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Principles of Disease-Megan > Antimicrobial Chemotherapy > Flashcards

Antimicrobial Chemotherapy Flashcards

1
Q

What are antibiotics active against

A

Only bacteria

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2
Q

Define bactericidal

A

Antimicrobial that kills bacteria

e.g. penicillins

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3
Q

Define bacteriostatic

A

Antimicrobial that inhibits growth of bacteria

e.g. erythromycin

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4
Q

Define sensitive

A

Organism is sensitive if it is inhibited or killed by the antimicrobial available at the site of infection

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5
Q

Define resistant

A

Organism is resistant if it is not killed or inhibited by the antimicrobial available at the site of infection

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6
Q

Define MBC

A

Minimal bactericidal concentration

Minimum concentration of antimicrobial needed to kill a given organism

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7
Q

Define MIC

A

Minimal inhibitory concentration

Minimum concentration of antimicrobial needed to inhibit growth of a given organism

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8
Q

How can antimicrobials be administered

A

Topically
Systemically
Parenterally

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9
Q

What is topical administration

A

Applied to a surface (skin or to mucous membranes

e.g. conjunctiva)

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10
Q

What is systemic administration

A 
Taken internally
(orally or parenterally)
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11
Q

What is parenteral administration

A

Administered intra-venously (iv) or intra-muscularly (im), occassionally subcutaneously

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12
Q

What are the three different areas of metabolic activity that antibiotics can use as their mechanism of action

A

Inhibition of cell wall synthesis (e.g. penicillins & cephalosporins)
Inhibition of nucleic acid synthesis (e.g. trimethoprim & ciprofloxacin)
Inhibition of protein synthesis (e.g. gentamicin & erythromycin)

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13
Q

Why can humans use antibiotics which inhibit cell wall synthesis

A

Humans don’t have a cell wall

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14
Q

What are penicillins and cephalosporins

A

β-lactams

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15
Q

How do β-lactams work

A

They disrupt peptidoglycan synthesis by inhibiting the enzymes (penicillin-binding proteins, PBPs)
responsible for cross-linking the carbohydrate chains

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16
Q

What types of antibiotics inhibit cell wall synthesis

A

β-lactams

Glycopeptides

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17
Q

What type of cell walls can glycopeptides penetrate

A

Gram positive

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18
Q

How must glycopeptides be administered

A

Parenterally (except in special circumstances)

as it cannot be absorbed from the GI tract

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19
Q

What is the mechanism of action for glycopeptides

A

They act on cell wall synthesis at a stage prior to β-lactams so inhibit assembly of a peptidoglycan precursor

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20
Q

Give examples of glycopeptides

A

Vancomycin

Teicoplanin

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21
Q

How is vancomycin administered to avoid the common toxicity

A

Careful I.V. infusion to avoid local tissue damage
Important to monitor levels of vancomycin
serum drug concentration is high enough to be therapeutic but not toxic

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22
Q

What are the advantages of teicoplanin

A

Its less toxic than vancomycin and has the advantage of single daily dosing

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23
Q

What types of antibiotics inhibit protein synthesis

A 
Aminoglycosides
Macrolides
Tetracyclines
Oxazolidinones
Cyclic Lipopeptide
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24
Q

What is protein synthesis

A

The translation of messenger RNA at the ribosome

The differences between the bacterial ribosome and the mammalian ribosome allow selective action on bacterial protein synthesis

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25
Q

What are aminoglycosides useful for

A

Treatment of serious Gram negative infection (e.g. coliform)

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26
Q

Give an example on an aminoglycosides

A

Gentamicin which is toxic and requires a careful dosing regime and monitoring of levels

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27
Q

What are macrolides useful for

A

Useful as alternatives to penicillins in treatment of gram positive infections in patients who are penicillin allergic

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28
Q

Give an example of macrolides

A

Erythromycin

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29
Q

Give an example of oxazolidinones

A

Linezolid which can be given orally

Tends to be held in reserve for the treatment of serious infection

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30
Q

Give an example of a cyclic lipopeptide

A

Daptomycin has activity against Gram positives in general and MRSA in particular
Used in serious infections on specialist advice

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31
Q

How can nucleic acid synthesis be inhibited

A

Directly or indirectly by interrupting the supply of precursors for DNA synthesis

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32
Q

What types of antibiotics can be used to inhibit nucleic acid synthesis

A

Trimethroprim
Sulphoamindes
Combined form of co-trimoxazole could be used
Fluoroquinolones

