The Public Semester 2 Flashcards
Give examples of Healthcare Associated Infections.
Wound/soft tissue infections Bloodstream infections UTIs Respiratory tract infections GI infections
Give the six divisions of microbiology.
Viruses Bacterium Algae Fungi Protozoa
Define microbiology.
The study of microorganisms, too small to be seen by the naked eye.
What are the four general properties of microorganisms?
Have microscopic dimensions
Ubiquitous
Independent growth/survival
Exist as single cells/clusters/consortia
What is the relevance of microbiology to pharmacy?
Antibiotic resistance Sterilisation Microbial disease Vaccination Quality Assurance
What is the general size of a bacteria?
0.12-5um
What are the four general bacterial shapes?
Rod, cocci, ovoid, filamentous
What are the functions of bacterial cell walls?
Determine cell shape and rigidity
Mechanical strength
Metabolically inert
What are bacterial cell walls composed of?
Carbohydrates (alternating NAM and NAG chains)
Peptide chains
How thick is a bacterial cell membrane?
8nm
What is the bacterial cell membrane composed of?
Phospholipids, proteins, fatty acids (no sterols)
What are the functions of a bacterial cell membrane?
Permeability barrier
Metabolically active
No endo or exocytosis
Describe the morphology of a bacterial chromosome.
Circular, covalently closed 1-2mm long Supercoiled domains 1 per cell Double stranded DNA
What is the function of a bacterial plasmid?
They carry specialist genes i.e. antibiotic resistance
What are the size of bacterial ribosomes?
30s + 50s = 70S
What are bacterial exopolysaccharides?
Slime capsule- providing protection and helping to avoid desiccation
98% water
Describe the morphology of bacterial flagellae.
Helical
12-18nm in diameter
Used for motility
What is the function of bacterial fimbriae?
Used in attachment and clumping.
Describe the morphology of bacterial fimbriae.
3um long
6nm in diameter
Heavily proteinaceous
What are the functions of bacterial pili?
Adhesion
Genetic exchange
Describe the morphology of bacterial pili.
> 3um long
6nm diameter
1-2 per cell
How do bacteria reproduce?
Asexually
Describe the cell surface of a gram positive bacteria.
Outer layer- peptidoglycan teichioc alcohols
Below- cell membrane
Describe the cell surface of a gram negative bacteria.
Outer membrane
Periplasm
Peptidoglycan
Below-cell membrane
Give examples of specific targets in bacterial composition for drugs to attack.
D-forms of amino acids
Meso-DAP on NAM residues.
What percentage of the cell wall of a gram positive bacteria is peptidoglycan?
40-70%
What percentage of the cell wall of a gram negative bacteria is peptidoglycan?
5-15%
What kind of bacteria contain teichoic acid in their outer membranes?
Gram-positive
What kind of bacteria contain lipoproteins and lipopolysaccharides in their outer membranes?
Gram-negative
What are the unique components of lipopolysaccharides in gram-negative bacterial cells?
Lipid A: toxic to humans in high levels- embedded into the outer face of the outer membrane
Core: keto-deocyoctonic acid
amino sugars
O-Antigen: dideoxy sugars (e.g. abequose) waves into surrounding environment
What is the role of lipoproteins in Gram-negative bacteria?
Hold the outer membrane to the peptidoglycans.
What is the role of teichoic acid in Gram-positive bacteria?
Hold the cytoplasmic membrane to the peptidoglycans.
How thick is the gram-negative peptidoglycan layer?
1-3 layers thick
What is the outer membrane in gram-negative cells?
It is an asymmetric membrane that reacts with the outside world.
What is a psychrophile?
Organism with growth range of approximately 0-30 degrees.
What is a mesophile?
Organism with growth range of approximately 20-50 degrees.
What is a thermophile?
Organism with growth range of approximately 30-80 degrees.
What is the optimum pH for most bacteria to grow?
7.2-7.6
What is an obligate aerobe?
Prefer oxygen for growth
What is an obligate anaerobe?
Prefer no oxygen for growth
What is a facultative organism?
Will grow regardless of oxygen presence.
What is Superoxide Dismutase?
The enzyme required by organisms to survive in oxygen. It breaks down oxygen into its free radicals.
How do you calculate water availability?
Aw= vapour pressure of solution/vapour pressure of pure water
What is water availability expressed as?
A percentage or decimal
What effect does water availability have on growth and survival of gram negative organisms?
Effects are similar, both require large amount of water (around 90% Aw). Outer membrane is osmotically fragile, alterations in osmolarity can cause damage.
What effect does water availability have on growth and survival of gram positive organisms?
Growth- can occur as low as 85% water availability.
Survival- can occur as low as 75% water availability.
