Microbiology - Edwards Flashcards
1
Q
Difference bn prookaryotic + eukaryotic cell
A
Prokaryotes:
- much smaller
- often single celled
- single circular chromosome
- introns are rare
- 70s ribosomes
- rigid cell walls
- rapid cell cycle
Eukaryotes:
- complex, compartmental
- frequently multicellular
- linear chromsome + histones
- introns/exons
- 80s ribosomes
- flexible cell wall
- cell cycle, mitosis/meiosis
2
Q
Gram +
A
- rich, thick, peptidoglycan cell wall
(hence can stand bigger osmotic pressures) - no outer membrane
- no LPS , bc no outer membrane
- no periplasmic space
3
Q
Gram -
A
- peptidoglycan is reduced
- has an additional outer membrane
- often the additional outer membrane is decorated with LPS
** LPS referred to as ENDOTOXIN + linked to SEPSIS/SEPTIC SHOCK
** Antigen + Endotoxin + B cells + Inappropriate immune response
- has periplasmic space
v thin cytoplasmic cell wall
EXAMPLES:
- neisseria spp (STD/STI + meningitis)
- escherichia coli (GI tract)
4
Q
Bacterial growth + requirements
Prokaryotic Growth
A
- NUTRITION
- TEMPERATURE
- HYDROGEN ION CONCENTRATION
human commensals - approx 7 pH - OSMOTIC PROTECTION
human commensals - approx 0.85% NaCl
BACTERIAL GROWTH CURVE
- lag phase
- exponential growth phase
- stationary phase
- decline phase
5
Q
TB
A
- bacterium Mycobacterium tuberculosis
- primarily affects the lungs but can also spread to other parts of the body, including the brain, kidneys, spine, and lymph nodes
- spreads through the air when an infected person coughs, sneezes, or talks, releasing droplets containing the bacteria
- Persistent cough (lasting three weeks or longer), sometimes with blood-tinged sputum.
- Chest pain.
- Fever.
- Night sweats.
- Weight loss.
- Fatigue.
- Loss of appetite.
6
Q
Protozoa
single/multi?
living? non-living?
euk/prok?
A
single celled
eukaryotes
7
Q
Fungi
single/multi?
living? non-living?
euk/prok?
A
eukar
8
Q
Bacteria
single/multi?
living? non-living?
euk/prok?
A
single celled
PROKARYOTES
9
Q
Viruses
single/multi?
living? non-living?
euk/prok?
A
non-living
obligate parasites
Viruses are neither prokaryotic or eukaryotic. Viruses are not made of cells. Viruses cannot replicate on their own. Most scientists do not consider viruses to be livingm
Obligate parasite = a parasitic organism that is not able to complete its life cycle without exploitation of suitable host
10
Q
microbiome
A
collection of microorganisms, including bacteria, viruses, fungi, and protozoa, along with their genetic material, that live in a specific environment, such as the human body or a natural habita
11
Q
microflora / microbiota
A
community of microorganisms, including bacteria, fungi, viruses, and protozoa, that live on or within different parts of an organism, such as the human body, plants, or animals. These microorganisms a
12
Q
Difference in cell structure bn eukaryotes + prokaryotes
A
Eukaryotes:
- Cell membrane
* Nucleus
* Centriole/Centrosome
* Nucleolus/Ribosomes
* Endoplamsic Reticulum (ER)
* Cytosol
* Mitochondria
* Golgi
* Cytoskeleton
* Secretory Vessicles, Lysosomes
Prokaryotes:
- Plasma Membrane
* Cell Wall (Peptidoglycan)
* Nucleoid (DNA & associated proteins)
* Ribosomes
* Cytoplasm
* Capsule, Flagellar, PiliF
13
Q
Fermentation VS Anerobic respiration
A
both processes used by cells to generate energy in the absence of oxygen
14
Q
Fermentation
A
energy is produced by breaking down glucose (or other organic molecules) into smaller compounds without using the electron transport chain or an external electron acceptor.
○ Involves glycolysis only. ○ Pyruvate or its derivatives act as the final electron acceptors. ○ Produces a small amount of ATP (2 ATP per glucose).
END PRODUCTS:
○ Alcohol fermentation: Produces ethanol and CO₂ (e.g., in yeast).
○ Lactic acid fermentation: Produces lactic acid (e.g., in muscle cells under low oxygen).
common in:
- yeast
- bacteria
15
Q
Anaerobic respiration
A
A process that uses an electron transport chain to generate ATP, with a molecule other than oxygen (e.g., nitrate, sulfate, or carbon dioxide) serving as the final electron acceptor.
