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4 - Y5 a Path lectures 2021/22 > Microbiology 2: Antimicrobials 1 > Flashcards

Microbiology 2: Antimicrobials 1 Flashcards

1
Q

What are some targets of antimicrobials?

A
  • Peptidoglycan layer of cell wall
  • Inhibition of bacterial protein synthesis
  • DNA gyrase and other prokaryote specific enzymes
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2
Q

What are some antibiotic classes that inhibit peptidoglycan synthesis

A

beta-lactam antibiotics, glycopeptides

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3
Q

Give some examples of Beta lactam antibiotics

A

penicillins, cephalosporins, carbapenems

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4
Q

Give some examples of Glycopeptides antibiotics

A

vancomycin, teicoplanin

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5
Q

Do Beta lactam antibiotics target gram positive or gram negative bacteria?

A

broad spectrum

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6
Q

Do Glycopeptides antibiotics target gram positive or gram negative bacteria?

A
  • Gram-positive
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7
Q

What is the difference between gram positive and gram negative bacteria?

A
  • Gram-positive cell wall = thick peptidoglycan cell wall (made of NAG and NAM components)
  • Gram-negative cell wall = thinner peptidoglycan cell wall, outer membrane conferring resistance to some antibiotics
    • Can be more resistant and harder to treat due to outer membrane
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8
Q

What is beta lactam antibiotics’ mechanism of action?

A
  • Inactivate enzymes involved in terminal stages of cell wall synthesis = transpeptidases / penicillin binding proteins
    • Beta lactam is a structural analogue of the enzyme substrate
  • Bactericidal (active against rapidly dividing bacteria) – if cell wall has already been formed, they have no effect
    • Ineffective against bacteria lacking peptidoglycan cell walls (mycoplasma, chlamydia)
    • Cause cell lysis
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9
Q

What type (gram positive or gram negative) of bacteria does penicillin target? Give some examples

A
  • gram +ve,
  • streptococci, clostridia
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10
Q

What is penicillin broken down by?

A
  • beta-lactamase
  • produced by S. aureus (SA) and many other gram -ve organisms
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11
Q

What type (gram positive or gram negative) of bacteria does amoxicillin target? Give some examples

A
  • broad-spectrum
  • (enterococci to gram -ve)
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12
Q

What is amoxicillin broken down by?

A
  • beta-lactamase
  • produced by S. aureus (SA) and many other gram -ve organisms
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13
Q

What type (gram positive or gram negative) of bacteria does flucloxacillin target? Give some examples

A
  • gram negative, ONLY S. aureus
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14
Q

What is flucloxacillin broken down by?

A
  • Not broken down by beta-lactamase produced by SA
  • used to treat SA infections (S. aureus)
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15
Q

Compare flucloxacillin and penicillin

A
  • Similar to penicillin, less reactive
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16
Q

What type (gram positive or gram negative) of bacteria does Piperacillin target? Give some examples

A
  • broad-spectrum
  • (pseudomonas, non-enteric gram -ve)
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17
Q

What is Piperacillin broken down by?

A
  • Broken down by beta lactamase
  • (produced by SA and many other gram -ve organisms)
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18
Q

Which antibiotic is Piperacillin similar to?

A

amoxicillin

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19
Q

What is the antibiotic name for Clavulanic acid

A

Co-amoxiclav

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20
Q

What is the antibiotic name for tazobactam?

A

Tazocin / Piptazobactam

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21
Q

What is clavulanic acid and how does it work?

A

beta lactamase inhibitors –> protect penicillin from enzymatic breakdown

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22
Q

What is the point of combining Clavulanic acid (Co-amoxiclav) and tazobactam (Tazocin / Piptazobactam)?

A
  • Inhibit beta lactamase from being broken down by bacteria (protect penicillins from breaking down)
  • Increase coverage to include SA, gram -ve (i.e. E. coli), anaerobes
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23
Q

Which organisms are resistant to cephalosporins? What should be used instead

A

ESBL producing organisms resistant to cephalosporins –> use carbapenems

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24
Q

Give some examples of cephalosporins antibiotics

A
  • Cefuroxime
  • Ceftriaxone
  • Ceftazidime
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25
Q

What is Cefuroxime broken down by?

