Microbiology Flashcards
1
Q
Define pathogens
A
Organisms that cause or are capable of causing disease
2
Q
Define commensal
A
Organism that colonises the host but causes no disease in normal circumstances
3
Q
Describe opportunist pathogen
A
Microbe that only causes disease if host defences are compromised
4
Q
What is asymptomatic carriage?
A
When a pathogen is harmlessly carries at a tissue site where it causes no disease
5
Q
What is virulence / pathogenicity?
A
Degree to which an organism is oathogenic
6
Q
Rank microbes from largest to smallest
A
Protists
Eukaryotes
Spiral bacteria
Try beacteria
Virus < 1 um
7
Q
Areas with bacterial colonisation vs sterilisation
A
Bacteria - moist mucosal e.g. groin, skin, gut
Sterile - lungs, blood, heart, kidneys,gallbladder
8
Q
Gram stain positive vs negative results
A
Gram Positive = purple
Gram Negative = Pink
9
Q
Classes of bacterial shapes
A
Coccus (circular) - chain, cluster, diplcoccus
Bacillus (rods) - chain, curved
Spirochaetes - spiral rods
Vibrio - curved rod
10
Q
How is gram negative bacteria different to gram positive?
A
Has 2 membranes - inner and outer separated by lipoproteins, periplasmic space and peptidoglycan
Positive = large area of peptidogylcans links to single membrane by lipoteichoic acid
11
Q
Typical bacterial cell contains
A
No nucleus- circular, double stranded DNA
Some have capsule
Some have pills of flagella
12
Q
What is gram stain?
A
Crystal Violet to heat fixed bacteria
Then Iodine which fixes it to cell wall
Decolourise with ethanol / acetone
Counter stain with safranin
13
Q
Bacterial culture environment
A
Temperature < 80 or 120 for spores
pH 4-9
Light - UV
Without water for 2 hours - 3 months
14
Q
Phases of bacterial growth
A
Initial lag
Exponential (log)
Stationary (run out of nutrients)
Viability (die once nutrients run out)
15
Q
2 types of bacterial toxins
A
Endotoxin - component of the outer membrane of bacteria (gram negative) e.g. lipopolysacchrides
Exotoxins- secreted specific, strong proteins of gram positive and negative bacteria can be converted to toxoids
16
Q
3 methods of gene transfer
A
Transformation e.g. plasmids
Transduction e.g. via phage
Conjugation e.g. via sex pilus
17
Q
What does the coagulate test identify?
A
Positive = S.aureus from other staphylococci
(Add rabbit p,as a for fibrin)
18
Q
What are bacteria that CANT be cultured on artificial media called?
A
Obligate Intracellular bacteria
Only grow inside host cells e.g. chlamydia
19
Q
Bacteria that grow on artificial media with a cell wall called?
A
Grow as a single cell - rods, cocci, spirochaetes
Grow as filaments
20
Q
Bacteria grown on artificial media without a cell wall called?
A
Mollicutes
21
Q
A group of bacteria don’t gram stain due to a different cell wall but do stain what?
A
Ziehl-Neelsen stain
E.g. mycobacteria
22
Q
What does an oxidase test determine?
A
If the micro-organism contains a cytochrome oxidase and can use oxygen as the terminal electron acceptor
23
Q
3 haemolysis results
A
Alpha - green by production of hydrogen peroxide using haemoglobin
Beta - complete lysis of red blood cells e.g. Streptolysin O
Gamma - implies no haemolysis
24
Q
Sero grouping to further seperate B-haemolytic strep
A
Antiserum added and clumping indicates recognition
Group A - S.pyogenes
Group B - S.agalactiae
25
Describe Staphylococcus. Aureus
Gold, round gram positive cocci - Coagulase positive
26
How does Lancfield grouping occur?