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33
Q

What do sulphonamides do

A

Inhibit dihydropteroate synthase to stop purine formation

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34
Q

What does trimethoprim do

A

Inhibit dihydrofolate reductase to stop purine formation

Commonly used for UTIs

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35
Q

Describe fluoroquinolones

A

Used orally as well as parenterally
Particularly effective against gram negative organisms
Cannot be used in children (interference with cartilage growth)
Newer quinolones (e.g. levofloxacin) may have more activity against gram positives

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36
Q

What is the clinical definition of resistance

A

An organism is considered resistant to a given drug when it is unlikely to respond to attainable levels of that drug in tissues

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37
Q

Why have antibiotic sensitivity tests been developed

A

To predict whether an infection will respond to treatment with that antibiotic

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38
Q

What types of resistance are there

A

Inherent
Intrinsic
Acquired

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39
Q

What are gram negative organisms always resistant to

A

Gram negative organisms always resistant to vancomycin

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40
Q

What is streptococci always resistant to

A

Aminoglycosides

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41
Q

What is resistance normally due to

A

Inability of the drug to penetrate

the bacterial cell wall to exert its action

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42
Q

How can resistance be acquired

A

Spontaneous mutation

Spread of resistance

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43
Q

What does a spontaneous mutation cause (in regards to resistance)

A

A change in structure or function which no longer allows the antibiotic to act
(target may have changed)

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44
Q

How spread of resistance occur

A

Gene/s that code for resistance can spread from organism to organism or from species to species
Genes can be carried on plasmids (extra chromosomal packages of DNA) or on transposons (packets of DNA which insert themselves into the chromosome)

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45
Q

What does the widespread use of antibiotics cause

A

Selective pressure

Encourages new resistant organisms to outgrow sensitive strains

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46
Q

What is a current issue in antibiotic resistance

A

β-lactamase production

Alteration of penicillin binding protein (PBP) target site

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47
Q

What does β-lactamase production cause

A

They are bacterial enzymes which cleave the β–lactam ring of the antibiotic
and thus render it inactive

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48
Q

Where are β-lactamases common

A

Gram negative bacilli

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49
Q

How can β-lactamase be combated

A

Introduce a second component to the antibiotic (β-lactamase inhibitor) protecting the antibiotic from enzymatic degradation
Modify the antibiotic side chain producing new antibiotic resistant to the actions of β-lactamase

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50
Q

What are ESBLs

A

Extended spectrum β–lactamases

Produced by some Gram negative organisms

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51
Q

How do ESBLs work

A

Break down of third generation cephalosporins and penicillins then are
resistant to all β–lactam antibiotics is developed

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52
Q

What is CPE and CRE

A

Carbapenemase Producing Enterobacteriaceae

Carbapenem Resistant Enterobacteriaciae

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53
Q

How can some microorganisms develop resistance to to β–lactams

A

By changing the structure of their PBPs (enzymes involved in peptidoglycan synthesis inhibited by binding of penicillins and cephalosporins)

Mutations in PBP genes result in a modified target site to which β–lactams will no longer bind

54
Q

What occurs in vancomycin resistant enterococci (VRE)

A

The peptidoglycan precursor to which vancomycin normally binds has an altered structure

55
Q

Name some commonly used β-lactams: penicillins

A 
Benzyl penicillin (Penicillin G)
Flucloxacillin
Amoxicillin, ampicillin 
Co-amoxiclav
Flucloxacillin
Piperacillin
Imipenem, meropenem
56
Q

Describe benzyl penicillin

A

Works against Gram positive organisms

Intravenous treatment of pneumococcal, meningococcal and Strep pyogenes infection

57
Q

Describe flucloxacillin

A

Resistant to staphylococcal β-lactamase action.
First choice treatment for
staphylococcal infections

58
Q

Describe amoxicillin, ampicillin

A

Has Gram negative activity (20-30% of coliform now resistant)
Oral absorption
It covers streptococci and some coliforms

59
Q

Describe co-amoxiclav

A

Combination of amoxicillin and β-lactamase enzyme inhibitor clavulanic acid
Extended spectrum to cover β-lactamase producing coliforms

60
Q

Describe piperacillin

A

Has extended gram negative cover
Activity against Enterococcus faecalis and Pseudomonas
Anti-anaerobic activity,
(for intra-abdominal infection)
Combination with the β-lactamase inhibitor tazobactam

61
Q

Describe imipenem, meropenem

A

Are close relatives of the penicillins (carbapenems)

All active against most bacteria, including anaerobes

62
Q

What do β-lactams: Cephalosporins act against

A

Activity against Gram negative organisms increases through generations
Activity against Gram positive organisms decreases through generations

63
Q

How many generations of cephalosporins are there

A

3

64
Q

Name some cephalosporins

A

First generation: cephradine
Second generation: cefuroxime
Third generation: ceftriaxone, ceftazidime

