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Principles of Disease > Antimicrobial chemotherapy booklet > Flashcards

Antimicrobial chemotherapy booklet Flashcards

1
Q

Bactericidal

A

An antimicrobial that kills bacteria (e.g. the penicillins)

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2
Q

Bacteriostatic

A

An antimicrobial that inhibits growth of bacteria (e.g. erythromycin)

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3
Q

Sensitive

A

An organism is considered sensitive if it is inhibited or killed by levels of the antimicrobial that are available at the site of infection.

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4
Q

Resistant

A

An organism is considered resistant if it is not killed or inhibited by levels of the antimicrobial that are available at the site of infection

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5
Q

Minimal inhibitory concentration (MIC)

A

minimum concentration of antimicrobial needed to inhibit visible growth of a given organism

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6
Q

Minimal bactericidal concentration (MBC)

A

minimum concentration of the antimicrobial needed to kill a given organism.

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7
Q

Routes of Administration:

Topical

A

Applied to a surface, usually skin or to mucous membranes e.g. conjunctiva.

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8
Q

Routes of Administration:

Systemic

A

Taken internally, either orally or parenterally.

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9
Q

Routes of Administration:

Parenteral

A

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

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10
Q

Sites of antibiotic action

A
  • Inhibition of cell wall synthesis (eg, penicillins
    & cephalosporins)
  • Inhibition of protein synthesis (eg, gentamicin
    & erythromycin)
  • Inhibition of nucleic acid synthesis (eg, trimethoprim & ciprofloxacin)
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11
Q

gentamicin & erythromycin inhibit

A

protein synthesis

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12
Q

penicillins & cephalosporins inhibit

A

cell wall synthesis

  • also known as b-lactams
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13
Q

trimethoprim & ciprofloxacin inhibit

A

nucleic acid synthesis

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14
Q

β-lactam antibiotics disrupt

A

peptidoglycan synthesis by inhibiting the enzymes which are responsible for cross-linking the carbohydrate chains.

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15
Q

human cells are not effected by antibiotics that

A

inhibit cell wall synthesis as human cells do not have cell walls.

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16
Q

Benzyl penicillin was

A

original naturally occurring β-lactam discovered by Fleming

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17
Q

Penicillins and cephalosporins are the two groups of

A

b-lactam antibiotics

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18
Q

b-lactams inhibit

A

cell wall synthesis

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19
Q

Vancomycin and teicoplanin are the two

A

glycopeptide antibiotics in common clinical usage.

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20
Q

Vancomycin and teicoplanin both act on

A

cell wall synthesis at a stage prior to β-lactams, inhibiting assembly of a peptidoglycan precursor.
- act only on gram positive organisms

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21
Q

penicillin-binding proteins (PBPs)

A

enzymes involved in the synthesis of Peptidoglycan.

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22
Q

Vancomycin and teicoplanin are not absorbed

A

from the GI tract and are only given parenterally, except in special circumstances.

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23
Q

common problem with vancomycin

A

Toxicity

  • intravenous infusion must be given carefully to avoid local tissue damage if it leaks from the veins
  • should be infused slowly over a period of hours
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24
Q

vancomycin side effects

A

ototoxicity - affects ears
nephrotoxicity - affects kidney
skin rashes

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25
Q

Protein synthesis involves

A

translation of messenger RNA at the ribosome.
Differences between the bacterial ribosome and the mammalian ribosome allow selective action on bacterial protein synthesis.

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26
Q

Aminoglycosides example

A

gentamicin

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27
Q

Aminoglycosides (e.g. gentamicin) are especially useful in

A

the treatment of serious Gram negative (e.g. coliform) infection.

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28
Q

primary use of aminoglycosides is to

A

treat gram negative infection and they are injectable rather than oral antibiotics.

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29
Q

problem with gentamicin

A

toxic and requires a careful dosing regime (follow local guidelines) and monitoring of levels.

