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Y2 Clinical Pathology > Antibacterial & Antifungal Agents > Flashcards

Antibacterial & Antifungal Agents Flashcards

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1
Q

What is the purpose of antimicrobial agents?

In which 2 circumstances are they used?

A

they are used to kill microorganisms while preserving the life of the patient

they are used in treatment of established infections

and

prophylaxis of possible infections

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2
Q

What is the difference between treating an established infection and prophylactic treatment?

A

established infections:

  • these are infections that have already been diagnosed

prophylactic treatment:

  • this involves treatment of infections that haven’t yet happened, but may happen
  • e.g. giving an antibiotic to someone in close contact with an infected person
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3
Q

What is meant by an antibmicrobial agent having selective toxicity?

A

they must kill the organisms whilst preserving the life of the patient

the antimicrobial must be non-toxic to the person with the infection

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4
Q

What are the 3 stages involved in the strategy of antibiotic use?

A

1. empiric therapy

  • this is known as “best guess” therapy

2. targeted therapy

  • this is used once the organism has been identified through laboratory tests

3. susceptibility-guided therapy

  • you know exactly what the organism is and what it is susceptible to after antimicrobial susceptibilty results
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5
Q

What is the first stage in diagnosing an infection?

What type of antibiotic therapy should be used at this stage?

A

clinical diagnosis based on history and examination

you know the organism that is involved, but not exactly what is causing the disease

empiric therapy is used based on where the infection is, the organisms which are likely to cause it and the antibiotics that are effective against the suspected organisms

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6
Q

Once you have received results from laboratory examinations, what type of antibiotic therapy is used?

A

the lab results identify the organism that is causing the infection

targeted therapy is used based on the organism’s likely antimicrobial sensitivity

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7
Q

What type of therapy is used once you have received the antimicrobial susceptibility results?

A

susceptibility-guided therapy

you now know exactly what organism is causing the infection and which antibiotics it is sensitive to

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8
Q

How does the antimicrobial spectrum change as knowledge increases?

A

as the level of knowledge of the infecting organism increases, the antimicrobial spectrum of the agent(s) used decreases

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9
Q

What are the 3 stages involved in choosing the right empiric antimicrobial agent?

A

1. know the likely organism causing infection

  • body site
  • immunological status of patient
  • microbiological history

2. select agent with appropriate antimicrobial spectrum

3. match pharmacokinetics with patient

  • distribution
  • interactions
  • adverse effects
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10
Q

Why is it important to know a patient’s immunological status when choosing the right empiric antimicrobial agent?

A

an immunocompromised patient will have a different spectrum of organisms which are able to cause infection

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11
Q

What are the definitions of antimicrobial agents and antibiotics?

A

antimicrobial agents:

  • these are any agents which kill microorganisms
  • e.g. antibacterial, antifungal, antiviral

antibiotics:

  • these are chemical products of microbes that inhibit or kill other organisms
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12
Q

What are the 3 main categories of antimicrobial agents?

A
  • antibiotics
  • synthethic compounds with similar effect e.g. sulfonamides
  • semi-synthetic compounds i.e. modified from antibiotics
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13
Q

Why are semi-synthetic antimicrobials used?

A

these are antibiotics that have been chemically modified to improve them in some way

e.g. to make it less toxic or more broad spectrum

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14
Q

What is meant by a bacteriostatic/fungistatic organism?

What is an example?

A

this will not actually kill the organism, it will just inhibit growth

the immune system then destroys the organism

e.g. protein synthesis inhibitors

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15
Q

What is meant by a bacteriocidal/fungicidal antimicrobial?

What is an example?

A

these will kill the organism that they are targeting

e.g. cell wall-active agents

without a fully functional cell wall, the bacteria or fungi will die

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16
Q

What is meant by minimum inhibitory concentration (MIC)?

A

minimum concentration of antimicrobial agent at which visible growth is inhibited

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17
Q

What is meant by minimum bactericidal/fungicidal concentration (MBC/MFC)?

A

the minimum concentration of antimicrobial agent at which most organisms are killed

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18
Q

What is meant by synergy / synergism?

A

when the activity of two antimicrobials given together is greater than the activity of either if given separately

“additive effect” is used to describe this

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19
Q

What is meant by antagonism?

A

when the activity of two antimicrobials given together is less than the activity of either if given separately

i.e. the second antibiotic that is given will inhibit the function of the original antibiotic

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20
Q

Why is synergy and antagonism important in clinical practice?

A

there are some combinations of antibiotics which can be used together to improve patient outcome

there are some combinations which should not be used together

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21
Q

What is meant by the antimicrobial spectrum?

A

the range of bacterial/fungal species likely to be sensitive to a particular antibacterial/antifungal agent

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22
Q

What is the difference between a broad spectrum and a narrow spectrum antimicrobial?