○ Includes glycolysis, the Krebs cycle, and an electron transport chain. ○ Uses inorganic molecules like nitrate (NO₃⁻) or sulfate (SO₄²⁻) as the terminal electron acceptor instead of oxygen. ○ Yields more ATP than fermentation but less than aerobic respiration (e.g., 20-30 ATP per glucose).
END PRODUCTS
-> Depends on the final electron acceptor. Examples:
§ Nitrate reduction produces nitrogen gas or ammonia.
§ Sulfate reduction produces hydrogen sulfide.
common in:
- some bacteria
- archaea
16
Q
Peptidoglycan cell wall
in bacteria
structure
A
peptide side chain:
- D-Ala-D-Ala
- Transpeptidation
repeated sugar chains:
- transglycosylation
Target of PENICILLIN
DD-Transpeptidase, a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls
17
Q
Flagella + Fimbriae
A
present in both Gram - and + bacteria
injection of toxins + genetic material
adherence, sex, motility
18
Q
Syphilis
A
an infection caused by bacteria. Most often, it spreads through sexual contact. The disease starts as a sore that’s often painless and typically appears on the genitals, rectum or mouth.
19
Q
E.Coli
A
20
Q
Facultative Anaerobs
A
Organisms that can survive and grow in both oxygen-rich (aerobic) and oxygen-poor (anaerobic) environments.
Metabolism:
Prefer aerobic respiration when oxygen is available because it yields more ATP.
Switch to anaerobic respiration or fermentation in the absence of oxygen.
Examples: Escherichia coli, Saccharomyces cerevisiae (yeast), and many species of Staphylococcus.
21
Q
Obligate Anaerobes
A
Organisms that cannot survive in the presence of oxygen. Oxygen is toxic to them due to the lack of protective enzymes (e.g., catalase, superoxide dismutase).
Metabolism:
Use anaerobic respiration or fermentation to generate energy.
Oxygen exposure can lead to the production of harmful reactive oxygen species (ROS).
Examples: Clostridium botulinum, Bacteroides fragilis, Methanogens.
Environment: Found in oxygen-free environments, such as deep soil, intestines, or anaerobic chambers.
22
Q
diagnostic approaches to identify prokaryotic pathogens
A
MOLECULAR TESTS:
- antigens (immunological)
- DNA sequencing 16sRNA, qPCR
- protein profiling (mass spec)
METABOLIC TESTS:
- Haemolysis (strepoccocci only) -> destruction of red blood cells
- catalse test/coagulase
GROWTH REQUIREMENTS:
- aerobic/anaerobic
- requirement for blood products (e.g. serum proteins)
- sensitivity to agens (bile / NaCl)
APPEARANCE
- shape
- size
- cell wall (Gram +/-)
23
Q
Gram stain classification
A
Retention of crystal violet/iodine complex by Gram+ bacteria
distinguishing Gram + and Gram - bacteria according to cell wall structure
stain with crystal violet and rinse:
+ = purple
- = purple
treat with gram’s iodine:
+ = crystal/violet iodine complex
_ = ‘’ ‘’
briefly decolorise with acetone:
+ = purple
- = no colour
counter stain with basic safranin, pink dye, rinse
+= purple
- = pink
** TB , myocobacterium tuberculosis will NOT stain, has lipid rich cell wall
** Treponema will NOT stain
24
Q
spore + toxin
A
25
Growth conditions
growth media
biochemical progiling
26
Antibodies
DNA
protein
ANALYSES
27
Streptococci
genus of gram-positive,
spherical bacteria
typically form chains or pairs when observed under a microscope
facultative anaerobes,
classified based on their hemolytic activity (their ability to lyse red blood cells)
serological properties (based on the Lancefield grouping system).
Diagnosis and Identification:
1. Growth on blood agar to observe hemolysis patterns.
2. Biochemical tests, such as catalase (x catalase-negative,
28
Staphylococci
catalase positive
a genus of gram-positive,
spherical bacteria
tendency to form clusters resembling grape bunches when observed under a microscope.
They are facultative anaerobes
Staphylococcus aureus:
Commonly associated with skin infections, abscesses, pneumonia, sepsis, and food poisoning.
29
SHAPES OF BACTERIA + examples
cocci
bacilli
spiral shaped
SPHERED:
* Staphylococcus (forms chains)
* Streptococcus (forms clumps)
RODS:
* Excherichia
* Bacillus
form chains
SPIRAL SHAPED:
*Syphillis
- flexible spiral:
* Treponema - causes Syphilis - transmitted trhough sexual contact
* Borella - causes Lyme disease (Spread by ticks)
30
Endometriosis + Fusobacterium
* Endometriosis is derived from the word “endometrium,” which is the tissue that lines the uterus. Patients with endometriosis have endometrial-type tissue outside of the uterus
FUSOBACTERIUM:
- anaerobic
- fusiform-shaped
- potential contributor to endometriosis
dysbiosis in the gut and reproductive tract microbitoa in women, could promote inflammation
chronic inflammation in endometriosis, this exacerbated through:
§ Releasing toxins.
