Infection And Defence: Bacterial Structure And Function, Routes Of Transmission

Front 1

Describe the structure of the bacterial cell membrane (+ve and -ve).

Back 1

>Composed primarily of protein and phospholipid. It performs many functions, including transport, respiration biosynthesis of phospholipid, and energy transduction.
>Space between the plasma and outer membranes of Gram neg. bacteria is the 'Periplasmic space'.
>Teichoic acids are negatively charged polymers found in Gram positive bacteria peptidoglycan - strongly antigenic.
>Lipoteichoic acids are antigenic polymers anchored in the membrane.
- Antigenic, cytotoxic and adhesins.
>Lipopolysaccharides (LPS) are complex molecules consisting of a Lipid A anchor, a polysaccharide core, and a chain of carbohydrate molecules.
- Present on the outer leaflet of the outer membrane of Gram-neg. bacteria.
- Responsible for symptoms of gram negative sepsis (hence called endotoxin).

Front 2

What are bacterial endospores?

Back 2

>E.g. Anthrax (Bacillus anthracis)
>These are developed by bacteria usually in response to nutrient deprivation.
>Allows the bacterium to produce a dormant and highly resistant cell to preserve the cell·s genetic material in times of extreme stress.
>Endospores can survive environmental assaults that would normally kill the bacterium.
- These stresses include high temperature, high UV irradiation, desiccation, chemical damage and enzymatic destruction
- Why C.Diff diarrhoea is so persistent in hospitals and care homes

Front 3

Describe the stages of a bacterial growth curve.

Back 3

>During the lag phase the bacteria is adapting to its environment.
>Growth flattens out after rapid growth due to limitations of environment (otherwise would grow exponentially - bacteria grow by binary fission).
>Eventually the bacteria enter the death phase.

NB. Bacteria only produce enzymes if the substrate is present e.g. lac operon.
They are more susceptible to attack when adapting to a new environment.

Front 4

Describe how and which bacteria metabolise O2.

Back 4

>Several commensal and pathogenic bacteria e.g. streptococci are unable to complete the final stages and secrete hydrogen peroxide.

Examples:
>Strict aerobe: molecular O2
>Facultative aerobe: molecular O2 or an organic molecule
>Strict anaerobe: organic molecule, NO3, SO4
>Microaerophiles - 2-10%
>Capnophiles e.g. Strep pneumoniae - nasopharynx - ideal growth in increased CO2 5-10%.

Front 5

Describe how bacteria conduct respiration.

Back 5

Front 6

Describe the structure of the Gram +ve bacteria cell wall.

Back 6

>Protective layer that determines the shape of bacterial cells.
>Contains superantigens (teichoic and lipoteichoic acids)
- Can overstimulate the immune response causing sepsis and toxic shock.
>Stains positive for Gram

Front 7

Describe the structure of gram -ve bacterial walls.

Back 7

>Plasma membrane is covered with a thin layer of peptidoglycan cell wall which is then covered by a further outer membrane which may be covered by a polysaccharide capsule.
>Similar to Gram +ve bacteria, there are antigenic LPS (lipopolysaccharides) on the outer cell membrane which when broken down can act as a pro-inflammatory mediator - causing sepsis; also known as ENDOTOXIN.

Front 8

Identify this bacteria class.

Back 8

>Gram +ve
>Streptococcus
>E.g. S. Pyogenes

Front 9

Identify this bacterial class and an example of its pathology in humans.

Back 9

>Spirochaetes - comma shaped cells
>e.g. Campylobacter Jejuni:
- common cause of diarrhoea
- microaerophilic - require low oxygen tension and thermophilic (can grow at 42C)
- Infection is via contaminated water milk or food - especially poultry.
>Stimulated by organic farming; post infection association with Guillain Barre syndrome.

Front 10

What are these? Describe their characteristics.

Back 10

>Chlamydiae (0.2-0.8 μm)
>Obligate intracellular parasites with a Gram -ve cell wall
>Unique developmental cycle with an infectious extracellular elementary body and a non-infectious intracellular reticulate body.
>Cause eye and genital tract infections.

Front 11

What are flagella?

Back 11

>Organ of locomotion, expressed by both Gram +ve and -ve bacilli but rarely cocci.
>Less than 12μm long (i.e. longer than the bacterium) and less than 30nm in diameter.
>Made of proteins assembled into a long hollow cylinder anchored to the cell membranes via a hook and a basal body.
>Rotates fast in helical twists which create movement towards nutrition (chemotaxis) or air (airotaxis) or away from noxious stimuli.
>Amount and distribution of flagella are characteristic for any given species:
- Polar or peritrichous

Front 12

What are bacterial pili?

Back 12

>Protein structures that are important in enabling pathogens to attach to surfaces.
>Play roles in the acquisition of external DNA and are required for twitching motility.
>Hair like appendages of varying length and shorter than flagella.

Front 13

Describe the structure of the mycobacterium cell wall.

Back 13

>Thick lipid rich cell wall which does not take gram stain
- Contain arabinogalactan and mycolic acids
- Can be readily seen using a fluorochrome stain (needs UV microscope)
>Mycobacterium include the pathogens that cause tuberculosis and leprosy.

Front 14

What type of stain is this?