A
  • Stable to many beta lactamases made by gram -ve
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26
Q

Compare co-amox and Cefuroxime

A
  • Similar cover to co-amox (less active against anaerobes)
  • if anaerobes suspected, add metronidozole to cefuroxime
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27
Q

What is ceftriaxone associated with?

A
  • C. difficile
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28
Q

What is ceftriaxone used to treat?

A
  • Treat meningitis (IM ceftriaxone)
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29
Q

Which organism does ceftriaxone NOT cover against?

A
  • NO COVER against Pseudomonas
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30
Q

Which organisms does ceftazidime provide cover against?

A
  • Activity against pseudomonas (HAIs often)
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31
Q

What is the advantage of using Ceftazidime over Ceftriaxone?

A
  • Ceftazidime = activity against pseudomonas (HAIs often)
  • Ceftriaxone = no activity against pseudomonas
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32
Q

Which type of patients is Cefotaxime used to treat?

A
  • Cefotaxime = the paediatric ceftriaxone
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33
Q

Are ESBL producing organisms resistant to carbapenems?

A

ESBL producing organisms NOT resistant to carbapenems

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34
Q

Give some examples of carbapenem antibiotics

A
  • Meropenem, imipenem, ertapenem
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35
Q

Why do MDR organisms pose a threat to carbapenem use?

A

production of carbapenemase enzymes becoming more widespread

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36
Q

Which bacterial species are becoming more multi-drug resistant (MDR)?

A

Acinetobacter and klebsiella species

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37
Q

Give an example of a Monobactam antibiotic

A
  • Carumonam
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38
Q

What are the key features of beta lactam antibiotics?

A
  • Relatively non-toxic
  • Renally excreted so decrease dose if renal impairment
  • Short T1/2 (many are type 2 drugs so aim to maximise the time > MIC)
  • Will not cross BBB
  • Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems
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39
Q

Do Glycopeptides antibiotics target gram positive or gram negative bacteria?

A

gram +

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40
Q

What is the mechanism of action for glycopeptide antibiotics?

A

inhibit cell wall synthesis (hence target gram +tive)

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41
Q

Why are glycopeptide antibiotics unable to target gram -tive bacteria?

A
  • Large molecules so unable to penetrate gram -ve
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42
Q

What are the important uses of glycopeptide antibiotics?

A
  • MRSA infections (IV)
  • C. difficile infection (oral – Vancomycin, teicoplanin)
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43
Q

What is the major complication/risk of using glycopeptide antibiotics?

A
  • Nephrotoxic – must monitor for accumulation
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44
Q

Which antibiotic classes are inhibitors of Protein Synthesis?

A
  • Aminoglycosides
  • Tetracyclines
  • Macrolides
  • Chloramphenicol
  • Oxazolidinones
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45
Q

Give some examples of Aminoglycoside antibiotics

A

gentamicin, amikacin, tobramycin

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46
Q

**Give some examples of tetracycline antibiotics

A

??

47
Q

Give some examples of macrolide antibiotics

A

erythromycin, lincosamides – clindamycin, streptogramins – synercid – MLS group

48
Q

Describe the mechanism of action of Aminoglycoside antibiotics

A
  • Bind to amino-acyl site of 30s ribosome subunit
  • Rapid, concentration-dependent bactericidal
  • Require specific transport mechanisms to enter
    • Accounts for some intrinsic resistance
49
Q

What are some possible complications of aminoglycoside antibiotics?

A
  • Ototoxic and nephrotoxic – monitor levels
50
Q

Which of the 3 aminoglycoside antibiotics are particularly active against pseudomonas aeruginosa?

A

Gentamicin and tobramycin

51
Q

When combined with beta lactams, what can aminoglycosides be used to treat?

A
  • Synergistic combinaton with beta lactams
    • Endocarditis treatment, pneumonia
52
Q

Do aminoglycosides have any activity against aenerobes?

A

no

53
Q

What type (gram positive or gram negative) of bacteria does Tetracyclines target?

A

Broad spectrum

54
Q

What kind of organisms (intracellular or extracellular) do tetracyclines target? Gice some examples

A
  • activity against intracellular pathogens –
  • chlamydia, rickettsia, mycoplasma
55
Q

What is the mechanism of action of tetracyclines?

A
  • Bacteriostatic (stops bacteria from reproducing)
56
Q

What are the problems with using tetracyclines?

