The document discusses various aspects of antimicrobial drug resistance. It begins by defining antimicrobial drugs and antimicrobial resistance. It then covers the genetic basis of resistance including chromosome-mediated resistance, plasmid-mediated resistance, and transposon-mediated resistance. Specific mechanisms of resistance to different drug classes such as penicillins, cephalosporins, carbapenems, and quinolones are described. Non-genetic bases of resistance and methods to test antibiotic sensitivity and combat resistance are also summarized.
Antibiotics Resistance is a new issue in Microbiology-Medicine aspects, taken from Lange Review of Medical Microbiology, this purpose is for education only
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
Antibiotics Resistance is a new issue in Microbiology-Medicine aspects, taken from Lange Review of Medical Microbiology, this purpose is for education only
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
Molecular mechanisms of antimicrobial resistance in bacteria Jobir Nadhi
Molecular mechanisms of antimicrobial resistance in bacteria by highlighting the aspects of antimicrobial resistance
through a discussion of:
Bacterial strategies involved in resisting antimicrobial actions and
The molecular basis for bacterial resistance to
antimicrobial actions
some note kept in phrase are completed visualizing the picture.
mechanism of resistance of antibiotics, ESBL, b lactums, enterobactericae, metallobactums, carbapenemases, types of mechanism of resistance, history of antibiotics and resistance
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
Molecular mechanisms of antimicrobial resistance in bacteria Jobir Nadhi
Molecular mechanisms of antimicrobial resistance in bacteria by highlighting the aspects of antimicrobial resistance
through a discussion of:
Bacterial strategies involved in resisting antimicrobial actions and
The molecular basis for bacterial resistance to
antimicrobial actions
some note kept in phrase are completed visualizing the picture.
mechanism of resistance of antibiotics, ESBL, b lactums, enterobactericae, metallobactums, carbapenemases, types of mechanism of resistance, history of antibiotics and resistance
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
Wastewater treatment is a process used to remove contaminants from wastewater and convert it into an effluent that can be returned to the water cycle. Once returned to the water cycle, the effluent creates an acceptable impact on the environment or is reused for various purposes (called water reclamation).
The treatment process takes place in a wastewater treatment plant. There are several kinds of wastewater which are treated at the appropriate type of wastewater treatment plant. For domestic wastewater (also called municipal wastewater or sewage), the treatment plant is called a sewage treatment plant. For industrial wastewater, treatment either takes place in a separate industrial wastewater treatment plant, or in a sewage treatment plant (usually after some form of pre-treatment). Further types of wastewater treatment plants include agricultural wastewater treatment plants and leachate treatment plants.
To minimize the initial generation of waste materials through source reduction, then through reusing and recycling to further reduce the volume of the material being sent to landfills or incineration compared to the conventional approach of simply focusing on disposal of solid waste.
Biowaste is all types of waste that contains or is likely to contain hazardous biological agents (= live infectious or otherwise hazardous micro-organisms).
Biowaste is mainly generated in diagnostic and research laboratories ("biosafety labs"), as well as in hospitals (biowaste thus includes part of the hospital waste).
Patients suffering from COVID-19 displayed hypocalcemia, vitamin D deficiency, and are often immobilized due to the disease, which will contribute to bone demineralization.
Moreover, the patients regularly present with joint and muscle pain. These symptoms resemble early aging characteristics observed during the development of OA.
Although no viral presence in the joint could be observed, early aging environmental changes could contribute to the development of this early OA-like phenotype.
Drugs that target the renin-angiotensin and immune system were explored as a treatment option for COVID-related musculoskeletal alterations.
This includes RAS modulating therapy, circadian clock modulators, immunomodulators, and chronotherapy
We believe that SARS-CoV-2 contributes to early aging perturbations, such as endothelial and adipose tissue dysfunction, the most frequent long-lasting symptoms of SARS-CoV-2 infection as the result of this accelerated aging process.
