Microbiology Flashcards

1
Q

What are the potential targets for antibiotics?

A
Inhibit cell wall synthesis
Inhibit protein synthesis
Inhibit folate synthesis 
Inhibit DNA synthesis
Inhibit RNA synthesis
Cell membrane toxin
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2
Q

Which classes of antibiotics inhibit cell wall synthesis?

A

Beta-lactams

Glycopeptiides

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3
Q

What are the diffreent types of beta-lactam?

A

Penicillins e.g. benzylpenicillin, penicillin V
Cephalosporins e.g. ceftriaxone
Carbapenems e.g. meropenem

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4
Q

What are the indications for beta-lactams?

A

Gram positive

3rd generation cephalosporin - gram negative

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5
Q

Give 2 examples of glycopeptides

A

Vancomycin, Teicoplanin

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6
Q

What are the indications for glycopeptides?

A

MRSA

C. difficile

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7
Q

Examples 1st generation cephalosporin

A

cephalexin

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8
Q

Examples 2nd generation cephalosporin

A

cefuroxime

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9
Q

Examples 3rd generation cephalosporin

A

ceftriaxone (has led to more C diff infections)
Ceftazidime (anti-pseudomonas)
cefotaxime

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10
Q

Which classes of antibiotics inhibit protein synthesis?

A
Aminoglycoside - 30s
Tetracycline - 30s 
Macrolides - 50s
Chloramphenicol - 50s
Oxazolidines - 23s of 50s
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11
Q

Examples of aminoglycosides

A

gentamicin
amikacin
tobramycin

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12
Q

Example of tetracycline

A

Doxycycline

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13
Q

Examples of macrolide

A

Erythromycin
Clarithromycin
Clindamycin

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14
Q

Example of chloramphenicol

A

eye drops

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15
Q

Example of oxazolidinone

A

Linezolid

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16
Q

Indications for aminoglycoside

A

e.g. gentamycin for Gram -ve sepsis

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17
Q

Indications for tetracycline

A

e.g. doxycycline for intracellular pathogens e.g. mycobacteria, chlamydia, rickettsiae

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18
Q

Indications for macrolides

A

e.g. erythromycin for gram +ve infection in penicillin-allergic patients

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19
Q

Indications for chloramphenicol

A

Bacterial conjunctivitis

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20
Q

Indications for oxazolidinones

A

Gram +ve, MRSA +ve, VRE

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21
Q

Tx for Gram +ve, VRE +ve

A

Linezolid

Daptomycin

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22
Q

Which classes of antibiotics inhibit DNA synthesis?

A

Quinolones (inhibit DNA gyrase)

Nitroimidazoles

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23
Q

Give examples of quinolones

A

ciprofloxacin

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24
Q

Give an example of a nitroimidazole

A

Metronidazole

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25
Q

Indications for quinolones

A

Gram -ve

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26
Q

Indications for nitroimidazole

A

Anarobes and protozoa

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27
Q

What classes of antibiotics inhibit RNA synthesis?

A

Rifamycin (inhibits RNA polymerase)

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28
Q

Give an example of a rifamycin

A

Rifampicin

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29
Q

Indications for rifampicin

A

TB, chlamydia

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30
Q

Tx for anaerobes and protozoa

A

Metronidazole

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31
Q

1st and 2nd line Tx for UTI

A

1st line: Trimethoprim (DHF redutase/folate inhibitor)

2nd line: Nitrofurantoin (DNA synthesis inhibitor)

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32
Q

What classes of antibiotics act as cell membrane toxins?

A

Polymyxin

Cyclic lipopeptide

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33
Q

Give an example of a polymyxin

A

Colistin

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34
Q

Give an example of a cyclic glycopeptide

A

Daptomycin

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35
Q

Indication for Polymyxins

A

Gram -ve 9pseudomonas, Klebsiella, Acinetobacter)

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36
Q

Indication for cyclic lipopeptide

A

Gram +ve, MRSA +ve, VRE +ve

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37
Q

What classes of antibiotics inhibit folate metabolism?

A

Sulfonamides (DHOp synthase inhibitor)

Diaminopyrimidines (DHF reductase inhibitor)

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38
Q

Give an example of a sulfonamide

A

Sulphamethoxazole

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39
Q

Indication for sulfonamides

A

PCP (With trimethoprim: co-trimoxazole)

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40
Q

Indications for diaminoprimidines

A

UTI (e.g. Trimethoprim)

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41
Q

What are some broad-spectrum antibiotics?

A

Co-amoxiclav (B lactam penicillin)
Tazocin (B lactam penicillin)
Ciprofloxacin (quinolone)
Meropenem (B lactam Carbapenem)

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42
Q

What is Tazocin?

