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Principles of Disease 16 > Antimicrobial Chemotherapy > Flashcards

Antimicrobial Chemotherapy Flashcards

1
Q

Define bactericidal

A

An antimicrobial that kills bacteria (e.g. the penicillin

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2
Q

Define bacteriostatic

A

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

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3
Q

Define a sensitive organism

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

Define a resistant organisms

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

Define MIC

A

Minimal inhibitory concentration is de ned as the minimum concentration of antimicrobial needed to inhibit visible growth of a given organism.

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6
Q

Define MBC

A

Minimal bactericidal concentration is de ned as the minimum concentration of the antimicrobial needed to kill a given organism.

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7
Q

Describe some routes of drug administration

A

Topical - to surface e.g. king
Systemic - internal, either oral or parenterally
Parenteral - IV, intramuscularly, subcutaneously

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8
Q

What are the three main mechanisms of action of antibiotics?

A

Inhibit cell wall synthesis e.g. penicillins and cephalosporins, glycopeptides (vancomycin and teicoplanin)
Inhibit nucleic acid synthesis e.g. trimethoprim and ciproflaxacin
Inhibit protein synthesis e.g. gentamicin and erythromycin

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9
Q

Why don’t penicillins and cephalosporins (Beta-lactams) affect human cells?

A

These antibiotics disrupt peptidoglycan synthesis, and PG is not found in human cells.

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10
Q

Describe the action of penicillins and cephalosporins

A

Both are beta-lactam antibiotics, which inhibit peptidoglycan synthesis by binding the enzymes responsible for cross-linking carbohydrate chains, the penicillin binding proteins (PBPs). Cells are then killed by autolytic enzymes. Inhibit cell wall synthesis!

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11
Q

What are glycopeptides and what is their antimicrobial action?

A

Examples include vancomycin and teicoplanin, and this group of drugs inhibit cell wall synthesis. Also inhibit cell wall synthesis, though inhibit a stage earlier than beta-lactam antibiotics. Only act on gram positive organism as they can not penetrate the gram negative cell wall. Given parenterally though they are not absorbed in the GI tract. Vancomycin is toxic, monitor serum levels.

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12
Q

Define the antimicrobial effect of aminoglycosides

A

Example is gentamicin, which are used to treat serious gram negative infections by injection, and inhibit protein synthesis. Serum levels need to be monitored as gentamicin is highly toxic.

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13
Q

Define the antimicrobial effect of macrolides and tetracyclines?

A

Macrolides (e.g. erythromycin, clarithromycin) and the tetracyclines both inhibit protein synthesis, and are useful alternatives to penicillin in those with penicillin allergies for the treatment of gram positive infections.

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14
Q

Define the antimicrobial effect of oxazolidinones

A

Linezolid is the only example of this new class of protein synthesis inhibitors. Has good activity against serious MRSA infections and given orally.

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15
Q

Define the antimicrobial effect of cyclic lipopeptides

A

Daptomycin is a novel agent used against serious gram positive and MRSA infections, and inhibits protein synthesis.

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16
Q

Which drugs inhibit purine synthesis?

A

Trimethoprim and sulphamethoxazole

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17
Q

What class of drugs includes trimethoprim and sulphamethoxazole, and what are they used for together?

A

Inhibit purine synthesis and commonly used in combined form co-trimoxazole to treat chest infections to reduce the risk of subsequent C.difficile infections

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18
Q

What is trimethoprim used for?

A

On its own for UTIs, and in conjunction with sulphamethoxazole for chest infections

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19
Q

Which bacteria are more susceptible to the action of penicillin and cephalosporins?

A

Gram positive organisms such as streptococci and staphylococci. Gram negative cell walls are relatively impermeable.

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20
Q

Give some examples of glycopeptides

A

Vancomycin and teicoplanin. These inhibit the assembly of a peptidoglycan precursors in gram positive organisms.

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21
Q

How are glycopeptides administered?

A

Parenterally (IV, not absorbed well orally)

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22
Q

What are aminoglycosides?

A

Inhibit protein synthesis e.g. gentamicin

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23
Q

What is gentamicin used for?

A

Inhibits protein synthesis, given IV to treat gram negative infections e.g. E.Coli and coliforms. Requires a careful dosing regime as it is highly toxic

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24
Q

Describe the macrolides and tetracyclines

A

Includes erythromycin and clarithromycin
Prevent protein synthesis
Used to treat gram positive infections in those allergic to penicillin

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25
Q

What drugs are used to treat gram positive infections in those who are allergic to penicillin?