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30
Q

antibiotics which act on protein synthesis

A
  • Aminoglycosides
  • macrolides
  • tetracyclines
  • Oxazolidinones
  • Cyclic Lipopeptide
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31
Q

macrolides example

A

erythromycin

clarithromycin

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32
Q

Macrolide antibiotics are useful alternatives

A

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

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33
Q

new class of protein synthesis inhibitors in common use

A

Linezolid

- has good activity against MRSA and can be given orally

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34
Q

Linezolid is generally held in reserve for

A

the treatment of serious infection. eg MRSA

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35
Q

Cyclic Lipopeptide example

A

Daptomycin

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36
Q

Oxazolidinones example

A

Linezolid

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37
Q

Daptomycin used against

A

Gram positives in general
- MRSA in particular

At present it is used in serious infections on specialist advice.

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38
Q

A wide range of antibiotics inhibit DNA synthesis

A

either directly, or indirectly by interrupting the supply of precursors for DNA synthesis.

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39
Q

Inhibitors of nucleic acid synthesis

A
  • Trimethoprim and sulphamethoxazole

- Fluoroquinolones

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40
Q

Trimethoprim and sulphamethoxazole inhibit

A

different steps in purine synthesis, and are used in a combined form in the drug co-trimoxazole.

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41
Q

Trimethoprim is also used for

A
  • chest infections

- urinary tract infections

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42
Q

Fluoroquinolones example

A
  • ciprofloxacin

- levofloxacin

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43
Q

Ciprofloxacin is effective against

A

Gram negative organisms and can be taken orally and parenterally.

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44
Q

Ciprofloxacin cannot be used in

A

children as it could interfere with cartilage growth.

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45
Q

levofloxacin has more activity against

A

gram positive bacteria

sometimes used for chest infections

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46
Q

Types of Resistance:

A
  • Inherent or intrinsic resistance

- Acquired resistance

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47
Q

Acquired resistance

A

may be present in some strain species but not in others.

this can happen through:

  • spontaneous mutation
  • genes coding for resistance may be passed on from organism to organism or species to species. (more common)
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48
Q

widespread use of antibiotics causes

A

selective pressure and encourages new resistant organisms to outgrow sensitive strains.

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49
Q

plasmids

A

extra chromosomal packages of DNA

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50
Q

transposons

A

packets of DNA which insert themselves into the chromosome

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51
Q

genes that have acquired resistance can be carried in

A
  • transposons

- plasmids

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52
Q

Resistance to b–lactam antibiotics

A

two mechanisms:

  • b-lactamase production
  • Alteration of penicillin binding protein (PBP) target site
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53
Q

b−lactamases are

A

bacterial enzymes which cleave the b–lactam ring of the antibiotic and thus render it inactive.

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54
Q

ways to combat β-lactamase

A
  • introduce a second component to the antibiotic which is a b-lactamase inhibitor and therefore protects the antibiotic from enzymic degradation
  • modify the antibiotic side chain to produce an antibiotic which is resistant to the actions of b-lactamase
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55
Q

b-lactamase inhibitor example

A

clavulanic acid (in co-amoxiclav, antibiotic is amoxicillin)

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56
Q

Flucloxacillin is

A

b-lactamase resistant, and can be used to treat b-lactamase producing Staph. aureus.

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57
Q

Some organisms (eg, MRSA) have

A

genetically altered target sites (PBPs) to which b-lactams cannot bind.

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58
Q

MRSA are resistant to

A

all penicillins and cephalosporins.

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59
Q

ESBLs (extended spectrum β-lactamases) are

A

produced by some gram negative organisms and render them resistant to all β-lactam agents.

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60
Q

Vancomycin resistance is unusual in

A

Gram positive organisms.

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61
Q

Vancomycin resistant enterococci (VREs) have

A

appeared recently.
- the peptidoglycan precursor to which vancomycin normally binds has an altered structure - example of an altered target site

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62
Q

Antibacterial agents may be described as

A

broad spectrum or narrow spectrum, depending on the range of organisms against which they are active.