Lung cancer is the most common cancer in males and second most common in females after breast cancer.
it is the third most commonly diagnosed and leading cause of cancer death in Pakistan, with an estimated 6,800 (4.6%) new cases and 6,013 (5.9%) deaths occurring in 2012
We have compared our data with the international statistics to see where do we stand.
In Pakistan, we do not have a valid central cancer registry at present which can provide a true picture of lung cancer. This calls for an urgent need to formulate a valid central cancer registry in the country in association with the local bodies.
Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus.
Most people who fall sick with COVID-19 will experience mild to moderate symptoms and recover without special treatment.
HOW IT SPREADS
The virus that causes COVID-19 is mainly transmitted through droplets generated when an infected person coughs, sneezes, or exhales. These droplets are too heavy to hang in the air, and quickly fall on floors or surfaces.
You can be infected by breathing in the virus if you are within close proximity of someone who has COVID-19, or by touching a contaminated surface and then your eyes, nose or mouth.
Microbial fuel cells are devices that use bacteria to turn the energy stored in chemical bonds into electrical current that we can use without the need for combustion. Essentially, we are harnessing the power of metabolism for electricity.
“Cytogenetics traditionally refers to the study of chromosomes by microscopy following the application of banding techniques, permitting identification of abnormalities of chromosome number, loss or gain of chromosomal material or positional changes”. Standardized nomenclature is critical for the accurate and consistent description of genomic changes as identified by karyotyping, fluorescence in situ hybridization and microarray. The International System for Human Cytogenomic Nomenclature (ISCN) is the central reference for the description of karyotyping, FISH, and microarray results, and provides rules for describing cytogenetic and molecular cytogenetic findings in laboratory reports. These laboratory reports are documents to the referring clinician, and should be clear, accurate and contain all information relevant for good interpretation of the cytogenetic findings.
This presentation is all about fuels & industrial chemicals.
Important highlights of this presentations are following
*Importance Of Organic Compounds in Fuel Industry
» Introduction of Organic Compounds & Organic Acids
» Why Organic Acids are of interest??
» Role of Organic Chemistry in oil industry
» Organic compound of gasoline
» Alkanes & Importance Of Alkanes
» Bioconversion of Maize Starch
» Starch
» Bioconversion
» Bio products From Starch Waste
» Maize & it’s Products
» Important Products From Maize
» Process OF Bioconversion Of Maize
» Fungal biomass protein production from Starch processing Water
» Ethanol production from various substrates
» Ethanol production from barley β-glucan by yeast displaying Aspergillus
» Ethanol production in solid substrate fermentation using thermo tolerant yeast
» Ethanol production by solid state fermentation of sweet sorghum using thermo tolerant yeast strain
» Ethanol production from agricultural biomass substrates
» Ethanol production From Starch & Molasses
» Industrially Important Amino Acids Production
» l-Lysine production & its uses
» Citric Acid Production & its uses
» Guluconic Acid Production & its uses
» Lactic Acid production & its Uses.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. Contents
• Introduction &History
• Principles of
Antibiotic Resistance
• Genetic Basis of
Resistance
• Specific Mechanisms
of Resistance
• Non – genetic basis
of Resistance
• Selection of
Resistant Bacteria
• Antibiotic Senstivity
Testing
• Use of Antibiotic
Combination
• Intresting Facts
About Antibiotics
2
3. 3
Antimicrobial Drugs
•Antimicrobial drugs are chemical
substances of natural or synthetic origin
that suppress the growth of, or destroy,
micro-organisms including bacteria,
fungi, helminths, protozoa and viruses.
4. 4
•They include penicillin
G, procaine penicillin,
benzathine penicillin,
and penicillin V.
