Beestjes wk 6 Flashcards
1
Q
Name a bacteriostatic antibiotic
A
clarithromicin
2
Q
Antibiotic Spectrum
A
the range of bacterial species effectively treated by the antibiotic
NB: Important to distinguish between lack of activity and resistance. Spectrum normally refers to wild type bacteria (i.e. those that haven’t yet acquire resistance genes)
3
Q
Broad Spectrum Abx
A
Antibiotics that are active against a wide range of bacteria
downside- also have a substantial effect on colonising bacteria. tend to cause other infections like C. diff and candida
4
Q
Narrow Spectrum
A
Antibiotics that are active against a limited range of bacteria
Useful only where the cause of the infection is well defined
Have a much more limited effect on colonising bacteria
5
Q
Guided therapy
A
Depends on identifying the cause of infection and selecting agent based on sensitivity testing
Used principally for relatively mild infections for which treatment can be delayed until the results of a lab culture are available
6
Q
Empirical therapy
A
Used when therapy cannot wait for culture, i.e. in patients with more severe infections:
- Sepsis
- Bacterial meningitis
Use antibiotic which has extensive action against any bacteria which might be causing infection
Need to penetrate broadly throughout body because the site of infection may be unknown or the infection may be disseminated.
7
Q
Prophylactic therapy:
A
Used to prevent an infection before it begins
May be used in healthy people who have been exposed to:
- Surgery → e.g. hip replacements, bone marrow transplants, colorectal surgery
- Injury
- Infective material
Also used in immunocompromised individuals:
- HIV
- Transplantation
- Splenectomy
8
Q
β-lactam antibiotics
A
Defined by the presence of a beta-lactam ring
This ring is structurally analogous to peptidoglycan that makes up the bacterial cell wall
Beta lactam antibiotics are penicillin binding protein inhibitors → stop the development of the cell wall
Interfere with peptidoglycan metabolism, and impair the bacteria’s ability to lay down the cell wall by inhibiting cross-linking
Beta lactams cause cell lysis -> bactericidal
9
Q
Classes of β-lactam antibiotics
A
1) penicillins
2) cephalosporins
3) Carbapenems (usually the broadest spectrum)
4) Monobactams
5) Combinations
PCCMC
10
Q
List 3 penicillins
A
1) benzylpenicillin
2) amoxicillin
3) flucloxacillin
11
Q
Name a cephalosporin
A
Ceftriaxone
12
Q
Name a carbepenem
A
meropenem
13
Q
Name a monobactam
A
aztreonam
14
Q
Name two beta lactam combination drugs
A
1) co-amoxiclav = Amoxicillin/clavulanic acid (Augmentin)
2) Piperacillin/tazobactam (Tazocin)
15
Q
Beta lactamases
A
Enzymes that lyse and inactivate beta-lactam drugs
Confer high level resistance to antibiotic
16
Q
what classes of bacteria commonly secrete beta lactams?
A
Gram negatives and S.aureus
17
Q
Beta lactam absorption
A
Most β-lactams poorly absorbed from GI tract:
must be given IV
18
Q
Which β-lactams can eb given orally?
A
1) amoxicillin
2) flucloxacillin
NB: vomiting limits dose
19
Q
β-lactam excretion
A
Usually excreted unchanged in urine, some also via bile
renal function is therefore the key determinant in beta lactam dosing
20
Q
β-lactam adverse effects
A
By and large very safe even in very high doses.
GI effects are the most common - nausea, vomiting, diarrhoea, cholestasis
Other:
- hypersensitivity t1 = urticaria, anaphylaxis (rare)
- t2 hypersensitivity -= haemolytic anaemia
- t3 = vasculitis
- t4 hypersentsitivity - mild to severe = 4th day rash to stevens johnson syndrome
21
Q
β-lactam allergy
A
1/10 reports penicillin allergy
Often reported hypersensitivity syndrome is non-allergic
cross reactivity = Patients allergic to a penicillin will usually be allergic to other penicillins
22
Q
Benzylpenicillin administration
A
IV
NB: oral agent (Penicillin V) is similar but not often used
23
Q
Benzylpenicillin spectrum/activity
A
Narrow spectrum
first choice antibiotic for serious streptococcal infection
also has good activity against neisseria
24
Q
first choice antibiotic for serious streptococcal infection
A
Benzylpenicillin
25
Amoxicillin administration
Much more orally bioavailable than natural penicillins
26
most commonly used beta lactam
Amoxicillin
27
Amoxicillin spectrum/activity
principally used against streptococci because of extensive resistance
e.g. in upper respiratory tract infections
also has good activity against enterococci
28
Flucloxacillin
Synthetic penicillin developed to be resistant to beta-lactamase produced by staphylococci
29
Flucloxacillin spectrum/activity
```
highly active against
Staphylococcus aureus (not MRSA)
```
Streptococci (mildly effective)
No activity at all against gram negative organisms
30
Flucloxacillin administration
Can be given orally but nausea limits dose
31
Effect of Beta-lactamase inhibitors
Effectively inhibit some beta-lactamases
Greatly broadens spectrum of penicillins against Gram negatives and S. aureus
32
How does the susceptibility of cephalosporins to beta lactmases compare to that of penicillins?