A method of grouping catalase negative, coagulase negative bacteria based on carbohydrate cell surface antigens
27
Features of Staphylococci (aerobic gram positive cocci)
Spread by aerosols, surface-to-surface contact and cell associated virulence factors
28
Gram positive virulence factors
Pore forming toxins
Proteases
Toxic shock syndrome toxin
Protein A
29
Gram positive staphylococcus which are coagulase negative
S. Epidermis (white and round)
30
Classifying aerobic gram positive cocci
Chains = Streptococcus
- Haemolysis Alpha -> Optochin
Sensitive = S.pneumonia
Resistant = Viridans strep
- Haem Beta -> antigenic groups
- Haem Gamma
Cluster = Staphylococcus
- Coagulase +ve S. aureus
- Coagulase -ve
31
Examples of gram positive bacilli (rods)
Clostridia - spore and toxin forming
C. Tetani
C. Botulinum
C. Diphtheriae
32
How are gram positive bacteria managed?
With antimicrobials and vaccination
33
4 major groups of gram negative pathogens
Proteobacteria - all rod shaped
Bacteroids - rod shaped
Chlamydia - round pleimorphic
Spirochaetes - spiral/helical
34
2 Pathogenicity factors
Colonisation factors - adhesions, invasions, nutrient acquisition, defence
Toxins - secreted proteins for damage, subversion
35
Gram negative rods classification
Anaerobic - Bacteroides
Aerobic
- Coliforms
- Pseudomonads
- Vibrio
- Parvobacteria
36
Describe coliforms
Gran negative rods with flagella for motility and colonises intestinal tract
= Use metabolic processes e.g. fermenting lactose to differentiate
37
5 agar types
Blood - for alpha/ beta strep
Chocolate - for fastidious neisseria
MacConkey - lactose fermenters produce acid (pink)
CLED - stops motility and for lactose (yellow)
Xylose Lysine Deoxycholate agar (XLD agar) - selective isolation of salmonella and shigella (both lactose ferment red, but salmonella turns black)
38
What is a gram negative rod, short and stubby?
E. coli (commensal aids digestion)
Pathogenic when lateral gene transfers form hybrids
39
Most severe form of shigella
S. dysenteriae (bloody diarrhoea)
40
2 species of salmonella
S. bongori - rare
S. enterica- 3 forms of salmonellosis:
1. Gastroenteritis
2. Enteric fever
4. Bacteraemia
41
What are pseudomonas aeruginosa
Rod shaped, free living, motile, opportunistic, resistant to multiple antibiotics
Can cause acute or chronic (CF) infections
42
Pathogenesis of Vibrio cholera
Will bind to intestinal wall and sit there but release toxins
43
Spiral shaped with tuft of polar flagella
Helicobacter pylori
44
What is Nisseria meningitidis?
Gram negative diplococci
45
What is Bacillus cereus?
Gram negative rod
46
What are bacteria that CANT be cultured on artificial media called?
Obligate Intracellular bacteria
Only grow inside host cells e.g. chlamydia
47
3 examples of parvobacteria
Haemophilus influenza - non motile opportunistic capsular infection
Bordetella pertussis - short rods highly aerosol, produces 2 toxins (whooping cough)
Legionella pneumophila - severe inflammation pneumonia in immunocompromised = influx of neutrophils into lungs
48
Describe bacteroides
Non motile strict anaerobic rods
Mostly beneficial in gut but opportunistic with enterobacteria
49
Gram negative Cocci examples
Aerobic Veilonella
Anaerobic Nisseria = non flagellated diplococci
- N. Meningitidis - cytokine cascade = sepsis can kill in 4 hrs
- N. Gonorrhoeae - multi drug resistant STD can lead to infertility and death
50
Describe spirochaetes
Long, helical, highly flexible mostly free living and non-pathogenic
Modified outer sheath, lacks LPS with endoflagella for corckscrew motion
51
3 examples of spirochaetes
Borrelia burgdoferi (lyme’s disease) - bulls eye rash
Leptospira interrogans - rat faeces in water causes multi organ infection
Treponema pallidu (syphillis STD) - has 3 stages
52
3 main groups of obligate Intracellular bacteria (can’t be artificially cultured)
Rickettsia
Chlamydia - detect by serum Ab or PCR
Coxiella
53
Life cycle of chlamydia
1. Elementary bodies enter through endocytosis but prevents lysosome
2. Differentiates into reticulate bodies which replicate and acquire host nutrients
3. Conversion back to EB and cell lysis for release
54
What accounts for ~10% community acquired pneumonia?