•Penicillin antibiotics
are historically
significant because
they are the
first drugs that were
effective against many
previously serious
diseases, such as
syphilis, and infections
caused by
6. 6
Antimicrobial -Resistance
Antimicrobial resistance is the ability of
microbes to grow in the presence of a
chemical (drug) that would normally kill them
or limit their growth. Antimicrobial
resistance makes it harder to eliminate
infections from the body as
existing drugs become less effective
7. Antimicrobial resistance
•You are twice as likely to carry resistant bacteria after a single
course of antibiotics compared to someone who has not. The
greatest risk is 30 days following antibiotic treatment and is likely to
persist for up to 12 months.
•The longer the exposure to antibiotics, the greater the risk of
acquiring and spreading resistant bacteria.
• Prof Chris Del Mar (Bond Uni) “antibiotic resistance decays with
time with no antibiotic use”.
•The spread of antibiotic resistance is influenced by human
migration, travel, agricultural practices and indiscriminate use of
antibiotics.
8. 8
Antimicrobial Resistance in the
community
•The average consumer in the
community is more familiar with
the term antibiotic rather than
antimicrobial.
•Estimating antibiotic usage in the
community is a lot harder
compared to hospital use.
13. Bacteria produce enzymes
that inactivate the drug;
eg, lactamases
can inactivate
penicillins and
cephalosporins by
cleaving the
lactam ring of the
Bacteria synthesize
modified targets against
which the drug has no
effect;
eg, a mutant protein in the
30S ribosomal subunit
can result in resistance to
streptomycin, and a
methylated 23S rRNA can
resuk in resistance to
Bacteria decrease their
permeability such that
an effective intracellular
concentration of the drug
is not achieved
eg, changes in porins
[membrane transport
proteins can reduce
the amount of
penicillin entering the
Antibiotic Resistance
13
(1) . There are four major mechanisms that mediate
bacterial resistance to drugs
14. • The MDR pump
imports protons
and, in an
exchange-type
reaction, exports
a variety of
foreign
molecules
including
certain
antibiotics, such
as quinolones 14
Bacteria
actively
export
drugs using
a
"multidrug
resistance
pump"
MDR pump, or
"efflux" pump
16. High level Resistance
16
•The term high-level resistance refers to
resistance that
•cannot be overcome by increasing the dose of the
antibiotic.
•A different antibiotic, usually from another class
of
drugs, is used.
• Resistance mediated by enzymes such as
β-lactamases often result in high-level resistance,
as all the
drug is destroyed
17. Low level Resistance
17
•Low-level resistance refers to
resistance
that can be overcome by increasing the
dose of the antibiotic.
•Resistance mediated by mutations in the
gene encoding
a drug target is often low level, as the
altered target can
still bind some of the drug but with
reduced strength.
21. Chromosome -Mediated
Resistance
“It is due to mutation in the gene that code for either
the target of the drug or the transport system in the
membrane that controls the uptake of the drug”.
Frequency of spontaneous mutation ranges from 10–7
to 10–9 which is much lower than the frequency of
resistance plasmid.
22. Principle.
Lorem Ipsum
Lorem Ipsum Lorem Ipsum
Although an
organism
may become
resistant to
one
antibiotic ,
it will be
effectively
treated by
other
antibiotic.
03
Chances
that the
bacterium
will become
resistant to
both
antibiotics ,
is the
product of
two
probabilities
02
Frequency at
which bacterium
mutates to
becomes
resistant to
antibiotic A is
10^-7 and the
frequency at
which same
bacterium
mutates to
become resistant
to antibiotic B is
10^-8
01
24. Plasmid -mediated resistance.
“It is the transfer of antibiotic resistance genes which are
carried on plasmid”.
It is mediated by resistance plasmid.
25. Resistance plasmid (R factor)
Lorem Ipsum
They are
extrachromosomal
,circular,double
stranded DNA
molecules.
Lorem Ipsum
They carry the
genes for a variety
of enzymes that can
degrade antibiotics
and modify
membrane
transport system.