Back 14

>Ziehl-Neelsen
- Involves heat to allow stain to penetrate the cell wall
- decolourises with acid (cold) and counter stains
>Acid Fast Bacteria are visible (stain red), NAFBs stain green.

Front 15

Identify this microorganism and describe its characteristics.

Back 15

Mycoplasmas:
>The smallest organisms capable of growth on cell-free media
>Lack a rigid cell wall
>Require sterols for growth
>Include four species that cause human disease:
- Mycoplasma pneumoniae
- M. genitalium
- M. hominis
- Ureaplasma urealyticum
>"Fried egg" morphology of colonies
>Causes bronchopneumonia

Front 16

Describe the structure of the fungal cell wall.

Back 16

Made up of:
- Mannose
- Glucosamine and chitin
- Contain proteins

Front 17

Identify this organism, and its staining and its associated pathology.

Back 17

>Cryptococcus:
- India ink preparation (negative stain), showing capsules
- Environmental yeast
- Causes meningitis

NB: Some fungi grow unicellularly, e.g. yeast, and multiply by budding or splitting; dimorphic fungi switch between yeast and mycelial forms.

Front 18

Identify this pathology.

Back 18

>Oral thrush / milk tongue
>Caused by Candida spp.
>Associated with antimicrobial therapy that disturbs the commensal bacterial microbiota and results in fungal overgrowth.

Front 19

Identify these conditions.

Back 19

RINGWORMS:
A. Tinea corporis - annular lesion spreading from centre
B. Tinea cruris - jock itch
C. Tinea capitis - scaling and hair loss on scalp

NB. Athlete's foot another example.

Front 20

Describe the infection of Entamoeba histolytica.

Back 20

>Cysts are ingested and parasites emerge and multiply in the upper GI tract.
>Pathogenic trophozoites form in the colon and form cysts in unfavourable conditions.

Front 21

Describe the infection cycle of intestinal nematodes.

Back 21

Front 22

Describe what is meant by 'bacterial capsule'.

Back 22

>Some bacteria form capsules which constitute the outermost layer of the bacterial cell and may be too think to be detected or up to 10μm thick.
>Bacterial capsules enable bacteria to survive inside the host and avoid phagocytosis.
>Some organisms lack a well defined capsule but have loosely bound layers of polysaccharide-based slime which covers the organism.
>Overproduction of slime may help to form biofilms.

NB. Appear to have mucoid morphology.

Front 23

Describe the 5 key principles of ecological succession.

Back 23

1. Transmission - spread
2. Acquisition - gain a foothold
3. Succession - divide and shed
4. Increase species diversity - vary colonisation
5. Climax community - reach the optimum ecosystem (finding a balance)

Front 24

Which ecological factors influence microbiota? (7)

Back 24

>Attachment or retention at surface (Skin, upper respiratory tract, GU tract)
>Humidity (skin)
>Levels of oxygen and CO2
>Nutrients
>pH (mouth, stomach, vagina) e.g. helicobacter survive in a low pH
>Antagonists
- From host
- From commensal microbiota e.g. collicins

Front 25

What particular characteristics of human skin allow bacteria to colonise it?

Back 25

>Hair increases humidity and temperature of the skin's surface
>Sebaceous glands secrete sebum used as a nutrient by microbes
>Apocrine and eccrine sweat glands affect pH, moisture, nutrients and temperature
- Strict anaerobes can grow at these sites

Front 26

Describe the environment of the skin and its commensals.

Back 26

>Dry environment with a slightly acid pH
- Gram +ve cocci are common
>More bacteria are found in moist areas e.g. scalp, armpits and groin
>Anaerobic bacteria e.g. Proprionibacterium Acnes live in sweat glands and release free fatty acids from sebum which inhibit other organisms.

Front 27

Describe the environment of the eyes and its commensals.

Back 27

>Tears contain lysozyme which inhibits bacteria but Gram +ve rods (coryneform) bacteria occur.

Front 28

Describe the environment of the nose and its commensals.

Back 28

>Gram +ve cocci - staph epidermidis and aureus, coryneform bacteria, streptococci.
>Healthy individuals may carry MRSA.

Front 29

Describe the environment of the GU tract and its commensals.

Back 29

>Staph epidermidis, streptococci, Gram -ve rods, yeasts (candida), gut flora
>Adult women carry lactobacilli

Front 30

Describe the environment of the mouth and its commensals.

Back 30

>Rich and complex microbiota
- streptococci
- actinomycetes
- v. strict anaerobes - gram -ve rods and cocci
- spirochaetes
- yeasts

Front 31

Describe the environment of the stomach and small bowel and its commensals.

Back 31

>Streptococci, lactobacilli, possibly gram -ve potential pathogens (Helicobacter spp.)
>At distal end - coliforms, strict anaerobes (Bacteroides spp.)

Front 32

Describe the environment of the large bowel and its commensals.

Back 32

2 distinct populations:
1. Wall microbiota - non cultivable bacteria
2. Lumen microbiota

>Gut contains approx 1000 species and is believed to be vital for the development of the gut and systemic immune systems.
>Colonisation after birth with bifidobacteria (occurs in breast-fed infants) protects against diarrhoea.
>Gut contains the greatest density of bacteria 10^12 in the body and sheds the highest number.

Front 33

What is the role of the commensal microbiota?

