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Pathology > MB7 Antimicrobials 2 > Flashcards

MB7 Antimicrobials 2 Flashcards

1
Q

Lecture Outcomes (for general perusal)

A

Aim

Introduce antibacterial agents

Outcomes

  1. Outline the features of the bacterial cell that are relevant to antimicrobials
  2. Identify the different classes of cell wall active antimicrobials, their site of action and common usage
  3. Identify the different classes of antimicrobials acting at intracellular bacterial sites, their site of action and common usage
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2
Q

How is the topic relevant? (for general perusal)

A

Lots of physiological bacteria get killed by antibiotics

Antibiotic resistance: drive to limit antibiotics

Sepsis: drive to give antibiotics

No single definitive clinical or laboratory marker for infection

30-40% of all hospital inpatients are being prescribed one of the following drugs at any given time

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3
Q

What is covered in this lecture (for general perusal)

A
  1. Beta lactams
  2. Glycopeptides
  3. Inhibitors of protein synthesis
    i. Macrolides
    ii. Aminoglycosides
    iii. tetracyclines
  4. Quinolones
  5. Others
    i. Metronidazole
    ii. Nitrofurantoin
    iii. Trimethoprim
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4
Q

Which drug groups act upon

  1. Cell wall
  2. Intracellular Bacterial Site
A
  1. Beta-lactams, glycopeptides
  2. Inhibitors of protein synthesis (Macrolides, Aminoglycosides, Tetracyclines), Quinolones, Others (i.Metronidazole, ii.Nitrofurantoin, iii.Trimethoprim )
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5
Q

Outline the antibacterial tree

A
  1. Beta-lactams
    1. Penicillins - Benzylpenicillin, Flucloxacillin, Amoxicillin
    2. Penicillin-Beta-lactamase inhibitor combinations - Co-amoxiclav, PiperacillinC-tazobactam
    3. Cephalosporins - Cefuroxime, Ceftriaxone
    4. Monobactam - Aztreonam
    5. Carbapanems - Meropenem, Ertapenem
  2. Glycopeptides - Vancomycin, Teicoplanin
  3. Macrolides - Clarithromycin, Erythromicin
  4. Aminoglycosides - Gentamicin
  5. Tetracyclines - Doxycycline
  6. Quinolones - Ciprofloxacin, Levofloxacin
  7. Others - Metronidazole, Trimethoprim, Nitrofurantoin

3,4,5 are the protein synthesis inhibitors

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6
Q

What is the spectrum of activity of the antibacterial tree?

A
  • Gram-positive cocci
    • Staphylococcus aureus

Staphylococcus epidermidis

β-haemoyltic Streptococci:

(Lancefield group A, B, G)

Streptococcus oralis

Streptococcus pneumoniae

Enterococcus faecalis

  • Gram-positive rods
    • ​

Clostridium tetani

Clostridium difficile

Clostridium perfringens

Listeria monocytogenes

Bacillus species

Proprionibacterium acnes

Lactobacillus acidophilus

  • Gram-negative cocci
    • ​

Neisseria meningitidis

Neisseria gonorrhoeae

Haemophilus influenzae

  • Gram-negative rods
    • ​

Escherichia coli

Klebsiella pneumoniae

Proteus mirabilis

Salmonella enteritidis

Bacteroides fragilis

Pseudomonas aeruginosa

Campylobacter jejuni

  • Others (cell wall deficient - don’t gram stain)
    • Legionella pneumophila

Chlamydia trachomatis

Mycoplasma pneumoniae

Treponema pallidum

* Mycobacterium tuberculosis
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7
Q

Beta-Lactams

  1. What is the base structure of all beta-lactam drugs?
  2. What is their site of action?
A
  1. Beta-lactam ring
  2. Beta lactam ring binds to the transpeptidase enzyme (also known as the penicillin binding protein)
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8
Q
  1. What is the bacterial cell wall made from?
  2. Describe the structure of this wall
A
  1. Peptidoglycan
  2. Monomers of n-acetyl muramic acid (NAMA) and n-acetyl glucosamine (NAG)

Formed in chains

Chains ‘cross-linked’ by action of the transpeptidase enzyme

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9
Q

Beta-Lactams - Penicillins

Benzylpenicillin (the original antibiotic)