What effect does water availability have on growth and survival of yeast and fungi?
Growth- can occur as low as 75% Aw.
Survival- can occur as low as 70% Aw.
What is a halophile?
Require high salt concentrations to survive and grow.
What is a halotolerant organism?
Are able to survive at high salt concentrations but unlikely to grow.
What is an osmophile?
Require high sugar concentrations for survival and growth.
What is an osmotolerant organism?
Are able to survive at high sugar concentrations but unlikely to grow.
What is a bacterial endospore?
Specialised structures produced internally.
What roles do bacterial endospores play?
Protection from high temperatures, radiation and nutrient deprivation as survival mechanisms.
Give examples of bacterium that produce endospores.
Bacillus sp.
Clostridium sp.
From the inside, describe the layers of a bacterial endospore?
Core- Spore wall- Cortex- Spore coat- Exosporium
What is sporulation?
The process whereby a vegetative cell produces a spore due to an aggrevated factor (high temperature).
What is germination?
The process whereby a spore produces a vegetative cell.
What is contained in the core of a bacterial endospore?
The bacterial genetic information
Acids to allow for survival
Dehydrated, high calcium ion content to keep the nucleic acids alive
What is contained in the cortex of a bacterial endospore?
Peptidoglycans provide it with strength.
What is contained in the exosporium of a bacterial endospore?
Proteins such as keratin provide the bacteria with protection from its surroundings.
What occurs in germination?
Outgrowth from the spore to reproduce the vegetative cell.
How does bacterial cell growth occur?
Binary fission- DNA replication and cell elongation occur before septum formation and complete cleavage to form two identical daughter cells.
What is the generation time?
The time it takes for one cell to become two (doubling time).
How many stages are there in bacterial growth?
4
What occurs at stage I of bacterial growth?
LAG PHASE
No multiplication
Cell adaptation
Phase variable in length due to factors such as age, growth media
What occurs at stage II of bacterial growth?
EXPONENTIAL PHASE
Replication of cells occurs
What is the relevance of doubling times?
Antibiotic susceptibility, the slower an organism grows the more resistant and vice versa.
What occurs at stage III of bacterial growth?
STATIONARY PHASE
Constant cell number
Variable length of phase
Induced by number of factors e.g. lack of essential nutrient, accumulation of toxic compound
What occurs at stage IV of bacterial growth?
DEATH PHASE
Net loss of cells
Autolysis occurs
Variable phase length depending on surrounding environment, nutrients released
What are the main features of the Bacillus bacteria?
It is a large gram positive rod
Spore former
Aerobic
Found in air, soil and water
Give examples of species of Bacillus.
B. anthracis causes anthrax
B. cereus causes food poisoning (rice)
What are the main features of Clostridium bacteria?
Gram positive rod
Anaerobic
Spore former
Produces gas
Give examples of species of Clostridium.
C. tetani causes tetanus
C. botulinum causes food poisoning
What are the main features of Listeria bacteria?
Gram positive rods
Common in the environment
Can grow at fridge temperature
What are the main features of Corynebacterium?
Gram positive rod
Found in air, water and skin
Irregular in shape
Aerobic
What are the main features of Staphyloccocus bacteria?
Gram positive cocci
Found in air, soil and skin
Facultative anaerobe
Opportunistic pathogen
What are the main features of Streptococcus bacteria?
Gram positive cocci
Found in air, soil and throat
Facultative anaerobe
Opportunistic pathogen
Give examples of species of Streptococcus.
S. pneumonia- bacterial pneumonia
S. pyogenes- sore throats and scarlet fever
What are the main features of Pseudomonas bacteria?
Gram negative rod Aerobic Opportunistic pathogen Antibiotic resistant Biochemically versatile
Give examples of species of Pseudomonas.
P. aeruginosa causes 50% of gram negative infections e.g. cystic fibrosis, conjunctivitis, secondary wound infections
What are the main features of Escherichia bacteria?
Gram negative rod
Found in soil, water and vegetation
Facultative aerobe
Enteric (lives in the gut)
Give examples of species of Escherichia.
E. coli causes 80% of UTIs
What are the main features of Neisseria bacteria?
Gram negative cocci
Found in air and throats
Facultative anaerobe
Diplococci
Give examples of species of Neisseria bacteria.
N. meningitidis causes bacterial meningitis
N. gonorrhoeae causes gonorrhoea
What are the main features of Mycoplasmas bacteria?
Neither gram positive or negative
No cell wall
Very small genome
Smallest free living organisms
What are the main features of Mycobacteria?
Neither gram positive or negative Very slow growing Unusual cell wall structure Contains mycolic acid Stained using Ziel-Nielson stain
What are the main features of Obligately intracellular bacteria?
