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Pathology by week > W3 - Antimicrobial agents 1 > Flashcards

W3 - Antimicrobial agents 1 Flashcards

1
Q

What are 3 general sites on the bacteria for abx to target?

A
  1. peptidoglycan layer of cell wall
  2. Inhibition of bacterial protein synthesis
  3. DNA gyrase and other prokaryote-specific enzymes
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2
Q

Which abx classes (2) are inhibitors of cell wall synthesis?

A

(a) B-lactam antibiotics (penicillins, cephalosporins and carbapenems)
(b) Glycopeptides (Vancomycin and Teicoplanin)

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3
Q

Briefly describe Gram staining of G+ and G- bacteria

A

G+ = stain is trapped = stains purple

G- = peptidoglycan is thinner, and they have an outer membrane also = don’t retain the colour = stain pink

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4
Q

What are the subunits of a typical peptidoglycan wall?

A 
NAG = N-acetylglucosamine 
NAM= N-acetylmuramic acid

and interdispersed peptide bonds

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5
Q

Describe MOA of B-lactams?
Which group of bacteria are they most efficient against?

A

MOA:
Inactivate the enzymes that are involved in the terminal stages of cell wall synthesis called transpeptidases (also known as penicillin binding proteins)

β-lactam is a structural analogue of the enzyme substrate = results in no peptide cross-links = cell walls not formed properly = bacteriolysis

  • Active against rapidly-dividing bacteria
  • Ineffective against bacteria that lack peptidoglycan cell walls (e.g. Mycoplasma or Chlamydia)
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6
Q

Are B-lactams bactericidal or bacteriostatic?

A

Bactericidal

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7
Q

Name the 4 main groups of B-lactam abx

A
  1. Penicillin (i.e. ampicillin)
  2. Cephalosporin (i.e. cefotaxime)
  3. Carbapenems (i.e. imipenem)
  4. Monobactam (i.e. carumonam)
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8
Q

Describe antibacterial spectrum of penicillin

A

Gram positive organisms; Streptococci, Clostridia; broken down by an enzyme (β-lactamase) produced by S. aureus

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9
Q

Describe antibacterial spectrum of amoxicillin

A

Broad spectrum penicillin; extends coverage to Enterococci and Gram negative organisms; broken down by β-lactamase produced by S. aureus and many Gram negative organisms

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10
Q

Describe antibacterial spectrum of flucloxacillin

A

Similar to penicillin although less active. Stable to β-lactamase produced by S. aureus.

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11
Q

Describe antibacterial spectrum of piperacillin

A

similar to amoxicillin, extends coverage to Pseudomonas and other non-enteric Gram negatives; broken down by β-lactamase produced by S. aureus and many Gram negative organisms

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12
Q

What are clavulanic acid and tazobactam? MOA?

A

β-lactamase inhibitors.

Protect penicillins from enzymatic breakdown and increase coverage to include S. aureus, Gram negatives and anaerobes

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13
Q

What is the difference between first, second, and third generation cephalosporins?

A

Increasing activity against G- bacilli with newer generations

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14
Q

Give drug names of cephalosporins belonging to 1st, 2nd, and 3rd generations

A

First generation = cephalexin

Second generation = cefuroxime

Third generation = cefotaxime, ceftriaxone, ceftazidime

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15
Q

Difference when prescribing co-amoxiclav and cefuroxime

A

Similar cover to co-amoxiclav but less active against anaerobes. Cefuroxime must be given with metronidazole to cover G-

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16
Q

Describe antibacterial spectrum of ceftriaxone

A

G+ and G-, but is associated with C diff - avoid usage in elderly patients if possible

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17
Q

Describe the antibacterial spectrum of ceftazidime

A

G+ and G-, anti-psuedomonas

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18
Q

What is the current issue with cephalosporins?

A

The rise in ESBL - extended spectrum beta-lactamase producing organisms which are resistant to ALL cephalosporins

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19
Q

Give drug names of carbapenems

A

Meropenem, Imipenem, Ertapenem

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20
Q

Describe antibacterial spectrum of carbapenems

A

G+ and G-, stable to ESBL enzymes

carbapenemase enzymes becoming widespread - multi-drug resistant Actinobacter and Klebsiella

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21
Q

Describe toxicity, excretion, half life, BBB coverage, and allergic profile of b-lactams

A
  • Relatively non-toxic
  • Renally excreted (so ↓dose if renal impairment)
  • Short half life
  • Will not cross intact BBB
  • Cross-allergenic (penicillins approx 10% cross-reactivity with cephalosporins or carbapenems)
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22
Q

Describe antibacterial spectrum of glycopeptides

A

Large molecules = unable to penetrate G- outer cell wall
ONLY active against G+ organisms

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23
Q

Give 2 uses of glycopeptides

A

MRSA (esp UTI)
serious C difficile

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24
Q

Are glycopeptides bactericidal or bacteriostatic?

A

slowly bactericidal

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25
Q

Caution with using glycopeptides?