Chlamydia Pneumonia
55
What are mycobacteria?
Gram negative single rod cells that identify with Ziehl-Neelson stain
56
7 mycobacteria of medical importance
M. tuberculosis - tuberculosis
M.leprae - leprosy
M.avium - disseminated infection in AIDS, chronic lung infection
M.kansasii - chronic lung infection
M.marinum - fish tank granuloma
M.ulcerans - Burundi ulcer
M.fortutium - skin and soft tissue infections
57
How many deaths per year by TB?
1.5 million
58
Describe Mycobacterium tuberculosis
Slightly curved beaded bacilli, gram negative, red in Ziehl-Neelon stain
Aerobic, non spore forming, non-motile
Survive inside macrophage even in low pH
Slow growth, reproduction or response to treatment
59
What is Acid fast bacilli?
Stain used to identify organisms with wax-like, thick cell walls e.g. mycobacteria which are resistant to germ stain = stains red
60
Challenges of TB
Thick lipid rich wall hard for immune cells to kill and drugs to penetrate
Slow growth=
Takes longer to diagnose and treat
61
Stages of TB infection
Primary in lungs
Latent (decades) - T cell contains primary but cell mediated immune persists
Pulmonary - granulomas form around bacilli in apex of lungs, can cause necrosis, abscess etc
62
Why does granulomas form in apex of lungs?
More air and less blood supply so fewer immune cells
63
What does our body do to protect us from TB?
Mycobacteria are phagocytoses by alveolar macrophages (some may escape to cytosol)
CD4 T-cells generate cytokines
Hallmarks granuloma formation to signal other immune cells (forms cavity for TB reactivation)
64
Clinical diagnostic methods of TB
Nuclei Acid detection - PCR has 88% sensitivity and 98% specificity
Liquid culture - 1-3 weeks
Solid culture - 2-8 weeks
Tuberculin skin test - Tcells after 3-9 weeks
65
4 types of TB drug resistance
Drug inactivation
Drug titration
Alteration of drug target
Altered cell envelope
66
How do we study TB?
Using zebra fish (transparent embryos are genetically maniptable and quick)
To find host-derived therapies (activate the immune system as well as administering antibiotics)
67
What is Hypoxia Inducible factor?
A genetic switch activated during hypoxia is a drug target to trick wbc into an immune response to treat TB
68
Some common viruses and significant causes
CMV, Rubella - Miscarriage
Outbreaks - Measles, Mumps, Covid
Cancer - HIV, HPV, Epstein-Barr
MERS, Ebola
= Morbidity and mortality
69
What is a virus?
An infectious, obligate Intracellular parasite comprising of genetic material (DNA or RNA) surrounded by a protein coat
70
Why is a virus dependent on a host cell?
Does not have membrane or organelles so cannot carry out metabolic reactions
71
Viruses from largest to smallest
Pox virus
Rhabdovirus
Herpes virus
Adenovirus
Parvovirus
72
Different shapes and structures of virus
Helical
Icosahedral
Complex
Non- enveloped or enveloped
73
How do virus replicate?
1. ATTACHMENT to specific receptors
2. CELL ENTRY via unloading of virion
3. INTERACTION + REPLICATION using host materials
4. ASSEMBLY occurs in nucleus / cytosol or cell membrane
5. RELEASE via bursting or exocytosis
74
How do viruses cause disease?
