Antibacterials Flashcards
1
Q
What are the two most important antibiotics which act in bacterial cell wall?
A
- Beta lactams
- Glycopeptides
2
Q
What are the 4 main classes of beta-lactam antibiotics?
A
- penicillins
- cephalosporins
- carbapenems
- monobactams
3
Q
What is the combination beta lactam antibiotics?
A
penicillin-betalactamase inhibitor combinations
- beta lactam combined with molecule designed to make the antibiotics less susceptible breakdown
4
Q
What is the structure in bacteria targeted by the beta lactam antibacterials?
A
- Bacterial wall made of peptidoglycan
- peptidoglycan chains cross linked by a transpeptidase enzyme (penicillin binding protein)
- beta lactams inhibit this enzyme
5
Q
What is the mode of action of beta lactam antibacterials?
A
- inhibit the penicillin binding protein enzyme
- weakens wall of bacteria
- results in bacterial cell lysis
6
Q
What is the common structure of beta lactams?
A
beta lactam ring N-CH2-CH2-CO (ring so last CO group connected to N)
7
Q
What can Benzylpenicillin be used to treat?
A
- Mainly gram positive bacteria
- Often used for Beta-haemolytic streptococci
8
Q
What clinical syndromes are caused by Beta-haemolytic streptococci?
A
- Streptococcal tonsilitis (given oral or IV)
- Streptococcal cellulitis (given IV antibiotics)
9
Q
What are the two preparations of benzylpenicillin?
A
IV - benzylpenicillin
Oral - Penicillin V
10
Q
What can amoxicillin be used to treat?
A
- Streptococcus pneumoniae
- infections caused by enterococcus faecalis
- infections caused by listeria monocytogenes
Amoxicillin better oral absorption than benzylpenicillin so can be used as step down from benzylpenicillin so can be used for beta-haemolytic streptococci and strep pnemoniae
11
Q
What clinical syndromes are treated by amoxicillin?
A
- Chest infections
- listeria Infections
12
Q
What is Flucloxacillin used to treat?
A
- Staphylococcal aureus infection
- Beta-Haemolytic streptococci but not reliable against group B Streptococci
13
Q
What clinical syndromes are treated by flucloxacillin
A
- Skin/soft tissue infection
- Bone/joint infection
- Endocarditis
14
Q
What is the only drug in the class monolactam?
A
Aztreonam
15
Q
What is aztreonam used to treat?
A
- gram negative organisms
- can also be given safely in penicillin allergies
16
Q
What are the clinical syndromes treated by aztreonam?
A
- UTI
and in combination therapy for: - intra-abdominal infections
- hospital acquired chest infections
17
Q
What are ceftriaxone/cefotaxime used to treat?
A
- neisseria meningitidis
- Streptococcus pneumonias
18
Q
What are the differences in uses of ceftriaxone/cefotaxime?
A
- ceftriaxone used for syphilis
- ceftriaxone contraindicated for neonates as can display bilirubin from binding to albumin but cefotaxime can be used
- ceftriaxone is drug on formulary for adults in hospitals
19
Q
What clinical syndromes are treated by ceftriaxone/cefotaxime?
A
- meningitis
- out-patient parenteral antimicrobial therapy e.g. soft tissue infections and intra-abdominal infections
20
Q
What preparations are ceftriaxone/cefotaxime given in?
A
IV
21
Q
What preparations are Azetreonam give in?
A
IV
22
Q
What preparations are flucloxicillin given in?
A
IV or oral
23
Q
What preparations are amoxicillin given in?
A
IV or oral
24
Q
What are the two main antibiotics in the glycopeptide class?
A
- Vanomycin
- Teicoplanin
25
What is the difference between between beta lactams and glycopeptides?
glycopeptides larger than beta lactams so unable to penetrate external membrane of gram negative bacteria also means too large to leave compartment put in i.e. stay in gut (if given orally) or blood (if given IV)
26
What is the MoA of glycopeptides?
- bind to peptidoglycan prevention addition of new NAG-NAMA building blocks to the cell wall (i.e. prevent peptidoglycan formation)
27
What are Vanomycin/Teicoplanin used to treat?