Neither gram positive or negative
Must be cultivated in living tissue
What kind of cells are fungi?
Eukaryotic
What are the three major groups of fungi?
Moulds
Yeast
Mushrooms
What pH do fungi prefer?
Lower/acidic pH
Where are fungi found?
Terrestrial (plant matter, soil)
Aquatic (fresh water)
How do fungi survive?
Secrete hydrolytic enzymes Aerobic Can be facultative anaerobes (fermentation) Saprophytic (uses dead organic matter) Parasitic
What are the features of a fungal cell wall?
Provides rigidity
Multilayered
80-90% polysaccharide
What do the cell walls of moulds contain?
Chitin
Glucans
Cellulose
What do the cell walls of yeast contain?
Mannans
What are the features of a fungal cell membrane?
Similar to higher eukaryotes
Ergosterol instead of cholesterol
6% sterol
Regulates osmotic pressure
What are the features of yeast cells?
3-30µm Unicellular Spherical, oval or cylindrical shape Sexual reproduction (spores) Asexual reproduction (budding)
What are the features of moulds?
Branched, threadlike filaments called hyphae
Form mycelium
Multinucleate
What is a septate mould?
Contains cross walls
What is a coenocytic mould?
Has a continuous cytoplasm
What are mushrooms?
Fruiting body of fungi
Occurs when conditions are favourable
What is fungal dimorphism?
Two different morphological forms:
To allow more rapid reproduction under adverse environmental stress
Competitive advantage
What occurs in fungal asexual reproduction?
Fission occurs. The offspring are genetically identical
What occurs in fungal sexual reproduction?
Mixing of genetic material occurs so offspring exhibits traits of both parents
How does asexual reproduction occur in moulds?
Unique reproductive structures
Mycelial differentiation
Exospores
How does sexual reproduction occur in moulds?
Some moulds reproduce using sexual spores
Fusion of unicellular gametes or specialised hyphae
What are ascospores?
Formed in an enclosed sac
What are basidospores?
Formed in club shaped basidium
How are fungi medically relevant?
Colonisation- superficial mycoses
Hypersensitivity- fungal spores etc
Toxin- mycotoxicoses
What are superficial mycoses?
Colonisation of the surface layers of the body - athlete’s foot
What are subcutaneous mycoses?
Colonisation of deeper layers of the body
What are systemic mycoses?
Growth in internal organs- unlikely to survive and often due to immunosuppression
What are candida infections?
Yeast infections
Who are vulnerable to candida infections?
Immunocompromised patients
How is candidiasis often treated?
Topical clotrimazole, nystatin, ketoconazole or oral fluconazole.
Give examples of types of ergosterol inhibitors?
Polyenes- bind ergosterol and disrupt membrane function
Azoles- inhibit ergosterol biosynthesis
Allyamines
What do polyoxins do?
Treat anti fungal infections- inhibit chitin biosynthesis
What is 5-fluorocytosine?
Nucleic acid synthesis inhibitor
How big are viruses?
28-200nm
Describe the features of viruses.
Variety of shapes
No metabolic machinery of their own
Only one type of nucleic acid
Protein coat (capsid)
What are the two geometric forms of viruses?
Icosahedral
Helical
Describe the features of an icosahedral virus?
Geometry: 20 triangular faces, 30 sides, 12 vertices
Capsomeres are pentanes or hexons
What is a bacteriophage?
A virus that attacks bacteria
How do viral plaques form?
Require a bacterial host
What is the most common way to transmit a virus?
Via the respiratory tract.
Give examples of viral transmission.
Respiratory: Influenza A virus (and rhinovirus). Transmission in the form of aerosols during coughing and sneezing.
Faecal-oral: Enteroviruses (e.g. poliovirus) A lot of viruses are excreted in faeces following high levels of replication in the gut.
Blood borne: Hepatitis B (and HIV). Transferred through contaminated blood products or via shared needles with drug abuse.
Sexual transmission: HIV
Animal/insect vector: Rabies. In many instances the virus infection is a specific pathogen of the animal and is not normally transmitted to humans by any other means.
How do viruses target cells?
Tissue tropism- very specific affinity for particular tissues.
What is viraemia?
Virus in the blood
What are the properties of the Influenza A virus?
Myxovirus Enveloped virus with segmented RNA genome Infects a wide range of animals Undergoes extensive antigenic variation Major cause of respiratory infections
What causes fever in Influenza?
Altered cytokine expression
What methods do humans have to protect from influenza?
Filtration of droplets containing virus by fine hairs and cilia in the nasal cavity
Muco-cilliary cells lining the trachea can trap virus particles
Alveolar macrophages can engulf the virus if it reaches the lungs
What are the key characteristics of antiviral drugs?