A

Piperacillin (penicillin) + Tazobactam (B lactamase inhibitor)

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43
Q

What is Co-amoxiclav

A

Amoxicillin (penicilli) + Clavulonic acid (B lactamase inhibitor)

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44
Q

Examples of narrow spectrum ABx

A

Flucloxacillin, Metronidazole, gentamicin

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45
Q

MOA of B lactams
Activity
Ineffective against

A

Inactivate transpeptidase enzymes/PBP, stop terminal stages of cell wall synthesis
Bactericidal, active against rapidly dividing bacteria
Ineffective against bacteria with no PtG cell wall e.g. Chlamydia, Mycoplasma

46
Q

Penicillin uses

Broken down by

A

Gram +ve organisms e.g. Strep, Clostridia

B lactamase -produing S. Aureus

47
Q

Amoxicillin uses

Broken down by

A

Broad spectrum, extends coverage to enterococci and Gram -ves
B lactamase producing S Aureus and many Gram -ves

48
Q

Flucloxacillin uses

Broken down by

A

similar to penicillin, less active

STABLE to B lactamase produced by S Aureus

49
Q

Use piperacillin

A

Similar to amoxicillin, extends to pseudomonas coverage and other non-enteric Gram -ves
Broken down by Gram -ve and B-lactamase producing S Aureus

50
Q

Clavulonic acid + tazobactam

A

B lactamase inhibitors, extend coverage to S Aureus , Gram -es and anaerobes

51
Q

What changes within generations of cephalosporins?

A

More activity against Gram -ve bacilli

52
Q

Example 1st generation cephalosporin

A

cephalexin

53
Q

Example 2nd generation cephalosporin

A

cefuroxime

54
Q

Example 3rd generation cephalosporin

A

Cefotaxime
Ceftriaxon
Ceftazidime

55
Q

What are ESBL organissm resistant to?

A

penicillins + cephalosporins

56
Q

Use of cefuroxime

A

Stable to B lactamases produced by Gram -ves. Similar cover to Co-amoxiclav but less active against anaerobes

57
Q

Ceftriaxone associated with

A

C. Diff infections

58
Q

Use of ceftazidime

A

anti-pseudomonas

59
Q

Use of carbapenems

What is an issue?

A

stable to ESBL enzymes

Cabapenemase enzymes more widespread, and now MDR Acinetobacter and Klebsiella species

60
Q

Key points for B lactams

A

Relatively non-toxic

renally excreted (dec dose if renal impairment)

Short half life

dont cross intact BBB
cross -allergenic (penicillins approx 10% cross-reactivity with cephalosporins)

61
Q

Why are glycopeptides effective against Gram +ves?

A

Glycopeptides inhibit cell wall synthesis, bactericidal
Large molecules, unable to penetrate Gram -ve outer cell wall
active against Gram +ve organisms

62
Q

Tx for MRSA

A

Vancomycin (glycopeptide)

IV only

63
Q

What is used to treat C diff?

A

oral Vancomycin

64
Q

Issue with glycopeptides?

Consequence?

A

Nephrotoxic

Monitor drug levels to prevent accumulation

65
Q

Examples glycopeptides

A

Vancomycin, Teicoplanin

66
Q

Adverse effects Teicoplanin

A

leucopaenia, neutropaenia

67
Q

Features of aminoglycosides

What is significant

A

Bind amino-acyl site of 30s ribosomal subunit
Rapid, conc dependent bactericidal
Ototoxic, nephrotoxic

68
Q

Combination of B-lactams and aminoglycosides?

A

Synergistic

69
Q

Aminoglycosides no activity against

A

anaerobes and low pH (abscess)

70
Q

Examples of tetracyclines

A

Doxycycline

71
Q

Features of tetracyclines

What is significant

A

Broad spectrum, activity against intracellular pathogens (chlamydia, rickettsiae, mycoplasmas)
bacteriostatic

Widespread resistance limits usefullness

72
Q

MOA tetracyclines

A

bind 30s subunit, stop binding of aminoacyl-tRNA to ribosomal acceptor site, inhibit protein synthesis

73
Q

Contra-indications tetracyclines (Doxycycline)

A

children, pregnant women

also cuases light-sensitive rash

74
Q

Examples macrolides

A

Erythromycin
Clarithromycin
Clindamycin

75
Q

MOA macrolides

A

bind 50s ribosome subunit, interfering with protein translocation and stimulate dissociation of peptidyl-tRNA

