Infection And Immunity Workshops Flashcards
Where do polymixins work? How do they work?
Only work on gram negative bacterias Outer membrane
Work on LPS
They bind to the lipid A component of LPS
They increases the outermembranes permeability
May also interact with the cytoplasmic, inner membrane
Interact with phospholipids here and increase permeability
What’s the difference between polyenes and polymixins?
Polymixins work in bacteria (antibiotic)
Polyenes work in fungi (antifungal)
Both Work on cell membranes/ outer membrane
How could a bacteria become resistant to polymixin antibiotics ?
A change in the LPS of the bacteria (in the lipid A component) results in polymyxins being unable to bind.
This resistance is quite rare
Where in a bacteria does chloramphenicol act?
Bacterial ribosomes
It binds to the 50S subunit and decreases peptide bond formation between amino acids so inhibits bacteria protein synthesis
How could a bacteria become resistant to chloramphenicol?
Through CAT genes
Chloramphenicol Acyl transferase genes
This enzyme will inactivate chloramphenicol
What antibiotic targets the nucleoid in bacterial cells?
Trimethoprim
How does trimethoprim work?
Works in the nucleus
It inhibits dihydrofolate reductase enzyme
This enzyme is needed to convert dihydrofolic acid into trihydrofolate, and trihydrofolic acid is needed to make bases in the bacteria. So it stops bacterial DNA being formed.
How could a bacteria become resistant to trimethoprim?
Alterations in dihydrofolate reductase enzyme so that trimethoprim can no longer bind
Also alterations in the uptake of the antibiotic into the bacteria
Glycopeptides act at the cell wall of bacteria. How do they work?
Bind to the d-ala d-ala sequence
Therefore inhibit binding of more monomers to the peptidoglycan chains; stop these stop these from Crosslinking so decrease stability in the cell wall of bacteria
How could a bacteria become resistant to glycopeptides?
Mutation in d-ala d-ala becoming d-ala d-lactate
Glycopeptides can no longer bind
This mutation is common in Enterococci
What bacteria cause catheter associated UTIs? Which is most common?
E.coli (most common) Enterococcus faecilis (quite common) Both these are from the gut Staph epidermis, staph aureus (quite common) Psudomonas Klebsiella Proteus
What do we use to treat catheter associated UTIs?
All the bacteria that cause this are a mixture of gram positive and negative. Therefore need to treat with broad spectrum antibiotics.
IV antibiotics used:
Gentamicin (1st choice) + amoxicillin and Coamoxiclav to fight resistant bacteria
Or
Vancomycin
Ciprofloxacin
What TYPICAL agents cause community aquired pneumonia?
Streptococcus pneumoniae
Haemophillus influenza
Streptococcus pyogenes
What ATYPICAL agents may cause intracellular infections?
Legionella pneumophila
Mycoplasma pneumonia
Chlamydia pneumonia
Cause intracellular infections so need to choose antibiotics that GET into cells
What Do we use to treat community aquired pneumonia?
Amoxicillin/ co-amoxiclav orally
Or if patient is allergic to penicillin: Clarithromycin
Doxycycline
What is Cellulits?
Inflammation of the skin
May occur from an insect bite
Or an operation opening up the skin
Could get in the blood stream and affect the heart: endocarditic Cellulitis
What organisms cause cellulitis?
Staph aureus
Streptococcus pyogenes
Staph epidermis
(Remember it’s the staphs and streps: common on the skin!!)
What do we use to treat cellulitis ?
Flucloxacillin (oral/ IV)
Vancomycin (IV)
Could maybe chose Clarithromycin or doxycycline or penicillin V
What microorganisms can cause acute exacerbations in COPD?
Haemophilus influenzae
Streptoccocus pneumonia
Staph aureus
Remember it’s the ones you’d expect in the lungs: influenzae and pneumonia
What can we use to treat COPD?