Less Susceptible To beta-lactamases than penicillins because of the presence of a side chain (their structure is more complicated)
33
Carbapenems spectrum and use
Ultra-broad spectrum beta-lactam antibiotics
should be held back for patients in who it is really necessary
Excellent spectrum of activity against Gram +ves and Gram –ves
No activity against MRSA
Resistant to beta- lactama
34
What are CPEs?
cabapenemase producing Enterobacteriaceae
New beta-lactamases that lyse carbapenems
35
Which beta lactam can be given to patients who are penicillin allergic?
Aztreonam (monobactam)
structure is very different to penicillin therefore no cross reactivity to penicillins (except anaphylactic allergy)
36
Aztreonam administration
Only given IV – no oral absorption
37
Which drug can be used as a substitute for gentamicin in patients who can’t have gentamicin due to renal toxicity?
Aztreonam
38
Vancomycin mechanism of action
Inhibits cell wall formation in Gram +ves only
no Gram –ve action - the molecule is too large to get through the outer membrane
Not dependent on PBP (penicillin binding proteins) binding so effective against resistant organisms who have mutated their penicillin binding protein
39
Vancomycin spectrum
Broad-spectrum antibiotic
- clostridium
- streptococcus
- enterococcus
- staphylococcus
40
Vancomycin administration/uses
Indicated for penicillin-allergic patients who cannot receive, or who have failed to respond to penicillin/cephalosporin-antibiotics
Main use is in the treatment of MRSA infection
Not absorbed from GI tract so almost always given IV
Careful drug monitoring is required due to narrow therapeutic index. Main issue in clinical use is underdosing
Oral route only used for treatment of C. diff
41
vancomycin toxicity
1) Nephrotoxicity – more likely with higher doses
2) hypersensitivity - red man syndrome and anaphylaxis
3) ototoxicity (rare)
42
Which antibiotic would you prescribe for cellulitis?
Flucloxacillin
43
Protein synthesis inhibitors targeting the 50S Ribosomal Subunit
1) macrolides -> erythromycin, clarithromycin, azithromycin
2) clindamycin
3) chloramphenicol
44
Protein synthesis inhibitors targeting the 30S Ribosomal Subunit
1) aminoglycosides -> gentamycin
| 2) tetracyclines - > doxycycline
45
Protein synthesis inhibitors
1) macrolides
2) aminoglycosides
3) tetracyclines
46
macrolides spectrum
Good activity against Gram positive pathogens and respiratory Gram negatives (haemophilus and moraxella)
47
Most commonly used macrolide
clarithromycin
Active against “atypicals” i.e. organisms causing atypical pneumonia, which is nonresponsive to penicillins
1) Legionella
2) Mycoplasma
3) Chlamydia
48
Clarithromycin adverse effects
Diarrhoea & Vomiting
QT prolongation
Hearing loss with long term use
Drug interactions
49
Clarithromycin Drug interactions
over 400 drug interactions
binds to and inhibits CYP-3A4
Statins - Avoid co-prescription. Temporarily stop simvastatin to avoid simvastatin toxicity
Warfarin
50
Which drug should be stopped if clarythromycin is prescribed?