Lorem Ipsum
Plasmid carrying
resistance
plasmid gene is
twofold
Lorem Ipsum
They may carry one
antibiotic resistance
gene or may carry
two of these genes .
Lorem Ipsum
1. A bacterium
containing that
plasmid can be
resistant to more
than one class of
antibiotic.
2.Use of an antibiotic
that selects for an
organism resistant to
one antibiotic will
select for an organism
that is resistant to all
the antibiotics whose
resistance genes are
carried by the plasmid.
26.
27. Properties of R factor.
They can replicate independently of the bacterial chromosome .
Therefore a cell can contains many copies.
They can be transferred not only to cells of the same species but also to other species
and genera.
28.
29. R-factor
LARGE PLASMIDS.
• Molecular weight of about
60 million .
• They are conjugative R-
factor, which contains the
extra DNA to code for the
conjugation process.
SMALL PLASMIDS.
• Molecular weight of about
10 million .
• They are not conjugative ,
and contains only the
resistance genes.
30. Additional properties.
1. Resistance to metal ions (e.g.
they code for an enzyme that
reduces mercuric ions to
elemental mercury.
2. Resistance to certain bacterial
viruses by coding for restriction
endonucleases that degrade the
DNA of the infecting
bacteriophages .
31. Clinical importance.
1.
2.
3.
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sit amet, nibh est. A
magna maecenas,
quam magna nec
quis, lorem nunc.
Occurs in many
different species ,
especially in gram
negative rods.
Plasmids frequently
mediate resistance to
multiple drugs.
They have high rate of
transfer from one cell
to another , usually by
conjugation.
1.
2.
3.
34. Transposons.
• Genes that are transferred either within or between large pieces
of DNA.
• e.g. bacterial chromosomes and plasmids.
Drug resistance transposon.
“It is composed of three genes flanked on both
sides by shorter DNA sequence , usually a
series of inverted repeated bases that mediate
the interaction of transposons with the larger
DNA ”.
35. Three genes code.
• Transposase .
Enzyme that catalyzes excision and reintegration of
the transposon.
• Repressor.
• Regulates synthesis of transposase .
• Drug resistance gene.
39. Penicillins &
Cephalosporins
Several mechanisms of
resistance to these drugs.
• Cleavage by β-
Lactamases
(penicillinases and
cephalosporinases)
• β-Lactamases produced
by various organisms
have different properties.
• For example,
staphylococcal
penicillinase is inducible
by penicillin and is
secreted into the
40.
41. • Some β-lactamases produced by
several gram-negative rods are
located in the periplasmic space
near the peptidoglycan
• Not secreted into the medium.
• The β-lactamases produced by
various gram-negative rods have
different specificities:
• Some are more active against
cephalosporins.
• Others against penicillins.
42. • Penicillin analogues that bind strongly
to
β-lactamases and inactivate them are:
• Clavulanic acid
• Tazobactam
• Sulbactam
• Avibactam
• Combinations of these inhibitors and
penicillins (e.g., clavulanicacid and
amoxicillin [Augmentin]) can overcome
resistance mediated by many but not all
β-lactamases.
43. Extended-
spectrum beta-
lactamases
(ESBLs)
• Produced by several enteric bacteria, notably
• E. coli
• Klebsiella
• Enterobacter
• Proteus.
• ESBLs endow the bacteria with resistance to
all penicillins, cephalosporins, and
monobactams.
• However, these bacteria remain sensitive to
combinations
• such as piperacillin/tazobactam.
44. NDM 1
• In 2009, a new strain of highly
resistant Klebsiella was isolated in
India
• carrying a plasmid that encoded New
Delhi metallo-beta-lactamase(NDM-
1).
• This plasmid confers high-level
resistance to many antibiotics and has
spread from Klebsiella to other member
of the Enterobacteriaceae.
45.
46. Carbapene
ms
• Resistance to carbapenems, such as imipenem,
is caused by carbapenemases that degrade the
β-lactam ring. This enzyme endows the organism
with resistance to penicillins and cephalosporins
as well.