Back 33

1. Provides colonisation resistance
- Prevents overgrowth and colonisation by extraneous pathogens
- Modulates acquisition of external pathogens

2. Supplies micronutrients to the host
- Gut microbiota produces vitamin B12
- Oral microbiota releases hydrogen peroxide used in salivary peroxidase antimicrobial system

3. Essential for initial immune priming of host
- Development of immune competence against pathogens
- Ensures tolerance to food antigens and commensal microbiota

Front 34

How may commensal microbiota cause disease?

Back 34

>If the flora is disrupted:
- it hasn't achieved stability or maturity
- antibiotics

>Host susceptibility is increased by:
- Immunosuppression: HIV, drugs, pregnancy
- Other illness
- Poor nutrition

Front 35

Describe the microbiota of the gut (oesophagus to anus)

Back 35

Front 36

Which oral diseases can be caused by commensal microbiota? (5 examples)

Back 36

>Dental caries
>Periodontal diseases
>Dento-alveolar abscess
>Candidiasis (Thrush)
>Sub-acute bacterial endocarditis

Front 37

What disease can be caused by overgrowth post antibiotic treatment?

Back 37

>Clostridium Difficile
- Spore forming gram +ve bacillus
- Strict anaerobe
- lives in gut as minor commensal
- Spores survive antibiotics so can overgrow -> serious infection -> death
- Pseudo membranous colitis
>Picked up from contaminated surfaces

Front 38

How are infections acquired by individuals in a population?

Back 38

Infection takes place due to the:
>Host:
- A population may have 'herd immunity' e.g. immunity transferred to the whole community
- Susceptibility of individuals vary due to genetics, previous exposure, underlying medical condition, exposure to infection, and physical or mental stress
>Microorganism:
- Most are harmless to healthy individuals
- Microbes able to cause damage are termed 'virulent'
>Environment:
- Overcrowding and poor sanitation encourage rapid spread of infections
- Spread of infection is influenced by building design and air conditioning systems e.g. TB hospitals are cliff-facing.

Front 39

Give an example of how anatomy might make one more susceptible to an infection.

Back 39

E.g. UTIs are much more common in females due to their GU morphology compared with males.

Front 40

Describe common routes of infection.

Back 40

>Microbial attachment / penetration:
- Skin
- Respiratory tract (provides the creates opportunity for infections in the body)
- GI tract
- GU tract
>Biting arthropod
>Skin wound/animal bite
>Commensal microbiota where antimicrobial defences are impaired
>Vertical transmission (rare)

Front 41

What are common sources of UTIs?

Back 41

Front 42

Describe how the GI tract may become infected.

Back 42

>Infections arise via milk or food from infected animals, or that have been contaminated by unclean water or unwashed hands
>Localised infections usually result in diarrhoea
>Systemic infections often cause fever, headache and/or jaundice

NB. Infection may be toxin related

Front 43

List some examples of STDs, their genus/species and their general characteristics.

Back 43

>Syphilis - Treponema Pallidum
>Gonorrhoea - Neisseria Gonorrhoeae
>Chlamydia Trachomatis
>Chancroid - Haemophilus ducreyi
>Trichomonas vaginalis
>Genital Herpes (HSV)
>Genital warts
>HIV

- There is no exposure to the environment with STDs so pathogens do not withstand drying, sunlight and often need extra CO2 to grow.
- Syphilis and gonorrhoea can be readily treated with penicillin if they are detected but they may be overlooked.

NB. Gono resistance is developing towards penicillins.

Front 44

How is malaria transmitted?

Back 44

>Normally by the bite of a female 'anopheline' mosquito which needs a supply of blood in order to produce and lay eggs
>Malaria can also be transmitted by:
- Blood transfusion
- Contaminated needles and other sharps
- Rarely, malaria can be transmitted from mother to child before and or during birth

Front 45

Describe different routes of bacterial transmission from person to person.

Back 45

>Aerosol spread:
- smaller droplets travel further
- dry aerosol products may float in the air
>Hand to nose:
- Most common means of rapid spread of infection
>Respiratory or salivary spread:
- not readily controllable
>Faeco-oral spread
- controllable by public health measures
>Sexually transmitted:
- difficult to control as social factors involved

Front 46

Which viruses may be transmitted by infectious aerosols?

Back 46

1. Influenza
2. Rhinovirus
3. Adenovirus
4. Mumps
5. Measles
6. Rubella
7. Varicella Zoster
8. Epstein Barr

Front 47

Which bacteria may be transmitted by infectious aerosols?

Back 47

>Bordetella pertussis
>Corynebacterium diptheriae
>Haemophilus influenzae
>Mycobacterium tuberculosis
>Mycoplasma pneumoniae
>Neisseria meningitidis
>Streptococcus pyogenes
>Streptococcus pneumoniae

Front 48

Describe how hospital cross infection can be spread and controlled.

Back 48

Hint 48

Patient evaluation: medical history
Personal protection: immunisation/protective clothing
Instrument sterilisation
Surface and equipment disinfection
Working methods
Waste disposal

Front 49

Describe some common routes of bacterial transmission (diagram).

Back 49

Front 50

Describe the systemic and local spread of gonorrhoea.