A

broad spectrum:

  • kills most types of bacteria/fungi encountered

narrow spectrum:

  • kills only a narrow range of organisms
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23
Q

Why is it important to have knowledge of the antimicrobial spectrum?

A

it is important in choosing appropriate empiric antimicrobial therapy

the narrowest spectrum antibiotic that is appropriate should be used at all times

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24
Q

In general, how do antimicrobial agents work?

A

through inhibition of critical process in bacterial/fungal cells

“antimicrobial targets” are the critical processes in the cell that the antibiotic inhibits

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25
What processes / molecules act as antimicrobial targets?
**enzymes, molecules or physical structures** * cell wall * protein synthesis * DNA synthesis * RNA synthesis * membrane function
26
what is meant by the antimicrobial agent exhibiting selective toxicity?
the target is not present in the human host or the target is present in the human host, but it is inaccessible to the antimicrobial agent
27
What is the bacterial cell wall made from? What is the structure like?
**peptidoglycan** this makes up the cell wall of gram-positive and gram-negative bacteria it is a polymer of glucose derivatives - *N*-acetyl muramic acid (NAM) and *N*-acetyl glucosamine (NAG)
28
Why is the peptidoglycan cell wall a good target for selective toxicity?
there is no cell wall present in human cells
29
What are examples of cell wall synthesis inhibitors?
B-lactams and glycopeptides B-lactams are most commonly used, but some patients have an allergy to penicillin, so the second line is glycopeptides
30
What do all the B-lactam antibiotics have in common?
they all contain the B-lactam ring this is a four-membered ring structure (C-C-C-N)
31
How do B-lactam antibiotics work?
they interfere with the function of **penicillin binding proteins** these are ***transpeptidase*** and ***carboxypeptidase*** enzymes that are involved in the cross-linking process that forms the peptidoglycan cell wall
32
What are the 4 main categories of B-lactam antibiotics?
1. penicillins 2. cephalosporins 3. carbapenems 4. monobactams
33
What are 3 examples of penicillins? What is their antimicrobial spectrum like?
1. benzylpenicillin 2. amoxicillin 3. flucloxacillin they are relatively narrow spectrum
34
How has the antimicrobial spectrum of penicillins changed over time and why?
they were originally broad spectrum antibiotics but are now relatively narrow spectrum this is due to the increasing number of organisms becoming resistant to the antibiotic
35
What are examples of cephalosporins? What is their antimicrobial spectrum like?
1. cefuroxime 2. ceftazidime they are broad spectrum (all generally start with "cef")
36
What are examples of carbapenems?
1. meropenem 2. imipenem they are extremely broad spectrum antibiotics currently, most bacteria that cause infection are sensitive to meropenem
37
What is an example of a monobactam? How are they different to the other B-lactam antibiotics?
**aztreonam** most B-lactams have a double ring structure aztreonam has only a single ring structure and consequently has Gram-negative activity only
38
In which types of patients is aztreonam commonly used?
in patients with an allergy to penicillins or other beta-lactams
39
What are the 2 most commonly used glycopeptides?
1. vancomycin 2. teicoplanin
40
How do glycopeptides work?
they are large molecules that bind to terminal amino acids on NAM pentapeptides this inhibits the **binding of transpeptidases**, and consequently peptidoglycan cross-linking
41
Which types of bacteria are glycopeptides effective against?
**Gram-positive bacteria** they are unable to penetrate the Gram-negative outer membrane
42
What is the process of protein synthesis like in a bacterium?
translation of RNA into a protein takes place on the ribosome this involves ribonucleoprotein complexes (2/3 RNA, 1/3 protein) 50S (large) and 30S (small) subunits combine to form the **70S initiation complex**
43
What type of antibiotics are protein synthesis inhibitors?
they are **bacteriostatic** they inhibit the process of protein synthesis at some point e.g. prevent binding of the ribosomal subunits
44
What are the 6 main categories of protein synthesis inhibitors?
45
What are examples of aminoglycosides?
1. gentamicin 2. amikacin gentamicin is commonly used, but is quite toxic
46
What are examples of macrolides?
**macrolides:** * erythromycin * clarithromycin **lincosamides:** * clindamycin
47
What are examples of tetracyclines?
doxycycline tigecycline and eravacycline are synthetic derivatives of tetracyclines with a similar mechanism of action and a much broader spectrum
48
When is linezolid used?
in gram positive infections
49
When is mupirocin used?
it is a topical agent for staphylococcus / streptococcus infection
50
51
What are the main DNA synthesis inhibitors?
trimethoprim and sulfonamides
52