Statins
51
clindamycin activity
Principle action against Gram positives
52
What is useful about clindamycin?
highly effective at stopping exotoxin production because it is such a potent ribosome inhibitor
Added to patients with Gram positive toxin mediated disease because it is thought to add prognostic benefit:
- Toxic shock syndrome
- Necrotising fasciitis
53
Which antibiotic is given to patients with Gram positive toxin mediated disease to minimise toxin production?
clindamycin
54
C. Differgic Antibiotics
4C antibiotics:
1) Clindamycin
2) Co-amoxiclav
3) Cephalosporins
4) Ciprofloxacin
55
Chloramphenicol
inhibits the 50S ribosome
Excellent Broad spectrum of activity
Very toxic:
- Bone marrow suppression
- Aplastic anaemia
- Optic neuritis
Only used for topical therapy to eyes or in bacterial meningitis with beta lactam allergy
56
Aminoglycosides
30s inhibitors
57
Aminoglycoside example
gentamicin
58
Gentamicin mechanism of action
Two mechanisms
1) Bactericidal action on the cell membrane at high concentrations
2) bateriostatic action by binding to 30s ribosomes, causes a prolonged post-antibiotic effect
59
Gentamicin toxicity
1) Nephrotoxicity - particularly with prolonged use
2) Ototoxicity - common:
Hearing loss
Loss of balance
Oscillopsia
3) Neuromuscular blockade:
can exacerbate myaesthenia gravis
60
Gentamicin dosing
Once-daily dosing
high initial dose
long dosing interval (24-48hrs) to minimise toxicity
Give for 3 days only
61
Tetracyclines
30s inhibitors
Relatively non-toxic
Avoid in children and pregnant women:
Bone abnormalities
Tooth discolouration
62
Which populations should not be given tetracyclines?
children and pregnant women:
Bone abnormalities
Tooth discolouration
63
Tetracycline example
doxycycline
64
Which classes of antibiotics affect DNA Repair and Replication?
1) Quinolones
Ciprofloxacin
Levofloxacin
2) Rifampicin
65
Quinolones
Broad spectrum, bactericidal antibiotics
Very widely used
DNA gyrase inhibitors
excellent oral bioavailability
66
Commonly used Quinolones
ciprofloxacin (stronger gram - action)
levofloxacin (stronger gram + action)
67
Quinolones toxicity
Gastrointestinal toxicity
QT prolongation
Tendonitis
68
Rifampicin indications
Tuberculosis (in combination therapy)
In addition to another antibiotic in serious Gram positive infection (esp. Staph. aureus)
69
TB therapy - problems
1) Slow growing infection - requires much longer antibiotic courses
2) High bacterial burden
3) poor penetration to the site of infection - Limited access of drugs to granuloma (no vascular supply)
70
TB therapy
Prolonged courses of therapy (usually 6 months)
Combination therapy
```
RIPE
R - rifampicin
I - isoniazid
P - pyrazinamide
E - ethambutol (bacteriostatic)
```
71
Inhibitors of Folate synthesis
Trimethoprim
Co-trimoxazole
72
Trimethoprim
orally administered
| Good range of action against Gram +ves and Gram –ves
73
Trimethoprim use
limited to use in uncomplicated UTI
74
Co-trimoxazole
Combination antibiotic with trimethoprim and sulphamethoxazole
synergistic effect of two folate synthesis inhibitors
Significant additional toxicity
75
Metronidazole
Effective Against Most anaerobic bacteria
Added Therapy in intra-abdominal infections
Unpleasant reaction with alcohol
Peripheral Neuropathy with long term use
76
Treatment of lower UTI
Treatment only needs to sterilise urine
No need for systemic activity
Low risk infection so can often wait for culture results - good evidence that given an ibuprofen prescription is as good as antibiotics
77
Antibiotic Treatment of lower UTI
1) Trimethoprim
first line agent for most cases
Avoid in 1st trimester of pregnancy
Penetrates well into prostate so good choice for men
2) Nitrofurantoin:
Excellent, broad spectrum of activity
Concentrated in urine
Avoid in renal failure
78
Most common cause of UTI
E coli
| other coliforms
79
Treatment of complicated UTI
Ciprofloxacin
80
Treatment of complicated UTI if severely unwell
Amoxicillin
| Gentamicin
81
Abx Thought to be safe
| in pregnancy
Most beta-lactams
Macrolides
Anti-tuberculants
82
Abx Thought to be unsafe
| in pregnancy
Tetracyclines - Bone/tooth abnormalities
Trimethoprim - Neural tube defects (1st Tri)
Nitrofurantoin - Haemolytic anaemic (3rd Tri)
Aminoglycosides - Ototoxicity (2nd/3rd Tri)
Quinolones - Bone/joint abnormalities
83
What type of bacteria tend to cause UTIs?
