired other resistance factors and most are already resistant to aminoglycosides and fluoroquinolones.
The addition of NDM-1 production has the ability to turn these bacteria into true superbugs (bacteria resistant to usually two or more antibiotics) which are resistant to virtually all commonly used antibiotics.
There are two different approaches to managing antibiotic resistance:
1.Managing existing resistant pathogens
2.Avoiding future evolution of more resistance
The first can be done by, in the case of MRSA, improving hygiene in hospitals, screening hospital visitors and isolating patients