- Direct destruction of host cells
- Modification of host cell structure or function
- Over-reactivity of immune system
- Cell proliferation (inserting viral DNA)
- Evasion of Extracellular and molecular host defences
75
Examples of how virus evade molecular level host defences
Antigenic variability
Prevention of host cell apoptosis
Down regulation of interferon and other defence proteins
Interference with host cell antigen processing pathways
76
4 ways to identify virus
PCR (genetic information)
Serology (immune memory)
Histopath (viral infection features)
Culture + electroscopy (Limited as too much time, effort and expense)
77
How does immunity develop?
5 types of immunoglobulins:
Active - cell and antibody mediates response when exposed to a pathogen
Passive - Transfer of antibodies from immune individuals but only temporary immunity
78
Types of vaccines
Active:
Inactivated
Attenuated
Secreted products
Constituents of cell walls/ subunits
Recombinant components
Passive:
Human normal immunoglobulin injected
79
What is herd immunity?
The more people vaccinated, the harder it is for pathogen to spread to immunocompromised
80
2 types of vaccine failure
Primary - Person doesn’t develop immunity from vaccine
Secondary - Initial protection wanes over time so needs more doses
81
Where can we find all UK immunisation schedules?
Green book
82
Examples of vaccine preventable diseases
Diphtheria
Tetanus
Pertussis
Polio
Haemophilus influenza type B
Meningococcal disease
83
What is contact tracing
Any close contact needs to be identified to prevent further cases (no need to learn list)
84
How to protect the community from communicable disease?
Surveillance for early warning
Investigate severity
Identify and protect close contact
Exclude high risk person
Educate, raise awareness
Multi agency responses
85
3 groups of worms
Nematodes (roundworms)
- Intestine, larva, tissue
Trematodes (flatworms)
- Blood, liver, lungs, intestine
Cestodes (tapeworms)
- Can be invasive or non-invasive
86
What is the prepatent period?
Interval between infection and appearance of eggs in stool
87
What is meningitis?
Inflammation of the meninges (dura, pita, arachnoid)
88
Causes of meningitis
Bacteria
Virus
Fungi, Protozoa, or other parasites
Medications
Cancers
Autoimmune diseases
89
What is invasive meningococcal disease?
Gram negative diplococci Neisseria meningitidis infection through droplets
90
2 manifestations of invasive meningococcal
Meningitis - local
Septicaemia - widespread systemic infection and organ damage
91
Risk factors of of invasive meningococcal
Extremes of ages
Smokers
Immunocompromised
Frequent close contact
Travellers to high risk areas
Overcrowded housing or cholla
Winter coughs and colds
Asplenia, cancer, organ dysfunction
Sickle cell, contagious diseases
92
Meningococcal meningitis symptoms
Babies - slow, irratible, vomiting, feed poorly, avoid neck stretching
Adults - fever, stiff neck, headache, confusion, vomiting, light sensitivity
93
Meningococcal septicaemia symptoms
Fever
Fatigue
Vomiting
Diarrhoea
Cold hands and feet
Severe aches and pain
Rapid breathing
Non blanching rash
94
How to test for meningococcal
Blood sample + PCR
CSF for microscopy, culture
Throat swab for culture
95
Should meningitis cases be notified?
ALL CASES OF SUSPECTED MENINGITIS ARE NOTFIED IMMEDIATELY
Close contacts identified
96
What is given to eradicate throat carriage (passing it) of meningococcal?
Antibiotics
(Prophylaxis for contact)
97
Public health actions of meningococcal
Contact school/nursery/uni
If two cases confirmed = cluster
Standard / customised letters
Other support / helpline
98
What is an affordable meningitis vaccine?
MenAfriVac (2010)
99
Epidemiology of meningococcal
Occurs sporadically in clusters globally
Group B+C common in Europe, America
Group A common in Asia, Africa
Seasonal variations
100
When are meningococcal vaccinations taken?
8 weeks
16 weeks
1 year
14 years
(Original sugar vaccine was not effective in kids so conjugated with proteins)
101
Features of fungi
Eukaryotic (DNA/RNA , protein synthesis)
Chitinous cell wall
Ergosterol instead of cholesterol in plasma membrane
Heterotrophic
Move by growth, generations of pores carried by air or water
102
2 types of fungi: yeast vs mould
Yeast - small single celled that divide by budding
Moulds - form multicellular hyphae and spores
103
What is dimorphic fungi?