- only gram positive bacteria
- Staph Aureus specifically MRSA
- C difficile also treated by Vancomyin only
28
What clinical syndromes is Teicoplanin used to treat and in what form?
- OPAT (out-patient parenteral antimicrobial therapy) e.g. soft tissue infection and intra-abdominal infections
- Combination therapy in penicillin allergy
(all via IV)
29
What are the downfalls of glycopeptides?
- can cause renal toxicity
| - inferior to beta lactams for some organisms
30
What clinical syndromes are treated by vancomyin?
- Soft tissue infection (must be IV)
- Combination therapy in penicillin allergy for intra-abdominal infections (must be IV)
- C difficile colitis (must be oral)
31
What are the three antibiotics that act within the cell of bacteria?
1) protein synthesis inhibitors
2) Nucleic acid synthesis inhibitors
3) Miscellaneous antibiotics
32
What are the three main classes of protein synthesis inhibitors?
- Macrolides
- Aminoglycosides
- Tetracyclines
33
What are the three most common macrolides?
- Clarithromycin
- Erythromycin
- Azithromycin
34
What are Clarithromycin/Erythromycin used to treat?
- gram positive cover for soft tissue infections or chest infections in penicillin allergic patients
- Streptococcus pneumoniae
- haemophilus influenzae
- Legionella
- Chlamydia
- Mycoplasma
(these bacteria don't have cell walls so are not susceptible to beta lactams)
35
is Clarithromycin or Erythromycin more commonly used?
Clarithromycin
- better tolerated as Erythromycin causes vomiting and diarrhoea
- better bioavailability
Erythromycin used in pregnancy
36
What clinical syndromes is Clarithromycin used to treat?
chest infection used in combination with beta lactams to treat community acquired pneumoniae
37
What are the three classes of ahminoglycosides?
- Gentamicin (1st line)
- Amikacin (better against highly resistant gram neg)
- Tobramycin (better pseudomonas cover)
38
What are the aminoglycosides used to treat?
- Gram neg organsims
- staphylococci including MRSA
- can be used in combination with beta lactams to treat streptococci, act after cell wall has been broken down
39
What are the clinical syndromes treated by aminoglycosides?
- Sepsis
| - UTI
40
What are the downfalls of aminoglycosides?
- nephrotoxic and ototoxic so drug monitoring required to prevent toxicity
- hydrophilic so stay in blood and urine rather than penetrating tissues
41
What are the three drugs in tetracycline class?
- Doxycycline (most commonly used in hospitals)
- Minocycline
- Tetracycline
42
When are tetracyclines contraindicated
Contraindicated in pregnancy and in children under 12
43
What is doxycycline used to treat?
- Staphylococci
- Streptococci
- chest pathogens e.g. haemophilus influenzae and in combination with beta lactam for atypical infections (legionella pneumonia, chlamydia trachomatis and mycoplasma pneumoniae)
- activity against many MRSA isolates also
44
What clinical syndromes are treated by doxycycline?
- Chest infections
| - Oral treatment of MRSA
45
In what form is Doxycycline given?
oral
46
What are the three main classes of nucleic acid synthesis antibiotics?
- Quinolones
- Nitroimidazoles
- trimethoprim
47
What is the most common drug in Nitroimidazoles class?
Metronidazole
48
What are the three most common Quinolones?
- Ciprofloxacin (best for gram neg)
- Levofloxacin
- Moxifloxacin (best for gram pos)
49
What is the important problem with quinolones?
increased risk of tendopathy or tendon rupture so should not be prescribed for non-severe infections
- Ciprofloxacin also associated with MRSA and C.difficle colitis
50
What is Ciprofloxacin used to treat?
excellent for pseudomonas
| - good gram neg coverage
51
What is levofloxacin used to treat?
- better gram pos cover than Ciprofloxacin but worse gram neg cover than moxifloxacin
52
What are the clinical syndromes treated by Ciprofloxacin?
- oral treatment for pseudomonas auruginosa
| - Combination therapy in penicillin allergic patients
53
What is levofloxacin/moxifloxacin used to treat?