Able to enter infected cells
Interfere with viral nucleic acid synthesis/regulation
Interfere with ability of virus to bind to cells
Stimulate body’s immune system
What is Amantadine?
Narrow spectrum antiviral active against influenza A
Used prophylactically when vaccine is unavailable
Reduce recovery time
Has CNS and GI side effects
What is Aciclovir?
Synthetic nucleoside analog used to suppress replication of Herpes and Varicella viruses
What are antiretroviral drugs?
Used in management of HIV
Highly active antiretroviral therapy includes numerous medications
Reverse transcriptase inhibitors
What are prions?
Proteinaceous Infectious Agents- ‘slow viruses’
Cause plaques in the brain- transmissible spongiform encephalopathies
What are the three types of TSEs?
Infectious- transfusion, latrogenic spread, eating infected material
Sporadic
Familial- autosomal dominant mutation of PrP, inherited
What are the characteristics of TSEs?
Inevitably fatal Transmissible Long incubation periods No antibody response Neuronal vacuolation Accumulation of PrP protein Afebrile
Where is microbial DNA found?
Plasmids
Chromosomes
What is transformation?
Genetic transfer process by which DNA is incorporated into a recipient cell bringing about genetic change.
Who discovered bacterial transformation?
Fredrick Griffith who worked with Streptococcus pneumoniae
How many cells are contained within one bacterial colony?
~10^8
How many genes are contained in one bacterial cell?
~10^3
What are transformation competent cells?
Cells capable of taking up DNA and being transformed, competence is regulated in naturally transformable bacteria.
In certain strains, specific procedures are required to make cells competent.
What is electroporation?
Electricity can be used to force cells to take up DNA
What is microbial transduction?
Transfer of DNA from one cell to another by a bacteriophage
What are the two modes of transduction?
Generalised- DNA from any portion of the host genome is packaged inside the virion.
Specialised- DNA from a specific region of the host chromosome is integrated directly into the virus genome.
What are the features of generalised transduction?
Virus can be temperate or virulent
Low efficiency
Defective virus particle incorporates fragment of the chromosome randomly
What are the features of specialised transduction?
DNA from a specific region is integrated directly into the virus genome.
DNA of temperate virus excises incorrectly, taking host genes along with it.
Transducing efficiency can be high.
What is bacterial conjugation?
Mechanism of genetic transfer that involves cell-to-cell contact (mating)
What are features of the cells involved in conjugation?
Plasmid encoded mechanism
Donor cell contains conjugative plasmid
Recipient cell does not contain plasmid
What is the F plasmid?
Fertility plasmid- circular DNA molecule, ~100kbp
Contains genes that regulate DNA replication, several transposable elements that allow the plasmid to integrate into the host chromosome, contains tra genes that encode transfer functions.
What is a sex pilus?
Essential for conjugation, produced by the donor cell and used to transfer genetic information.
What are Hfr strains?
High frequency of recombination- cells that possess an integrated F plasmid.
An F plasmid is an episome that can integrate into host chromosomes.
What happens in the presence of the F plasmid?
Ability to synthesis F pilus
Mobilisation of DNA for transfer to another cell
Alteration of surface receptors so that a cell can no longer act as a recipient in conjugation
What is pathogenicity?
The ability to damage the host i.e. cause disease
What influences the nature of a disease?
Type of microorganism
Virulence factors produced by the organism
Health of the host
Site of infection
What are the potential forms of damage caused by a pathogen?
Localised organisms- damage through toxin production Superficial, partial invasion Blockage Invasion Tissue destruction
What are the natural methods of elimination of bacteria?
Physical removal
Starvation
Killing
How can bacteria accumulate?
Adhesion to host tissues
Rapid growth
Survival
What are microbial biofilms?
Cells attached to a surface covered in an extracellular matrix.
Composed of one or more species of microorganism.
Extremely resistant to antimicrobials and host defences.
Act as a reservoir of infection or contamination.
What is virulence?
A measure of the ease with which a microorganism can establish disease in a susceptible host.
What is infectivity?
A measure of the ease with which a pathogen can become transferred from an infected host to a susceptible one.
What is susceptibility?
A measure of the ease with which an individual may become infected.
What is the minimum infective number?
The number of microbial cells that are required to be introduced to particular sites in the body in order to initiate infection.
How can transmission occur into the body?
Via skin, respiratory tract, GI tract, eyes, urinary genital tract
How can transmission occur out of the body?
Faeces, urine, saliva, semen, blood, cannibalism
How can the pharmacist advise on pathogenicity?
Safe sex, personal hygiene, disinfection, vaccination advice to public.
Antibioitic stewardship, resistance, infection management advice to GPs.
Prescription advice to customers such as completing treatment course and potential side effects/interactions.