§ Activating toll-like receptors (TLRs) on immune cells.
§ Inducing pro-inflammatory cytokine production.
31
Helicopacter pylori
causing stomach ulcers
32
Syphilis
cause by Treponema bacteria (spiral shaped)
- sexualyl transmitted
Syphilis in stages
1. Painfless sores
2. Skin rashes, mucous membrane lesions
3. Latent asymptomatic
4. Tertiary: severe organ damage .e.g cardio/neuro issues if left untreated
33
Lyme disease
spread by ticks
associated with Borrelia spiral shaped bacterium
- Bulls eye rash
- Fatigue
- Joint pain
Neuro problems
34
Influenza type B + Capsule
35
Spores
C.Difficile
- metabolically inert
- analogous to seeds
- resistant to physical and chemical challenge
- BINARY FISSION
- causing gastroenteritis
persistence
spread in aerosols
no cell wall, no cell membrane, no active respiration, no active protein synthesis, all the ribosomes have been dehydrated
36
C.Difficile
Spore - bacterium
using disinfectants
persistence to antibiotics
causing nasty gastroenteritis
37
obligate anaerobes
killed by O2
38
obligate aerobes
require oxygen in lav
39
facutlative anaerobes
tolerate O2
40
Identifying streptococcus
HAEMOLYSIS
alpha - partial
- greening of colonies on blood agar
------- not destroying RBCs
** Enterococci
**S. pneumoniae
beta - complete
----- destroying the RBC
** Streptococci + Langefield Grouping
gamma - no hemolysis
41
Serological Tests
Ab/Ag interaction
* Detect presence of specific IgM Ab to virus/microbe
* Demonstrate in vitro by agglutination (aggregation) reaction
* Rapid detection of viruses (24 hours),
**** Lateral Flow Tests core response to COVI19 pandemic
42
qPCR
amplification of DNA target
or 16sRNA
primers amplifying specific piece of DNA or
DNA product
e.g. virulence factor
43
MALDI-TOF
** not great for streptococci + stahpylococci
a mass spectrometry method that works by analyzing the unique protein profiles (or mass spectra) of microorganisms, including bacteria, fungi, and even viruses.
44
Virulence
capacity of a microbe to cause damage to the host
45
Protozoan diseases
Malaria
Toxoplasma
GI infections
Leishmaniasis
46
Fungal infections
Candida spp.
Yeast (budding)
47
Gram + prokaryotic pathogens
Streptococcus spp
staphylococcus spp
enterococcus spp
clostridium
48
Gram- prokaryotic pathogens
Neisseria spp
- Neisseria meningitidis, causing bacterial meningitis - aerosol, close contact
- Neisseria gonorrhoea, sexually transmitted --> antibiotic resistance
Escherichia sppG
49
GI tract dominated by gram- bacteria
some commensal bacteria in the gut
Enterobacter spp
found in small numbers, aprt of metabolism
Escherichia spp
e.g. Escherichia coli
some are pathogenic strains, some are commensals in the gut
50
Coliform
broad group of gram- bacteria
rod shaped
subgroup under the group enterobacteriaceae
ferment lactose
aerobic and facultative anaerobes
used to test quality of water
many of them part of normal bowel flora
e.g. Eshcerichia coli
- escherichia
- salmonella
- enterobacter
anythign that getrs into sterile site can cause infection
- UTIs
- peritonitis
- biliary tract
GENTAMICIN --> 1st line antibiotic for coliform infections
- TEMOCILLIN??? FOR GRAM - spectrum --> b-lactamase resistant form of penicillin
ENDOTOXIN/LPS release is virulent + patients with sepsis become very unwell very quickly
51
significant gut pathogens
salmonella
shigella
verotoxin (VTEC) producing E.Coli --> outbreaks of uncooked meat
## Footnote
E.Coli = Gram -
52
SEPSIS - what it is, consequences
a host response to severe infection mediated by LPS/Endotoxin from Gram - bacteria
Small blood vessels become “leaky” and lose fluid into the tissues
* Lower blood volume requires heart to work harderto maintain oxygenation of tissues (↑HR)
* Poor tissue oxygen perfusion mean blood supply to less essential organs (skin, kidneys, liver) is shut down to try to maintain blood supply to brain
* Blood clotting system is activated causing blood clotting in tiny blood vessels→ uses up all clotting factors→ increased risk of haemorrhage
extreme fever with sudden early onset
most human pathogens grow best at 37 degrees
53
Gram +
Streptococcus - hemolysis
- pneumonia
- oral streps
Enterococcus
Staphylococcus
- skin infections + biofilms
Clostridia
- anaerobic bacilli
- C.difficile
54
70% of sore throats will be viral
bacterial sore throats 25-30%, most of them Group A streptococci
55
Group A streptococci
most pathogenic streptococci
hemolysis - beta
sore throat + scarlet fever
invasive disease -> necrotising fasciitis
puerperal sepsis (infection of pregnant + postnatal women)
## Footnote
Fasciitis is an inflammation of the fascia,[1] which is the connective tissue surrounding muscles, blood vessels and nerves.