76
Q

Macrolide effective against

Features of macrolides

A

Gram +ve ONLY, Campylobacter and Legionella

given to penicillin-allergic pts for Staph/Strep infections

77
Q

Treatment for Campylobacter and L. pneumophilia

A

Macrolide

78
Q

MOA aminoglycoside

A

bind 30s ribosomal subunit
prevent elongation polypeptide chain
cause misreading f codons along mRNA

79
Q

MOA chloramphenicol

A

bind to peptidyl-transferase of 50s ribosomal subunit

bacteriostatic

80
Q

Significant adverse effects of chloramphenicol

A

Aplastic anaemia

Grey baby syndrome in neonates (inability to metabolise drug)

81
Q

MOA Oxazolidinones

A

binds 23s of 50s subunit, stops 70s complex

82
Q

Examples of Oxazolidinones

A

Linezolid

83
Q

Linezolid used as Tx for

A

MRSA and VRE Gram +ves

84
Q

Cautions with Linezolid

A

Very expensive
thrombocytopenia
optic neuritis
use with Micro/ID input

85
Q

Antibiotics: Inhibitors of DNA synthesis

A

Quinolones

Nitroimidazoles

86
Q

Examples of Quinolones

A

Ciprofloxacin, Moxifloxacin, Levofloxacin

87
Q

MOA Quinolones

Used for

A

inhibit DNA gyrase and topoisomerase IV

Gram +ve, intracellulars e.g. Chlamydia

88
Q

Uses of Ciprofloxacin

A

UTIs
atypical pneumonias
gastroenteritis

89
Q

MOA Nitroimidazoles

A

under anaerobic conditions, active intermediate produced that causes DNA strand breakage

90
Q

Examples Nitroimidazoles

A

Metronidazole, Tinidazole

91
Q

What are nitrofurans?

A

Compounds related to nitroimidazoles e.g. nitrofurantoin used for UTIs

92
Q

Antibiotics: inhibit RNA synthesis

A

Rifampicin

93
Q

Rifampicin MOA

A

RNA polymerase inhibitor

94
Q

Rifampicin used for

A

TB

Chlamydia

95
Q

Consider when treating with Rifampicin

A

Monitor LFTs
beware with other drugs metabolised in live
Orange secretions

96
Q

Why should you never use rifampicin as a single agent?

A

develops rapid resistance (due to chromosomal mutation)

97
Q

Antibiotics: cell membrane toxins

A

Glycolipids e.g. Daptomycin

Polymyxins e.g. Colistin

98
Q

Tx for MRSA and VRE +ve organisms

A

Daptomycins and Linezolid (Oxazolidinones)

99
Q

Features of colistin

A

Active against Gram -ves (Pseudomonas, Acinetobacter, Klebsiella pneumoniae)
Not absorbed by mouth
Nephrotoxic
Used for MDR organisms

100
Q

Antimicrobials: Folate synthesis inhibitors (which then indirectly act on DNA)

A

Sulhonamides

Trimethoprim

101
Q

Why is sulphonamide and trimethoprim combined treatment useful?

A

synergistic action as they act on sequential stages of same pathway

102
Q

Co trimoxazole components

A

Trimethoprim + sulphonamide

used for Pneumocystis jirovecii pneumonia

103
Q

Trimethoprim uses

A

community acquires UTIs

104
Q

What are the mechanisms of antibiotic resistance?

AIR-B

A

Altered target
Inactivation
Reduced accumulation (impaired uptake, enhanced efflux)
Bypass Abx sensitive step

105
Q

How does resistance to B lactams occur?

NB

A

Inactivation

Beta lactamases

Not in the mechanism of resistance in penicillin resistant pneumococci and MRSA

106
Q

How does B lactam resistance develop in MRSA?

A

ALTERED TARGET

mecA encodes new PBP (2a) which has low affinitiy for B lactams

107
Q

How does Strep pneumonia resist Beta lactams?

A

ALTERED TARGET
penicillin resistance is the result of acquisition of step-wise mutations in PBP genes, lower level resistance can be overcome by increasing the dose

108
Q

What are ESBLs?

What can they do?

NB

A

Extended spectrum beta lactamases
Able to break down cephalosporins, becoming more common (in E Coli and Klebsiella)
Resistant to cephalosporins regardless of in vitro finding

109
Q

What are carbapenemases?

A

Break down all B lactams

Emerging CRO Klebsiella strains

110
Q

What leads to macrolide resistance?

A

ALTERED TARGET
Adenine-N6 methyltransferase modifies 23s rRNA
modification reduced binding of MLS ABx and leads to resistance
encoded by ERM genes (erythromycin ribosome methylation)

111
Q

Mechanism flucloxacillin resistance

A

Alteration of target

112
Q

Mechanism of ESBL E Coli resistance

A

Due to enzymatic inactivation of antibiotic

can use carbapenems