- streptococcus pneumoniae
- Atypical chest infections e.g. legionella pneumophila, chlamydia trachomatis and mycoplasma pneumoniae
- haemophilus influenzae
54
What clinical syndromes are treated by levofloxacin/moxifloxacin?
- chest infections in penicillin allergic patients
55
What can metronidazole be used to treat?
Anaerobes
| clostridium difficile
56
What clinical syndromes are treated by metronidazole?
- Polymicrobial infections e.g. intra-abdominal infections
| - Clostridium difficile colitis (oral)
57
What preparation is metronidazole given in?
IV or oral
58
What is Trimethoprim used to treat?
- E.Coli
- Klebsiella
- Proteus
- resonable staphylococcal cover
59
What clinical syndromes is trimethoprim used to treat?
uncomplicated lower UTIs (oral prep)
60
What are the two types of miscellaneous antibiotics?
- Nitrofurantoin
| - Fidaxomicin
61
What is nitrofurantoin used to treat?
- only lower UTIs as only achieves adequate concentrations in urine
- gram neg organisms in urine
- Enterococcus faecalis in urine
62
When is nitrofurantoin contraindicated?
- patients with 6-phosphate dehydrogenase deficiency due to risk of haemolytic anaemia
- pregnancy due to risk of haemolysis of immature neonatal RBC
- Patients with renal impairment as renal excretion of drug reduced which can lead to treatment failure
63
What is fidaxomicin used to treat?
clostridium difficile colitis
| as efficacious as oral vancomycin but fidaxomicin has lower risk of relapse but more expensive
64
What are the three ways bacteria can develop resistance?
1) Enzymatic degradation: break down antibiotic
2) Target site modification: change in structure of site at which antibiotic acts reducing efficacy or rendering non-active
3) Restricted access to bacterium: can have efflux pumps which take antibiotic out of bacteria or can get reduction in bacteria porins which means antibiotics can't get into bacteria
- Multiple of these may be possible and are likely
65
What is the important antibiotic which bacteria are resistant to via enzymatic degradation?
Beta lactams - Beta lactamases (bacteria which produce beta lactase) breakdown penicillin but can't break down flucloxacillin
66
What are the main beta lactamases?
- Staph Aureus
- E.Coli
- Klebsiella
67
What are the group of antibiotics which have a compound added to them to prevent resistance to beta lactamses?
BetaLactamse Inhibitor compounds
68
What are the two most common Beta Lactamase inhibitor compounds?
- Clavulanate (added to amoxicillin to become co-amoxiclav)
| - Tazobactam ( added to piperacillin to become piperacillin-tazobactam)
69
How do beta lactamase inhibitor compounds protect the partner penicillins?
Either:
- surrogate substrate for the beta lactamase
- bind to the beta lactamase permanently inhibiting it
70
What antibiotics are the most resistant to beta lactamases?
1) Carbapenems (greatest gram neg activity)
2) aztreonams, 3rd gen cephalosporins and beta lactamase inhibitor compounds
3) amoxicillin
4) Penicillin (lowest gram neg activity)
71
What can Co-amoxiclav treat?
```
All bacteria which amoxicillin can treat + beta lactamases e.g. E.Coli (gram neg pathogens)
So:
- E.Coli
- Klebsiella
- Proteu
- Enterococcus Faecalis
```
72
What clinical syndromes are treated with Co-amoxiclav?
- Intra-abdominal infections
- Complicated UTIs
- Complicated ear, nose, throat and sinus infections
73
What is the relationship between Resilience to gram neg beta-lactamases and spectrum of gram neg activity?
Inversely related so inc in one means dec in other
74
Preparation of Co-amoxiclav?
- Oral
| - IV
75
What is treated by Piperacillin-tazobactam?
- Same as Co-amoxiclav
- + Pseudomonas
- performs better against E.coli and Klebsiella than Co-amoiclav
76
What clinical syndromes are treated by Piperacillin-tazobactam?
- Sepsis
| - Infection in severely immunosuppressed patients where source is unknown
77
Preparation of Piperacillin-tazobactam?
IV
78
What is Meropenem used to treat?