How many bacterial cells are estimated to be in the human body?
10^14
What roles to bacteria play within the human body?
Aid immune development
Colonisation resistance
Metabolic organ
May still cause disease in immunocompromised host
What are obligate human pathogens?
Not part of commensal flora, disseminate solely through causing disease in humans with poor survival outside the host.
What kind of things cause a host to be immunocompromised?
Damage to epithelia- skin infections
Disruption of normal flare i.e. by antibiotics
Impairment of immune system by infection
Introduction of bacteria to new sites
What are virulence factors?
A bacterial product or strategy that contributes to virulence or pathogenicity
What are the two main categories of virulence factors?
Those that promote colonisation/invasion
Those that damage the host
What characteristics allow flagella to act as virulence factors?
Thin, hollow appendages, movement via rotation, basal rotary engine, microbial taxes.
What characteristics allow pili to act as virulence factors?
Proteinaceous surface appendages, mediate movement (type IV), attachment (type I), biofilm formation.
What characteristics allow capsules to act as virulence factors?
Polysaccharide layer, surface attachement, resists desiccation, immune system evasion, molecular mimicry.
What characteristics allow endotoxins to act as virulence factors?
Integral part of outer membrane of gram negative bacteria, lysis causes release, stimulate complement and cytokine release.
What characteristics allow exotoxins to act as virulence factors?
Toxic bacterial metabolites, actively excreted from focus of infection, movement to distal parts of the body, often specific target.
What is necrotising fasciitis?
Infection of the fascia associated with M3 serotype of S. pyogenes. Treatment with IV antibiotics and debridement must be rapid.
What is toxic shock syndrome?
Caused by a superantigen exotoxin produced by S. aureus. Involves multiple organ systems, causing fever, hypotension, rash, desquamation of skin on soles and palms
What are antibiotics?
Naturally produced antimicrobial agents that can be modified to enhance efficacy.
What are broad spectrum antibiotics?
Antibiotics that are effective against both gram positive and gram negative bacteria.
What are beta lactam antibiotics?
Antibiotics with a beta lactam ring including penicillins, cephalosporins and cephamycins, account for more than half of all antibiotic production.
What produces penicillin?
The fungus, Penicillium chrysogenum
What is the mechanism of action of beta lactam antibiotics?
Potent inhibitors of cell wall synthesis, transpeptidases bind to the beta lactam ring so the cross linking of the wall does not occur. This weakens the wall and results in osmotic lysis.
What are the features of Cephalosporins?
6 member dihydrothiazine ring
Same mode of action as penicillin
Semi-synthetic- broader spectrum of activity
Often more resistant to beta-lactamases
What are the features of aminoglycosides?
Contain amino acid sugars joined with glycosidic bonds
Inhibit protein synthesis at the 30s subunit
Active against gram negatives
Examples: streptomycin, kanamycin, neomycin, gentamycin
Describe the features of macrolides?
Contain large lactone rings connected to sugar moieties
Inhibit protein synthesis at the 50s subunits
Used in patients allergic to penicillins
Example- erythromycin
Describe the features of tetracyclines?
First broad spectrum antibiotics
Basic structure consists of a naphthacene ring system
Interferes with 30s ribosomal subunit function
Wide use in veterinary medicine
What is a growth factor analogue?
Blocks the ability for microbes to obtain growth factors as they cannot synthesise them.
Structurally similar to growth factors but cannot duplicate their function.
Describe the features of Sulfanilamide?
An analogue of p-aminobenzoic acid which is a component of folic acid.
Blocks folic acid synthesis as bacteria synthesise their own folic acid whereas eukaryotes rely on obtaining it from their diet.
What is isoniazid?
A growth analogue effective only against mycobacterium as it interferes with synthesis of mycolic acid.
What are quinolones?
Synthetic antibacterial compounds that interfere with DNA gyrate
e.g. ciprofloxacin
What are nucleic acid bases analogues?
Formed from the nucleic acid base but have the addition of bromine or fluorine.
What are nucleoside analogues?
Most effective and commonly used antivirals that block reverse transcriptase
e.g. AZT
What are non nucleoside reverse transcriptase inhibitors?
They bind directly to reverse transcriptase to inhibit reverse transcription.
What are protease inhibitors?
Antivirals that inhibit the processing of large viral proteins into individual components.
What are fusion inhibitors?
Antivirals that prevent viruses from successfully fusing with the host cell.
What two drug categories successfully limit influenza infection?
Adamantanes
Neuraminidase inhibitors
What are interferons?
Small proteins that prevent viral multiplication by stimulating antiviral proteins in uninfected cells.
Why are fungi hard to treat?
As eukaryotes their cellular machinery is similar to that of animals and humans, as a result many antifungals are topical.
