Antimicrobial Chemotherapy Flashcards
(189 cards)
1
Q
Define bacterial
A
An antimicrobial that kills bacteria (e.g. the penicillins)
2
Q
Define bacteriostatic
A
An antimicrobial that inhibits growth of bacteria (e.g. erythromycin).
3
Q
Define 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.
4
Q
Define 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.
5
Q
Define MIC
A
Minimal inhibitory concentration is defined as the minimum concentration of antimicrobial needed to inhibit visible growth of a given organism.
6
Q
Define MBC
A
Minimal bactericidal concentration is defined as the minimum concentration of the antimicrobial needed to kill a given organism.
7
Q
What are the routes of medication administration?
A
Topical
Systemic
Parenteral
8
Q
What is topical administration?
A
Applied to a surface, usually skin or to mucous membranes e.g. conjunctiva.
9
Q
What is systemic administration?
A
Taken internally, either orally or parenterally.
10
Q
What is parenteral administration?
A
Administered either intra-venously (iv) or intra-muscularly (im), occassionally subcutaneously.
11
Q
What are the ways antibiotics can kill or inhibit bacteria?
A
By acting at one of three different areas of metabolic activity
12
Q
What are the sites of antibiotic action/areas of metabolic activity?
A
- Inhibition of cell wall synthesis (eg penicillins & cephalosporins)
- Inhibition of nucleic acid synthesis (trimethoprim & cipofloxacin)
- Inhibition of protein synthesis (gentamicin & erythromyscin)
13
Q
Why are humans not affected by inhibition of cell wall synthesis?
A
Humans do not have cell walls so these antibiotics have no effect on them
14
Q
What are examples of antibiotics that are β-lactams?
A
Penicillins and cephalosporins
15
Q
What do β-lactam antibiotics such as penicillin and cephalosporins do?
A
Disrupt peptidoglycan synthesis by inhibiting the enzymes which are responsible for cross-linking the carbohydrate chains.
16
Q
What is Peptidoglycan an important structure of?
A
The bacterial cell wall
17
Q
What name is given to enzymes involved in the synthesis of peptidoglycan?
A
Penicillin-binding proteins (PBPs)
Once cell wall synthesis has been disrupted, the organism is finally killed by autolytic enzymes.
18
Q
What inhibit cell wall synthesis?
A
β-lactams
19
Q
What type of bacterial organism is resistant to benzylpenicillin and why?
A
In particular, many gram negative organisms are resistant to benzylpenicillin because of the relative impermeability of the gram negative cell wall.
20
Q
What is the second largest group of β-lactams?
A
Cephalosporins form the second large group of β-lactam antibiotics, and are often described in ‘generations’, more or less in chronological order of first appearance.
21
Q
What are two examples of glycopeptide antibiotics in common clinical use?
A
Vancomycin and teicoplanin
22
Q
Where do vancomycin and teicoplanin act?
A
These both act on cell wall synthesis at a stage prior to β-lactams, inhibiting assembly of a peptidoglycan precursor.
23
Q
What organisms do glycopeptide antibiotics act on?
A
Due to their inability to penetrate the gram negative cell wall, they act only on gram positive organisms, both anaerobic and aerobic.
24
Q
How are vancomycin and tecioplanin administered?
A
Vancomycin and teicoplanin are not absorbed from the GI tract and are only given parenterally, except in special circumstances.
25
What is a common problem associated with vancomysin?
Toxicity
26
How must vancomysin be administered?
Intravenous infusion must be given carefully to avoid local tissue damage if it leaks from the veins.
It should be infused slowly over a period of hours.
27
What are the side effects of vancomysin?
Ototoxicity (when a person develops hearing or balance problems due to a medicine)
Nephrotoxicity(rapid deterioration in the kidney function due to medication)
Skin rashes
28
Why is it important to monitor trough levels of vancomycin (i.e. pre-dose levels)?
To ensure that the serum drug concentration is high enough to be therapeutic but not so high as to cause toxicity
29
What are the advantages of using teicoplanin?