63
Q

Benzyl penicillin (Penicillin G) is still the best choice for

A

intra- venous treatment of serious pneumococcal, meningococcal and Strep pyogenes (Group A) infection

64
Q

Amoxicillin, ampicillin has much better

A

oral absorption orally than benzylpenicillin.

- covers streptococci (including enterococci) and some coliforms.

65
Q

Flucloxacillin is resistant to the actions of

A

staphylococcal b-lactamase and is therefore first choice treatment for staphylococcal infections.

66
Q

Piperacillin and spectrum

A

broad spectrum penicillin with extended gram negative cover.

67
Q

carbapenems are

A

close relatives of the penicillins

- the widest spectrum of all and are active against most bacteria, including anaerobes.

68
Q

parenteral use only drugs include

A
  • Aminoglycosides

- Glycopeptides

69
Q

Azithromycin

A

part of Macrolides

- useful for single dose treatment of Chlamydia infection.

70
Q

Urinary tract agents

A
  • Nalidixic Acid
  • Nitrofurantoin
  • used on gram negative bacteria
71
Q

Miscellaneous antibiotics

A
  • Metronidazole
  • Fusidic acid
  • Trimethoprim
  • Tetracyclines
  • Clindamycin
72
Q

lincosamide antibiotic

A

Clindamycin

73
Q

important side effect of antibiotic therapy

A

Clostridium difficile infection (CDI)

74
Q

Allergic reaction types:

A
  • Immediate hypersensitivity
  • Delayed hypersensitivity
  • Gastrointestinal side effects
75
Q

Immediate hypersensitivity causes

A

Anaphylactic shock

- IgE mediated and occurs within minutes of administration

76
Q

Delayed hypersensitivity

A

may take hours or days to develop and can have an immune complex or cell mediated mechanism.
- Drug rashes are the most common manifestation, but drug fever, serum sickness and erythema nodosum may also occur

77
Q

Delayed hypersensitivity and Stevens-Johnson syndrome

A

severe and sometimes fatal form of delayed hypersensitivity associated with the sulphonamides, in which both skin and mucous membranes are involved.

78
Q

Gastro-intestinal side effects are commonly encountered with

A

antimicrobial usage.
Nausea and vomiting are common, but diarrhoea associated with toxin production by Clostridium difficile has now become a major problem in healthcare acquired infection

79
Q

Restricted prescribing of broad spectrum antibiotics according to local protocols

A

helps minimise Clostridium difficile infection (CDI) caused by antibiotic therapy.

80
Q

Clostridium difficile infection (CDI) is treated with

A

oral metronidazole or oral vancomycin.

Other antibiotic treatment is discontinued if clinically appropriate and Infection Control measures put In place.

81
Q

Therapy with broad spectrum penicillins or cephalosporins for example may be complicated by

A

overgrowth of the yeast Candida albicans, resulting in oral and/or vaginal candidiasis, also known as ‘thrush’.

82
Q

liver is susceptible to a variety of side effects as

A

its an important organ of metabolism and excretion

83
Q

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

A

hepatotoxicity as has flucloxacillin.

- common in patients with pre-existing liver disease and in pregnancy.

84
Q

The kidney is the most important

A

route of drug excretion

Nephrotoxicity (Renal toxicity) is dose related and is more common in patients with pre-existing renal disease

85
Q

Renal toxicity is most commonly seen with

A

aminoglycoside group of antibiotics (e.g. gentamicin, netilmicin and amikacin) or with vancomycin.
- is reversiable but can may be permenant

86
Q

Neurological toxicity

A
  • Ototoxicity
  • Optic Neuropathy
  • Encephalopathy and convulsions
  • Peripheral neuropathy
87
Q

Ototoxicity is most commonly seen following

A

aminoglycoside or vancomycin use.

88
Q

Ethambutol (an anti-tuberculous drug) is associated with

A

dose related optic nerve damage, and regular monitoring of optic nerve function during therapy is recommended.

89
Q

Encephalopathy and convulsions may result from

A

high dose penicillin and cephalosporin use, or with aciclovir.