56
pneumonia
acute inflammation of the lungs
sreptococus pneumoniaer????
alveolei and bronchioles of the lung become plugged with a fibrous exudate (fluid that leaks out of blood vessels into nearby tissues. The fluid is made of cells, proteins, and solid materials. Exudate may ooze from cuts or from areas of infection or inflammation. It is also called pus.)
57
streptococcus pneumoniae
Gram +
a-hemolytic
part of normal upper respiratory tract flora
commonest cause of pneumonia - also causes severe meningitis
58
meningitis
Meningitis is inflammation of the lining around your brain and spinal cord. It can be very serious if not treated quickly.
Symptoms of meningitis include being sick, a headache, a stiff neck and a dislike of bright lights. You may sometimes get a rash.
Meningitis is usually treated with antibiotics in hospital. Treatment should start as soon as possible.
Vaccinations can protect you against some types of meningitis.
## Footnote
Meninges are three layers of membranes that cover and protect your brain and spinal cord (your central nervous system [CNS]). They're known as: Dura mater: This is the outer layer, closest to your skull. Arachnoid mater: This is the middle layer. Pia mater: This is the inner layer, closest to your brain tissue.
59
meninges
Three layers of membranes known as meninges protect the brain and spinal cord.
---The delicate inner layer is the pia mater.
---The middle layer is the arachnoid, a web-like structure filled with fluid that cushions the brain.
---The tough outer layer is called the dura mater.
60
non-hemolytic cocci
Enterococci
AMR
VRE - vancomysin resistance enterococci)
part of normal bowel flora
not pathoegnic, but can cause problems if they get into a normally sterile site
common cause for UTIs
most strains sensitive to amoxicillin , but not penicillin
v.antibiotic resistance strains -- Enterococcus faecium --> VRE -- can cause outbreaks of infections in hospitals
61
Staphylococci
Gram +
clumps/clusters - bunch of grapes
S.aureus
non-motile
aerobe + facultative anaerobe
catalese + usually
coagulase + or -
tolerate 15% NaCl
oxidase -
62
S.aureus infections
COAGULASE +
Methicillin-resistant Staphylococcus aureus (MRSA)
- surgical pateinets
- elderyly ++ immunocompromised
- intravenus lines
- dialysis patients
- mainly nosocomial
- burns patients
- ICU
skin, soft tissue + wound infection
bone and joint infection
food poisoning - enterotoxin producing strains
multiplies at site of infection causing local infection and inflammation - abscess
gets into bloodstream
sepsis = life threatening
abscess in spleen, liver, kidneys
63
abscess
An abscess is a buildup of a pus that can affect any part of your body. There are many different types of abscesses. They can occur on your skin, in your mouth or around your organs. Skin abscesses may look red and swollen. Bacterial infections usually cause abscesses.