• Carbapenemases are produced by many enteric
gram-negative rods, especially
• Klebsiella
• Escherichia
• Pseudomonas.
• Carbapenem-resistant strains of Klebsiella
pneumoniae are an important cause of hospital-
acquired infections and are resistant to almost all
known antibiotics.
47.
48.
49. Vancomyc
in
• Resistance to vancomycin is caused by a
change in the peptide component of
peptidoglycan from d-alanyl-d-alanine,
which is the normal binding site for
vancomycin, to d-alanine- d-lactate, to
which the drug does not bind.
• Of the four gene loci mediating vancomycin
resistance, VanA is the most important.
• It is carried by a transposon on a plasmid
and provides high-level resistance to both
vancomycin and teicoplanin.
• The VanA locus encodes those enzymes
that synthesize d-alanine-d-lactate as well
as several regulatory proteins.
50.
51.
52. Aminoglycosi
des
• Resistance to aminoglycosides occurs by three
mechanisms:
(1) modification of the drugs by plasmid-encoded
phosphorylating, adenylylating, and acetylating
enzymes.
(2) chromosomal mutation
e.g., a mutation in the gene that codes for the target
protein in the 30S subunit of the bacterial ribosome
(3) decreased permeability of the bacterium to the drug.
53.
54. Tetracyclin
es
• Resistance to tetracyclines is the result of failure of the drug to
reach an inhibitory concentration inside the bacteria.
• This is due to plasmid-encoded processes that either reduce
the uptake of the drug or enhance its transport out of the cell.
55.
56. Chloramphenicol
• Resistance to chloramphenicol is due to a plasmid-encoded
acetyltransferase that acetylates the drug, thus inactivating it.
57. Erythromyci
n• Resistance to erythromycin is due primarily to a plasmid-
encoded enzyme that methylates the 23S rRNA, blocking
binding of the drug.
• An efflux pump that reduces the concentration of erythromycin
within the bacterium causes low-level resistance to the drug.
• An esterase produced primarily by enteric gram negative rods
cleaves the macrolide ring, which inactivates the drug.
58.
59. Sulfonamid
es
• Resistance to sulfonamides is mediated primarily by two
mechanisms:
• (1) a plasmid-encoded transport system that actively exports
the drug out of the cell
• (2) a chromosomal mutation in the gene coding for the target
enzyme dihydropteroate synthetase, which reduces the binding
affinity of the drug.
60.
61. Trimethopri
m
• Resistance to
trimethoprim is due
primarily to mutations in
the chromosomal gene
that encodes dihydrofolate
reductase, the enzyme
that reduces dihydrofolate
to tetrahydrofolate.
62. Quinolone
s
• Resistance to quinolones is due primarily to chromosomal
mutations that modify the bacterial DNA gyrase.
63. Rifampi
n
• Resistance to rifampin is due to a chromosomal
mutation in the gene encoding the bacterial RNA
polymerase, resulting in ineffective binding of the drug.
• Because resistance occurs at high frequency (10–5),
rifampin is not prescribed alone for the treatment of
infections.
• It is used alone for the prevention of certain infections
because it is administered for only a short time
64.
65. Isoniazid
• Resistance of M. tuberculosis
to isoniazid is due to mutations
in the organism’s catalase–
peroxidase gene. Catalase or
peroxidase enzyme activity is
required to synthesize the
metabolite of isoniazid that
actually inhibits the growth of
M. tuberculosis.
66.
67.
68. Ethambut
ol• Resistance of M. tuberculosis to ethambutol is due to mutations
in the gene that encodes arabinosyl transferase, the enzyme
that synthesizes the arabinogalactan in the organism’s cell wall.
69. Pyrazinami
de• Resistance of M. tuberculosis to pyrazinamide(PZA) is due to
• Mutations in the gene that encodes bacterial amidase, the
enzyme that converts PZA to the active form of the drug,
pyrazinoic acid.
