LRTI URTI and ANTIBIOTICS Flashcards
1
Q
Synthetic vs Semi-synthetic antibiotics
A
semi-Synthetic antibiotics are altered versions of naturally occurring antibiotics with altered pharmacological properties. Eg reduced toxicity
2
Q
Bacteriostatic vs Bacteriocidal
A
Static = stops division. Cidal = kills bacteria (classification is based on killing 99.9% of bacteria)
3
Q
What are tetracyclines, list 2. Why are they not favoured over B-lactam antibiotics for example?
A
4 ringed antibiotics - Minocyclin and doxycycline. They have a short half life and need to be taken 4 times per day.
4
Q
How does penicillin work
A
Blocks transpeptidase - leads to loss of cell wall and the bacterium’s ability to maintain hydrostasis. The bacterium becomes hypERtonic and is osmotically lysed.
5
Q
What is the strucutre of Penam
A
6
Q
Name 3 natural antibiotics
A
Penacillan G
Cephalosporin C
Clavulanic acid
7
Q
Benefits and drawbacks of Penacillan G
A
Non toxic - can be used in high doses even in children
Acid labile so needs to be given intramuscularly
8
Q
What bacteria are the Penicillins effective against/not effective against?
A
Used against Gram + Cocci and Rods, and Gram - cocci (gonococci, meningocococcal mengitis)
Not effective against Pseudamonas aeruginosa - they have thick cell walls and chromosomally encoded beta-lactamase expressed in significant amounts
9
Q
Methicilin
Flucloxacillin
Dicloxacillin
MRSA
A
It is effective against Pen G resistnat staphylococci. Nephrotoxic - given via IV.
Diclocacillin used more (less nephrotoxicity) or flucoxacillin (some hepatotoxicity) are used - can be given orally.
MRSA are resistant to every penicillin including methicillin
10
Q
Ampicillin and Amoxycillin
A
Same thing basically
Broad spectrum antibiotics - active on GN bacteria (as well as GP)
H. Influenzae and E. Coli
11
Q
Carbenicillin
A
Effective against gram negative rods (Pseudamonas aeruginosa) which is intrinsically resistant to ampicillan and penicillan etc)
12
Q
What do Penicillans, Ampicillan, Methicilin, Flucoxacilin and Carbenicillin all have in common?
A
Beta lactams
13
Q
Clavulanic acid
A
Beta lactam derived from streptomyces = not a penicilin
14
Q
Fill in the following table
% resistance to plasmid mediated B-lactamase
Staphylococci
E. coli
Haemophilus spp.
N. gonorrhoeae
A
Staphylococci 80-90%
E. coli ≥50
Haemophilus spp. ≤50
N. gonorrhoeae ≤50
15
Q
Which of the follow two species will clavulanic acid work against: Pseudomonas aeruginosa or Escherichia coli? Why?
A
Works against P. aeruginosa because Pseudomonas species have genome encoded beta-lactamase but E. coli uses a plasmid encoded beta-lactamase. Clavulanic acid works only against plasmid encoded beta-lactamases.
16
Q
genii of Gram negative rods
A
Escherichia, Pseudomonas, Klebsiella, Vibrio (as in Virbio cholerae), Salmonella, Yersinia
17
Q
How do aminoglycosides and tetracyclines work?
A
they target the ribosomes and inhibit protein synthesis. Aminoglycosides interfere at the C-site on ribosome.
18
Q
What is the action of sulphonomides
A
Inhibit the synthesis of folic acid. Many bacteria synthesize this (it is essential for there growth). Non toxic to humans as we are not able to synthesize rather it is an essential nutrient.
19
Q
Draw the structure of peptidoglycan:
A
Alternating chains of N-acetylglucosamine and N-acetylmuramic acid. M attached to L-Ala, D-Glu, L-Lys, D-Ala. Pentaglycines linking L-Lys and D-Ala.
20
Q
How does vancomycin work?
A
Binds to terminal D-Ala D-Ala and stops pentapeptide-tetrapeptide linkage in peptidoglycan cell wall synthesis.
21
Q
Which does Vancomycin not work against: Gram (-) or (+), and why?
A
Does not work against Gram (-) because it is too large and too charged to pass through the outer cell membrane.
22
Q
Explain the basis of Vancomycin resistant enterococci?
Why are they worrying?