64
Clostridiodes
spores - spread + antimicrobial resistance
Gram +
anaerobic bacilli
part of normal bowel flora - found in faeces + soil
EXOTOXINS
- C.difficile, antibiotic associated diarrhoea
- C. perfringens - gas gangrene, soft tissue infection following contamination of a wound
- C. tetani - tetanus, fatal paralytic illness
65
Narrow spectrum antibiotics
Penicillin -> Gram + bacteria
66
Broad spectrum antibiotics
Tetracycline -> for both Gram + and -
67
Bacteriostatic
Bacteriocidal
68
antibiotic targets
cell wall
ribosomes - protein synthesis
dna replciation
metabolic pathways
cell membrane function
69
pharmacodynamics
whay you do to the target
70
pharmacokinetics
what the body does to it
ADME
71
Cell wall targeting antimicrobials
1. PENICILLINS -> b-lactam
penicillin
amoxicillin
tazobactam
2. CEPHALOSPORINS -> b-lactam
wider spectrum
3. GLYCOPEPTIDES -> NOT b-lactam
vancomycin
72
b-lactams
b-lactam ring (e.g. in penicillin)
TARGET: PBP - penicillin binding proteins
resembles D-ALA-D-ALA dipeptide + irreversibly binds to PBP
prevents the enzyme (transpeptidase) from processing the normal substrate
PG synthesis stops (peptidoglycan)
cell wall compromisation
suicide substrate
***** PENICILLINS (narrow spectrum)
- amoxicillin (extended spectrum)
- flucloxacillin (methicillin / meticillin) -> resistance to Stap B- lactamases
- co-amoxiclav
***** Cephalosporins
1st generation active against Staph + Strep
***** Carbapenems
broad spectrum for both + and -
resistant to b-lactamase
last resort for Gram -
73
Cell wall structure
Crosslinking of peptide side chains
Terminal D-Alanine D-alanine -> cleaved by transpeptidase
transpeptidase = cell wall synthesising enzyme
energy released from D-ALA-D-ALA is then used to form cross-link (peptide bridge)
74
empiric prescribing
Treatment given based on experience, without precise knowledge of the cause or nature of a disorder.
75
penicillin limitations, although empiric
- patients can be hypersensitive, allergic
- rapid excretion via kidneys (frequent dosing needed)
- resistance
76
penicillin
amoxicillin
flucloxacillin
co-amoxiclav
temocillin
tazobactam/piperacillin / tazocin
77
b-lactam antibiotics
78
glycopeptide antibiotics
79
antibiotics for Gram+
Flucloxacillin (IV, oral)
80
antibitoics for Gram -
Temocillin (IV only)
81
antibiotics for both Gram+ and -
Amoxicilin (IV, oral)
Co-amoxiclav (IV, oral)
Tazocin/Tazobactam/Piperacillin (IV only)
82
penicillin class
b-lactams
Gram +
narrow
intestine absoprtion
sensitive to stomach acid
83
amoxicillin
IV + oral
derivative of penicillin
good tissue distribution
broader spectrum (both + and -)
stable in presence of stomach acid
will enter CSF if meninges inflamed
most common prescription
disturbing gut unnecessarily - target enterococci --> opportunistic infection + VRE
84
co-amoxiclav
amoxicillin + clavulanic acid
b lactam + b-lactamase inhibitor
clavulanic acid does not have antibiotic properties on its own
85
Flucloxacillin
narrow spectrum
STAPHYLOCOCCI + STREPTOCOCCI ONLY
IV and oral
**CLASSIC ANTIBIOTIC FOR STAPH. AUREUS
**
replaced methicillin (MRSA)
MRSA resistant to flucloxacillin
commonly prescribed for those skin infections
86
Temocillin
b-lactamase resistant form of penicillin
IV only
for Gram -
for COLIFORMS
- escherichia
- salmonella
- enterobacter
active againe ESBL (extended spectrum beta lactamse) producers
87
Tazobactam/Piperacillin (Tazocin)
v. broad spectrum antibiotic
b-lactamase inhibitor
enhances penetration into Gram-bacteria
used as empiric prescription
HUGE IMPACT ON MICROBIOME OF HOST
88
CPE
CPE (carbapenemase-producing Enterobacterales) are bacteria (bugs) that live in the gut. CPE are a type of superbug. These are bugs that are resistant to many antibiotics.
89
VRE
vancomycin-resistant enterococci. Enterococci are bacteria (germs) that live in the gastrointestinal tract (bowels) of most people without causing illness. This is called colonisation. Vancomycin is an antibiotic used to treat infections caused by enterococci.