Back 50

>Not always perceived as a serious infection there can be serious systemic disease in the mother and severe conjunctivitis can occur in her infant after birth.

Front 51

Describe different routes and types of zoonotic infection.

Back 51

Front 52

Describe the pathway for toxoplasmosis infection.

Back 52

>Acquired by eating cysts in undercooked meat or cat faeces.
>Parasite spreads via the blood.
>Usually controlled by the host immune response.
>Congenital infections of the foetus can lead to severe complications.

Front 53

Define what is an antibiotic and some examples of antibiotic producing microbes.

Back 53

>Antibiotic: Substance produced by a microorganism that in small amounts inhibits the growth of another microbe.

Antibiotic producing microbes:
>Gram +ve rods:
- Bacillus Subtilis: Bacitracin
- Bacillus Polymyxa: Polymyxin
>Fungi:
- Penicillium notatum: Penicillin
- Cephalosporium spp.: Cephalothin
>Actinomycetes:
- Streptomyces venezuelae: Chloramphenicol
- Streptomyces griseus: Streptomycin
- Streptomyces nodosus: Amphotericin B
- Micromonospora purpurea: Gentamicin

Front 54

List 5 examples of antibacterial mechanisms of action.

Back 54

1. Cell wall synthesis inhibition
2. Protein synthesis inhibition
3. Plasmamembrane toxicity
4. Inhibition of nucleic acid synthesis
5. Inhibition of essential metabolite synthesis

Front 55

Describe the effect of cell wall synthesis inhibition.

Back 55

>Inhibits peptidoglycan synthesis:
- Results in cell lysis
- Low toxicity
E.g. Penicillin (by acting as a peptide analogue, inhibiting the enzymes) and Vancomycin (prevents wall subunits joining together)

Front 56

Describe the effect of protein synthesis inhibition.

Back 56

>Interfere with prokaryotic (70S) ribosomes (also found in mitochondria)
- Most have broad spectrum of activity
- E.g. Tetracyclin, Chloramphenicol, Erythromycin and Streptomycin

Front 57

Describe the effect of plasma membrane toxicity.

Back 57

>Causes changes in membrane permeability:
- Results in loss of metabolites and or cell lysis
- Many polypeptide antibiotics
- E.g. Polymyxin B (antibacterial) or Miconazole (antifungal; specific to ergosterol)
- Toxic antibiotics due to presence of cell membranes in microbes and eukaryotic cells.

NB. Polymyxin D (Colistin) is highly reno and CNS toxic, so is only used as a last resort in resistant bacterial infection.

Front 58

Describe the effect of nucleic acid synthesis inhibition.

Back 58

>Interferes with DNA replication and transcription:
- Inhibits DNA gyrase and topoisomerase
- E.g. Quinolones (Cipro)

Front 59

Describe the effect of essential metabolite synthesis inhibition.

Back 59

>Involve competitive inhibition of key enzymes:
- Closely resemble substrate of enzyme
- E.g. Sulpha drugs inhibit the synthesis of folic acid (here never given to pregnant women because neonates can't develop folate)

NB. Folate is a precursor to purines and pyrimidines.

Front 60

What influences antibiotic efficacy?

Back 60

>Distribution (pharmacodynamics): in the body; membrane permeability - lipid solubility/active transport
- Concentrations in tissues, bone, CSF, bile etc.
>Metabolism (pharmacokinetics): can the antibiotic be broken down by the patient's body and rendered ineffective?
>Excretion (liver, kidneys): is the drug removed by the patient's own purification systems before it can be effective.

NB. Failure of systems can produce toxicity; dosage must ensure sufficient therapeutic concentration; some drugs e.g. amino glycosides require monitoring such as the aminoglycosides.

Front 61

How are antibiotics typically administered?

Back 61

>External (topical) or systemic (blood stream)
>Systemic drugs can be:
- Intravenous
- IM
- Oral
>Frequency of doses can vary

Front 62

What are the primary safety concerns over using antimicrobials?

Back 62

>Toxicity (kidney/liver damage)
>Interactions with other medications (Rifampicin neutralises effectiveness of contraception - via priming of CYP450)
>Hypersensitivity reactions (anaphylaxis to penicillin - doesn't preclude all β-lactams)
>Foetal damage/risk to pregnant women (tetracycline causes discolouration of teeth in children and may cause liver damage in pregnant women; fluoroquinolones may cause cartilage damage)
>Antibiotic resistance

Front 63

How are enzymes becoming resistant at a cellular level?

Back 63

>New enzyme that degrades antibiotic:
- β Lactamases, aminoglycoside modifying enzymes
>New pump that pumps out antibiotic
- Mef (macrolides); Tet A-E (tetracyclines); MexABOprm (Carbapenems)
>Loss of channel used by antibiotic for entry:
- D2 porin (carbapenems)
>New protein with lower affinity for antibiotic
- PBP2a (flucloxacillin), Rpob (rifampicin)
>New enzyme/pathway allowing bypass
- Folate biosynthesis (trimethoprim)

Front 64

How has antibiotic resistance occurred?

Back 64

>Through random genetic events:
- Acquisition of DNA: Plasmids, Transposons and Naked DNA
- Alteration of DNA: mutation
- Loss of DNA: deletion

NB. Staphylococcus aureus strains are all resistant to antibiotics now.