What are the 5 modes of action for anti fungal agents?
Polyenes bind to ergosterol and disrupt membrane integrity
Polyoxins inhibit chitin synthesis/azoles and allylamines inhibit ergosterol synthesis
Griseofulvin disrupts microtubule aggregation during mitosis
5-fluorocytosine is a nucleotide analogue that inhibits nucleic acid synthesis
What are ergosterol inhibitors used for?
Targeting the unique fungal plasma membrane component ergosterol
What are echinocandins?
Antifungals that inhibit 1,3 beta-d glucan synthase for treatment of Candida infections.
What is the most effective method of developing new antimicrobials?
Modification of current antimicrobial compounds (vancomycin)
How has drug discovery been sped up?
Automated chemistry methods- screening of potential compounds must occur.
Use of computers to design molecules e.g. saquinavir
Why do large companies not want to invest in novel antimicrobials?
Resistance, limited use.
Rather invest in a drug that a patient will take everyday for the rest of their lives than a one week course.
What is epidemiology?
Study of the pattern of occurrence, spread and control of (infectious) diseases within defined population groups based on a collection of detailed statistical information.
What is epidemiology used for?
Record diseases affecting a population.
Identify causes and modes of transmission of infectious disease.
What four different groups can be studied in epidemiology?
Age
Race
Geography
Behaviour
What disease caused a peak in mortality in 1918?
Influenza (Spanish flu)
What is miasma?
Bad air- containing pathogens and xenobiotics
What breakthrough did Ignaz Semmelweis make in epidemiology?
Use of epidemiology in order to control infection, hand washing and other basic sanitary processes. Due to increase in puerperal fever where doctors were present.
What is an infection?
A pathogen that establishes itself within a person.
What is the latent period of an infection?
The pathogen has established itself but is not infectious.
What is the incubation period of an infection?
The pathogen has established itself but there are no obvious symptoms.
What is a disease?
Where a pathogen is established and symptoms are present.
What is the period of communicability of an infection?
The period in which a person is infectious.
What are the two methods of spread of infectious disease?
Horizontal and vertical transmission
Direct and indirect
What is horizontal transmission?
Very broad- any sort of transmission from person to person where the people are not in a parent-child relationship.
What is vertical transmission?
Transmission of infection from mother/father to baby e.g. via the placenta, during birth, breast milk
What is direct transmission?
Person to person spread e.g. influenza, measles
What is indirect transmission?
Transmission via inanimate or animate means e.g. vectors, fomites, vehicles (water, food)
What is the role of vectors in infection?
Able to carry pathogens, don’t always support long term hosting
What are fomites?
Inanimate objects e.g. bedding, toys, surgical instruments
What is the role of fomites in infection?
When they become contaminated they can transfer a pathogen to a host- healthcare associated infection
What is the role of vehicles in infection?
Non living sources of pathogens that infect large numbers of individuals, cause common source epidemics e.g. food, water
What is a reservoir of infection?
Sites in which viable infectious agents normally reside, multiply in and rely upon for their survival- the natural habitat of the infectious agent
How are animals involved in infection spread?
Can transmit infectious agents to humans (zoonosis), act as reservoir therefore control in humans is achieved through eradication of animal reservoirs.
Give examples of diseases found in animal reservoirs.
Viral e.g. rabies
Bacterial e.g. salmonella
Prions e.g. vCJD
What is zoonosis?
The ability of an animal to transmit infectious agents to humans.
What is a human carrier?
An infected individual with no signs of disease, a source of infection for others
What is an acute carrier?
A carrier for the incubation period of a pathogen
What is a chronic carrier?
A carrier who harbours the pathogen for an extended period of time
Give examples of environmental carriers.
Water
Soil
What is prevalence?
The proportion of diseased individuals in a population at any one time
What is incidence?
The number of cases or diseased individuals within a population
What is mortality?
The incidence of death within a population
What is morbidity?
The incidence of illness in a population (fatal or non fatal)
What is sporadic level classification?
Occasional cases occurring at irregular intervals
What is endemic level classification?
Persistent occurrence with a low to moderate level
What is an epidemic/outbreak?
Occurrence clearly in excess of the expected level for a given time period
What is a pandemic?
Epidemic spread over several countries or continents, affecting a large number of people.
What are the two main types of epidemic?
Common source
Propagated (host-host)
What do epidemic curves tell us?
Mode of transmission
Timing of exposure
Course of exposure
What are common source epidemics?
Infected individuals have shared a common experience
What is a common point source of infection?
Exposure occurs in less than the incubation period
What is a common continuous source of infection?
Exposure occurs over multiple incubation periods
What interventions can be made in the case of a pandemic?