Less toxic than vancomycin and has the advantage of single daily dosing due to its longer half life.
30
What could influence the choice between vancomycin and teicoplanin?
It has the same spectrum of activity as vancomycin and the choice between the two may be influenced by cost.
31
What classes of antibiotics inhibit protein synthesis?
Aminoglycosides
Macroslides and tetracyclines
Oxazolidinones
Cyclic Lipopeptide
32
What is an example of an aminoglycoside?
Gentamicin
33
What are aminoglycosides useful for?
The primary use of aminoglycosides is to treat gram negative infection and they are injectable rather than oral antibiotics
34
What is the cheapest and most commonly used aminoglycoside and why must it be monitored?
Gentamicin is the cheapest and most commonly used, but serum levels must be monitored regularly and careful dosing must be used to avoid toxicity to renal function and hearing.
35
What are examples of macrolides?
Erythromycin, clarithromycin
36
When are macrolides used?
Aa alternatives to penicillins in treatment of gram positive infections in patients who are penicillin allergic.
37
What are resistant to macrolides?
A significant percentage (10% or more) of Staph. aureus, Strep. pyogenes and Strep. pneumoniae strains are resistant,
38
What is an example of a newer macrolide and what is it used for?
Clarithromycin for organisms such as Haemophilus influenzae.
39
What is an example of an oxalidinone?
Linezolid
40
What is Linezolid used against?
MRSA and can be given orally.
Generally held in reserve for the treatment of serious infection.
41
What is an example of a cyclic lipopeptide and when is it used?
Daptomycin - activity against Gram positives in general and MRSA in particular.
Used in serious infections on specialist advice.
42
What classes of antibiotics inhibit nucleic acid synthesis?
Trimethoprim and sulphamethoxazole
Fluoroquinolones
43
What do trimethoprim and sulphamethoxazole do and how are they used?
Trimethoprim and sulphamethoxazole inhibit different steps in purine synthesis.
Used in a combined form in the drug co-trimoxazole.
44
What is co-trimoxazole increasingly being used for and why?
Treatment of chest infection,
Less likely than other broad spectrum agents to cause Clostridium difficile infections.
45
What is a common use for Trimethoprim on its own?
Treatment of urinary tract infection.
46
What is an example of Fluoroquinolones?
Ciprofloxacin
47
How does ciprofloxacin inhibit DNA synthesis?
Inhibit DNA synthesis more directly
48
How can ciprofloxacin be administered?
Orally as well as parenterally
49
What is ciprofloxacin effective against?
Gram negative organisms, including Pseudomonas
50
Why can't ciprofloxacin be used in children?
Due to the danger of interference with cartilage growth.
51
What are the two types of antibiotic resistance?
Inherit or intrinsic resistance
Acquired resistance
52
What is inherit or intrinsic resistance?
In some cases, all strains of a given species are naturally resistant to an antibiotic.
53
What causes inherit or intrinsic resistance?
Inability of the drug to penetrate the bacterial cell wall to exert its action.
54
What is streptococci always resistant to and what type of resistance is this?
Streptococci are always resistant to aminoglycosides
Inherit or intrinsic resistance
55
What are gram negative organisms always resistant to and what type of resistance is this?
Gram negative organisms are always resistant to vancomycin)
Inherit or intrinsic resistance
56
What is acquired antibiotic resistance?
Resistance may be present in some strains of the species but not in others.
57
Why is laboratory sensitivity testing needed in acquired antibiotic resistance?
Laboratory sensitivity testing is required to estabIish the likely sensitivity of any individual isolate from a patient.
58
What are the two ways in which acquired antibiotic resistance can be developed?
1. A spontaneous mutation during multiplication of bacterial DNA can result in a change in structure or function which no longer allows the antibiotic to act as its target may have changed.
2. The gene or genes that code for resistance can spread from organism to organism or indeed 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).
59
What is the most common mode of spread of antibiotic resistance?