Front 65

How can doctors control antibiotic resistance?

Back 65

>Resistance usually carries a biological cost to the micro-organism
- decreased fitness
- biological disadvantage in the absence of antibiotic pressure (additional protein, loss of transport pathway, additional energy expenditure, less efficient enzymes/pathways
>Overwhelming selective advantage under antibiotic pressure.
>By carefully exerting antibiotic pressure doctors can control the selection of bacteria.

Front 66

What are the main groups of antibiotics?

Back 66

>β lactams
>Macrolides
>Glycopeptides
>Aminoglycosides
>Quinolones
>Anti-folates

Front 67

Which antibiotics are considered 'lone rangers'?

Back 67

- Rifampicin (contraind. for contraceptive pill users)
- Sodium fusidate
- Chloramphenicol
- Doxycycline
- Nitrofurantoin
- Metronizadole

Front 68

Which new and rarely used antibiotics are there?

Back 68

>Linezolid
- Glycopeptide resistant enterococci
- VISA / VRSA
>Daptomycin
- VISA / VRSA
>Tigecycline
- ESBLs and MRSA

Front 69

What are the β-lactams?

Back 69

>Class of antibiotics with three groups:
1. Penicillins
2. Cephalosporins
3. Carbapenems
>Inhibit enzymes involved in cell wall assembly
>Have no activity agains atypical organisms:
- Chlamydia
- Mycoplasma
- Legionella

Front 70

What are the β lactamases?

Back 70

>Enzymes which confer resistance to bacteria against β lactam antibiotics:
- Differ in substrate specificity and inhibitor susceptibility
- New variants constantly emerge
- Often plasmid mediated (easily transfer between bacteria)

Front 71

Which bacteria produce β lactamases?

Back 71

>Some bacteria never produce β-lactamase
- gram +ve rods e.g. listeria/corynebacteria, streptococci, neisseria meningitidis, treponema, most anaerobes
>Main producers:
- Staph aureus and coagulase negative staph.
- Gram negative rods including Haemophilus influenzae
- Bacteroides fragilis (gram negative gut anaerobe involved in abdomen-pelivic sepsis)
>Some gram negative cocci (gonorrhoea)

Front 72

Which penicillins are becoming less effective?

Back 72

>Beta lactamase labile:
- Penicillin
- Ampicillin
- Amoxicillin
- Ticarcillin
- Piperacillin

Front 73

How does beta lactam resistance manifest?

Back 73

>Alteration in target site affinity for transpeptidase and d-ala decarboxyl transpeptidase
>Beta lactamase production (breaking open of the lactam ring).

Front 74

What would give a positive coagulase test?

Back 74

>Staphylococcus aureus
- Highly virulent
- Wide variety of infections

Front 75

How can the issue of β lactamases be overcome?

Back 75

>Through use of inhibitor combinations such as:
- Co amoxiclav (abdomino pelvic sepsis, pyelonephritis, pneumonia)
- Piperacillin Tazobactam
- Ticarcillin Clavulanate
- These can have issues with penetration and inhibitor susceptibility.
>Through stabilising β lactams
- Flucloxacillin (modified penicillin stable against staphylococcal β lactamase; staph aureus infections)
- Cephalosporins
- Carbapenems

Front 76

How can loss of target site affinity be overcome?

Back 76

>Different β lactams attack different peptide binding proteins
- possible to use an alternate β lactam e.g. cephalosporin
>Some bacteria lose affinity to all β lactams
- use non β lactam antibiotic (e.g. glycopeptides, aminoglycosides, doxy, rifampicin, trimethoprim, sodium fusidate)

Front 77

List some examples of the superbugs (antibiotically resistant strains).

Back 77

>Multi-drug resistance Mycobacterium tuberculosis
>Methicillin resistant Staphylococcus aureus
>Extended-spectrum β lactamase producing enterobacteriaeccae
>Penicillin resistant Streptococcus pneumoniae
>Penicillin resistant Neisseria gonorrhoeae
>Vancomycin resistant Enterococcus faecalis
>Multi resistant Pseudomonas and Acinetobacter
>Ciprofloxacin resistant Salmonella typhi

>>Vancomycin Resistant MRSA

Front 78

What are the main causes of antibiotic resistance?

Back 78

>Over the counter antibiotics
>Misuse of antibiotics by doctors
>Antibiotics in animal feed

Front 79

Give an overview on the cephalosporins.

Back 79

1st generation (cefradine, cefalexin, cefadroxil):
- Gram +ve organisms (incl. β lactamase producers); NOT enterococci.
- Some β lactamase negative (e. coli, klebsiella, proteus)

2nd generation (cefuroxime, cefaclor):
>Good gram +ve activity
- NOT enterococci
>Enterobacteriaceae
>Some β lactamase stability
- cefuroxime stable to TEM-1

3rd generation (cefotaxime, ceftriaxone, ceftazidime):
>High risk of C. diff. infection
>Activity
- Moderate to poor anti-staphylococcal activity
- Good activity against most other gram +ve organisms (NOT enterococci)
- Very good activity against ESBL negative Enterobacteriacea
>Ceftazidime has anti pseudomonal activity.

Front 80

Give an overview on the carbapenems.