Fungi exist as both yeast and mould switching when conditioned suit best
104
Why only few fungal infections?
Inability to grow at 37 degrees
Innate and adaptive immune system
Common fungi have low morbidity
Invasive fungi easily missed
105
Antifungal drug targets
DNA/RNA, protein synthesis
= Flucytosine, Griseofulvin
Plasma membrane (ergestrol)
= Polynesian, Azores, Allylamines
Cell wall (not in humans)
= Echinocandines
106
Describe mucosal candadis (thrush)
= common commensal causing significant recurrent morbidity when overgrown
Risk = mucosal disruption, antibacterial, immunosuppressed
Treatment = Topical or oral Azoles
107
What are dermatophytes?
Mould causes skin and nail infections
(Human or animal to human transmit)
Treatment = topical, oral azoles, terbinafine
108
Is ringworm a worm?
No! It’s a fungi
109
6 Life threatening fungal infections
Dimorphic fungi - Mould at warm temp
- Chlamydia via spore inhalation converts to yeast at 37 (true pathogen)
Coccidioides - Rectangles read to release spores in warm arid areas
- mostly asymptomatic, but develop systemic (sepsis) or local (pneumonia) disease
Invasive candidiasis (candida invades blood)
Cryptococcus - common in children but only in immunocompromised
Invasive aspergillus - secondary infection in ITU, commonly elderly
- Fever, respiratory failure
= Voriconazole
Mucoraceous moulds - raid,y progressive infections crossing tissue plains only in immunocompromised
110
Which 3 types of fungi are most commonly seen in Sheffield?
Candida, Aspergillus, PCP found in all departments
111
Aim of antimicrobial drug therapy
= Achieve inhibitory levels of agent at site of infection without host cell toxicity
112
How does antimicrobial drug therapy work?
Identifies molecules with selective toxicity e.g.
- non human targets
- increased permeability to compound
- Modification in organism
- Drug more concentrated in organism
- Human cells rescued from toxicity by alternative metabolic paths
113
Why is fungi challenging to treat?
We only have relatively few classes of effective agents
114
What are Protozoa?
Single celled eukaryotic
Phagocytose bacteria, algae, micro fungi
Important in parasitic and symbiotic relationships
115
5 major groups of Protozoa
Flagellates - have flagella and binary fission to reproduces
Amoebae - move by flowing cytoplasm and production of psudopodia
Sporozoans - all species parasitic, no locomotives and reproduce by multiple fission
Ciliates - cilia beat and 2 types of nuclei - micro/macro
Microsporidia - production of resistant spores with polar filament coiled inside
116
5 Examples of flagellates
African trypanomiasis - transmitted by setse fly bite, developing sleepy, flu-like, CNS symptoms and death
American trypanosomiasis - spread by triatomine bug faeces developing acute flu-like symptoms, megacolon, chronic cardiomyopathy etc
Leishmaniasis - spread by sandfly bite
Cutaneous + muscutanoues ulceration = pneumonia, sepsis
Visceral fever, weight loss,
= fatal anaemia, hepato/splenomegaly
Trichomonas vaginalis - STI asymptomatic, dysuria, fishy smell, yellow froth discharge= metronidazole
Giardiasis - faeco-oral spread associated with recent travel. Cramps, bloating, cysts seen in stool
= metronidazole
117
2 examples of sporazoa
Cryptosporidiosis - water borne spread
Causes diarrhoea, vomiting, fever, oocytes in stool but sever in immunocompromised
Toxoplasmosis- Ingestion of contaminated causes choriorenitis, disseminated disease
118
1 example of amoebae
Amoebiasis - faeco-oral spread
Produces GI - dysentery, colitis
Liver, brain and lung absesses
Cysts in stool
= Metronidazole + amoebicide
119
Travel + Fever = always assume what?