A
  • Widespread resistance now
  • Deposited in growing bone
    • Don’t give to children (<12 yrs), pregnant women
  • SE: photosensitivity rash (summer effect)
57
Q

What is the mechanim of action of macrolides?

A
  • Bacteriostatic (stops bacteria from reproducing)
58
Q

What are the benefits of using macrolides?

A
  • Useful agent for treating mild staphylococcal or streptococcal infections in pen-allergic patients
  • Active against campylobacter species, legionella, pneumophilia
59
Q

What are some newer macrolide agents, and why are they useful?

A
  • Newer agents include clarithromycin and azithromycin
  • due to a better half-life
60
Q

Are macrolides useful against gram -tive bacteria?

A
  • Little activity against gram -ve bacteria (membrane)
61
Q

What type (gram positive or gram negative) of bacteria does chloramphenicol target?

A

broad spectrum

62
Q

What is the mechanism of action of chloramphenicol?

A
  • Bacteriostatic
63
Q

How often is chloramphenicol used?

What are the risks/complications of its/their use?

A
  • Rarely used apart from eye preparations
    • Risk of aplastic anaemia
    • Risk of grey-baby syndrome in neonates because of inability to metabolise the drug
64
Q

What is the main antibiotic in the Oxazolidinone class?

A

Linezolid

65
Q

What type (gram positive or gram negative) of bacteria does Oxazolidinones target?

A
  • Highly active against gram +ve (MRSA & VRE)
  • Not active against most gram -ve
66
Q

What are the downsides of Oxazolidinones?

A
  • Expensive,
  • may cause thrombocytopenia & optic neuritis;
  • should only be used with micro/ID approval
67
Q

What is the mechanism of action of Oxazolidinones ?

A
  • Binds to 23S component of 50s subunit à prevents formation of a functional 70s initiation complex
68
Q

Name the antibiotic classes that are inhibitors of DNA synthesis

A
  • Quinolones / Fluoroquinolones
  • Nitroimidazoles
69
Q

Name some examples of Fluoroquinolones

A
  • ciprofloxacin (old),
  • levofloxacin (new),
  • moxifloxacin (new)
70
Q

What type (gram positive or gram negative) of bacteria do Fluoroquinolones target?

A
  • Broad antibacterial activity versus gram -ve (pseudomonas aeruginosa)
71
Q

What is the mechanism of action of Fluoroquinolones

A
  • Act on alpha unit of DNA gyrase, bactericidal
72
Q

What are the newer agents of fluroquinolones? Which organisms are they better against?

A
  • Newer agents (levofloxacin, moxifloxin)
  • better against gram +ve and intracellular bacteria (Chlamydia spp.)
73
Q

What are Fluoroquinolones used to treat?

A
  • UTI,
  • pneumonia,
  • atypical pneumonia,
  • bacterial gastroenteritis
74
Q

Name some examples of Nitroimidazoles

A
  • metronidazole,
  • tinidazole
75
Q

What is the mechanism of action of Nitroimidazoles?

A
  • Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
  • Rapidly bactericidal
76
Q

Which organisms are Nitroimidazoles active against?

A
  • Active against anaerobic bacteria and protozoa (Giardia)
77
Q

What are nitrofurans? What are they used to treat?

A
  • Nitrofurans are related compounds to Nitroimidazoles
  • nitrofurantoin is good for cystitis and lower UTIs – take after voiding bladder
78
Q

Which classes of antibiotics are inhibitors of RNA Synthesis?

A

Rifamycins

79
Q

Name some examples of Rifamycins

A
  • rifampicin
  • rifabutin
80
Q

What is the mechanism of action of Rifamycins?

A
  • Inhibits protein synthesis by binding to DNA-dependent RNA polymerase, inhibiting initiation
  • Bactericidal
81
Q

Which organisms are Rifamycins active against?

A
  • mycobacteria
  • chlamydia
82
Q

Where is rifamycin metabolised? And hence which bloods must be done regularly?

A
  • Interactions with other drugs metabolised in the liver (e.g. OCP)
  • and so need to monitor LFTs
83
Q

How might you check compliance with Rifamycins?

A
  • Turns secretions orange (urine and contacts) – can check compliance
84
Q

Which of the Rifamycin antibiotics have bacteria developed resistance to? And how?