Doxycycline good as it works against all three
Amoxicillin (if you suspect resistance then give co-amoxiclav which contains a beta lactamase inhibitor)
Clarithromycin
Meningitis is the inflammation of the membranes lining the brain and spinal chord. It is rarely caused by bacteria, but when it does, what happens if you don’t treat it rapidly with antibiotics?
Death
Where do bacteria invade in meningitis?
It is inflammation of the membranes lining the brain and spinal cord
They invade the back of the throat, pass into the blood stream and invade the CSF
Bacteria that cause meningitis live in the back of the nose and throat in 1/10 people.
But most people who carry these bacteria become immune to them so they don’t usually cause disease.
The germs can be spread by secretions from nose and throat. But must have had close contact with the person or occasionally passed through respiratory droplets
Symptoms of meningitis occur suddenly after an incubation period of ______ days
1-3 days
What does the rash look like that’s associated with meningitis?
Rash of tiny red/ purple pin prick spots
May spread to look like fresh burning
If you press on the rash- it doesn’t go away!!
It’s a result from bleeding capillaries close to the surface, as bacteria release toxins in the blood which break down blood vessel walls
What is meningococcal septicaemia?
Blood poisoning
Occurs when bacteria in the blood multiply uncontrollably
Meningococcal disease can appear as meningococcal meningitis or meningococcal septicaemia
Or a combination of both of these
What will very severe cases of meningitis go on to cause?
Hearing loss
Damage to the brain
Learning impairments
Epilepsy
What can septicemia cause in the long run?
Scarring to skin
Amputations
What is first line treatment if bacterial meningitis is suspected?
High dose benzyl penicillin IV
Or a high dose 3rd generation cephalosporin such as ceftriaxone (IV) or cefotaxime (IV)
What shall I use to treat meningitis if my patient has anaphylaxis with penicillins or rash with cephalosporins?
IV chloramphenicol 12.5mg/kg QDS
Why is benzyl penicillium a good first line treatment for bacterial meningitis?
It has a broad spectrum
Rapidly absorbed into blood stream
Non toxic at high concentration
Good penetration into CSF
This is the same for cephalosporins
What is the most common bacteria causing meningitis?
Neisseria meningitidis (meningococcal meningitis) most common
Type B accounts for most cases
Mostly in under 5 years olds or 15-24s
It’s a gram negative bacteria so uses LPS LIpid A which is very toxic so can cause septic shock
What other bacteria can cause meningitis?
Streptococcus pneumonia (2nd most common) In under 2s and over 65s and immunocompromised It's the most dangerous type: 20% mortality whereas N.menigtiis is 10%
Haemophilus influenza B in under 5s
Less common: Staph aureus Listeria monocytogenes Mycobacterium tuberculosis E.coli
What antibiotic can we use for N.meningitis?
Penicillin G or ampicillin
Or if penicillin resistant: use 3rd generation cephalosporin like ceftriaxone or cefotaxime
Sensitive to both these: then chloramphenicol
What can we treat strep pneumonia bacterial meningitis with?
Ceftriaxone or cefotaxime IV
If penicillin resistant or pneumonococci suspected add in rifampicin or vancomycin
Sometimes with bacterial meningitis, relatives should be treated as prophylaxis. What can be given as prophylaxis for N.meningitis?
Rifampicin
Or ciprofloxacin
These are different to the actual treatments as we want to decrease chance of resistance
What prophylaxis can be used for bacteria caused by s. Pneumoniae?
No prophylaxis
What prophylaxis should be given for haemophilus influzae meningitis?
If patient lives with unvaccinated child under 4, the entire household should be given Rifampicin as prophylaxis
What vaccines are available for meningitis?
HiB vaccine (H. Influenzae type B) N.meningitidis Type C (Men C) N. Meningitidis type A, C, Y, W135 N. Meningitidis type B S.pneumonia vaccines
What are the S.pneumonia vaccines?
Polysaccharide vaccine (PPV) Not used in under 2s Good for over 65s Pneumonococcal Conjugate Vaccine (PCV) Given IM. At 2,4 and 13 months old
You can also get viral meningitis. Is this as bad as bacterial?