A
Enterococci uses a sugar residue instead of D-Ala D-Ala: L-Lys - D-Ala - D-lac
Don’t want it to confer vancomycin resistance to MRSA
23
Q
VISA
A
Vancomycin intermediate Staph aureus - has a thicker cell wall to reduce permeability of vancomycin. The problem is that we can’t increase vancomycin doses too much because of side effects.
24
Q
What is new/different about MRSA
A
They have altered penicillin binding proteins (i.e. transpeptidases) which penicillans cannot bind to.
25
What is the basis of resistance to aminoglycosides?
Enzymatic modification, ribosomal modification, outer wall modification
26
List three aminoglycosides.
Gentomycin, tobramicin, amikacin
27
How do bacteria defend against antibiotics?
1. Reduced entry into cell
2. Increased efflux from cell - pumps
3. Ribosomal mutation - drug no longer effective
4. Failure to activate prodrug (metronidazole - bacteria rid themselves of the enzyme which activates the drug).
28
3 intrinsic resistances to antibiotics
1. Pseudamonas aeruginosa - B lactamase
2. Mycoplasma spp. No cell wall
3. GN bacteria - resistant to vancomycin (cannot get through outer membrane of cell)
29
What are the three mechanisms of hotizontal gene transfer?
1. Transformation
2. Phage-mediated transduction
3. Plasmid mediated conjugation
30
Describe the process of Transfromation
A donor bacteria may lyse, fragments are thus released into the surrounding environement. A competent cell (i.e. one with homologies to the original bacteria) will take up the DNA and undergo homologous recombination.
31
Describe the process of phage mediated transduction
A bacteriaphage may infect a cell, this bacterial cell will then go on to replicate the phage. The new phages will be released into the environment. In the process of phage production it is possible that a rare abnormal phage will be produced which carries some sort of mutation which will confer resistance to the bacteria. The rare phage may then go on to infect a new bacterial cell - the genetic material obtained from the phage then undergoes recombination and may confer some sort of resistance.
32
what is plasmid mediated conjugation?
This is perhaps the most dangerous thing form of acquired resistance. Two bacteria (totally unrelated) will form a cytoplasmic bridge, the plasmid will then replicate and the copy will transfer to the attached bacteria. The cells will then seperate and the bacteria will not be able to trancribe the genes in the plasmid.
33
Name some naturally competent bacteria
H. Influenzae
Pnuomococci (strep pneumonia)
Gonococci (Neisseria gonorrhoeae)
Staph epidermis (it is a low grade pathogen with loads of resistance genes) - it can transfer to staph aureus (high grade pathogen)
34
Where can we find the most intriniscally resistant bacteria
The normal human flore has the most intrinsically resistant microbiota
35
what is lysogenic conversion?
When a bacteria is lysogenized (infected with a phage) the phage can insert its genes leading to bacteria which may give rise to a different phenotype.
36
Name the phases that a phage can be in after infecting a bacteriawhen the :
1. Temperate phage (lysogenic cycle) - this is where the phage is not replicating and not doing damage to the bacteria (bacteria can divide and give phage DNA to daughter cells)
2. Virulent phage (lytic cycle)
When the phage is replicating directly
37
Name a situation in which a bacterial infection should not be treated with antibiotics?
What is the toxin produced?
If a phage has infected a bacteria and is in the lysogenic cycle stress to the bacteria may trigger the lytic cycle resulting in the upregulation of phage genes and the overproduction of toxin. This is the case with diarrhoea cased by E.Coli - (i.e. it will cause serious damage)
Shiga Toxin
38
What are the 4 resistances that are typically seen on a multi-resistant plasmid?
Ampicillin gene - B-lactamase
Tetracycline gene - Efflux pump (TetM gene)
Kanamycin - Phosphorylase
Chloramphenicol - chloramphenicol acetyl transferase
39
What is a multiresistant plasmid?
Antibiotic resistance is encoded on cassettes, these cassettes can become integrated into a single plasmid.
40
What is so dangerous about plasmid mediated conjugation?
bacteria can transfer plasmids between non-homologous, genetically unrelated bacteria.