72. There are several non-genetic
reasons for the failure of drugs to
inhibit the growth of bacteria:
• Bacteria can be walled off within an
abscess cavity that the drug cannot
penetrate effectively. Surgical drainage is
therefore a necessary adjunct to
chemotherapy.
73. Bacteria can be in a resting
state
• they are therefore insensitive to cell wall inhibitors
such as penicillins and cephalosporins.
• This is particularly true for certain bacteria such
as Mycobacterium tuberculosis that
remains in resting stage in tissues for many years,
during which it is insensitive to drugs. However,
when these bacteria begin to multiply, they become
susceptible to antibiotics.
74. •Under certain circumstances, organisms
that would ordinarily be killed by
penicillin can lose their cell walls,
survive as protoplasts, and be insensitive
to cell wall–active drugs. Later, if such
organisms resynthesize their cell walls,
they are fully susceptible to these drugs.
75. • The presence of foreign bodies makes
successful antibiotic treatment more difficult.
This applies to foreign bodies such as surgical
implants and catheters as well as materials that
enter the body at the time of penetrating
injuries, such as splinters and shrapnel.
76. • Several artifacts can make it appear that
the organisms are resistant.
• e.g., administration of the wrong drug or
the wrong dose or failure of the drug to
reach the appropriate site in the body.
78. Serious outbreaks of diseases
• Serious outbreaks of diseases caused by gram-
negative rods resistant to multiple
antibiotics have occurred in many developing
countries.
79. EXAMPLE
• In North America, many hospital acquired
infections are caused by multidrug-resistant
organisms.
80. Overuse and Misuse of Antibiotics
• Three main points of overuse and misuse of
antibiotics increase the likelihood of these
problems by enhancing the selection of resistant
mutants:
81.
82. 1. Some physicians use multiple antibiotics when one
would be sufficient, prescribe unnecessarily long courses
of antibiotic therapy, use antibiotics in self-limited
infections for which they are not needed, and overuse
antibiotics for prophylaxis before and after surgery.
83. 2. Antibiotics are used in animal feed to
prevent infections and promote growth.
This selects for resistant organisms in the
animals and may contribute to the pool of
resistant organisms in humans.
84.
85.
86. 3. In many countries, antibiotics are sold
over the counter to the general public;
this practice encourages inappropriate
and indiscriminate use of the drugs.
89. Antibiogram
• Term used to describe the results of antibiotic
susceptibility tests performed on the bacteria isolated
from patient.
• These results are the most important factor in
determining the choice of antibiotic which treat the
patient.
90. • Others factors such as the patient’s renal function &
hypersensitivity profile must be considered in
choosing antibiotics.
91. Types of Tests
• There are two types of tests used to determine the
antibiogram:
1ST Type
• The Tube Dilution test that determines the minimal
inhibitory concentration.
92. 2nd Type
Disk Diffusion (Kirby-Bauer) test determines the
diameter if zone of inhibition.
93. Minimal Inhibitory Concentration
(MIC)
• For many infections, the results of sensitivity testing
are important in the choice of antibiotic.
• These results are commonly reported as the minimal
inhibitory concentration,
Defined as;
“Lowest concentration of drug that inhibits the growth
of organism”.
94. • The MIC is determined by inoculating the organism
isolated from the patient into series of tubes or cups
containing twofold dilution of drug.
• After incubation of at 35°C for 18 hours, the lowest
concentration of drug that prevents the visible growth of
organism is the MIC .
95.
96. A second method of determining antibiotic sensitivity
is the disk diffusion method,
in which disks impregnated with various antibiotics
are placed on the surface of an agar plate that has
been inoculated with the organism isolated from
patient.