- one of broadest spectrum antibiotics so almost anything
| - Stable to almost all beta lactamases
79
What clinical syndromes is Merepenem used to treat?
- Severe sepsis
| - infection if severe and unknown source
80
Preparation of Merepenem?
IV
81
What beta lactamase has resistance to all beta lactam antibiotics?
carbapenemases
82
Why are carbapenemases so significant?
- gene encoding carbapenemase enzyme is plasmid mediated
- so can be passed between bacteria
- Can also receive other resistance genes from other bacteria
83
What precautions should be taken for a patient infected with carbapenemases?
- Isolated in own room
| - healthacare workers must don gown and gloves and wash hands before and after contact
84
What bacteria are resistant due to target site modification and what is the modification?
MRSA have become resistant to flucloxacillin - Alter shape of penicillin binding proteins on peptidoglycan bacteria wall meaning antibiotics can't bind to it
85
What PBP does Staphylococcus Aureus produce instead of the normal Penicillin binding proteins and what gene encodes this?
PBP2A (protein)
| mecA (gene)
86
What are flucloxacillin resistant Staphylococcus aureus called?
MRSA
87
How are MRSAs treated?
1) Clindamycin (carries risk of C.Difficile)
| 2) Glycopeptides (nephrotoxic and less effective than flucloxacillin)
88
What precautions are taken for patients infected with MRSA?
- Isolated
| - Don Gloves and aprons and wash hands before and after contact
89
How do bacteria restrict antibiotics access as a form of resistance?
1) lose access channels (porins)
| 2) Increase production of efflux pumps
90
What is an example of a bacteria with restricted access resistance?
Pseudomonas Aeruginosa which has efflux pumps
91
What drugs are active against Pseudomonas Aeruginosa without the restricted access resistance?
1) piperacillin tazobactam
2) Meropenem
3) ceftazidime
4) Aminoglycosides
5) Ciprofloxacin
6) Aztreonam
92
What is the only antibiotic which can treat Pseudomonas Aeruginosa with restricted access resistance?
Aminoglycosides
93
Why is documentation of drug allergies important?
1) Patient safety - prevent fatal reactions
2) Treatment efficacy - prevent superior drugs being withheld from patients who don't have true allergy
3) Antimicrobial stewardship - if non-allergic may be given broad-spectrum or 'reserve' treatments for resistant infections when don't need it
94
What is the most common antibiotic allergy?
Beta lactams but 98% of allergy reports are negative on investigation
95
What symptoms would suggest a significant allergy?
- Fast-onset
- Urticarial rash
- Swelling of lips or tongue
- Breathing difficulties
- antihistamine treatment
96
What questions should be asked in an allergy history taking?
- Onset
- Symptoms evolution
- Rash type
- treatment required
- Exposure prior to reaction
- Other medications
- Antibiotic or relative since tolerated?
- Other drug allergies
- Similar reactions in absence of drug?
97
When should beta-lactams definitely be avoided?
IF
1) Immediate reaction
2) Severe reaction
3) systemic involvement
98
What is sepsis?
Life-Threatening organ dysfunction caused by dysregulated host response to infection
99
Why is recognition of sepsis early so important?
Earlier treated lower risk of death
| - every hour risk of death increases by 10%
100
What criteria are needed to diagnose sepsis?
1) Resp rate of 22 or more
2) GCS 13 or less
3) Systolic BP below 100
(need two of three)
101
What is first step in investigating sepsis?
- Identify pathogen
- reduces risk of C.Diff
- reduced risk of resistance
102
What samples can be sent in septic screen?
- Always Blood culture (peripheral and central line if present) always before antibiotics given
depending on source on infection:
- Urine culture
- Sputum
- Wound swab
103
What should be considered in choosing antibiotic to treat sepsis?
1) Source of infection
2) pathogens which usually cause infection at that site
3) Whether patient has any known antibiotic allergy
104
What form of administration should be used in patients with sepsis?
IV as may be reduction in GI absorption
105
What are the first antibiotics given to patients with sepsis?
Broad spectrum but when know cause can change to narrower spectrum
- can give piperacillin tazobactam or meropenem