90
cephalosporins
bactericidal + inhibit cell wall synthessi
safe in pregnancy
more resistant to b-lactamases
broad spectrum, significantly affecting normal bowel flora, overgrowth of C.difficile -- causing nasty gastroenteritis
many hospitals try to avoid using these
excreted via kidneys + urine
few side effects , reduced allergy
91
b-lactamase inhibitors (IV only)
clavulanic acid
tazobactem (IV only)
92
resistant forms insensitive to b-lactamases
carbapenems -- last resort antibiotic
now under threat from carbapenemases (CPE)
93
Glycopeptides
(NOT b-lactam antibiotics)
VANCOMYCIN (IV)
TEICOPLANIN (IV)
act on cell wall
binds to end of D-ALA-D-ALA + prevent their incrorportaion into the cell wall (binds to the substrate, NOT the enzyme)
bactericidal
inhibtis peptidoglycan synthesis
weaken bacterial cell wall
blocks access to substrate by PBP (transpeptidase)
excreted via kidneys and urine --
restricted activtiy to Gram + bacteria cell wall
ORAL VANCOMYCIN CAN TARGET Gram + as it builds up in intestine
NO ACTIVTIY AGAINST GRAM - , excluded by outer membrane
94
treatment for MRSA
Vancomysin
95
Protein synthesis inhibitors
BACTERIOSTATIC
- tetracyclines
- macrolides
BACTERICIDAL
- aminoglycosides
96
Aminoglycosides
(bactericidal)
protein synthesis inhibitor
GENTAMYCIN
- not absorbed from the gut -- IV needed
- binding to 30s ribosomes, irreversibly
- mainly against Gram -
- used in serious Gram - infections
- excreted in urine
- TOXICITY!!!! damage to kidneys + VIII (8th) cranial nerve (dizziness, deafness)
97
Tetracycline
(bacteriostatic)
protein synthesis ihibitor
Deoxyxycline / minocycline
- binds to 30s on ribosomes, preventin tRNA attachment
**doxycyline / minocycline more efficient absorption
broad spectrum
for intracellular bacteria
ADVERSE EFFECTS --- destruction of normal intestinal flora --> secondary infections
RESTRICTED USED IN CHILDREN, INFANTS, PREGNANCY
impairment of structure of bones + teeth
98
macrolides
(bacteriostatic)
erythromycin
- 50s subunit binding or ribsosomes
- excreted via the LIVER, biliary tract and into the gut
NOT excreted in urine
for intracellyualr bacteria (lipophilic)
ERYTHROMYCIN safe in pregnancy
**** GO TO DRUG FOR PEOPLE WITH PENICILLIN ALLERGY
99
Antibiotics targeting Nucleic acid
Fluroroquinolones (both Grams)
Metronidazole (Anaerobes + Protozoa)
Trimethoprim
- primary use for UTIs
Rifampicin + Rifampin
- common use for Mycobacteria, Bacterial meningitis prophylaxis
100
Quinolones
Bactericidal
Bind to A subunit of DNA gyyrase (topoisomerase), preventing supercoiling of DNA, indirectly inhibiting DNA synthesis
- bones
- UTIs, excreted in urine
*RESTRICTED FOR USE IN C.difficile GI infection --- BC it is broad spectrum
*
*** Ciprofloxacin - largely Gram- activtiy
good intracellular activity
101
Nitroimadazoles
** metronidaole (oral + IV)
- for anaerobes + protozoa
- drug activated by reduction process
- forms toxic intermediate, inducing DNA breakage
- RARE to resistance
- ADVERSE REACTIONs limited
NOT given in combination with alcohol!!!
_ metallic state
_ furred tongue
102
inhibitors of folic acid synthesis
* key untermediate metabolism
Sulphonamide
Trimethroprim - good for UTIs
103
Trimethoprim
some Gram -, some Gram +
excreted via urine, concentrates urine
common for acute UTIs e.g. E.Coli
orally ok
combo therapy with sulphamethaxozole
BOTH inhibitors of folic acid synthesis - key intermediate metabolism is blocked
104
ERYTHROMYCIN/CLARYTHROMYCIN
GENTAMICIN
METRONIDAZOLE
105
High risk/ resticted use antibiotics for
C. diff
The 4C's
SOS!!!!!!!!!!!
NO TO
- Cephalosporins
- Co-amoxiclav
- Cirpofloxacin
- Clindamycin
| The "4 C's" refer to a group of antibiotics that are associated with a h
106
High risk/restricted use antibiotics for sore mouth
antibiotic sore mouth for Candida Albicans
107
Other interactions of
Careful prescribing
1. antibiotics generally
2. Gentamicin
3. Ciprofloxacin
4. Metronidazole
1. Nausea, vomiting, diarrhoea + may affect absorption of oral contraceptives + disrupt the gut bacterial flora
2. renal + CN VIII damage (deafness + dizziness)
3. Tendonitis - avoid use in pregnant or breast feeding women
4. interacts with alcohol
108
Primary use of antibiotics for UTIs
+ other?