97. After the incubation at 35°C
for 18 hours, during which
time the antibiotic diffuses
outward from the disk,
the diameter of the zone of
inhibition is compared with
the standards to determine
the sensitivity of the
organisms to drug.
98. Minimal Bactericidal Concentration
(MBC)
• For certain infections, such as endocarditis, it is
important to know the concentration of drug that
actually kills the organism rather than the conc. that
merely inhibits growth.
• This conc. called the minimal bactericidal
concentration(MBC),determined by taking a small
sample(0.01 or 0.1ml) from the tubes used for MIC
assay spreading it over the blood agar plate.
99. • Any organisms that were inhibited but not killed now
have a chance to grow because the drug has been
diluted significantly.
• After incubation at 35°C foe 48 hours, the lowest
concentration that has reduced the No. of colonies by
99.9%, compared with the drug-free control, is the
MBC.
100. • Bactericidal drugs usually have an MBC equal or very
similar to the MIC, whereas bacteriostatic drugs
usually have an MBC significantly higher than the
MIC.
101. Serum Bactericidal Activity
• In the treatment of endocarditis, it can be useful to
determine whether the drug is effective by assaying
the ability of the drug’s in the patient’s serum to kill
organism.
• This test is called serum bactericidal activity.
102. • This test is performed in a manner similar to that of
the MBC determination, except that it is a serum
sample from the patient, rather than a standard drug
solution, that is used.
103. • After a standard inoculum of the organism has been
added and the mixture has been incubated at 35°C
for 18 hours,
a small sample is sub cultured onto blood agar plates,
and the serum dilution that kills 99.9% of the
organisms is determined.
105. β-Lactamase Production
• For severe infections caused by certain organisms, such as S.
aureus and Haemophilus influenzae, it is important to know
as soon as possible whether the organism isolated from the
patient is producing β-lactamase.
• For this purpose,rapid assays for the enzyme can be used that
yield an answer in a few minutes, as opposed to an MIC test or
a disk diffusion test, both of which take 18 hours.
106. Beta-lactamases (dark orange) bind to
the antibiotics (light blue) and cleave the
beta-lactam ring.
The antibiotic is no longer able to inhibit
the function of PBP (orange sunburst)
Beta-lactamases
107. • A commonly used procedure is the chromogenic β-
lactam method, in which a colored β-lactam drug is
added to a suspension of the organisms.
• If β-lactamase is made, hydrolysis of the β-lactam
ring causes the drug toturn a different color in 2 to
10 minutes.
• Disks impregnated with a chromogenic β-lactam
can also be used.
108. β-lcatamase containing
microbes
• Gram-positives(e.g., S. Aureus)
• Gram-negative (e.g., E. Coli)
• Vancomycin-intermediate S. Aureus (VISA)
• S. Pneumoniae, gonococcus
• Gram-negative bacteria(e.G., Ps.
Aeruginosa)
109.
110. Combinational drugs
• Two drugs can interact in one of several ways.
• They are usually indifferent to each other.
• Sometimes there is a synergistic interaction, in
which the effect of the two drugs together is
significantly greater than the sum of the effects of the
two drugs acting separately.
• Rarely, the effect of the two drugs together is
antagonistic, in which the result is significantly
lower activity than the sum of the activities of the
two drugs alone.
111. Use of Antibiotic Combinations
• Two or more antibiotics are used under certain
circumstances,
• To treat life-threatening infections before the
cause has been identified
112. • To prevent the emergence of resistant
bacteria during prolonged treatment
regimens,
• To achieve a synergistic (augmented)
effect.
113. USE OF ANTIBIOTIC
COMBINATIONS
• In most cases, the single best antimicrobial
agent should be selected for use because this
minimizes side effects.
• However, there are several instances in which
two or more drugs are commonly given:
(1) To treat serious infections before the identity
of the organism is known.
114. (2) To achieve a synergistic inhibitory effect
against certain organisms.