A
  • Rifampicin resistance (never used as a single):
    • Resistance due to chromosomal mutation
    • Causes single amino acid change in beta subunit of RNA polymerase which fails to bind rifampicin
85
Q

Which classess of antibiotics act by releasing Cell Membrane Toxins?

A
  • Daptomycin
  • Colistin
86
Q

What type (gram positive or gram negative) of bacteria does Daptomycin target?

A

activity limited to gram +ve

87
Q

What is the molecular structure of Daptomycin?

A

Cyclic lipopeptide

88
Q

What can Daptomycin be used to treat? When may this be necessary?

A
  • MRSA and VRE infections
  • as an alternative to linezolid and synercid (e.g. if patient is intolerant)
89
Q

How is Colistin administered?

A

IM/IV

90
Q

What is the structure of Colistin?

A

Polymyxin antibiotic

91
Q

What type (gram positive or gram negative) of bacteria does Colistin target? Give some examples

A
  • Active against gram -ve including:
  • pseudomonas aeruginosa, Acinetobacter baumannii, klebsiella pneumoniae
92
Q

What are some possible complications of Colistin use? Hence, what is it reserved for?

A
  • Nephrotoxic
  • reserved for use against multi-resistant organisms
93
Q

Which classes of antibiotics are Inhibitors of Folate Metabolism?

A
  • Sulphonamides
  • Diaminopyrimidines
94
Q

How do antibiotics that are Inhibitors of Folate Metabolism work?

A

These act indirectly on DNA through interference with folic acid metabolism

95
Q

Give an example of synergistic action between 2 drug classes

(Synergistic action between 2 drug classes because they act on sequential stages in the same pathway)

A
  • I.E. co-trimoxazole = sulphamethoxazole + trimethoprim
96
Q

What is the problem with Sulphonamides

A

Resistance is common

97
Q

What combination is important in treating pneumocystis jiroveci pneumonia? (PCP – HIV-defining disease)

A

Combination of sulphamethoxazole + trimethoprim (co-trimoxazole)

98
Q

Give an example of a Diaminopyrimidines

A

trimethoprim

99
Q

What is trimethoprim (Diaminopyrimidine) used to treat?

A

Used as treatment for community acquired UTIs

100
Q

What is the acronym for methods of antibacterial resistance?

A

BEAT

101
Q

Which antibiotic classes are susceptible to inactivation?

A
  • beta lactams
  • aminoglycosides
  • chloramphenicol
102
Q
A
103
Q

Which antibiotic classes are susceptible to altered targets (method of antibiotic resistance)?

A
104
Q

Which antibiotic classes are susceptible to reduced accumulation (of the antibiotic)?

A
105
Q

Which antibiotic classes are susceptible to bypass antibiotic-sensitive step (method of antibiotic resistance)?

A
  • trimethoprim
  • sulphonamides
106
Q

Which organisms produced beta lactamases as a major mechanism of resistance to beta lactam ABx?

A

SA and gram -ve bacilli (coliforms)

107
Q

Which organisms are not penicillin resistant?

A
  • group A (strep pyogenes), B, C, or G beta haemolytic streptococci
108
Q

What is MRSA’s method of antibiotic (methicillin) resistance?

A
  • altered target
  • mecA gene encodes novel penicillin binding protein (PBP)(2A) / novel PBP 2a
  • Low affinity for binding beta lactams
  • Substitutes for essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotics
109
Q

How is Streptococcus pneumoniae resistant to penicillin?

A
  • Penicillin resistance is the result of acquisition of stepwise mutations in PBP genes
  • Lower level resistance can be overcome by increasing dose of penicillin used
110
Q

How is resistance to macrolides acquired by bacteria?

A
  • Adenine-N6 methyltransferase modifies 23S rRNA à reduces binding of MLS antibiotics and results in resistance
  • Encoded by erm (erythromycin ribosome methylation) genes.
111
Q

What is ESBL-based Resistance?

A

Extended spectrum beta lactamases

112
Q

Which antibiotic classes can ESBLs break down?

A
  • cephalosporins (cefotaxime, ceftazidime, cefuroxime) as well as penicillins
    • But, not carbapenems
113
Q

Which organisms produce ESBLs?

A
  • More common in E. coli and Klebsiella
114
Q

What are new beta lactamases spreading?

A

New beta-lactamases are spreading MDR instead of just the ESBL-component of resistance

4 - Y5 a Path lectures 2021/22 (37 decks)

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