Genes that code for resistance can spreading from organism to organism
60
What are the two mechanisms of β–lactam antibiotics?
β–lactam production
Alternation of penicillin binding protein (PBP) target site
60
What are β–lactamases?
β−lactamases are bacterial enzymes which cleave the β–lactam ring of the antibiotic and thus render it inactive
61
What can produce B-lactamase and what is it resistant to?
Staphylococcus aureus produce β-lactamase and are therefore resistant to benzylpenicillin.
62
What are β-lactamases common in?
Gram negative bacilli
63
What are two ways to combat β-lactamase?
1. Introduce a 2nd component to the antibiotic which is a β-lactamase inhibitor and therefore protects the antibiotic from enzymic degradation – the best known example is co-amoxiclav, which consists of the antibiotic amoxicillin plus the β-lactamase inhibitor clavulanic acid.
2. Modify the antibiotic side chain to produce an antibiotic which is resistant to the actions of β-lactamase. The commonest example of this is the antistaphylococcal drug flucloxacillin, which is a modified form of penicillin.
64
What is Flucloxacillin resistant to and what can it be used to treat?
Flucloxacillin is β-lactamase resistant, and can be used to treat β-lactamase producing Staph. aureus.
65
What are Extended spectrum β–lactamases (ESBLs)?
Enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Infections with ESBL-producing organisms have been associated with poor outcomes.
66
What is the outcome of infections with ESBL-producing organisms?
Poor outcomes.
67
What are ESBLs produced by and what are they resistant to?
ESBLs (extended spectrum β-lactamases) are produced by some gram negative organisms and render them resistant to all β-lactam agents.
68
What is Carbapenemase Producing Enterobacteriaceae (CPE), also sometimes referred to as Carbapenem Resistant Enterobacteriaciae (CRE)?
Significant emerging clinical problem.
A group of extremely resistant Gram negative organisms, resistant the carbapenems - a very broad class of antibiotics.
69
What are organisms with CPE aka CRE also resistant to and what is the outcome in some cases?
Organisms with this type of resistance, are usually also resistant to multiple other classes of antibiotics, in some cases leaving NO antimicrobial options for therapy.
70
CPE aka CRE in hospital settings
Now endemic in healthcare facilities in many countries.
This makes hospitalisation abroad a significant risk factor for acquisition of these organisms.
Infection prevention and control measures are very important to prevent patient to patient spread in the hospital setting.
71
What does a mutation in the PBP cause?
A modified target site to which β–lactams will no longer bind.
72
What is the relationship between modified PBP target sites and β–lactam agents?
Resistant to all β–lactam agents (i.e. all penicillins and cephalosporins)
The addition of a β-lactamase inhibitor makes no difference since β-lactamase plays no part in this resistance mechanism
73
What is a well known example of altered PBP target sites?
Staph aureus, and these strains are known as meticillin resistant Staph aureus or MRSA.
74
What is MRSA resistant to?
MRSA are resistant to all penicillins and cephalosporins.
75
What is MRSA a major cause of?
MRSA are now a major cause of cross infection in hospital and are often difficult to treat.
76
What is an example of an organism, other than MRSA, that is resistant to β–lactam due to altered PBPs?
Penicillin resistance in Streptococcus pneumoniae due to altered PBPs is now quite common in continental Europe, although still found in less than 5% of isolates in the UK.
77
Is glycopeoptide resistance common?
Until very recently, resistance to vancomycin among gram positive organisms was virtually unknown.
78
What is an example of glycopeptide resistance?
Vancomycin resistant enterococci (Enterococcus faecalis and Enterococcus faecium).
79
What has happened in vancomycin resistant enterococci (VRE)?
In vancomycin resistant enterococci (VRE), the peptidoglycan precursor to which vancomycin normally binds has an altered structure (i.e. this is another example of an altered target site)
80
What is the major concern amongst microbiologists regarding VRE?
This mechanism of resistance might spread from enterococci to Staph aureus, producing vancomycin resistant Staph aureus.