A

Macrolides (erythromycin and clarithromycin) and tetracyclines

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26
Q

Give an example of an oxazolidinone and their therapeutic action

A

Linezolid, inhibits protein synthesis. Used to treat serious MRSA orally

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27
Q

What drug is given to treat serious MRSA infections?

A

Linezolid

Daptomycin

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28
Q

How is Linezolid administered?

A

Orally

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29
Q

Give an example of a cyclic lipopeptide

A

Daptomycin

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30
Q

What is daptomycin used for?

A

Inhibits protein synthesis in gram positive infections, particularly useful in MRSA infections

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31
Q

Give an example of fluoroquinolones

A

Ciprofloxacin, used to inhibit DNA synthesis to treat gram negative infections

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32
Q

What is ciprofloxacin used for?

A

Gram negative infections

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33
Q

When is an organisms considered resistant to a drug?

A

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

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34
Q

What is meant by inherent or intrinsic resistance?

A

In some cases, all strains of a certain species of a organism are naturally resistant to a drug e.g. inability of cell wall synthesis inhibitors to lyse gram negative bacterium

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35
Q

How can resistance be acquired?

A

Spontaneous mutations

Genes for resistance spread via transposons or plasmids

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36
Q

What are the two major mechanisms of resistance to beta-lactams?

A

Beta-lactamase production

Alteration of PBP target sites

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37
Q

What are the two ways you can tackle beta-lactamase production?

A

Use alongside beta lactase inhibitors e.g. clavulanic acid

Modify antibiotic side chain to reduce actions of beta lactamase

38
Q

What is co-amoxiclav?

A

Amoxicillin and cavulanic acid (beta lactamase inhibitor)

39
Q

What beta-lactam is resistant to the action of beta-lactamases?

A

Flucloxacillin

40
Q

Describe Extended Spectrum Beta-lactamases (ESBLs)

A

Beta lactamases produced by some gram negative organisms which can render organisms resistant to all beta-lactams

41
Q

Describe Carbapenemase Producing Enterobacteriacae (CPE)

A

Group of extremely resistant gram negative bacteria which are resistant to carbapenems (very broad class of antibiotics). Sometimes have no antimicrobial options.

42
Q

Describe the mechanism of glycopeptide resistance

A

There are some vancomycin resistant gram positive enterococci which have altered the structure of their peptidoglycan precursors so vancomycin cant bind

43
Q

Give some examples of drugs in the carbapenem class and what they act against

A

Imipenem, meropenem. Active against most bacteria, including anaerobes.

44
Q

What drug is effective against both gram positive and gram negative anaerobes?

A

Metronidazole, used in cases such as intra-abdominal infection or any situation which may involve anaerobic infection

45
Q

What is metronidazole used for?

A

Metronidazole is used in cases such as intra-abdominal infection or any situation which may involve anaerobic infection

46
Q

What drug is useful in staphylococcus infections, particularly in staphylococcus osteomyelitis and pneumonia?

A

Fusidic acid

47
Q

What drug is useful in some genital tract (chlamydia) and respiratory tract infections?

A

Tetracyclines

48
Q

How is linezolid administered?

A

Orally

49
Q

What is one side effect of linezolid acid?

A

Bone marrow suppression

50
Q

What two drugs are commonly used in urinary tract infections?

A

Nalidixic acid

Nitrofurantoin

51
Q

What is nalidixic acid used to treat?

A

UTIs caused by gram negative aerobic coliforms

52
Q

What is nitrofurantoin used for?

A

UTIs caused by gram negative bacteria and some gram positive bacteria

53
Q

What drugs are most commonly associated with allergic reactions?

A

Beta-lactam group

54
Q

What % of penicillin allergic patients will also be allergic to cephalosporins?

A

10%

55
Q

Describe immediate hypersensitivity

A

Type I - IgE mediated
Occurs within minutes
Itching, urticaria, nausea and vomiting, wheezing, shock

56
Q

Describe delayed hypersensitivity

A

Type III - immune complex formation
May take hours or days to develop
Rashes, fever, serum sickness, erythema nodosum

57
Q

What is Stevens-Johnson syndrome?