Vaccination
Infection control
Antivirals e.g. neuraminidase inhibitors (Tamiflu)
Where do anaerobic bacteria generally cause infection?
Mouth, teeth, throat sinuses, lower bowel
Where do gram positive bacteria generally cause infection?
Skin, chest
Where do atypical bacteria generally cause infection?
Chest, genitourinary system
Where do gram negative bacteria generally cause infection?
GI tract
What organisms are likely to have caused community acquired pneumonia?
Streptococcus pneumoniae
Haemophilus influenza
Staphylococcus aureus
How were antibiotics first developed?
In 1929 Alexander Fleming first isolated penicillin
What is AMS?
Antimicrobial Stewardship is a worldwide healthcare system approach to promoting and monitoring use of antimicrobials to preserve future effectiveness.
What is an empirical treatment?
Best guess first treatment using guidelines from AMS
What is target treatment?
Based on cultures and their sensitivity
Describe the main features of urinary tract infections.
Bacterial infection, mainly coliforms: escherichia coli, staphylococcus saprophytic, proteus mirabilis.
80% of community acquired UTIs are caused by E.coli
Causes: sex, pregnancy, diabetes, delayed urination, catheterisation
If untreated can cause kidney damage and scarring
What is the basic protocol for starting antibiotic treatment from AMS?
Drug allergy history
Initiate prompt, effective antibiotic treatment within one hour of diagnosis (reduce risk of sepsis)
Comply with local antimicrobial prescribing guidance
Document clinical indication, dose, route
Include review/stop date
Obtain cultures prior to commencing therapy if possible
What are the symptoms of urinary tract infections?
Burning sensation when urinating A need to urinate often Pain in the lower abdomen, back or sides Confusion Raised temperature Blood in the urine
How are urinary tract infections diagnosed?
Urine sample sent to labs, cultures and sensitivities analysed, causative organism identified, suitable antibiotic reported
What are the main features of Candida albicans infections?
Fungal (yeast) infection caused by pregnancy, steroids, AIDS, diabetes, antibiotics.
If untreated cam cause systemic infection or prolonged discomfort.
What are the symptoms of Candida infections?
Mouth/throat: sore, painful, furry tongue, metallic taste, white spots
Genital area: sore, painful, itchy, white discharge
How are Candida infections diagnosed?
Swab external sites of infection
Blood test if systemic
Cultures and sensitivities analysed and causative organism identified, suitable anti fungal reported
What are the main features of influenza?
Viral infection caused by: multiple strains of H1N1, Influenza type A or B.
At risk groups: elderly, pregnancy, diabetes, chronic conditions, HIV, healthcare professionals
If untreated: pneumonia, bronchitis, can be fatal.
What are the symptoms of flu?
Fatigue, congestion, headache, runny nose, muscle/body aches, sore throat/cough
How is influenza treated?
Treatment with antivirals such as Tamiflu should only be given if a positive result is found.
How is influenza prevented?
Flu vaccines for high risk groups with local initiatives to increase uptake of the flu vaccine.
What must be considered when choosing an antibiotic?
Sensitvity of culture, access to site of infection, allergies, liver/kidney function, most appropriate route of administration, dose, length of treatment, side effects, cost
Why are pregnant women more susceptible to infection?
Their immune system is dampened down to ensure they do not reject the baby, increasing the chances of opportunistic infection.
What is CURB-65?
Used as a guide for antibiotic treatment and route of administration
Confusion, urea, renal function, blood pressure, over 65
What are broad spectrum antimicrobials?
Effective on both gram negative and gram positive bacteria e.g. tetracycline
What are narrow spectrum antimicrobials?
Effective on a single group of bacteria e.g. Isoniazid (Mycobacteria)
What are bacteriostatic agents?
Frequently inhibitors of protein synthesis, binds to ribosomes, however if concentration is lowered growth resumes e.g. chloramphenicol
What are bactericidal agents?
Bind tightly to cells, causing them to die but they are not destroyed therefore cell numbers remain constant.
What are bacteriolytic agents?
Kill cells by lysis, decreasing cell number and reducing culture turbidity e.g. penicillins are cell wall synthesis inhibitors
How can antimicrobial activity be measured?
Minimum inhibitory concentration- determines the smallest amount of agent needed to inhibit bacterium growth
Disc diffusion assay- determines the zone of inhibition
How are cell walls target sites for antimicrobials?
Target peptidoglycan synthesis e.g. penicillins, cephalosporins
How is protein synthesis a target for antimicrobials?
Target 30s and 60s ribosomes e.g. tetracyclines, chloramphenicol
How are nucleic acids target sites for antimicrobials?
Target supercoiling e.g. rifamycin
How are cell membranes target sites for antimicrobials?
Causes membrane disruption e.g. polymixins
What are disinfectants?