90
Q

Metronidazole and nitrofurantoin may produce

A

reversible peripheral neuropathy of uncertain mechanism

91
Q

Antimicrobials may have a toxic effect on the bone marrow resulting in

A
  • selective depression of one cell line (eg, neutropenia)

- unselective depression of all bone marrow elements (ie, pancytopenia).

92
Q

Patient Characteristics to look out for

A
  • Age
  • Renal Function
  • Liver Function
  • Pregnancy
93
Q

Prophylaxis =

A

administration of antimicrobials to prevent the future occurrence of infection.

94
Q

Prophylaxis given if

A
  • patient has been exposed to other patients with highly communicable disease
  • patient is subjected to surgical procedures associated with high post-operative infection rates.
95
Q

Therapy is given when

A

the organism(s) causing infection is not known, empirical antimicrobial therapy may have to be commenced if urgent treatment is required

96
Q

Drug Related Considerations

A
  • Spectrum of antimicrobial agent
  • Monotherapy (best) vs combination
  • Penetration to site of infection
  • Monitoring
  • Dose and duration of therapy
97
Q

When antimicrobials are used in combination, there are three possible outcomes:

A
  • Their effects are additive.
  • They are antagonistic
  • They are synergistic
98
Q

synergistic outcome =

A

their combined effect is greater than the sum of their individual contributions. The most common example of this is the combination of penicillin and gentamicin in the treatment of streptococcal infective endocarditis. Penicillin breaks down the streptococcal cell wall, and allows gentamicin access to the ribosome. Streptococci are normally impermeable to gentamicin.

99
Q

antagonistic outcome =

A

their combined effect is less than the sum of their individual contributions.

100
Q

Vancomycin and gentamicin levels should be monitored to

A

avoid toxicity as they have a low therapeutic index.

101
Q

two main reasons for monitoring serum levels of an antimicrobial:

A
  • To ensure that therapeutic levels have been achieved

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

102
Q

Amphotericin B is used

A

intra-venously for serious yeast and other fungal infections.
it is also toxic as it can bind to cholesterol.

103
Q

Nystatin is used

A

topically or in oral suspension and is not an intra-venous agent for serious fungal infection

104
Q

Polyene drugs bind to

A

ergosterol, which is present in the fungal cell wall but not in the bacterial cell wall
This results in an increase in the permeability of the cell wall.
- they can also bind to other sterols like cholesterol

105
Q

polyene examples

A
  • Amphotericin B

- Nystatin

106
Q

Azoles inhibit

A

ergosterol synthesis.

107
Q

Fluconazole is used to treat

A

yeast (not filamentous fungal) infection.

Not all yeasts are sensitive to fluconazole.

108
Q

Voriconazole and itraconazole are used to

A

treat aspergillosis.

109
Q

Azoles example

A
  • Fluconazole
  • Voriconazole
  • itraconazole
110
Q

Allylamines inhibit

A

ergosterol synthesis.

- act at a different stage of the synthetic pathway from azoles.

111
Q

Terbinafine is used for

A

fungal infection of skin and nails.

eg - athletes foot, ringworm and onychomycosis

112
Q

Allylamines example

A

Terbinafine

113
Q

Echinocandins example

A

Caspofungin, Mycafungin and Anidulafungin

114
Q

Echinocandins are used for

A

serious Candida and Aspergillus infections

115
Q

Aciclovir is active against

A

Herpes Simplex virus and Varicella zoster virus

116
Q

Aciclovir is a

A

nucleoside analogue.
- Before it can work, it must first be converted into its active form by an enzyme (thymidine kinase) coded for by the virus genome

117
Q

Famciclovir and valaciclovir are used for

A

treatment of HSV and shingles.

118
Q

Ganciclovir, also a

A

nucleoside analogue, is active against CMV.

- restricted to treating life or sight threatening infections in the immunocompromised

119
Q

Foscarnet can be used for

A

some HSV, VZV and CMV infections.

- highly nephrotoxic and can only be given intravenously.