A

Nephrotoxic – hence important to monitor drug levels to prevent accumulation

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26
Q

MOA of glycopeptides

A

the peptide at the end of peptidoglycan precursors is formed of aa subunits. . Glycopeptide binds to the D-ala D-ala at the end –> stops formation of peptide bonds –> creates weak peptidoglycan walls –> daughter cells lyse

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27
Q

Which abx classes (5) are inhibitors of protein synthesis?

A
  1. Aminoglycosides (e.g. gentamicin, amikacin, tobramycin)
  2. Tetracyclines
  3. Macrolides (e.g. erythromycin) / Lincosamides (clindamycin) / Streptogramins (Synercid) – The MSL group
  4. Chloramphenicol
  5. Oxazolidinones (e.g. Linezolid)
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28
Q

MOA of aminoglycosides

A

Require specific transport mechanisms to enter cells –> bind to amino-acyl site of the 30S ribosomal subunit = Prevent elongation of the polypeptide chain & causes MISREADINGS of the codons along the mRNA

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29
Q

Are aminoglycosides bactericidal or bacteriostatic?

A

Rapid, concentration-dependent bactericidal action

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30
Q

Caution with using aminoglycosides?

A

Ototoxic & nephrotoxic, therefore must monitor levels
* hence usually only SHORT doses are used

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31
Q

Describe antibacterial spectrum of aminoglycosides

A

broad-spectrum abx

  • Gentamicin & tobramycin particularly active vs. Ps. aeruginosa
  • Synergistic combination with B-lactams
  • No activity vs. anaerobes
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32
Q

Describe antibacterial spectrum of tetracyclines

A

Broad-spectrum agents

with activity against intracellular pathogens (e.g. chlamydiae, rickettsiae & mycoplasmas, Legionella pneumophila) as well as most conventional bacteria

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33
Q

Are tetracyclines bactericidal or bacteriostatic?

A

Bacteriostatic

34
Q

Caution with using tetracyclines?

A

Do not give to children under 12, pregnant and breastfeeding women

Light-sensitive rash

G- are becoming resistant

35
Q

MOA of tetracyclines

A

Reversibly bind to the ribosomal 30S subunit = prevent binding of aminoacyl-tRNA to the ribosomal acceptor site = inhibiting protein synthesis.

36
Q

Are macrolides bactericidal or bacteriostatic?

A

Bacteriostatic

37
Q

Describe antibacterial spectrum of macrolides

A

G+ coverage, minimal activity against Gram –ve bacteria

38
Q

Give 2 example of usage for macrolides

A
  1. Useful agent for treating mild Staphylococcal or Streptococcal infections in penicillin-allergic patients
  2. Also active against Campylobacter sp and Legionella Pneumophila
39
Q

MOA of macrolides

A

Bind to the 50s subunit of the ribosome
–> interfere with translocation = stimulate dissociation of peptidyl-tRNA

40
Q

Are chloramphenicols bactericidal or bacteriostatic?

A

bacteriostatic

41
Q

Describe antibacterial spectrum of chloramphenicol

A

Very broad antibacterial coverage

42
Q

Usage of chloramphenicol and why?

A

Rarely used (apart from eye preparations and special indications) because risk of aplastic anaemia (1/25,000 – 1/45,000 patients)
AND
grey baby syndrome in neonates because of an inability to metabolise the drug

43
Q

MOA of chloramphenicol

A

Chloramphenicol binds to the peptidyl transferase of the 50S ribosomal subunit = inhibits formation of peptide bonds during translation

44
Q

What is the main oxazolidinone currently in use?

45
Q

MOA of oxazolidinones

A

Binds to 23S component of the 50S subunit = prevents formation of a functional 70S initiation complex*

*required for the translation process to occur

46
Q

Describe antibacterial spectrum of oxazolidinones

A

Highly active against Gram + organisms, including MRSA and VRE

Not active against most Gram - .

47
Q

Give 2 S/Es of oxazolidinones and 2 issues with its prescription

A

S/Es:

  1. thrombocytopaenia
  2. neuritis (usually after 4 weeks of use)

Issues with prescription:

  1. expensive
  2. only used with consultant ID approval
48
Q

Which abx classes (2) are inhibitors of DNA synthesis?

A
  1. Quinolones e.g. Ciprofloxacin, Levofloxacin, Moxifloxacin
  2. Nitroimidazoles e.g. Metronidazole & Tinidazole
49
Q

MOA of fluoroquinolones

A

act on a-subunit of bacterial DNA gyrase - block DNA synthesis

50
Q

Describe antibacterial spectrum of fluoroquinolones

A

Broad antibacterial activity, especially vs Gram –ve organisms, including Pseudomonas aeruginosa

Newer agents (e.g. levofloxacin, moxifloxacin)  activity vs G +ves and intracellular bacteria, e.g. Chlamydia spp

51
Q

Name 4 general uses for fluoroquinolones

A
  1. UTIs
  2. Pneumonia
  3. Atypical pneumonia
  4. Bacterial gastroenteritis
52
Q

Name 2 S/Es of fluoroquinolones

A
  1. Lower seizure threshold
  2. Achilles tendonitis so should be used with caution in elderly patients and those on steroids
53
Q

Describe antibacterial spectrum of nitroimidazoles

A

Anaerobic bacteria and protozoa (i.e. Giardia)

54
Q

Name drugs of fluoroquinolone class

A

Ciprofloxacin, Levofloxacin, Moxifloxacin

55
Q

Name drugs of nitroimidazole class

A

metronidazole & tinidazole

56
Q

MOA of nitroimidazole

A

Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage

57
Q

What are nitrofurans? usage?