Thus a bacteria can go from being totally susceptible to fully resistant in 1 generation
41
List 5 considerations in administering an antibiotic
1. Clinical diagnosis (i.e. LRTI/URTI)
2. Microbiological diagnosis (type of bacteria)
3. In vitro susceptibility (to antibiotics)
4. Host factors (allergies, pregnant, immunocompromised)
5. Properties of antibiotic
42
When they first discovered Streptomycin they believed Salmonella was extremely susceptible to it. But in practice, when they treated patients with Typhoid fever with Streptomycin, it did not work. Why?
Salmonella is a facultative intracellular parasite and is thus intrinsically resistant to streptomycin.
43
What is MIC?
MIC = minimum inhibitory concentration
44
How do we determine MIC?
MIC determined by progressive concentration halving. The point at which the bacterial growth is inhibited (indicated by non opacity) is the approximate MIC (the MIC lies between the opaque and clear tubes.)
45
How does an e-strip work?
Don't know it is patented (haha) but can read off the MIC off the strip
46
what are the considerations in best guess/empirical therapy?
1. Is antimicrobial treatment necessary
2. Is it safe/reasonable to wait before treating?
3. Are diagnostic samples required?
4. What is the likely agent and what is its likely antimicrobial susceotibility?
5. Is there evidence that treatment will benefit the patient?
47
What are the specific considerations regarding which antimicrobial to use?
1. Spectrum
2. Clinical efficiency
3. Route of administration
4. Pharmacokinetics/dynamics - half life, clearance, duration of action, MOA etc
5. Availability
6. Cost
48
What is the only known fungus susceptible to antibiotics?
Pneumocystis jirovecii.
49
List either two specific drugs or two classes of drugs that are used in combination therapy for endocarditis. Why?
Beta-lactam and aminoglycoside, eg Pen G and streptomycin - form a strong synergy against streptococci, which can cause endocarditis.
50
Would you prescribe antibiotics for a sore throat based on best guess practice? Why?
No - sore throat is probably viral.
51
What is co-trimoxazole?
Trimethoprim + amoxyzole
Amoxyzole is a sulphonamide
They both interfere with folic acid synthesis
52
What is Jawetz’s law?
Stat + stat = additive or indifferent
Stat + cidal = antagonistic
Cidal + cidal = synergistic
53
What are the areas of the RT with no bacteria?
nasal, paranasla sinuses, middle ear and area below the epiglotis
54
How are bacteria removed from areas below the epiglottis?
Cought it mucous and then either driven down the stomach or coughed up
55
What are 4 microbiota niches in the URT
Nasal washings, Saliva, Tooth surfaces, Gingival scrapings
56
List some common pathogenic residents of the URT (in more than 50% of people)
Viridans streptococci (alpha-heamolytic, causes infective endocarditis)
Neisserie Spp (gram negative)
Corynebacterium spp (diptheria)
Gram negative anearobes
H. Influenzae (not typable)
Candida albicans (fungus)
Strep pneumoniae (15-85% of pop)
57
Name 2 occasional (1-10% prevalence) pathogenic respiratory microbiota of the URT in health people:
Strep pyogenes (group A strep) - increases durign outbreak
Meningococci
58
Name 3 uncommon (\<1% prevalence) pathogenic respiratory microbiota of the URT in health people:
Enterobacateria
Pseudomonas
C. Diptheria (only has human carriers - most carried are non toxogenic)
59
What are the residents of the lung in a latent state?
Pneumocystis jeroveci (this is a fungus and is one of the aids defining illness (i.e. it only becomes active when a person is immunocompromised)
M. Tuberculosis about 1/3 of total world population have latent TB, \<1% relapse (but higher in HIV)
60
What are the residents of the lymph nodes?
CMV (Cytomegalovirus)
HSV (Herpes simplex virus)
EBV ( Epstein-Barr virus)
All of these can become resident infections (in CNS nerves) and will cuase a blister when the immune system is suppressed
61
Name the inflammations from top to bottom of the RT
Rhinitis (sinusitis)
Pharyngitis
Laryngitis
Tracheitis
Bronchitis
Briochiolitis
Pneumonia
62
Which parts of the RT are affected by the following?
## Footnote
Rhinovirus
Parainfluenzavirus
H. Influenzae
Influenza virus
Pertussis
RSV
Rhinovirus - Rhinitis and Pharyngitis
Parainfluenzavirus - Rhinitis, Pharyngitis, Laryngitis (can infect lower down but not common)
H. Influenzae - Rhinitis, Laryngitis, Tracheitis, Bronchitis and Bronchiolitis
Influenza virus - Everywhere with a preference for bronchioles and Bornchi
Pertussis - Laryngitis and below (though not so much pneumonia)
RSV - Rhinitis and Bronchitis - Pneumonia
63
What is the most common cause of the common cold?