Back 80

E.g. meropenem, imipenem, ertapenem:
>Very broad spectrum
>β lactamase stable
>Are vulnerable to resistance due to loss of penicillin binding protein affinity.
- Gram positives (not MRSA)
- Anaerobes
- Gram negatives

Front 81

Give an overview on the amino-glycosides.

Back 81

>Aminoglycosides include:
- Gentamicin
- Amikacin
- Streptomycin
- Tobramycin

>Activity: Inhibit ribosomal protein synthesis
- Staph. incl. MRSA
- GRAM NEG BACILLI (enterobacteriaeceae, pseudomonas aeruginosa)
- Mycobacteria
- Aerobes

>Poor tissue penetration
>Resistance growing amongst gram +ves
>Oto and nephrotoxic; requires close monitoring

Front 82

Give an overview on the quinolones.

Back 82

Quinolones (ciprofloxacin, moxifloxacin, levofloxacin):
MoA:
>Inhibit DNA gyrase and topoisomerase
>Activity:
- Gram +ves (not MRSA/enterococci)
- GRAM NEG. enterobacteriaceae, pseudomonas aeruginosa, neisseria
- Atypicals: Mycoplasma, legionella, chlamydia
- Mycobacteria
- Aerobes
>Excellent tissue penetration (not CSF)

>Growing resistance, 20% of enterobacteriaceae are resistant.

Front 83

Give an overview on the macrolides.

Back 83

Erythromycin:
>Largely redundant
Clarithromycin:
>Better absorption, tolerance, PK/PD

MoA: Inhibit amino acid binding during protein synthesis

Activity:
>Gram +ves (β lactam allergy)
>Some anaerobes
>Atypicals
>Mycobacteria (clarithromycin)

Front 84

What are azithromycin and clindamycin?

Back 84

>Macrolide related agents: stronger and good penetration in comparison.

Front 85

Give an overview of Glycopeptides.

Back 85

E.g. Vancomycin and Teicoplanin

MoA:
>bind to the D-ALA-D-ALA terminal end of peptidoglycan precursors.
- this inhibits the action of transglycosidase and transpeptidases (required for cross-linking of peptidoglycans - basic building block of cell wall)
- inhibits RNA synthesis

Resistance:
>Due to substitution of D-Ala with D-lactate which prevents glycopeptide binding

Activity:
>Gram +ves
>C. diff.

PK/PD:
>Poor tissue penetration

Tolerability:
>Nephrotoxic

Front 86

Give an overview of antifolates.

Back 86

E.g. Sulphonamides, Trimethoprim, Co trimoxazole, Dapsone

Activity:
>Sulphonamides - broad spectrum
>Trimethoprim
- Enterobacteriaceae (15% resistance)
- MRSA adjunctive therapy
>Co trimoxazole:
- Pneumocystis jirovecii
>Dapsone: Leprosy

MoA: inhibit nucleic acid precursor synthesis

Tolerability:
>Sulphonamides:
- Contraindicated in G6PD deficiency
- Allergic reactions
>Co trimoxazole:
- Myelotoxic (restricted use)

Front 87

How common is β lactam allergy?

Back 87

Many patients claiming penicillin allergy are not:
>7-23% true allergic
Risk of anaphylaxis with cephalosporins:
>0.1-0.0001%
Risk of cross reactivity overrated:
- 0.1% with 1st generation cephalosporins

Front 88

Which antibiotics are bactericidal?

Back 88

>β lactams
>Aminoglycosides
>Fluoroquinolones
>Rifamycins

Front 89

When did antibiotics come about?

Back 89

1940s - introduction of penicillin and sulphonamides.

Front 90

Which antibiotics are bacteriostatic?

Back 90

>Tetracyclines
>Trimethoprim

Front 91

What is meant by concentration dependent killing?

Back 91

>Some antibiotics exert bactericidal action that is related to the peak therapeutic concentration reached.
>Aminoglycosides and fluoroquinolones

Front 92

What is meant by time dependent killing?

Back 92

>Bactericidal action is related to the length of time an antibiotic exceeds the MIC, and not necessarily related to the peak concentration reached.

Front 93

What is meant by PAE?

Back 93

>Post antibiotic effect:
- bacterial regrowth is inhibited for several hours after the antibiotic concentration has fallen below the MIC.

Front 94

Describe the routes of administration of antibiotics.

Back 94

>Per Orum
>Per Rectum
>Topical
>Intra Muscular
>Intra Venous
>Nebulised

Front 95

What are the key pharmacokinetic factors to consider when choosing antibiotics?

Back 95

>Absorption:
- tetracyclines can be chelated by calcium containing preparations, preventing absorption
>Half life:
- variable (hours to days)
>Protein binding within the bloodstream and ECF
>Volume of distribution and tissue concentrations
>Penetration into difficult sites (CSF, bone)
>Metabolism (metabolite activity also)
>Excretion (renal, biliary)
>Other drug interactions

Front 96

How can antibiotic use be reduced?

Back 96

>Avoiding prescription for likely viral infections
>Gather knowledge of specific microbe(s) before treatment if patient not too ill
>Use narrow spectrum antibiotics first
>Treat as short as possible e.g. uncomplicated cystitis = 3 days
>Review prescriptions at 48h taking note of condition and microbiology results
>Rationalise broad spectrum antibiotics on the basis of microbiology results
>Avoid unnecessary prophylaxis
>Regularly updated antibiotic guidelines should be available
>Patient history should be taken into account

Front 97

When is antibiotic prophylaxis indicated? Use examples.