  1. What is it’s route of administration?
  2. What bacteria does it target?
A
  1. IV (oral equivalent = phenoxymethylpenicillin)
  2. b-haemolytic streptococci: Streptococcal pharyngitis/tonsillitis
    1. Severe soft tissue infection
    2. Septic Arthritis
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10
Q

Beta-Lactams - Penicillins

Flucloxacillin

  1. ​Why is this important?
  2. What is it active against?
  3. How is it given?
  4. What conditions does it treat?
A
  1. Amended penicillin to be stable against the staphylococcal beta-lactamase
  2. Staphylococcus aureus
  3. Oral or IV
  4. Skin and soft tissue infection

Bone and joint infection

Device related infection

Endocarditis

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11
Q
  1. What is Beta-lactamase?
  2. What antibiotic has been adapted to be stable against this?
A
  1. An enzyme which hydrolyses, breaks apart, the beta-lactam ring. Made by a bacteria to protect itself against a beta-lactam antibiotic

One of the most important antibiotic resistance mechanisms

  1. Flucloxacillin
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12
Q

Beta-Lactams - Penicillins

​Amoxicillin

  1. How has this antimicrobial been amended?
  2. What is it most active against?
  3. How is it given?
  4. What conditions does it therefore treat?
A
  1. to be better absorbed and broader spectrum
  2. Streptococcus pneumoniae
  3. PO/IV
  4. Pneumonia, Upper and lower respiratory tract infection
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13
Q

Beta-Lactams - Penicillin/Beta-lactamase inhibitor combinations

  1. How does the inhibitor help?
A
  1. Beta lactamase enzyme made by the bacteria to defend itself against the penicillin

Beta lactamase inhibitor limits the action of beta lactamase enzymes

Combination of penicillin with the inhibitor dramatically increases the spectrum of action

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14
Q

Beta-Lactams - Penicillin/Beta-lactamase inhibitor combinations

​Co-Amoxiclav

  1. What is this made up of?
  2. What is it used for?
  3. What is it active against?
  4. How is it given?

“the antibiotic of choice for people who don’t like to think about antibiotics”

A
  1. Amoxicillin & Clavulanic acid
  2. Intra-abdominal infection (both aerobic and anaerobic gram negative activity)

Complicated ear/ nose/ throat/ paranasal sinus infections

  1. Staphylococcus aureus

Streptococcus pneumoniae

Enterococcus faecalis

Escherichia coli

Klebsiella pneumoniae

Proteus mirabilis

Salmonella enteritidis and Bacteroides fragilis

  1. PO/IV
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15
Q

Beta-Lactams - Penicillin/Beta-lactamase inhibitor combinations

Piperacillin-tazobactam

  1. What is it active against?
  2. How is it given?
  3. What is it used for clinically?
A
  1. Pseudomonas
  2. IV
  3. Severe sepsis when organ site source is unknown and Pyrexia in neutropenic cancer chemotherapy patients
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16
Q

Beta-Lactams - Cephalosporins

Cefuroxime

  1. What is it’s common clinical usage?
  2. How is it given?
  3. What is it usually combined with?
A
  1. surgical prophylaxis
  2. IV
  3. Usually combined with Metronidazole (‘others’) (which covers anaerobic bacteria)
17
Q

Beta-Lactams - Cephalosporins

Ceftriaxone

  1. What is it’s clinical use?
  2. How is it given?
  3. When is it commonly used?
A
  1. First line treatment in bacterial meningitis
  2. IV
  3. Soft tissue infection, particularly as Outpatient Parenteral Antimicrobial Therapy (OPAT)
18
Q

Beta-Lactams - Monobactam

Aztreonam

  1. What is a common clinical use?
  2. What is it active against?
  3. How is it given?
  4. What is it used in combination with when given to patients with a penicillin allergy
A
  1. It is a Beta-Lactem safe to give to patients with life threatening penicillin allergy
  2. Only against Gram-negative species
  3. IV
  4. Used in combination with gram positive active agents
19
Q

Beta-Lactams - Carbapanems

Ertapanems

  1. What is it used for?
  2. How often is it given? How?
A
  1. Urinary tract infection, particularly as Outpatient Parenteral Antimicrobial Therapy (OPAT)
  2. Once daily. IV
20
Q