+ other?
e.g. E.Coli
- > Trimethoprim (Nitrofurantoin)
- > Quinolone (bind to A subunit of DNA gyrase preventing supercoiloing of DNA, inhibit DNA synthesis indirecgly -topoisomerase)
- > Trimethoprim (inhibitor of folic acid)
Trimethroprim:
- Nitrofurantoin
- combo with sulfamethoxacole (if poor renal function)
109
Common use antibiotic for Mycobacteria + Bacterial Meningitis prophylaxis
Rifampicing + Rifampin
- antibiotic targeting the nucleic acid
110
Intracellular antibiotics
Macrolides
Deoxycyline
Erythromycin
Ciprofloxacin
111
Penicillin allergy
Erythromycin
112
IV serous, Gram-
113
Deoxycycline (Tetracyclin)
intracellular activity good
side effects - bone + teeth
NOT given in pregnant women, children, infants
114
IV only, Gram-
Tazobactam
Temocillin
115
Facultative anaerobes
staphyloc
coliform (-)
streptococc
E.coli
116
Anaerobes
Clostridiodes
Fusobacterium + Endometriosis
Nucleic acid antibiotics
Nitromadazole antibiotics
Metronidazole antibiotics
117
Erytrhomycin RECAP
50s
intracellualr activtiy good
YES for pregnant
penicillin allergy
LIVER excretion
118
Trimethroprim RECAP
UTIs e.g. E.Coli
folic acid inhibitor
targetting nucleic acid
+ and - Gram
URINE excretion
Nitroflurantin antibiotics
119
Gentamicin RECAP
Gram - Coliform
E.Coli
toxicity - CN VIII (8th) - deafness, dizziness
aminoglycoside
120
Biofilms
on a cannula
catheter
A x is defined as a community of microorganisms attached to an inert or living surface by a self-produced polymeric matrix or an assemblage of microbial cells associated with a surface and enclosed in a matrix of primarily polysaccharide material.
- organism behaving as part of multicellular community
- making the organism more resistant to antimicroial agents + host defenses
- horizontal gene trasnfer, spore formation is more likely (Sacrifice one of your organisms to produce a spore, stress at the back cells)
- competition
fermentation for anaerboci at the back, thus producing lactose, generatting lactic acid, demineralising the tooth and causing teeth decayt -- -at the front those they don’t hace to do that, they have sugar, they will not ferment anythgin, they will do respiration, long way away from the tooth, not under oxygen stress)
121
Clinical resistance + MIC/MBC
Minimum inhibitory concentration
Minimum bactericidal concentration
122
PBP2 *MRSA
changes to ribosome prevent antibiotic bindins
123
efflux pumps
124
Horizontal gene transfer - spread of resistance - exchange of genetic material commonly occuring in the gut (HGT)
genetic variation confering resistance - selective pressure - evolution
125
difference between natural + acquired resistance
126
beta-lactam antibiotics + resistance
2 different ways of overocming it
1. produce beta lactamase inhibitor (IV only)
2. change the structure, so b-lactamase cannot degrade the b lactam
3. b-lactamases
** PENICILLINASE
resistant to amoxicillin
Gram+
***ESBL - extended spectrum b-lactamase
resistant to all penicillins
*** CPE - Carbapenamase (carbapenamase producing enterobacteriaceae)
metalloenzyme based
gram -, principally E.Coli + K.pneumoniae
resistant to all penicillins, cephalosporins, carbapenems
** CEPHALOSPORINASE
## Footnote
β-Lactam antibiotics are bactericidal agents that interrupt bacterial cell-wall formation as a result of covalent binding to essential penicillin-binding proteins (PBPs), enzymes that are involved in the terminal steps of **peptidoglycan cross-linking** in both Gram-negative and Gram-positive bacteria.
127
horizontal gene transfer mechanisms
3
transfer
proximity
ideal in biofilms
a) bacterial transformation - natural competence - antibiotic resistance gene released
b) bacterial transduction - phage infected donor cell, release of phage to recipient cell attack
c) bacterial conjugation - sex pii, trasnfer of plasmid
128
persistor cell
- Tolerance
- metabolically inert -- v slow growth, dormant-non living
- planktonic and biofilm populations
129
VRE
CPE
MRSA
ESBL
130
antimicrobial drug resistance examples of mechanisms
1. INACTIVATION
b-lactamase
2. ALTERED PERMEABILITY
altered influx (quinolones)
active efflux (tetracycline)
131
MRSA is resistant to...