120
Q

Cidofovir is used for

A

CMV retinitis when other anti-viral drugs are inappropriate.

121
Q

zidovudine

A

nucleoside analogue which interferes with the action of reverse transcriptase.
It slows the replication of the virus but does not kill it

  • first treatment for HIV
122
Q

Interferon-α is a protein that

A

forms part of the host immune response.

- subcutaneous injection

123
Q

Lamivudine is used

A

mainly for HIV treatment

- unlike Interferon-α its given orally

124
Q

Zanamavir and Oseltamivir used for

A

influenza A or B within 48 hours of the onset of symptoms

125
Q

Ribavarin is another

A

nucleoside analogue.

  • treatment of severe Respiratory Syncytial Virus (RSV) infections.
  • is inhaled
126
Q

Amphotericin B acts against a

A

narrow range of bacteria.

127
Q

The differing ribosomes of mammalian and bacterial cells allow

A

selective toxicity.

128
Q

Penicillin allergic patients may also be allergic to

A

cephalosporins

129
Q

Piperacillin has an

A

extended spectrum and is active against

Pseudomonas species.

130
Q

Metronidazole is widely used to treat

A

anaerobic infection.

131
Q

Vancomycin is only active against

A

anaerobes.

132
Q

Serum levels of gentamicin and vancomycin can be monitored in the laboratory to

A

minimise the risk of toxicity.

133
Q

Inherent or intrinsic resistance:

streptococci is always resistant to

A

aminoglycosides

laboratory sensitive testing not required

134
Q

Inherent or intrinsic resistance:

Gram-negative organisms always resistant to

A

Vancomycin.

laboratory sensitive testing not required

135
Q

laboratory sensitive testing required for

A

Acquired resistance as some strains are resistant ut some arent.

136
Q

MRSA is any strain of

A

S. aureusthat has developed, throughhorizontal gene transferandnatural selection,multiple drug resistancetoβ-lactam antibiotics

137
Q

MRSA can be treated with

A

vancomyin - glycopeptide

linezolid - oxazoilidinone

138
Q

Flucloxacillin is

A

β-lactamase resistant.

Can be used to treat β-lactamase producing S. aureus, but not MRSA.

139
Q

β-lactams: Cephalosporins and gram negative bacteria

A

Gram-negative activity (increases through generations).

- better to use 3rd generation antibiotics

140
Q

β-lactams: Cephalosporins and gram positive bacteria

A

Gram-positive activity
(decreases proportionately from first through to third generation drugs).
- better to use 1st generation drugs

141
Q

High dose penicillin and cephalosporin or (if the dose is not reduced in the presence of renal impairment) can cause

A

Encephalopathy and convulsions

142
Q

Anti MRSA agent linezolid toxicity

A

bone marrow suppression and may lower platelet counts.

143
Q

Pregnancy:

mutagenic

A

induce mutation in foetal chromosomes

144
Q

Pregnancy:

teratogenic

A

associated with congenital abnormalities

145
Q

Safe in pregnancy

A

penicillins, cephalosporins

urinary antiseptic nitrofurantoin.

146
Q

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

A

additive or synergistic.

147
Q

combination of one static and one cidal drug may result in

A

antagonism.

148
Q

Anti-Fungal Drugs:

A
  • polyenes
  • Azoles
  • Allylamines
  • Echinocandins
149
Q

Antibiotics have no action against

A

virus

150
Q

virucidal agents

A

those that will kill the virus

- only some

151
Q

virustatic

A

inhibit growth and/or replication

- all are this

152
Q

Many anti-viral drugs are

A

nucleoside analogues which interfere with nucleic acid synthesis.

153
Q

Combination therapy with at least three drugs

is now normal practice in

A

HIV treatment.

  • Two nucleoside analogue reverse transcriptase inhibitors, plus either a:
  • non-nucleoside reverse transcriptase inhibitor (nevirapine)
  • viral protease inhibitor (saquinavir).

Principles of Disease (27 decks)

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