Can be used on inanimate objects, important in infection control
What are antiseptics?
Can be used on living tissue, non toxic e.g. chlorhexidine and cetrimide (Savlon)
What are preservatives?
Maintains microorganisms at a low level, prevent spoilage e.g. paraben
What are biocides?
Do not necessarily sterilise, efficacy depends on concentration, microbial load and presence of organic matter
Give examples of intrinsic resistance?
Bacterium may lack target structure e.g. mycoplasmas don’t have a cell wall so not susceptible to penicillins
Bacterium is impermeable, low level of uptake e.g. in biofilm formation
Give examples of extrinsic resistance?
Production of degradative enzymes e.g. staphylococci produce β-lactamases which cleave penicillin
Modification of target site
Pumping agent out of cell by efflux
What drives antimicrobial resistance?
Not finishing antibiotic courses, use of inappropriate antimicrobials, weak surveillance systems, poor infection prevention/control, insufficient development of new products, irrational use of medicines
How can resistance be prevented?
Immunisation Avoid unnecessary parenteral devices Target specific pathogen Practice antimicrobial control Treat infection not contamination/colonisation Treat with least exotic antimicrobial Monitor usage Isolate the pathogen
What is a vaccination?
Administration of antigenic material to produce an immune response to a disease.
What is immunisation?
A broader term which can include passive immunisation as well as vaccines.
What is immunity?
The active ability of an organism to resist infection.
What is innate immunity?
The body’s built in ability to recognise and destroy pathogens or their products.
What is adaptive immunity?
Acquired ability to recognise and destroy pathogens or their products.
Who developed vaccination?
Edward Jenner, 1749-1823
What is active immunity?
Exposure to antigen, specific response generated by individual generating immunity, immune response maintained by stimulation of memory cells (boosters) and develops over a period of weeks.
What is passive immunity?
No exposure to antigen, immunity achieved by injecting antibodies, no immune memory activated, immunity is immediate but cannot be maintained.
What are antigens?
Foreign substances which induce an immune response in the body.
Why do we immunise?
Protect individual
Protect community
What is herd immunity?
If enough people in a community are immunised against certain diseases, then it is more difficult for the disease to get passed to those who aren’t immunised.
What makes an effective vaccine?
Low cost
Easy to administer
One step resistance
Dangers of vaccine significantly lower than with disease
What is sterilisation?
The killing or removal of all viable organisms within a growth medium.
What is inhibition?
Effectively limiting microbial growth.
What is decontamination?
The treatment of an object to make it safe to handle.
What is disinfection?
Direct targeting of the removal of all pathogens, not necessarily all microorganisms.
What is heat sterilisation?
The most widely used method of controlling microbial growth by denaturing macromolecules.
What is the decimal reduction time?
The amount of time taken to reduce viability tenfold by heat sterilisation.
What are endospores?
Resistant bacteria cells that can survive heat.
What are the methods of heat sterilisation?
Read heat (flaming) e.g. inoculating loop
Dry heat (hot air) e.g. glassware at 160-170º
for 4 hours
Autoclaving, steam under pressure
What is autoclaving?
Heat sterilisation in a sealed device that uses steam under pressure allowing water to reach above 100º.
What is pasteurisation?
The process of using precisely controlled heat to reduce microbial load in heat-sensitive liquids. It does not kill all organisms.
What is radiation sterilisation?
The use of microwaves, UV, X-rays, gamma rays and electrons to reduce microbial growth.
How does UV sterilisation work?
Has sufficient energy to cause modifications and breaks in DNA. Useful for decontamination of surfaces but cannot penetrate solid surfaces.
What is ionising radiation?
Electromagnetic radiation produces ions and other reactive molecules that generate electrons and radicals. Some microorganisms are more resistant than others.
What is the D value in ionising radiation?
It is comparable to the amount of energy required to reduce viability tenfold.
Give examples of sources of radiation for sterilisation?
Cathode ray tubes
X-rays
Radioactive nuclides
What is filter sterilisation?
Filtration avoids the use of heat on sensitive liquids and gases. Pores of filter are too small for organisms to pass through but allow liquid or gas.
Give examples of depth filters.
HEPA filters
Membrane filters
What are the microbial size ranges for filtration?
Yeasts 10µm
Bacteria 1µm
Mycoplasmas 0.125µm
Viruses as small as 0.01µm
What does filtration require?
Either pressure or vacuum.
What is chemical sterilisation?
Used to decontaminate heat sensitive materials via cold sterilisation.
Give examples of chemicals used in sterilisation and their method of action.
Volatile, toxic, gaseous: Ethylene oxide (alkylating) Formaldehyde (alkylating) Peroxyacetic acid (oxidising) Hydrogen peroxide (oxidising)