gram negative rods, e.g. E. coli, Kleibsella
84
Typical causes of pneumonia
Haemophilus influenzae
| Streptococcus pneumoniae
85
Atypical causes of pneumonia
Staphylococcus aureus
Mycoplasma pneumoniae
Legionella
86
Most common cause of cellulitis
Staphylococcus aureus
other gram positive cocci
87
Most common causes of intra-abdominal infections
gram negative rods
| Anaerobes
88
Gram positive cocci
```
Chains = streptococcus
Clusters = staphylococcus
```
89
Gram negative cocci
Neisseria meningitidis
Neisseria gonorrhoea
kidney bean shaped
90
Gram negative rods
```
E. coli
Kleibsella
pseudomonas aueroginosa
salmonella
shigella
proteus
serratia
```
91
Common treatment for penumonia
amoxicillin and clarithromycin
doxycyxline can give gram positive and gram negative cover
92
Which antibiotics need dose monitoring?
gentamicin
vancomycin
Both have a narrow therapeutic window
93
Gram positive rods
```
Clostridium difficle
clostridium tetani
Bacillus cereus
Listeria monocytogenes
Corynebacteria diptheria
Propionobacterium acnes
```
94
Name two common contaminants in blood cultures
coagulase negative staphylococci (most common)
staphylococcus aureus
NB: streptococci in blood cultures are not commonly contaminants
95
Which antibiotic provides cover for the majority of gram positive cocci?
vancomycin
96
Which antibiotic provides good cover for gram negative bacteria?
gentamicin
97
How are streptococci classified?
according to their ability to haemolyse blood agar
1) alpha-haemolytic
2) beta-haemolytic
3) gamma-haemolytic (non-haemolytic)
98
Which is the most common streptococcus species associated with bacterial endocarditis?
step viridans
99
What can group A streptococcus pyogenes cause?
wound infections
local infections - tonsilitis, pharyngitis
serious systemic infections - necrotising fasciitis, fulminant shock with bacteraemia
100
How would you treat streptococcal endocarditis of a native heart valve?
4 weeks therapy
benzylpenicillin + gentamicin (for 2 weeks)
synergisitc actio, benpen disrupts the cell wall, allowing gentamicin to enter the cell
101
What antibiotic would you use to treat anaerobes?
metronidazole
102
Which antibiotic provides gram positive cover?
amoxicillin
103
Which antibiotic provides gram negative cover?
gentamicin
104
What antibiotic would you use to treat an infection in a patient with a history of ESBL producing coliforms?
meropenem or imipenem (carbapenems)
105
Common causes of necrotising fasciitis
Type I - synergistic infection with aerobes and anaerobes
- anaerobes -> bacteriodes, peptostreptococcus
- aerobes -> streptococci, enterobacteriaciae
Type II: infection with Group A Streptococci
- s. pyogenes
- s. aureus (occasional)
106
Which antibiotic provides staphylococcus cover?
flucloxacillin
107
Which antibiotic provides streptococcus cover?
benzylpenicillin
108
What surgical prophylaxis would you give to a patient who is MRSA colonised?
vancomycin or teicoplanin
109
What would you give to a patient newly regonised as MRSA colonised?
nasal mupirocin - 5 days
| chlorhexidine wash - 5 days
110
Name 2 opportunistic infections
coagulase negative staph
aspergillus
111
which antibiotics are usually used to treat gastroenteritis (in the rare event that antibiotic therapy is indicated)?
quinolones -> ciprofloxacin
112
What types of bacteria is flucloxacillin active against?
streptococci and staphylococci
113
What types of bacteria is benzylpenicillin active against?
streptococci
114
What types of bacteria is amoxicilline active against?
some gram negatives and anaerobes
115
Addition of what compound can improve the activity of amoxicillin?
clavulanic acid - beta lactamase inhibitor
116
What should you prescribe for a Lower respiratory tract infection?
amoxicillin or doxycycline
117
What should you prescribe for a UTI?
trimethoprim or nitrofurantoin
118
What should you prescribe for mild cellulitis?
Flucloxacillin or doxycycline
119
What should you prescribe in the case of a severe/life-threatening infection?