How do trimethoprim and sulfonamides work?
both agents inhibit folate synthesis **sulfonamides:** * inhibit the enzyme *dihydropteroate synthase* **trimethoprim:** * inhibit the enzyme *dihydrofolate reductase*
53
When is trimethoprim commonly used?
to treat urinary tract infections
54
What is **co-trimoxazole**? When is it used?
it is a combination of **trimethoprim** and **sulfamethoxazole** it is an antibacterial agent that is effective against *Pneumocystis jirowecii* and *Toxoplasma gondii*
55
What is the role of fluoroquinolones?
they are **DNA synthesis inhibitors** they inhibit one or more of two related bacterial enzymes **DNA gyrase** and **topoisomerase IV** are involved in the remodelling of DNA during DNA replication
56
What are examples of fluoroquinolones?
1. ciprofloxacin 2. levofloxacin
57
What is the main RNA synthesis inhibitor that is used? How does it work and when is it commonly used?
**Rifampicin** this is an RNA polymerase inhibitor that prevents synthesis of mRNA it is the cornerstone of anti-tuberculous chemotherapy
58
What are the 2 different categories of cell membrane agents?
**gram-negatives:** * colistin * polymyxin E **gram-positives:** * daptomycin the cell membrane is important in homeostasis and must be fully functioning in order for the cell to survive
59
When is colistin used? What are the risks associated with its use?
it causes **nephrotoxicity** it had stopped being used, but has started being used again due to the increase in resistant gram-negative pathogens it is used in the treatment of **carbapenem resistant bacteria**
60
How does daptomycin work?
it is a cyclic lipopeptide that causes destruction of the outer membrane or cytoplasmic membrane
61
When is metronidazole used?
this is a DNA synthesis inhibitor that is only effective against anaerobic organisms
62
Which drugs act on the following locations of the bacterial cell?
63
What are the 2 main classes of fungi?
**filamentous:** * "moulds" * have a mycelium (hairy growth) **yeasts:** * unicellular structures * divide by budding
64
What is cryptococcus and what can it cause?
it is a yeast that can cause meningitis in immunocompromised patients
65
What is meant by a dimorphic fungus?
it exists in both yeast and mould forms they are the causes of "endemic mycoses"
66
What fungus does not fit into any of the categories (yeast, mould, dimorphic)?
*Pneumocystis jiroveci* this does not respond to any antifungal agents
67
Why is it more difficult to develop antifungals with selective toxicity?
fungal cells are more similar to human cells e.g. the nucleus contains chromosomes this means that it is more difficult to develop antifungals with selective toxicity
68
What is the cell wall of a fungal cell made from?
B-1,3-glucan this is a glucose based polymer the fungus needs to keep on reforming its cell wall - if this process is interrupted then the cell dies
69
What are the main targets for antifungal treatment?
1. DNA synthesis 2. Protein synthesis 3. Cell wall 4. Ergosterol in the cell membrane
70
How is a fungal cell membrane different to a human cell membrane?
the inner membrane is a bilayer composed of **ergosterol** humans have cholesterol in their cell membranes instead
71
What enzyme is involved in synthesis of the fungal cell wall?
B-1,3-glucan synthase
72
What is the main antifungal cell wall inhibitor? How does it work?
**echinocandins** they inhibit B-1,3-glucan synthase enzyme
73
What are examples of echinocandins?
1. anidulafungin 2. caspofungin 3. micafungin
74
What are the 3 categories of antifungal cell membrane agents?
1. azoles 2. terbinafine 3. amphotericin B (and nystatin)
75
What are examples of azoles? When are they used?
**clotrimazole:** * used topically to treat thrush infection * systemically toxic **fluconazole** and **voriconazole**: * given systemically - IV or orally * used to treat deep fungal infections within the body * e.g. candida in the blood, aspergillus in the lung
76
How does terbinafine work? What is it commonly used to treat?
it inhibits the synthesis of ergosterol by inhibiting **squalene epoxidase** it is used to treat athlete's foot and other superficial fungal infections
77
How does amphotericin B work? What is the problem with using this?
it binds to ergosterol and causes physical damage to the membrane it is not good at selective toxicity as it will also bind to cholesterol it has a narrow therapeutic window - if too much is given for too long then the host starts to suffer
78
What is the antifungal protein/DNA synthesis inhibitor?
5-fluorocytosine
79
How does 5-fluorocytosine work?
1. entry into the cell requires **cytosine permease** 2. converted into **5-fluorouracil** by cytosine deaminase 3. 5-fluorouracil is incorporated into fungal RNA to inhibit protein synthesis 4. it is metabolised to **5-fluorodeoxyuridine monophosphate** which inhibits DNA synthesis
80
Which antifungals work by the following mechanisms?

Y2 Clinical Pathology (76 decks)

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