No! A lot more common Slower onset Less severe No rash Lasts up to 3 weeks Self limiting: no real treatment, just get better yourself
Why do viruses produce less of an inflammatory response than bacteria?
Because viruses are usually present inside cells
Not visible to phagocytic macrophages
Macrophages aren’t activated to same extent
Less inflammatory cytokines produced
May be released into the blood but they rapidly reinfect other cells so are hidden again!
What viruses may cause meningitis?
Enteroviruses
Such as
coxsackie virus (most common) found in intestines and faeces/ sewage
Echovirus
Meningitis may also sometimes be caused by fungus. Examples?
This is VERY rare
Candidia albicans - espesh in babies of very low birth weight
Cryptococcus neoformans: causes of most fungal meningitis
Normally only develops in people with deficient immune systems
Treat with amphotericin B, fluticytosine and fluconazole
Histoplasma: can cause meningitis is immuno-deficient patients
One of the adverse effects of methotrexate, taken in RA, is stomatitis and mouth ulceration.
1) how often do RA patients usually take methotrexate?
2) what can be given to prevent the serious adverse effects of methotrexate?
Methotrexate taken WEEKLY
Folic acid used at an agreed time before or after the weekly methotrexate dose.
Why does methotrexate have general toxicity?
Because it effects all rapidly dividing cells
What is the tuberculosis vaccine commonly given?
BCG vaccine
Consider in under 35s going to live or work in endemic areas
Administer after negative Mantoux test (6 pricks in wrist)
What’s the vaccine commonly given for Hep A?
Monovalent vaccine (Havrix) Hep A Is spread by faecal oral route. Eg shellfish
How is hep B spread? What is the vaccine usually given?
Exposure to infected blood or body fluids
Energix B usually given
Can take up to 6 months to reach immunity
What’s the vaccine against meningitis ?
Meningitis A and C combines vaccine
Rapid immunity provided, long lasting: boosters given every 5 years if at continued risk
How many vaccinations of tetanus is considered to give life long immunity?
5
What is rabies?
Viral encephalomyelitits caused by members if the lyssavirus genus
Usually fatal
By bites and scratches from animals
What is tick-borne encephalitis?
Caused by the flavivirus carried by ticks or unpasteurised milk
Vaccinate anyone going to warm forested areas
Remove ticks ASAP with straight tweezers
When is the typhoid vaccination advised?
For areas where sanitation standards may be poor
What’s the typhoid vaccine?
Live attenuated oral vaccine (Ty21a)
Give 3 doses on alternate days
Give at least 3 days before starting malaria prophylaxis
Avoid antibacterials 3 days before and after
3,3,3!!
When to give yellow fever vaccine?
Vaccinate those travelling to endemic areas at least 10 days before travel
10 years immunity
What vaccines are recommended for those travelling to Egypt?
Hep A, hep B
Rabies
Tetanus
Typhoid
What’s the ABCD of malaria prophylaxis?
Awareness
Bite protection
Chemoprophylaxis
Diagnosis
What the first line prophylaxis of malaria?
Chloroquine (or proguanil)
What’s second and third line prophylaxis of malaria?
Second line: chloroquine PLUS proguanil
Third line: mefloquine Or doxycycline or malarone
What is mefloquine contraindicated in?
Epilepsy
It has some serious CNS side effects like hallucinations
What’s a good insect repellent to use?
Diethyltoluamide (DEET) 50%
Apply every 4 hours
Is malaria prophylaxis required for Egypt?
No risk currently
Beaut precautions essential
What are some of the possible bacterial causes of diahorrea?
Salmonella Shigella Campylobacter E. coli C. Difficile
What Protozoa may cause diahorrea?
Giardia
Cryptosporidium
Entamoeba histolytica
Whats the incubation period of giardia? What do we treat it with?
5- 25 days
Treat with metronidazole
What’s the incubation period of c.difficile and what can we treat it with?