A

Related compounds to nitroimidazole; used for treating simple UTI

58
Q

What abx class (1) are inhibitors of RNA synthesis?

A
  1. Rifamycins, e.g. rifampicin & rifabutin
59
Q

MOA of rifampicin

A

binds to DNA-dependent RNA polymerase = inhibits initiation of RNA = inhibits protein synthesis

60
Q

Are nitroimidazoles bactericidal or bacteriostatic?

A

Rapidly bactericidal

61
Q

Are fluoroquinolones bactericidal or bacteriostatic?

A

Bactericidal

62
Q

Are rifampicin bactericidal or bacteriostatic?

A

Bactericidal

63
Q

Describe antibacterial spectrum of rifampicin

A

Active against certain bacteria, including Mycobacteria & Chlamydia

reduced use with other bacteria as it is used to treat TB

64
Q

Caution with using rifampicin?

A
  1. enzyme inducer = monitor LFTs
  2. interacts with other drugs metabolised by liver, i.e. oral contraceptives and warfarin
  3. Urine, tear, and sputum may turn orange
  4. Except for short-term prophylaxis (i.e. meningococcal infection), should NEVER be used as single agent because resistance develops rapidly
65
Q

Name 2 classes of cell membrane toxins abx

A
  1. Daptomycin - cyclic lipopeptide
  2. Colistin - polymyxin abx
66
Q

Describe antibacterial spectrum of daptomycin

A

G+ pathogens

  • recently licenced for treating MRSA and VRE as an alternative to linezolid
67
Q

Describe antibacterial spectrum of colistine, cautions, use, & ROA

A

G- organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella. pneumoniae.

  • not orally absorbed
  • nephrotoxic
  • reserved for use against multi-resistant organisms
68
Q

What abx classes (2) are inhibitors of folate metabolism?

A
  1. Sulfonamides
  2. Diaminopyrimidines (i.e. trimethoprim)
69
Q

Describe MOA of Sulphonamides & diaminopyrimidines

A

Act indirectly on DNA through interference with folic acid metabolism

Synergistic action between the two drug classes because they act on sequential stages in the same pathway

70
Q

What is co-trimoxazole? use?

A

combination drug of Sulphamethoxazole (sulphonamide) and trimethoprim (diaminopyrimidine)

  • use: treatment of Pneumocystis. jiroveci pneumonia
71
Q

Common use of trimethoprim

A

Community-acquired UTIs

72
Q

Name 4 general mechanisms of bacterial drug resistance?

A
  1. Modification/inactivation of the abx
  2. Modification or replacement of target
  3. Reduced antibiotic accumulation
    A) Impaired uptake
    B) Enhanced efflux
  4. Bypass antibiotic sensitive step
73
Q

Describe mechanism of resistance to B lactams by staphylococcus aureus and G - bacilli (coliforms)

A

B lactamases

74
Q

Describe mechanism of resistance in penicillin resistant Pneumococci and MRSA

A

altered targets

MRSA - mecA gene encodes novel PBP(2a) = low affinity for binding B lactam = high level resistance

Penicillin-resistant pneumococci (streptococcus pneumoniae) = acquisition of a series of stepwise mutations in PBP genes = low level resistance = CAN be overcome by increasing [penicillin]

75
Q

Are ESBLs inhibited by co-amixoclav?

A

No - Treatment failures reported with ß Lactam/ ß Lactamase inhibitor combinations (eg. Augmentin/Tazocin)

76
Q

Bacterial groups known to produce ESBLs include… (3)

A
  • Escherichia coli (E. coli)
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa
77
Q

How many classes of beta-lactamases?

78
Q

How many main carbapenemases? Name them.
which is most common in the UK

A

5 - NDM, VIM, IMP, KPC, OXA-48
OXA-48 followed by NDM in NW London

79
Q

Describe mechanism of resistance to Macrolides

A

Adenine-N6 methyltransferase modifies 23S rRNA = modification reduces the binding of MLS abx (Macrolide, lincosamide and streptogramin)

Encoded by erm (erythromycin ribosome methylation) genes.

80
Q

MLS resistance - interpretation of susceptibility testing

  1. Erythromycin S/Clindamycin S
  2. Erythromycin R/Clindamycin R
  3. Erythromycin R/Clindamycin S
A
  1. susceptible to both
  2. Resistant to both (constitutive MLS-b)
  3. may have inducible resistance (inducible MLS-b)
81
Q

A pt has grown a fully susceptible E coli in their urine. Which of the following is the narrowest spectrum agent you should de-escalate to?

  1. Amoxicillin
  2. Ceftriaxone
  3. Co-amoxiclav
  4. Meropenem
  5. Piperacillin/tazobactam
A

amoxicillin

Pathology by week (70 decks)

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