Why can you be infected so many times with the same pathogen?
Rhinovirus
Over 100 serotypes though the same serotype can infect again - thought to be because it is superficial infection
64
65
What are 2 causes of a cold during summer?
Enterovirus and Coronavirus
66
How is entervirus spread?
Fecal oral route
67
What is a suggested reason as to why one is more likely to contract strep pneumonia in cold weather?
Cold weather is thought to suppress the cough reflex
68
Name 5 agents which can cause the common cold?
rhinovirus, parainfluenza virus, RSV, enterovirus, coron avirus, human metapneumovirus (HMPV)
69
Name 3 agents which can cause pharyngitis/tonsillitis with nasal involvement
Adenovirus, enterovirus, parainfluenza
70
What are the symptoms of pharyngitis/tonsillitis?
Sore throat and runny nose
Nasal involvement makes it more likely to be viral in origin
71
Name 4 viral agents which can cause pharyngitis/tonsillitis with no nasal involvement
Adenovirus, influenza, enterovirus, reovirus
72
Name 3 bacterial which can cause pharyngitis/tonsillitis with no nasal involvement
Strep pyogenes
group C and G strep
73
What strep a infects the pharynx/tonsils and how is it treated?
Strep pyogenese - can cause serious complications and thus treated with antibiotics
74
When is a rash likely to be present if a child has an URTI
If there is a rash it is more liklely to be bacterial. Though epstein barr will also form a rash when treated with ampicillin/amoxicillin
75
What percentage of pharyngitis/tonsillitis with no nasal involvement is bacterial?
10-20%
76
What are two causes of secondary sinusitis?
H. Influanzae and Strep Pneumoniae
77
What causes primary sinusitis?
It is viral (usually part of the presentation of a common cold)
78
Why are children more prone to ottitus media?
Children have shorter, more horiziontal and wider eustachian tubes which makes them more susceptible to ottitus media. When they swallow food can enter into the tubes which become non sterile.
79
Which community in aus is most at risk for otitis media?
The indigienous population and those in poorer populations
- they get acute OM which causes chronic OM leading to thick gluey secretions accumulating in the middle ear (this can cause hearing and subsequent learning and behavioural difficulties).
80
What is the most common cause of OM?
Pneumococci
81
What are some less common causes of OM?
H. Influenzae and Mraxella catarrhalis (GNC)
82
What are the causitive agents of epiglottitis?
H. Influenzae type B
83
Why is eppigoltitus rare in first world countries
There is a vaccine against HIB (conjugate vaccine)
84
What is the prognosis of epiglotitits and why?
Can be very poor, can cause spasms of the epiglottis also inflammation and oedema leading to blockage and occlusion of airway.
85
What is another name for croup? and what is its prognosis?
Laryngotracheo-bronchitis - good prog
86
Describe the pathogenesis of the common cold?
1. Virus adheres to nasla epithelial cell
2. Virus absorbtion
3. Viral replication
4. Clear fluid escaping from damaged cells
5. Host defence system activated with the invasion of phagocytes
6. Commensal bacteria start comming in and might produce pus
7. phagocytes come in and kill bacteria
By knocking out cells and cillia the viral infection can generate a secondary bacterial infection (it is known that other viral factors also contribute to its development)
87
Treatment and diagnosis for a common cold?
None
88
Should a doctor order tests for pharyngitis/tonsillitus?
Yes if possible (can be bacterial or viral), it is generally not a condition which demands immediate treatment so can wait to see if it is bacterial.
Should loop for strep group A
89
How do you treat pharyngitis/tonsilitus?
If bacterial then give antibiotics
It can progress to a peritonsular abscess (quincy) and cause acute rheumatic fever - treating early will prevent rare outcomes (cellulitus). Group A 100% susceptible to penicillin
unfounded beleif that treating with antibiotics will preent acute rheumatic fever.
90
Do we treat OM?
Yes if bacterial and severe
91
Do we need a patholgical diagnosis of OM?