Back 97

>Significant risk of infection
>Consequence of infection may be serious
>Period of highest risk can be ascertained
>Microbial causes can be predicted
>Antimicrobial sensitivity of infection is predictable
>Cheap and reasonable safe antimicrobial agents are available

Examples:
1. Co amoxiclav (prior to surgery e.g. colorectal)
2. Amoxicillin (prior to dental surgery)
3. Rifampicin (contact with meningococcal disease)

Front 98

What is the difference between intrinsic and acquired antibiotic resistance?

Back 98

>Intrinsic resistance depends on the natural properties of the bacterium e.g. cell wall impermeability to an antibiotic
>Acquired resistance occurs when the bacteria evolves to resist antibiotic pressure e.g. via mutation, transfer of resistance genes e.g. β lactamase production.

Front 99

What are side effects of different antibiotics?

Back 99

>Common reactions include skin rashes, diarrhoea, nausea, vomiting due to upset of natural microbiota
>Specific examples:
- Aminoglycosides, nephro- ototoxicity
- Co amoxiclav, cholestatic jaundice
- Fluoroquinolones, tendonitis, tendon rupture, seizures
- Rifampicin, disturbed LFTs (inhibits contraceptive pill effect)
- Chloramphenicol, aplastic anaemia
- Sulphonamides, Steven-Johnson syndrome

Front 100

What factors influence establishment of infection?

Back 100

>Minimum infective dose
>In vivo growth rate of pathogen
>Pathogen virulence factors
>Route of entry
>Integrity of host skin and mucosal surfaces
>Host: overall state of health and effectiveness of innate and adaptive immune mechanisms

Front 101

How may pathogens attach to host cells and what are the consequences of bacterial adherence?

Back 101

>Enteropathogenic E. coli (EPEC) produce pili and adhesins
- Aids adhesion to brush border of intestinal mucosa
- Causes local destruction of microvilli
>Enterotoxic E. coli (ETEC) possess pili which enable the organism to adhere to mucosal epithelial cells via specific receptors
- ETEC produce plasmid-associated enterotoxins

POTENTIAL CONSEQUENCES:
>No effect
>Altered morphology
- Invagination of cells to hide from immune defences e.g. pits
- Enabled via interaction by Actin cytoskeleton
>Cytokine release
>Apoptosis
>Invasion

Front 102

What are typical mechanisms of host damage during bacterial infection?

Back 102

>Lysis of host cells:
- Bacterial toxin that damages cell membrane
- Intracellular fission leading to lysis
- Programmed cell death (apoptosis) induced by bacteria
>Toxin-induced metabolic changes
>Mechanical causes
- sufficient numbers may cause obstruction
>Damage caused by host responses (immunopathology)
- e.g. sepsis: cells produce superoxides which will damage vascular endothelium, resulting in puerpera (blood leaking out)

Front 103

What are the virulence factors of Strep Pyogenes?

Back 103

>M-protein (adhesin)
>Hyaluronic acid capsule - antiphagocytic
>Lipoteichoic acid - antiphagocytic
>Erythrogenic toxins A, B, C - superantigens
>Hyaluronidase - spreading factor
>Streptolysin - O, S - Haemolysins
>DNases, hyaluronidase, proteases - virulence enhancers
>Pyrogenic exotoxins - rash of Scarlet fever
>Toxic shoc syndrome (TSS)

Front 104

Describe the mechanism of inhibiting complement.

Back 104

>Pathogens may mask surface components that activate the alternative pathway
>'Smooth' strains of G-ve bacteria hinder access of the MAC to its target
>Bacterial enzymes can digest complement components

Front 105

Describe the mechanisms of enzymatic lysis and pore formation by bacteria.

Back 105

ENZYMATIC LYSIS:
>Clostridium perfringens is a G+ve anaerobic rod
- Can cause gangrene
- Produces alpha toxin which hydrolyses phosphorylchlorine in the cell membrane
- Leads to lysis of the cell; allowing nutrients out for the bacteria
PORE FORMATION:
>Staph and strep haemolysins are pore forming toxins and can lyse many other types of cell
- Knock holes in red cells to absorb iron

Front 106

Give examples of pathogens causing local and invasive infections and their presentations.

Back 106

Front 107

Give examples of pathogens causing local and invasive infections and their presentations.

Back 107

Front 108

Where is staph aureus typically found and what are its virulence factors?

Back 108

>Commensal of skin and nasal passages
- usually causes local purulent abcesses
>Factors include:
- Capsule and slime - antiphagocytic
- Protein A - binds Fc terminues of IgG
- Lipoteichoic acid - adhesin
- Pore forming toxins - damage host cells
- Panton Valentine leucocidin (PVL) kills neutrophils
- DNAses, lipases and proteases enhance virulence
- Beta lactamase for antibiotic resistance
- Exfoliative toxins A and B - scalded skin syndrome
- Enterotoxins - food poisoning
- TSS - toxic shock toxins

Front 109

What might this be an effect of?

