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
What drugs are used to treat gram positive infections in those who are allergic to penicillin?
Macrolides (erythromycin and clarithromycin) and tetracyclines
26
Give an example of an oxazolidinone and their therapeutic action
Linezolid, inhibits protein synthesis. Used to treat serious MRSA orally
27
What drug is given to treat serious MRSA infections?
Linezolid | Daptomycin
28
How is Linezolid administered?
Orally
29
Give an example of a cyclic lipopeptide
Daptomycin
30
What is daptomycin used for?
Inhibits protein synthesis in gram positive infections, particularly useful in MRSA infections
31
Give an example of fluoroquinolones
Ciprofloxacin, used to inhibit DNA synthesis to treat gram negative infections
32
What is ciprofloxacin used for?
Gram negative infections
33
When is an organisms considered resistant to a drug?
An organism is considered resistant when it is unlikely to respond to attainable levels of that drug in tissues.
34
What is meant by inherent or intrinsic resistance?
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
35
How can resistance be acquired?
Spontaneous mutations | Genes for resistance spread via transposons or plasmids
36
What are the two major mechanisms of resistance to beta-lactams?
Beta-lactamase production | Alteration of PBP target sites
37
What are the two ways you can tackle beta-lactamase production?
Use alongside beta lactase inhibitors e.g. clavulanic acid | Modify antibiotic side chain to reduce actions of beta lactamase
38
What is co-amoxiclav?
Amoxicillin and cavulanic acid (beta lactamase inhibitor)
39
What beta-lactam is resistant to the action of beta-lactamases?
Flucloxacillin
40
Describe Extended Spectrum Beta-lactamases (ESBLs)
Beta lactamases produced by some gram negative organisms which can render organisms resistant to all beta-lactams
41
Describe Carbapenemase Producing Enterobacteriacae (CPE)
Group of extremely resistant gram negative bacteria which are resistant to carbapenems (very broad class of antibiotics). Sometimes have no antimicrobial options.
42
Describe the mechanism of glycopeptide resistance
There are some vancomycin resistant gram positive enterococci which have altered the structure of their peptidoglycan precursors so vancomycin cant bind
43
Give some examples of drugs in the carbapenem class and what they act against
Imipenem, meropenem. Active against most bacteria, including anaerobes.
44
What drug is effective against both gram positive and gram negative anaerobes?
Metronidazole, used in cases such as intra-abdominal infection or any situation which may involve anaerobic infection
45
What is metronidazole used for?
Metronidazole is used in cases such as intra-abdominal infection or any situation which may involve anaerobic infection
46
What drug is useful in staphylococcus infections, particularly in staphylococcus osteomyelitis and pneumonia?
Fusidic acid
47
What drug is useful in some genital tract (chlamydia) and respiratory tract infections?
Tetracyclines
48
How is linezolid administered?
Orally
49
What is one side effect of linezolid acid?
Bone marrow suppression
50
What two drugs are commonly used in urinary tract infections?
Nalidixic acid | Nitrofurantoin
51
What is nalidixic acid used to treat?
UTIs caused by gram negative aerobic coliforms
52
What is nitrofurantoin used for?
UTIs caused by gram negative bacteria and some gram positive bacteria
53
What drugs are most commonly associated with allergic reactions?
Beta-lactam group
54
What % of penicillin allergic patients will also be allergic to cephalosporins?
10%
55
Describe immediate hypersensitivity
Type I - IgE mediated Occurs within minutes Itching, urticaria, nausea and vomiting, wheezing, shock
56
Describe delayed hypersensitivity
Type III - immune complex formation May take hours or days to develop Rashes, fever, serum sickness, erythema nodosum
57
What is Stevens-Johnson syndrome?
Severe form of delayed hypersensitivity caused by sulphonamides affecting both the skin and mucosal membranes
58
What causes pseudomembranous colitis?
Antibiotic treatment leading to the overgrowth of C.difficile, causes severe diarrhoea and infection that requires surgical intervention
59
How is C.difficile infection induced diarrhoea diagnosed?
Detection of toxin in stools by enzyme immunoassay
60
What drugs are used to treat C. difficile infections?
Metronidazole or oral vancomycin
61
What are the 4 C's related to the increase in CDI over the last couple years?
``` Due to increased use of broad spectrum agents Cephalosporins Ciprofloxacin Clindamycin Co-amoxiclav ```
62
What broad spectrum antibiotics are linked to the overgrowth of Candida albicans and thrush development?
Penicillins and cephalosporins
63
What drugs are known to cause liver toxicity?
Tetracycline Isoniazid Rifampicin Flucloxacillin
64
What drugs are known to cause renal toxicity?
Aminoglycosides | Vancomycin
65
What drugs cause ototoxicity (drug related damage to inner ear)?
Aminoglycosides | Vancomycin
66
What drug causes optic neuropathy?
Ethambutanol (anti-TB drug)
67
What drugs can lead to encephalopathy and convulsions?
High dose penicillins and cephalosporins | Aciclovir
68
What drugs can cause peripheral neuropathy?
Metronidazole and nitrofurantoin
69
Whats the difference between neutropenia and pancytopenia?
Neutropenia - Selective depression of one cell line of BM | Pancytopenia - Unselective depression of all bone marrow elements
70
What drug is thought to affect growing cartilage so is not used in children?
Ciprofloxacin
71
Why is combination therapy useful?
Mixed infections Two drugs can be synergistic Minimise development of resistant strains
72
How long is the standard course of antimicrobial treatment?
7 days
73
How long is IV therapy for Staph Aureus bacteraemia?
14 days
74
How long is the antimicrobial treatment of osteomyelitis and endocarditis?
Several weeks
75
How long is the treatment for UTI infections?
3 days
76
What is the mechanism of action of polyenes?
"Pore forming" - bind to ergosterol in fungal cell wall which results in the increase in their permeability
77
What two polyenes are in clinical use and what are their indications?
Amphotericin B - IV serious systemic fungal infection | Nyastatin - topical and oral, candidiasis
78
Why are polyenes toxic?
Can bind to other sterols e.g. cholesterol in mammalian cell membranes
79
Describe the mechanism of action of azoles
inhibit ergosterol synthesis e.g. ketaconazole, fluconazole, intraconazole etc
80
What is fluconazole used to treat?
Yeast infections
81
What azoles are used to treat aspergillosis?
Voriconazole and itraconazole
82
What is the mechanism of action of allylamines?
Suppress ergosterol synthesis e.g. terbinafine
83
What is terbinafine used for?
Allylamine used to treat dermatophyte infections of the skin and nails
84
What are echinocandins used for?
Serious candida and aspergillus infections. Inhibit the synthesis of glucan polysaccharides. Examples include caspofungin, mycanfungin and anidulafungin
85
What effect do anti-viral have on viruses?
Virustatic, not virucidal
86
Name 4 examples of the Herpes virus
Herpes simplex virus Varicella-Zoster virus Epstein Barr virus Cytomegalovirus
87
Name some anti-herpes virus drugs
Aciclovir Famiclovir Valaciclovir
88
What is ganciclovir used against?
Active against CMV. IV infusion in serious infections of the immunocompromised
89
Describe the mechanism of action of zidovudine
Nucleoside analogue which interferes with the action of reverse transcriptase. Used for HIV treatment.
90
What is used to treat chronic hepatitis B and C infections?
Interferon-a
91
What is used to treat influenza A or B virus?
Zanamivir | Oseltamivir
92
What is used to treat severe respiratory syncytial virus (RSV) infections?
Ribavarin, inhaled