MALARIA!!
120
What is malaria?
Protozoa infection cause by 5 species of Plasmodia sprazoan:
P. falciparum, orale, vivax, malariae, knowlesi
Transmitted by female anopheles mosquito bite (3-4 weeks life span)
- Infection from another human, for life
121
Malaria symptoms and signs
FEVER
chills and sweat
Headache, fatigue
Nausea, vomiting, diarrhoea
Myalgia
Haemolysis causes:
Anaemia
Jaundice
Very dark urine
Hepatosplenomegaly
122
Describe malaria life cycle
Sporogenic cycle in mosquito
Infects human causing abdo pain
Exoerythrocytic cycle spread spores
Haemolysis in erythrocytic cycle causes cyclical fever (lies dormant)
123
Why is P. falciparum more complicated?
Causes adherence to each other and cells
Obstruction so RBC are not filtered like normal
= Highest mortality rate, harder to manage infections
= vascular occlusion
124
Malaria treatments
Complicated = IV artesunate
Uncomplicated - lots of options
125
How can P.ovale and P.vivax cause relapse?
Additional stage forms hypnozoites in the liver for years
126
Define infectivity
Infectivity - ability to become established in host, can involve adherence and immune escape
127
Define virulence
Ability to cause disease once established
128
Define invasiveness
Capacity to penetrate mucosal surfaces to reach normally sterile sites
129
Humorous vs cell mediated responses to virus
Humoral
- antibody (IgA) blocks binding
- Opsonisation (tags for phagocytosis)
- Complement
Cell mediated
- Antiviral action
- Kill infected cells
- Macrophages
(Peaks 7-10 days then declines)
130
How do virus evade immune system?
1. Interfere with specific or non specific defence
2. Change coat antigen
- Antigenic drift where spontaneous mutations give minor change
- Antigenic shift where sudden emergence of new subtype
131
How do bacteria enter host?
Respiratory tract
HI tract
Genitourinary tract
Skin break
132
Low number vs high number of virulence employ which defence mechanisms?
Low = phagocytes
High = immune response
133
3 ways of protozoan evasion
Surface antigen variation
Intracellular phase
Outer coat sloughing
134
2 ways of worm evasion?
Decrease antigen expression by adult
Glycolipid / glycoprotein coat (host derived)
135
5 antiviral drugs
Aciclovir + Valaciclovir
Ganiciclovir + Valganiciclovir
Foscarnet
Ribavirin
CoVID antivirals
136
5 immune modulation therapies
Lifting immunosuppresion
Specific immunoglobulins
Human NormalImmunoglobulins
Rituximab
CoVID immunomodulators
137
What is Aciclovir?
Anti-herpes virus drug with high selective toxicity and few side effects
138
Mechanism of Aciclovir
1. Activated to a monophosphate by viral thymidine kinase only in herpes
2. Host cell kinases add 2nd and 3rd phosphate group
3. Aciclovir triphosphate mimic guanine so inhibits herpes DNA polymerases
139
Chicken pox cause and symptoms
Varicella-zoster virus is a member of the herpes virus
Signs - lesions in warm areas harden, fill with pus and then crust
140
Shingles pathophysiology
Varicella -Zoster virus dormancy in dorsal root or cerebral ganglion
Reactivates and migrates along same sensory nerve = dermatomal shingles
141
When do we use IV Aciclovir?
Oral has poor bioavailability so frequent dosing
- Dissemnated herpes (neonates, congenital)
- Herpes in immunocompromised
- Severe shingles / herpes
- Herpes encephalitis
142
What is Valaciclovir and why is t better than Aciclovir?
Valine side change of Aciclovir increases 3-5x bioavailability so reduced dosing, less likely to forget.
Also a useful step down from IV therapy
143
What is Ganciclovir?
Anti CMV agent = primary use
For treatment and prophylaxis of CMV infection in immunosuppressed or transplant recipients
144
Mechanism of Ganciclovir?