Back 109

>Staphylococcal Exotoxins:
- Desquamation of hand due to TSS
- Scalded syndrome

Front 110

Describe the symptoms of S. Pyogenes infection and its virulence factors.

Back 110

>Virulence factors:
• M-protein – adhesin, anticomplementary
• Hyaluronic acid capsule – antiphagocytic
• Lipoteichoic acid – adhesin
• Erythrogenic toxins A,B,C – superantigens
• Hyaluronidase – spreading factor
• Streptolysin, O, S – haemolysins
• DNases, hyaluronidase, proteases – virulence enhancers
• Pyrogenic exotoxins – rash of Scarlet fever
• Toxic shock syndrome (TSS) toxins – TSS

Front 111

What is this pathology and what might it be caused by?

Back 111

>Clinical streptococcal disease
- Scarlet fever with rash and strawberry tongue
- Impetigo - often with staph aureus

Front 112

Describe the course of S. Typhi infection and its virulence factors.

Back 112

• G-ve facultative anaerobic rods
• The main antigens are somatic (O), flagellar (H) and capsular (K)
• There are many other species
which infect animals and can cause food poisoning in humans
• Specific human pathogen
• Penetrates the mucosal barrier in the distal ileum and colon by
bacterial-mediated endocytosis
• Resist lysosomal digestion and
pass to the lymphatic system.
• Can survive and grow within
phagocytes

Front 113

Which 3 ways are bacteria typically pathogenic?

Back 113

>Via exotoxins
>Invasion
>Immunopathology

Front 114

What are exotoxins?

Back 114

>Toxins which give rise to a recognisable illness
- have specific cellular target;
- or act upon host cell membrane leading to cell death and necrosis
- may be involved in intracellular invasion of host cells by pathogen
- in excess cause activation of the immune system

Front 115

Which toxins act on cell surfaces?

Back 115

>PAMPs
- e.g. Teichoic acid, LPS and flagellin
>Pore forming toxins
>Superantigens

Front 116

Describe Diptheria toxin's mode of action?

Back 116

>C. diptheriae is a G +ve aerobic club shaped rod
>Toxin genes are carried by a lysogenic bacteriophage integrated into the bacterial DNA
>Toxin producing strains of Corynebacterium diphtheria can produce 5000 toxin molecules/hour
>One molecule can kill a host cell

Front 117

What is this disease and its progression?

Back 117

>Bacteria multiply locally
>Toxin kills cells and an an ulcer forms with a necrotic exudate covered by a false membrane
>Death can occur due to respiratory obstruction or heart failure
>Immunisation with toxoid (inactive) prevents disease
>Treatment with antitoxin and antibiotics
>Surgery potentially necessary to clear the airway

Front 118

What is Cholera's mode of action?

Back 118

>V cholerae is a G -ve aerobic, comma shaped bacterium
>Vibrio cholerae toxin causes diarrhoea by activation of adenyl cyclase leading to high levels of cAMP in small intestine epithelial cells
>This leads to massive transport of fluid and nutrients into gut lumen

Front 119

Describe the symptoms of cholera and treatment.

Back 119

>Rice water stools
>Treatment = Oral rehydration therapy

Front 120

Explain the MoA of Tetanus neurotoxin.

Back 120

>Clostridium tetani is a G +ve anaerobic spore forming rod
>Tetanus toxin B subunit binds to ganglioside receptors on nerve cells
>A subunit then migrates to the CNS and blocks neurotransmitter release leading to continuous stimulation and spastic paralysis (i.e. tetany)

What is the course of infection and treatment?

Hint 120

>C. Tetani found in soil and manure
>Tetanus results from the penetration of a foreign object (garden fork, rusty nail) into the host causing tissue necrosis which allows spores to germinate and produce toxin
>Neonates become infected via the cut umbilical cord
>Death results from respiratory failure due to paralysis of chest muscles
>Immunisation with toxoid prevents disease
>Treatment is ant-toxin (must be rapidly given) and antibiotics
>Surgical debridement eliminates the focus of infection

Front 121

Describe the action of C. botulinum neurotoxin.

Back 121

>Enters via the intestine and crosses the gut wall
>Affects peripheral nerve endings at the neuromuscular junction
>Blocks peripheral nerve stimulation of muscle contraction leading to flaccid paralysis
>One of the most potent toxins known
- 400g could kill the entire planet

>What is the course of infection with C. Botulinum?

Hint 121

>Bacterium found in soil and can contaminate foods
- spores survive incomplete heat treatment
>Botulism is an intoxication by preformed toxin and food-borne disease is the tropical presentation
>Symptoms descend from cranium so lack of response to light in the eye is an early sign (within 6h)
>Neonates become ill due to toxin produced in the gut causing floppy baby syndrome
>Death results from respiratory failure due to muscle paralysis
>Treatment is anti toxin
- ventilatory support is vital
>Used in the cosmetics industry and in the treatment of migraine

Front 122

How may bacteria induce immune pathology?

Back 122

>Bacterial cell components e.g. LPS (endotoxin) of G -ve bacteria activate the host defence mechanisms in a way that causes tissue injury
- LPS binds to LPS binding protein found in plasma
- Complex binds to CD14 on macrophage cell membrane which activates it
- TNF and IL-1 are released
- LPS also activates coagulation complement and kallikrein cascades