65
Q

How are aminoglycosides administered

A

Parenteral use only

66
Q

What are aminoglycosides active against

A

Gram negative organisms including pseudomonas,
with very little resistance seen in the UK
Most staphylococci are sensitive

67
Q

Give an example of aminoglycosides

A

Gentamicin (cheapest)

68
Q

What must be monitiored when using aminoglycosides

A

Serum levels

because of potential toxicity

69
Q

How should glycopeptides be administered

A

Parenteral use only

70
Q

What are glycopeptides active against

A

Gram positive organisms only

Aerobic and anaerobic

71
Q

Give examples of glycopeptides

A

Vancomycin (levels must be monitored because of potential toxicity)
Teicoplanin

72
Q

Give examples of macrolides

A

Clarithromycin or Erythromycin

Activity is mainly against gram positive organisms

73
Q

When is clarithromycin or erythromycin used

A

As an alternative to penicillin in patients with penicillin hypersensitivity

74
Q

Whats is clarithromycin or erythromycin effective against

A

Organisms causing ‘atypical pneumonia’ Chlamydia psittacci, Coxiella burnetti and Mycoplasma pneumoniae)
First choice therapy against Legionella pneumophila

75
Q

When is azithromycin (a macrolides) used

A

Newer macrolide which is useful for single dose

treatment of Chlamydia infection

76
Q

What are first and second generation quinolones active against

A

They have a wide spectrum of action and are active against nearly all gram negative organisms including pseudomonas

77
Q

What are third generation quinolones active against

A

Active against pneumococci and the organisms causing atypical pneumonia
Activity against streptococci is generally poor

78
Q

Which group of antibiotics provide the only form of oral therapy against pseudomonas infections

A

Quinolones

79
Q

Name some quinolones

A

First generation: nalidixic acid
Second generation: ciprofloxacin
Third generation: levofloxacin

80
Q

When is metronidazole effective

A

Against anaerobes, both gram positive
(e.g., Clostridia) and gram negative (e.g. Bacteroides spp.)
Used in any situation which may involved anaerobic infection
(intra-abdominal sepsis)

81
Q

What is fusidic acid used as

A

Anti-staphylococcal drug

Should always be used in combination with other anti-staphylococcal drugs such as flucloxacillin

82
Q

What is trimethoprim used for

A

UTIs

83
Q

What is co-trimoxazole used for

A

A few specialised conditions and sometimes for treatment of chest infections on
the grounds that it does not predispose to Clostridium difficile infection

84
Q

What are tetracyclines

A

Broad spectrum agents which inhibit bacterial protein synthesis and have a few limited applications nowadays

85
Q

When should tetracyclines be used

A

For some genital tract (chlamydia) and respiratory tract infection (e.g. psittacosis, Mycoplasma pneumoniae)

86
Q

Why should pregnant women and children under 12 not be given tetracyclines

A

They are deposited in teeth and bone

87
Q

What does clindamycin

have good activity against

A

Gram positive organisms such as staphylococci and streptococci
Anaerobes

88
Q

What are the advantages and disadvantages of clindamycin

A

Advantages: clindamycin has very good tissue penetration – e.g. into bone – and can be taken orally

Disadvantages: common cause of
pseudo-membranous colitis

89
Q

What is linezolid active against

A

MRSA

Can cause bone marrow suppression

90
Q

What is daptomycin active against

A

Gram positive organisms only

May be useful for the treatment of serious MRSA infections

91
Q

Which agents are used only in treating lower UTIs (cystitis)

A

Nalidixic acid

Nitrofurantoin

92
Q

What is nalidixic acid

A

A urinary antiseptic with activity only against gram-negative aerobes (coliform) organisms
Completely excreted in urine

93
Q

What is nitrofurantoin effective against

A

Most gram negative organisms except of Proteus and Pseudomonas spp
Also effective against some gram positive organisms

94
Q

What is the incidence of adverse reactions dependent upon

A

The dose and duration of therapy

95
Q

When will allergic reactions from an antimicrobial occur

A

Following administration of any antimicrobial

Normally commonly associated with the β-lactam (penicillins and cephalosporins)

96
Q

When will immediate hypersensitivity from an antimicrobial occur

A

Follows parenteral administration of the antibiotic

This is IgE mediated occurs within minutes of administration

97
Q

What characterises immediate hypersensitivity

A

Itching, urticaria, nausea, vomiting, wheezing and shock

Laryngeal oedema may prove fatal unless the airway is cleared

98
Q

When will delayed hypersensitivity from an antimicrobial occur

A

May take hours or days to develop

can have an immune complex or cell mediated mechanism

99
Q

What characterises delayed hypersensitivity

A

Rashes are common, fever, serum sickness and erythema nodosum may occur

100
Q

What is the Stevens-Johnson syndrome

A

A severe and sometimes fatal form

associated with the sulphonamides (skin and mucous membranes are involved)