Less selective toxicity: Inhibitor of viral DNA polymerase like Aciclovir
(1st phosphorylation by deoxyguanosine kinase in CMV infected cells)
145
What is Valganciclovir?
L-valyl ester side chain for better oral absorption and bioavailability
146
GCV adv and Disv
Adv
- selective antiviral
- activity and sensitivity amplified
Disv
- haemolytic anaemia
- potential foetal toxicities / low fertility
- resistance due to mutations
- myelosupression = Pancytopenia
147
Cytomegalovirus signs (CMV)
Mostly asymptomatic (macular rash, febrile, lethargic poor appetite)
Atypical lymphocytes (RBC stick to wbc)
May stay and reactivate causing
- Pneumonitis, end organ disease
- Ultra-colitis
- Pizza pan retinas
- Internuclear intrusions in kidney
148
What is Foscarnet?
= Selectively inhibits phosphate binding on DNA polymerase for all herpes virus
149
Adv and Disv of Foscarnet (phosphonoformic acid)
Adv
- Does not require activation
- Retains activity against mutations
- Combination enhances activity
Dis
- Significant renal toxicity
- Acidosis, raised LDH, Alk Phos
- Crystal induced nephropathy
- Electrolyte disturbances leading to seizures
150
What is Rituximab?
Monoclonal antibodies that target CD20 molecules for immunisuprresion
151
Rituximab Adv and Disv
Adv
- Pre emptive use reduces risk of malignant transformation
Disv
- Risk of reactivation of TB
- Risk of hepatitis B
152
What is Immununoglibulin Post Exposure prophylaxis?
Pooled plasma product of people with high antibodies
153
Management of measles exposed
Acurate contact tracing
MMR vaccine checks
Prophylaxis for non-immunocompromised
Sero status check for immunosuppressed
Arrange for IVIg
154
What is Ribavirin?
Small molecule broad spectrum antiviral
(Guanosine mRNA production interference)
Used for Hep E + Lassa fever
155
Define antibiotic
Agents produced by micro-organisms that kill or inhibit the growth of other organisms in high dilution
156
Define antimicrobials
Molecules that work by binding at atarget site on a bacterium.
E.g.
- penicillin binding preteins on cell wall
- cell emembrane
- DNA
- ribosomes
- Topoisomeraxe IV or DNA gyrase
157
3 antibiotics classes
Cell wall synthesis
- Glycopeotides
- Beta Lactams (work against cell wall peptidoglycans so lysis + bursts)
- Vancomycin
- Bacitracin
Nucleic Acid synthesis
- Folate synthesis (precursor to substrates that generate nucleotides)
- DNA gyrase (stops this unwind DNA)
- RNA polymerase (inhibit e.g. Rifampin)
Protein synthesis
- 305 Subunit
- 505 subunit
158
Beta lactams are more effective on…
Gram positive
(Negative have additional lipopolysaccharide layer)
159
3 types of beta lactams
Ccephalosporins - more broad than penicillin
Carbapenems - high quality and last resort
Monobactams - very narrow spectrum
160
3 ways bacteria are pathogenic
Direct - destroys phagocytes or host
Indirect - inflammation or overimmune
Toxins - Exotoxins/ Endotoxin
161
Bactericidal vs Bacteriostatic Antibiotics
1 - Agent kills bacteria quickly (18-24hr)
- Beta lactams inhibit cell wall synthesis
- However bursting releases toxins
2 - Prevents growth and multiply
- Inhibit protein synthesis, DNA replication or metabolism
- Reduces toxin surge
162
How to find Minimum Inhibitory concentration (MIC)?
Incubate tubes with different volumes of microbial rich broth and antimicrobial agents
163
Is lowest MIC = best antibiotic and why?
NO!
Drug must attach to adequate number of inning sites and remain for enough time for metabolic processes to be sufficiently inhibited
164
2 major determinants of antibacterial effects
Time dependent killing
Concentration dependent killing (peak)
165
4 ways antibiotics not work
1. Change, blocks or mutates antibiotic binding site (e.g. MRSA)
2. Destroy antibiotic via enzymes or proteins (e.g. beta lactamase)
3. Prevent antibiotic access by modifying membrane porin channel size, number, selectivity
4. Removes antibiotic from bacteria
166
How do bacteria develop resistance?