(3) To prevent the emergence of resistant
organisms. (If bacteria become resistant to one
drug, the second drug will kill them, thereby
preventing the emergence of resistant strains.)
115. Synergistic
effect
• A synergistic effect is one in which the effect
of two drugs given together is much greater
than the sum of the effect of the two drugs
given individually.
• The best example of synergyis the marked
killing effect of the combination of a penicillin
and an aminoglycoside on enterococci
compared with the minor effect of either drug
given alone.
116. Examples of synergistic effect
• A synergistic effect can result from a variety of
mechanisms.
• For example, the combination of a penicillin and an
aminoglycoside such as gentamicin has a synergistic
action against enterococci (E. faecalis), because
penicillin damages the cell wall sufficiently to
enhance the entry of aminoglycoside.
• When given alone, neither drug is effective.
117. • A second example is the combination of a
sulfonamide with trimethoprim.
• In this instance, the two drugs act on the same
metabolic pathway, such that if one drug does
not inhibit folic acid synthesis sufficiently
• The second drug provides effective inhibition
by blocking a subsequent step in the pathway.
118. Combination Drugs
• Sulbactam
– With ampicillin (Unasyn®)
• Tazobactam
– With pipercillin (Zosyn®)
• Clavulanate/Clavulanic acid
– With amoxicillin (Augmentin®)
– With ticarcillin (Timentin®)
119. Antagonism
• Although antagonism between two antibiotics is
unusual, one example is clinically important.
• This involves the use of penicillin G combined
with the bacteriostatic drug tetracycline in the
treatment of meningitis caused by S.
pneumoniae.
• Antagonism occurs because the tetracycline
inhibits the growth of the organism, thereby
preventing the bactericidal effect of penicillin G,
which kills only growing organisms
120. 63
Combination Antibiotic therapy
• Life threatening sepsis of unknown cause
• Increased bactericidal effect against a specific microbe
is desired.
• E.g. treatment of infections caused by enterococcus
• Prevention of rapid emergence of resistant bacteria
E.g. tuberculosis.
• Empiric treatment of certain odontogenic infections
E.g. Penicillin G & Metronidazole
124. MYTH: All ear
infections, sinus
infections and
bronchitis need
antibiotics
• FACT: Most of these
infections will resolve
on their own. Now
recommend a “wait and
see” approach. Take
medication for pain and
symptom relief. If
symptoms don’t
improve in a few days
then see your doctor.
1
2
4
125. Antibiotics – Proper Use
125
•If you do require an antibiotic:
•Important to finish the entire
prescription even if you start feeling
better
•Do not share or keep unused antibiotics
for another time
•Antibiotics are specific to the infection
they are treating
•Some antibiotics are not safe in
children or for others.
127. Antibiotic resistance continues to
plague antimicrobial
chemotherapy of infectious diseases”
Keith.
Poole. J Antimicrob Chemother 2005;
56: 20-51
“Evolution of bacteria towards
resistance… …is unavoidable
because it represents a particular
aspect of the general
evolution of bacteria that is
unstoppable”
Patrice Courvalin. Emerg Infect Dis
2005; 11: 1507-6
“Antibiotic resistance has resulted
in a continuous need for
new therapeutic alternatives”
Carl Erik
Nord. Clin Microbiol Infect 2004;10
(Supp 4)
“There is a need to re-invigorate
antimicrobial development,
which has been downgraded by major
pharmaceutical houses”
David Livermore. Lancet Infect Dis
2005; 5:450-59
127
Summar
y
Anti microbial
drugs ;Resistance
Costelloe – meta-analysis of 24 studies. eg. children in pre-schools, 12% have acquired resistance
The current 2010 Therapeutic Guidelines on antibiotics - shorten the duration of most antibiotic courses to 5 to 7 days. Unless co-morbidities- immuno-compromised diabetes
Indiscriminate use can be inappropriate prescribing or use or sale of antibiotics - we know that antibiotics can be purchased OTC in many countries.