Beta-Lactams - Carbapanems

Meropanem

  1. What is it?
  2. How is it given?
  3. In what conditions is it used?
A
  1. The most broad spectrum agent; the antibiotic of last resort
  2. IV
  3. ICU, Cancer patients, severe structural lung diseases
21
Q

Glycopeptides

  1. Describe the molecule
  2. Where does it act?
A
  1. large polar (hydrophilic) molecule.
  2. Bacterial Cell wall where it i_nhibits the addition of the NAMA monomor to the peptidoglycan chain_
22
Q

Glycopeptides

Vancomycin and Teicoplanin

  1. What do they act on?
  2. What are they used for?
  3. When is oral vancomycin only ever given?
A
  1. Gram-positive bacteria
  2. MRSA (and other resistant gram positives), Penicillin/ Beta-lactam allergy
  3. for Clostridium difficile diarrhoea
23
Q

Which groups carry out Protein Synthesis Inhibtion?

Where do these groups act?

A
  1. Macrolides
  2. Aminoglycosides
  3. Tetracyclines

bacterial ribosome; inhibiting the production of bacterial protein

24
Q

Macrolides

Clarithromycin & Erythromicin

  1. What are they used for?
  2. How are they given?
  3. Which is better tolerated?
A
  1. Cover for ‘atypical’ causes of pneumonia. Oral alternative to penicillin in allergy
  2. PO/IV
  3. Clarithromycin
25
Q

Aminoglycosides

Gentamicin

  1. What is it used for?
  2. What are the problems?
  3. How is it given?
A
  1. Gram negative sepsis
  2. but nephrotoxic and ototoxic

Hydrophilic molecule that remains in the blood stream: use in sepsis

Concentrates in the kidneys: UTI treatment but risk of nephrotoxicity

Narrow therapeutic window: Therapeutic Drug Monitoring (TDM)

  1. IV
26
Q

Tetracyclines

Doxycycline

  1. What is it used for?
  2. What is a drawback?
  3. How is it given?
A
  1. Oral treatment for MRSA

Alternative in penicillin allergy

Respiratory tract infection, including causes of ‘atypical’ pneumonia

  1. Stains bones and teeth: not for children
  2. PO
27
Q

Quinolones

Broad spectrum, orally active, C difficile risk

  1. Give examples of this group
  2. What is their site of action?
A
  1. Ciprofloxacin, levofloxacin (and others)
  2. Inhibit enzymes that super-coil bacterial DNA (gyrase & topoisomerase)
28
Q

Quinolones

Ciprofloxacin

  1. What is it used for?
  2. How is it given?
  3. What does it cover well? And how is this useful clinically?
  4. What is a risk?
A
  1. Common clinical treatment for Pseudomonas
  2. PO/PI
  3. Excellent gram negative cover: UTI
  4. A ‘mutagen’. Drives resistance and associated with hospital outbreaks of Clostridium difficile
29
Q

Quinolones

Levofloxacin

  1. What is it useful as?
  2. What can it be called?
  3. How is it given?
A
  1. Excellent activity against streptococcus pneumoniae and causes of ‘atypical’ pneumonia
  2. Respiratory quinolone
  3. PO/IV
30
Q

‘Others’

What are the following used for?

  1. Metronidazole
  2. Trimethoprim and Nitrofurantoin
A
  1. anaerobic infection
  2. UTI
31
Q

Others

Metronidazole

  1. How does it act?
  2. What does it act on?
  3. How is it given?
  4. What is it used for?
A
  1. Nitroimidazole, Pro-drug: activated in low oxygen conditions. Once active is directly toxic through interaction with DNA
  2. Anaerobic ‘cover’
  3. PO/ IV
  4. Intra-abdominal infection

Oral infections

Clostridium difficile diarrhoea

32
Q

Others

Trimethoprim

  1. How does it act?
  2. What is it used for?
  3. How is it given?
  4. What can it be combined with?
  5. What does the above treat?
A
  1. Diaminopyrimidine, ‘folate antagonist’, Dihydrofolate reductase inhibitor
  2. Uncomplicated UTI
  3. PO
  4. Can be combined with the sulphonamide Sulfamethoxazole as C0-trimoxazole
  5. treat some multiresistant bacteria and Pneumonia caused by Pneumocystis jirovecii
33
Q

Others

Nitrofurantoin

  1. How does it act?
  2. What is it used for?
  3. Who is it contra-indicated for?
A
  1. Multiple mechanisms of action, poorly understood. Inhibition of bacterial protein synthesis and toxic to DNA. Therapeutic levels are only attained in the urine
  2. Uncomplicated UTI
  3. Not given to patients with renal failure as not enough drug will be filtered into the urine
34
Q

What is the mechanism of action for the following?