If less than 2 y.o or prolonged or severe
92
Do we need a path diagnosis for sinusitis and is it treated?
Not usually necessary, can be done by surgeons directly through the skin (not through nose - will just grow microbiota)
If bacterial and severe can treat
93
Should one take a sample to diagnose epiglottitis?
yes if possible, if it is a systemic infection can take blood
should NOT touch epiglottis - can cause sudden death by suffocation
94
How do we treat severe croup?
Inhaled steroids
95
Is there a treatment for bronchitis?
No - it is usually associated with a viralURTI
96
Do you produce sputum with bronchitis?
No -usually viral
97
Who usually has chronic bronchitis?
Smokers
98
what causes an exacerbation of chronic bronchitis?
Bacterial: Pneumococci and H. Influenzae
99
What is the cuase of bronchiolitis?
It is a viral infection caused by RSV (especially when epidemic)
100
What are the signs of an acute exacerbation of chronic bronchitis and why does it occur?
As a result of COPD lungs are compromised susceptible to infection.
There is usually a marked increase in sputum, respiratory distress and fever. Tends to get wors with each infection.
101
Presentation of bronchiolitis?
It presenta a lot like asthma - expiratory wheeze and a narrowing of the small airways due to inflammation (the bronchioles are not supported by cartilage and thus more prone to collapse)
102
Why is RSV more severe during early childhood/infancy?
Babies are born with maternal antibodies to RSV, when the baby is infected an Ag-Ab complex is formed which aggravates inflammation causing bronchiolitis - attracts complement.
Thus more severe in first year of life
103
What is the most common cause of bacterial pneumonia?
Pneumococci (strep pneumoniea) - 70-80% of cases in the community and 50% in hospital.
Usually own microbiota which enters into the alveoili
104
105
Besides pneumococi what are some other causes of pneumonia?
H. Influenza (not type B)
Staph (esp in hospital)
TB, legionella, Klebs
Clamia citici (comes from birds)
106
How does bacterial pneumonia usually present?
Lobar pneumonia
acute onset
consolidated mass
usually in the alveoli
107
What is atypical pneumonia and what causes it?
It is termed a walking pmneumonia - it has a diffuse pathology
- it is a bronchopneumonia (spread by the airways), it affects the interstitial space
108
what are some of the causes of atypical pneumonia?
Mycoplasma pneumonia (this is a bacteria without a cell wall and not fized shape - hard to fight with antibiotics)
RSV, Adenovirus
Chlamydia tracomatous (especially in neonates, baby asprates during brith it is a obligate intracellular pathogen and also an important source of eye infection)
109
What are some other causes of pneumonia?
Fungi
Histoplasma
Aspergillus
Pneumocystis jerovicii - AIDS defining illness
110
What cuases a lung abscess
Mixed anearobes of the URT - Staf or Klebs
111
What is empyema and what causes it?
It is a collection of pus in a body cavity, it is caused by staph aureus resuting from a penetrating injury or staph bacteraemia
112
What are 7 ways to get a speciment sample:
1. Properly collected sputum - deep cough
2. Transtracheal aspirate (tracheostomy and endotracheal tube)(
3. Aspiration via tracheostomy
4. Aspiration via bronchoscope
5. Pleural tap (if effusion)
6. Lung biopsy - by needle
7. Blood culture and serology
113
Treatment of pneumococcus
penicillin or cephalosporins
114
Treatment for klebsiella?
Gentamicin works better than penicillins
115
Treatment for Mycoplasma and legionella?
Can't use beta lactams
Mycoplasma has no cell wall
116
What is MERS and SARS-CoV
Middle East respiratory syndrome coronavirus (MERS-CoV),
Severe acute respiratory syndrome coronavirus
117
What does spp stand for?
species
118
What is the best guess treatment for community aquired pneumonia?
Pen G/amoxicillin (covers pneumococci)
Doxycycline/macrolide (these are bacteriostatic and cover atypical legionella and mycoplasma)
- once the bacteria has been obtained select the appropriate treatment
119
What are some vaccines which prevent pneumonia?
1. Influenza vaccine
2. Pneumococcal vaccines 23-valent polysaccharide (for older people and those at risk i.e. immunocompromised
3. there is also a 13 valent conjugate which is given to children
4. specialised vaccines for those at risk - eg anthrax or human plague vaccine (soldiers), q fever vaccine