Usually IV combination treatment (Beta lactam + Gentamicin) initially
e.g. amoxicillin + gentamicin
120
What should you prescribe in the case of a severe/life-threatening infection & staphylococcus aureus infection was suspected?
IV amoxicillin + gentamicin
ADD IV flucloxacillin
121
What should you prescribe in the case of a severe/life-threatening infection & MRSA infection was suspected?
IV gentamicin + vancomycin
122
What should you prescribe in the case of a severe/life-threatening infection & penicillin allergy?
IV gentamicin + vancomycin
123
What should you prescribe in the case of a severe/life-threatening infection & severe streptococcal infection was suspected?
IV amoxicillin + gentamicin
ADD IV clindamycin
124
Which antibiotic(s) would you prescribe for a lower UTI and for how long?
Trimethoprim or Nitrofurantoin
Women - 3 days
Men - 7 days
125
Which antibiotic(s) would you prescribe for an upper UTI and for how long?
Gentamicin
126
Indications for IV abx therapy
Sepsis syndrome, SIRS or rapidly progressing infection
Special conditions:
1) Infective endocarditis
2) CNS infection
3) Bacteraemia (S. aureus)
4) Osteomyelitis (initially)
Mod-severe skin and soft tissue infection
Infection and oral route compromised
No oral formulation of antibiotic available
127
How would you manage a case of cellulitis?
Flucloxacillin monotherapy
leg elevation
IV therapy usually required until significant reduction in heat, erythema, swelling and induration
on average 3-4 days IV
Oral 5 days if mild
IV-IVOST if moderately severe 7-10 days total
In very severe add IV Clindamycin and Gentamicin
128
What organism(s) most commonly cause(s) cellulitis?
Beta haemolytic Streptococci
Group A is most common
Staph aureus most commonly causes infection of surgical wounds
129
What organism(s) most commonly cause(s) necrotising fasciitis?
Beta haemolytic Streptococci
Group A is most common
Staph aureus
130
How would you manage a case of S. aureus bacteraemia
Flucloxacillin 2g 6 hourly
If true penicillin allergy - Vancomycin
Transoesophageal echo if fever persists/there is a further positive blood culture
IV therapy for ≥2 weeks
131
How would you manage a COPD exacerbation
Antibiotic Rx only if purulent sputum (60% = viral)
Do not give dual antibiotic therapy first line
Use amoxicillin or doxycycline
132
Common pathogens in septic arthritis
Staphylococcus aureus (MSSA/MRSA)
Haemophilus Influenzae (common in children)
Neissaria gonorrhoeae (disseminated gonorrhoea)
133
Common pathogens in osteomyelitis
Staphylococcus aureus (90% of cases)
Haemophilus Influenzae
Salmonella
134
Common pathogens in Cellulitis
S.aureus
strep pyogenes
135
Common pathogens in Necrotising fasciitis
beta-haemolytic streps Gp A >> B, C, G
S.aureus
136
Antibiotic management of Necrotising fasciitis
Fuck Bad GMC (mnemonic)
Flucloxacillin, Benzylpencillin, Gentamicin, Metronidazole, Clindamycin
Clincamycin is good at switching off exotoxin production and thus improves mortality.
137
most common causes of typical CAP
Streptococcus pneumoniae (50%)
Haemophilus Influenzae
Moraxella catharralis
Typical CAP present with cough, fever, sputum and pleuritic chest pain
138
most common causes of atypical CAP
Mycoplasma pneumoniae
Legionella pneumophila
Chlamydophila pneumoniae/psittaci
Presents with flu-like symptoms: malaise, headache, myalgia
139
Treatment of TB
```
RIPE:
• Rifampicin (has interactions - CYP450 inducer)
• Isoniazid
• Pyrazinamide (stop after 2 months)
• Ethambutol (stop after 2 months)
```
* Long duration - 6 months
* Combination of drugs to reduce the rise of resistance
140
How will Neiserria gonorrhoea infection look under the microscope?
gram negative intracellular diplococcus
141
What is the treatment for chlamydia?
Azithromycin + Doxycyclin
142
What is the treatment for gonorrhoea?
Ceftriaxone + Azithromycin
143
What condition does Treponema pallidum cause?
syphillis
144
What is the treatment for syphillis?
Penicillin injection
145
Which antibiotics cause tendinopathy?
Quinolones (e.g. ciprofloxacin)