  1. Beta-Lactams
  2. Glycopeptides
  3. Macrolides, Aminoglycosides, Tetracyclines
  4. Quinolones
  5. Others
    1. Metronidazole
    2. Trimethoprim
    3. Nitrofurantoin
A
  1. Beta lactam ring binds to the transpeptidase enzyme (also known as the penicillin binding protein)
  2. Cell wall where it inhibits the addition of the NAMA monomor to the peptidoglycan chain
  3. bacterial ribosome; inhibiting the production of bacterial protein
  4. Inhibit enzymes that super-coil bacterial DNA (gyrase & topoisomerase)
  5. Others
    1. Once active is directly toxic through interaction with DNA
    2. ‘folate antagonist’. Dihydrofolate reductase inhibitor
    3. Multiple mechanisms of action, poorly understood. Inhibition of bacterial protein synthesis and toxic to DNA
35
Q

What are the following used to treat?

Beta-Lactams

  1. Penicillins
    1. Benzylpenicillin
    2. Flucloxacillin
    3. Amoxicillin
  2. Penicillin/ beta-lactamase inhibitor combinations
    1. Co-amoxiclav
    2. Piperacillin & tazobactam
  3. Cephalosporins
    1. Cefuroxime
    2. Ceftriaxone
  4. Monobactam
    1. Aztreonam
  5. Carbapenems
    1. Ertapenem
    2. Meropenem
A
  1. Penicillins
    1. Targeting b-haemolytic streptococci: Streptococcal pharyngitis/ tonsillitis
    2. Staphylococcus aureus: Skin and soft tissue infection, Bone and joint infection, Device related infection, Endocarditis
    3. Step. Pneumoniae: Pneumonia Upper and lower respiratory tract infection
  2. PBICs
    1. Intra-abdominal infection (both aerobic and anaerobic gram negative activity). Complicated ear/ nose/ throat/ paranasal sinus infections
    2. Pseudomonas: Severe sepsis when organ site source is unknown, Pyrexia in neutropenic cancer chemotherapy patients
  3. Cephalosporins
    1. surgical prophylaxis
    2. First line treatment for bacterial meningitis
  4. Monobactam
    1. safe to give to patients with life threatening penicillin allergy. Only active against gram negative species
  5. Carbapenems
    1. UTI
    2. Last resort. ICU, Cancer patients, severe structural lung diseases
36
Q

What are the following used to treat?

  1. Glycopeptides
    1. Vancomycin and Teicoplanin
  2. Macrolides
    1. Clarithromycin & Erythromicin
  3. Aminoglycosides
    1. Gentamicin
  4. Tetracyclines
    1. Doxycycline
  5. Quinolones
    1. Ciprofloxacin
    2. Levofloxacin
  6. Others
    1. Metronidazole
    2. Trimethoprim
    3. Nitrofurantoin
A
  1. Glycopeptides
    1. Gram positive cover. MRSA. Penicillin/ Beta-lactam allergy
  2. Macrolides
    1. ‘atypical’ causes of pneumonia. Oral alternative to penicillin in allergy
  3. Aminoglycosides
    1. Gram negative sepsis: but nephrotoxic and ototoxic
  4. Tetracyclines
    1. MRSA. Respiratory tract infection, including causes of ‘atypical’ pneumonia
  5. Quinolones
    1. Pseudomonas. UTI (excellent gram neg cover)
    2. Excellent activity against streptococcus pneumoniae and causes of ‘atypical’ pneumonia
  6. Others
    1. anaerobic infection. Clostridium difficile diarrhoea
    2. UTI. treat some multiresistant bacteria and Pneumonia caused by Pneumocystis jirovecii
    3. UTI.

Pathology (35 decks)

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