101
Q

What type of allergic reactions can occur

A

Immediate

Delayed

102
Q

What are common GI side effects

A

Nausea and vomiting
Diarrhoea associated with toxin production
by Clostridium difficile

103
Q

How are the toxins produced by C. dificile from the antimicrobal treatment treated

A

Diagnosis done by detection of toxin in the stool by enzyme immunoassay (EIA)
Treatment with oral metronidazole or oral vancomycin

104
Q

How can antimicrobials cause thrush

A

Broad spectrum antimicrobials suppress normal flora in other parts of the body result in overgrowth of resistant organisms

105
Q

Which drugs have been associated with hepatoxicity

A

Tetracycline and the
anti-tuberculous drugs isoniazid (INH)
and rifampicin

106
Q

When is hepatoxicity common

A

In patients with pre-existing

liver disease and in pregnancy

107
Q

When is nephrotoxicity (renal toxicity) common

A

Dose related

Common in patients with pre-existing renal disease

108
Q

When is ototoxicity seen

A

Mostly seen following aminoglycoside or vancomycin use

109
Q

What is optic neuropathy associated with

A

Ethambutol (an anti-tuberculous drug) associated with dose related optic nerve damage
Regular monitoring of optic nerve function during therapy is recommended

110
Q

When are encephalopathy and convulsions seen

A

With high doses of penicillin and cephalosporin or aciclovir

111
Q

What can cause peripheral neuropathy

A

Metronidazole and nitrofurantoin

produce reversible peripheral neuropathy of uncertain mechanism

112
Q

What is haematological toxicity

A

Toxic effect on the bone marrow resulting in selective depression of one cell line (e.g. neutropenia)
or unselective depression of all bone marrow elements (i.e. pancytopenia)

113
Q

How can adverse reactions be prevented

A

Antimicrobials should be used only when indicated and in the minimum dose and duration necessary to achieve efficacy
Care should be exercised in administering antimicrobials
to susceptible groups
Antimicrobials with a low therapeutic margin
should be monitored to ensure maximal efficacy and minimal toxicity

114
Q

What should be thought of for the clinical usage of antimicrobials

A

Antibiotics should not be prescribed unless absolutely necessary and narrow spectrum antibiotics targeted at the likely infecting organism are less likely to encourage resistance

115
Q

What patient characteristics should be considered when choosing antimicrobals

A

Age
Renal Function
Liver Function
Pregnancy

116
Q

What are the indications for antimicrobials

A

Prophylaxis

Therapy

117
Q

How can antibiotics be used for prophylaxis

A

To prevent the future occurrence of infection

118
Q

How can antibiotics be used for therapy

A

When the organism(s) causing infection is not known

119
Q

State some drug related considerations

A

Spectrum of antimicrobial agent

Monotherapy vs combination

120
Q

What is Monotherapy vs combination

A

Monotherapy: the simplest approach
Combination: cover mixed infection by more than one organism, two antimicrobials sometimes have an enhanced effect together, minimises the development of resistant strains to any one agent

121
Q

What is the spectrum of antimicrobial agent

A

Antibiotic chosen should normally be effective against the known or likely causative organism(s)

122
Q

What are the possible outcomes of combination antimicrobal thearpies

A

Their effects are additive
They are antagonistic and their combined effect is less than the
sum of their individual contributions
They are synergistic and their combined effect is greater than
the sum of their individual contributions

123
Q

What is the combination of two cidal drugs or two static drugs

A

Additive or synergistic

124
Q

What is the combination of one cidal drugs and one static drugs

A

Antagonism

125
Q

What else should be considered when choosing antibiotics

A

Penetration to site of infection
Monitoring
Dose and duration of therapy

126
Q

What is the role of the laboratory on antimicrobials

A

Advice on choice of antimicrobials

127
Q

Why should serum levels of an antimicrobal be monitored

A

To ensure that therapeutic levels have been achieved

To ensure that levels are not so high as to be toxic

128
Q

How can the MIC of an antibiotic against one organism be measured

A

Using E-test

129
Q

What is an E-test

A

A paper strip which has a gradient of antibiotic concentration absorbed into it. The MIC of the organism can be read directly from the point where organism growth intersects the strip

130
Q

How does automated testing work

A

Growth of individual isolates is measured in the presence of different concentrations of each antibiotic and MIC calculated

131
Q

What factors can influence the outcome of an antibiotic in practice

A

Route of administration
Dosing schedule
Penetration of antibiotic to the target site
Interactions with other drugs

Principles of Disease-Megan (41 decks)

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