A

Severe form of delayed hypersensitivity caused by sulphonamides affecting both the skin and mucosal membranes

58
Q

What causes pseudomembranous colitis?

A

Antibiotic treatment leading to the overgrowth of C.difficile, causes severe diarrhoea and infection that requires surgical intervention

59
Q

How is C.difficile infection induced diarrhoea diagnosed?

A

Detection of toxin in stools by enzyme immunoassay

60
Q

What drugs are used to treat C. difficile infections?

A

Metronidazole or oral vancomycin

61
Q

What are the 4 C’s related to the increase in CDI over the last couple years?

A 
Due to increased use of broad spectrum agents
Cephalosporins
Ciprofloxacin
Clindamycin
Co-amoxiclav
62
Q

What broad spectrum antibiotics are linked to the overgrowth of Candida albicans and thrush development?

A

Penicillins and cephalosporins

63
Q

What drugs are known to cause liver toxicity?

A

Tetracycline
Isoniazid
Rifampicin
Flucloxacillin

64
Q

What drugs are known to cause renal toxicity?

A

Aminoglycosides

Vancomycin

65
Q

What drugs cause ototoxicity (drug related damage to inner ear)?

A

Aminoglycosides

Vancomycin

66
Q

What drug causes optic neuropathy?

A

Ethambutanol (anti-TB drug)

67
Q

What drugs can lead to encephalopathy and convulsions?

A

High dose penicillins and cephalosporins

Aciclovir

68
Q

What drugs can cause peripheral neuropathy?

A

Metronidazole and nitrofurantoin

69
Q

Whats the difference between neutropenia and pancytopenia?

A

Neutropenia - Selective depression of one cell line of BM

Pancytopenia - Unselective depression of all bone marrow elements

70
Q

What drug is thought to affect growing cartilage so is not used in children?

A

Ciprofloxacin

71
Q

Why is combination therapy useful?

A

Mixed infections
Two drugs can be synergistic
Minimise development of resistant strains

72
Q

How long is the standard course of antimicrobial treatment?

A

7 days

73
Q

How long is IV therapy for Staph Aureus bacteraemia?

A

14 days

74
Q

How long is the antimicrobial treatment of osteomyelitis and endocarditis?

A

Several weeks

75
Q

How long is the treatment for UTI infections?

A

3 days

76
Q

What is the mechanism of action of polyenes?

A

“Pore forming” - bind to ergosterol in fungal cell wall which results in the increase in their permeability

77
Q

What two polyenes are in clinical use and what are their indications?

A

Amphotericin B - IV serious systemic fungal infection

Nyastatin - topical and oral, candidiasis

78
Q

Why are polyenes toxic?

A

Can bind to other sterols e.g. cholesterol in mammalian cell membranes

79
Q

Describe the mechanism of action of azoles

A

inhibit ergosterol synthesis e.g. ketaconazole, fluconazole, intraconazole etc

80
Q

What is fluconazole used to treat?

A

Yeast infections

81
Q

What azoles are used to treat aspergillosis?

A

Voriconazole and itraconazole

82
Q

What is the mechanism of action of allylamines?

A

Suppress ergosterol synthesis e.g. terbinafine

83
Q

What is terbinafine used for?

A

Allylamine used to treat dermatophyte infections of the skin and nails

84
Q

What are echinocandins used for?

A

Serious candida and aspergillus infections. Inhibit the synthesis of glucan polysaccharides.
Examples include caspofungin, mycanfungin and anidulafungin

85
Q

What effect do anti-viral have on viruses?

A

Virustatic, not virucidal

86
Q

Name 4 examples of the Herpes virus

A

Herpes simplex virus
Varicella-Zoster virus
Epstein Barr virus
Cytomegalovirus

87
Q

Name some anti-herpes virus drugs

A

Aciclovir
Famiclovir
Valaciclovir

88
Q

What is ganciclovir used against?

A

Active against CMV. IV infusion in serious infections of the immunocompromised

89
Q

Describe the mechanism of action of zidovudine

A

Nucleoside analogue which interferes with the action of reverse transcriptase. Used for HIV treatment.

90
Q

What is used to treat chronic hepatitis B and C infections?

A

Interferon-a

91
Q

What is used to treat influenza A or B virus?

A

Zanamivir

Oseltamivir

92
Q

What is used to treat severe respiratory syncytial virus (RSV) infections?

A

Ribavarin, inhaled

Principles of Disease 16 (37 decks)

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