Flucloxacillin
Methicillin
Penicillin -PBP
Staph PBP2*
CAHNGES to ribosome preventing antibiotic binding (30s ribosome + 50s ribosome)
132
VRE
VRSA
VANCOMYCIN RESISTANT ENTEROCOCCUS
vancomycin resistant staphylococcus
133
E.coli variants + diseases they cause
Shiga toxin producing strains (S/VTEC)
134
VTEC
135
C.difficile
HAI
how to control the disease
spore formation
toxin production
antibiotic resistance
gram +
anaerobic
136
dysbiosis of the gut
IBD
137
cpe organisms
reside in the gut
HGT
138
GI tract
carbapenamase producing enterobacteriacae
big problem for healthcare
139
GI infections
E.Coli + proxy for water quality
C. difficile
Campylobacter -> food poisoning + poorly controlled hygiene + link with reheated rice, spore forming organism
salmonella
shigella
staph aureus -- even if you ingest the toxin alone --> acute, emetic response
fusobacterium nucleatum
vibrio cholera
140
symptoms for GI tract infections
dysbiotic relationship
diarrhoea
- dehydration, electrolyte loss
- vomiting
Gastroenteritis
- vomiting
- nausea
- diarhhoea
Dysentery
- blood and pus in faeces
- inflammatory response upregulated
Enterocolitis
- inflammation of small and large intestine
141
E.coli variants
S(V)TEC / EHEC
Shiga toxin-producing
Gram-
flagella movement
villi- injection of toxins
pili, fimbriae + flagella important
distinct types can produce distinct pathologies
HGT has driven variation in virulence factors (key toxins, adhesins)
dysentery
142
E.coli 0157
enterohemorragic strain (EHEC/STEC)
dysentery, severe form of diarrhoea
hemorrhagic colitis
hemolytic-uremic syndrome -> can lead to kidney failure + death
foecal - oral route transmission
undercooked food, bbq
abdominal cramps
little to no fever
fatigue
nausea
shigatoxin (VTEC/EHEC)
stx1 + 2 acquired by phage from shigella
loss of mucosal integrity + death
SHIGATOXIN=VIROTOXIN
EHEC = presentation
STEC = description of strain
143
C.difficile
anitbiotic associated diarrhea
pseudomembraneous colitis
spores survive
mild to severe diarrhea
nausea, fever, abdominal pain
mild bowel movements
severe = vomiting, high fever, rectal bleeding
toxin a enterotoxin + toxin B cytotoxin
- breakdown of cell junctions
RISK FACTORS ALL OF THEM:
- co amoxyclav
- cephalosporins
spores survive in gut also spread and survive in envrionment + RESIST ALCOHOL GELS
Handwashing with Soap and Water:
This is mandatory because C. difficile spores are not effectively removed by alcohol-based hand sanitizers.
treat with narrow spectrum antibiotic
e.g. VANCOMYCIN (not absorbed thrugh the GI tract, but it is concentrating in the GI tract) +++ steps to restore the microbiome by faeceal transplant
144
IBD
dysbiosis
inflammatory bowel disease
e.g. Crohn's disease
Ulcerative colitis
symptoms:
- bloating
- poor nutrition
- stool movements, icnreased bowel movements
- diarrhoea
- abdominal pain
145
Viral diseases of the GI tract
norovirus
rotavirus
cryptosporidium
146
sepsis VS abscess
**Sepsis:
**A systemic infection resulting from the body's extreme response to an infection.
It occurs when the immune system's response to infection causes widespread inflammation and organ dysfunction.
It can originate from infections anywhere in the body (e.g., lungs, urinary tract, skin).
*fever, chills, rapid heart rate, rapid breathing, confusion, low blood pressure, and organ failure in severe cases.
Symptoms are systemic, affecting the whole body.*
**Abscess:
**A localized collection of pus within a tissue, often caused by bacterial infection.
It is characterized by swelling, redness, pain, and warmth at the site.
Typically occurs due to an infection that the body has walled off to prevent the spread.
*Pain, tenderness, swelling, redness, warmth at the site of infection, and sometimes fever if the infection is severe.
Symptoms are localized to the area of the abscess.*
Relationship Between the Two:
An abscess can potentially lead to sepsis if the localized infection spreads into the bloodstream.
Sepsis is a more severe and life-threatening condition compared to an abscess, which is usually localized and easier to manage if treated early.
147
Beta lactams - b lactam
β-Lactam antibiotics are bactericidal agents that interrupt bacterial cell-wall formation as a result of covalent binding to essential penicillin-binding proteins (PBPs), enzymes that are involved in the terminal steps of peptidoglycan cross-linking in both Gram-negative and Gram-positive bacteria.
148
b lactamase
The beta-lactamase enzymes inactivate beta-lactam antibiotics by hydrolyzing the peptide bond of the characteristic four-membered beta-lactam ring rendering the antibiotic ineffective. The inactivation of the antibiotic provides resistance to the bacterium.
149
B LACTAM EXAMPLES
carbapenem
cephalosporins
penicillin
amoxicillin
150
PIC - narrow spectrum / broad spectrum
151
PIC - key penicillins
152
PIC - narrow spectrum / broad spectrum 2
153
PIC - penicillins
154
PIC - Gram +
155
PIC - Gram -
156
PIC - penicillin mindmap
157
PIC - folic acid
158
PIC - c.diff
159
PIC - c.diff
160
161
PIC - MALT