Intrinsic - naturally resistant
Acquired - Spontaneous gene mutation
- Horizontal gene transfer by conjugation/ transduction/ transformation
167
2 important resistant gram positive bacteria examples
MRSA - Methicillin resistant S. Aureus
- Bacteriophage mediated acquisition of chromosome mec (gene mecA)
- encodes penicillin binding protein 2a to all B-lactams as well
VRE - Vancomycin resistant enterococci
- Plasmid mediated acquisition of altered amino acid preventing vancomycin binding
- Promoted by cephalosporin use
168
2 Important resistant gram negative bacteria examples
ESBL - Extended Spectrum B-Lactamase inhibition by hydrolysis of side chains
= bind beta lactamase inhibitor to AB
Carbapenam Resistng / Producing Enterobacteriaceae (CRE / CPE) - treatment very few and toxic
169
5 Qs when choosing an antibiotic
What kind of bacteria will it cover?
Bioavailability- oral or IV
Is the bacteria resistant?
Allergies?
Is there an infection caused by bacteria?
170
7 Factors to consider when deciding if an antibiotic is safe
Intolerance, allergy
Side effects
Age
Renal and liver functions (dose)
Pregnancy and breast feeding
Drug interactions
Risk of C. difficile
171
Common presentations and treatments of gram positive cocci
S.aures + Group A,C,G strep
= purple swollen feet
= Fluxocallin
Group A,C,G strep
= Inflammed tonsils
= Penicllin
S.pneumonia
= Cloudy chest X-ray
= Amoxicillin
172
2 scenarios where IV vancomycin and telcoplanin are used
1. Gram positive bacteria resistant to beta lactams
2. penicillin allergy
173
3 examples of protein synthesis inhibitor antibiotics (gram positive)
Clarithromycin and erythromycin- oral
= penicillin allergy / severe pneumonia
Clindamycin - oral
= cellulitis, necrotising fasiculitis
Doxycycline - oral
= cellulitis and pneumonia
174
4 example antibiotics for gram negative
Gentamicin - IV
= UTI, infective endocarditis but toxic
Ciprofloxacilllin - oral
= penicillin allergy, UTI, intra-abdominal infections
Trimethhoprim - folate anatagonist
= UTI
Nitrofurantoin
= Lower UTI
175
4 examples of beta lactam antibiotics
Cefuroxime
Co-amoxickav
Piperacillin
Meropenem
176
Details of health care act 2006
Infection control is every health care worker’s responsibility
Prosectution possible under H&S law
177
How can we identify infection risks?
Risk factors - recent travel, previous
Screening
Clinical / Labdiagnosis
Routes and modes of transmission
Patient/Staff/ Environment
178
Things to do everyday to protect patients
- Hand hygiene = most effective way of preventing cross infection
- Personal Protective equipment
- Disposal of sharps (never overfill, resheathe, bend etc)
179
What is an endogenous infection and how to prevent it?
= Infection of patient by their own flora
- Good nutrition and hydration
- Antisepsis/skin prep
- Control underlying disease (drain pus, remove lines, reduce antibiotics)
180
When to wash hands and use alcohol gel?
Hands:
Before and after handling patients
After handling soiled items
After using toilet
Before and after aseptic procedure
After removing PPE
Alcohol gel:
Following hand wash when caring for a patient or ward based invasive
181
5 infection control policies
MRSA
Tuberculosis
Medical equipment management manual
Single use items
Outbreak control plan
182
How to differentiate between staph and strep?
Catalase test +ve = staph
(Hydrogen peroxide for bubbling)
183
What is the indole test?
Ability to decompose aa tryptophan to indole (gram negative rods)
184
What does option in test determine
S. Pneumoniae from other alpha haem strep