A few days
Metronidazole and vancomycin
What’s the incubation period of campylobacter? What can we treat it with?
2-11 days
Erythromycin
Hepatitis C is a single stranded RNA virus belonging to the Flaivirdae family.
It can take up to ___ months to develop antibodies post infection
3 months
How is hepatitis C spread?
Through bodily fluids
So those most at risk are those who share needles or are exposed to infected blood
Why may people who received blood transfusions before 1991 still be at risk of developing hepatitis C?
It can lie dormant for 30-40 years
There are two forms of chronic hepatitis, chronic persistent and chronic active. What’s the difference?
Chronic persistent: minimal degree of inflammation
Follows a benign course
You become an active carrier: I,e you’re infective to others
Chronic active: continual destruction of hepatocytes
People become ill with liver disease
What’s the course of illness with hepatitis C?
Acute infection- can be cured
But then further hepatocyte damage could lead to fibrosis , cirrhosis of the liver and cancer of the liver
Lichen planus Rhumatoid arthritis Cryoglobulinaemic Vasculitis Sjögren's syndrome (dry eyes and mouth) Are all what?
Extra manifestations of hepatitis C
Hep C: Genotype 1, 4, 5 ,6 usually classed together
Genotypes 2, 3 usually classed together
Which forms of hepatitis are you more at risk of getting when travelling?
Hepatitis A and B
So get vaccines!
Treating hepatitis C: how do we reduce the viral load?
Using interferon (peginterferon alpha) use in combo with
Ribavirin
Or protease inhibitors
Standard is 48 weeks of treatment
What’s a common side effect with peginterferon?
Depression
What combination therapy may we use for hepatitis C?
Peg interferon in combo with ribavirin
This will decrease mortality
But increase risks of adverse effects
We have seen protease inhibitors crop up twice so far in this course. What two viruses are they against?
HIV
Hepatitis C
Why may glucocorticoids be used in Hep C?
To treat the underlying disorders such as rheumatoid arthritis and sjorgrens syndrome
What types of typhoid vaccines are there?
Vi vaccine: SINGLE INJECTION for over 2 years old.
Ty21a: 3 capsules to take on alternate days. Not for under 6’s
Combined typhoid and HEP A vaccines for over 15 yr olds
Which is the most effective typhoid vaccine?
Vi vaccine generally more effective
Lasts around 3 years then need a booster
Ty21a lasts around 1 year
Ideally these should be given around 1 month before travel
Malarone is licensed as a malaria vaccine for trips lasting up to _______
28 days
Do not use doxycycline (malaria prophylaxis) in….?
Under 12 years or pregnancy !!
Which malaria prevention is safe in pregnancy ?
Chloroquine
Also proguanil
What’s the deal with mefloquine as malaria prevention?
If it’s not been used before, use 3 weeks before travel to detect for side effects (CNS side effects like bad dreams) then there’s time for adjustment.
Don’t use in depression or schizophrenia
Not licensed in Britain for use for over 1 year
What is miliara rubra?
Prickly heat
Where should insulin be kept on planes?
It will freeze and denature in the hold
So should be kept with you with all other medicines
What can cause travellers diahorrea?
E. coli
Salmonella
Parasites such as Giardia
Viruses such as norovirus
When should we not treat travellers diahorrea with eg Loperimide?
In under 2s
If there’s blood or mucus in the stool
High fever
Severe abdominal pain
What antibiotics can we use to treat travellers diahorrea?
Ciprofloxacin
Azithromycin
Rifaximin
What antibiotics can we use to prevent travellers diahorrea?
Ciprofloxacin
Rifaximin
What can bismuth subsalicylate be used for?
A non-antibiotic prophylaxis of travellers diahorrea
Can cause blackening of the stool or tongue
Don’t use for over 3,weeks
What’s giardiasis caused by?
Giardia lamblia or giardia duodenalis
What’s the incubation period of guardiasis?
9-15 days
So diahorrea may not start for a couple of weeks from when the traveller returns