81
What is another common mechanism of antibiotic resistance?
Blocking transport of the drug into the cell or actively transporting it out.
82
What are commonly used β-lactam Penicillins?
Benzyl penicillin (Penicillin G)
Amoxicillin, ampicillin
Co-amoxiclav
Flucloxacillin
Piperacillin
Imipenem, meropenem
82
What are commonly used β-lactam Penicillins?
Benzyl penicillin (Penicillin G)
Amoxicillin, ampicillin
Co-amoxiclav
Flucloxacillin
Piperacillin
Imipenem, meropenem
83
What is Benzyl penicillin (Penicillin G) used against?
Gram positive organisms (though meningococci, which are Gram negative, are an important exception).
It is still the best choice for intra- venous treatment of serious pneumococcal, meningococcal and Strep pyogenes (Group A) infection.
Phenoxymethylpenicillin (Pen V) is a derivative that has slightly better absorption when taken orally.
84
What does amoxicillin work against?
Streptococci (including enterococci) and some coliforms
85
What has a much greater oral absorption than benzylpenicillin?
Amoxicillin, ampicillin
86
What organisms are resistant to amoxicillin, ampicillin and why?
20-30% of coliform organisms are now resistant due to β-lactamase production
87
What does co-amoxiclav combine?
Amoxicillin with the β-lactamase enzyme inhibitor clavulanic acid, thus extending the spectrum to cover β-lactamase producing coliforms.
88
What is flucloxacillin resistant to and what is it the first response treatment for?
is resistant to the actions of staphylococcal β-lactamase and is therefore first choice treatment for staphylococcal infections.
89
What is Piperacillin?
A broad spectrum penicillin with extended gram negative cover.
90
What is Piperacillin active against?
Useful activity against Enterococcus faecalis and is active against Pseudomonas species.
It also has anti-anaerobic activity so it has a good spectrum of action to cover serious intra-abdominal infection.
91
What is the only penicillin active against pseudomonas species?
Piperacillin
92
What is Piperacillin commonly used in combination with?
β-lactamase inhibitor tazobactam
Commercial name Tazocin but is commonly referred to as “pip/taz” in everyday use.
93
What are Imipenem & meropenem?
Close relatives of the penicillins in a sub group called carbapenems.
These drugs have the widest spectrum of all and are active against most bacteria, including anaerobes.
94
Why has the use of cephalosporins has decreased markedly in recent years?
They appear to encourage Clostridium difficile infection (CDI)
95
How are cephalosporins divided?
often divided somewhat arbitrarily into generations, more or less in chronological order of first appearance.
96
How does activity against gram negative organisms increase?
Activity against gram negative organisms increases from first generation drugs (e.g. cephradine) through second generation (e.g. cefuroxime) to third generation (e.g. ceftriaxone) drugs.
97
What type of cephalosporins has activity against Pseudomonas species?
Only ceftazidime (third generation)
98
What do aminoglycosides used against?
Gram negative organisms including pseudomonas, with relatively little resistance seen in the UK currently.
98
What do aminoglycosides used against?
Gram negative organisms including pseudomonas, with relatively little resistance seen in the UK currently.
99
What is often used as an alternative to penicillin in patients with penicillin hypersensitivity?
Macrolides such as Clarithromycin or Erythromycin
100
What are macrolides also effective against?
Atypical pneumonia
(eg, Chlamydia psittacci, Coxiella burnetti, Mycoplasma pneumonia and Legionella pneumophila).
101
What is a useful antibiotic used for single dose treatment of chlamydia infection?
Azithromycin
102
What are newer versions of quinolones used against?
The newer quinolones (e.g. ciprofloxacin) have a much wider spectrum of action and are active against nearly all gram negative organisms including pseudomonas.
103
What group of antibiotics provides the only possibility for oral therapy in the treatment of pseudomonas infections?
Quinolones
104
What is the relationship between newer quionlone and community acquired pnuemonia?
Newer quinolone levofloxacin is active against pneumococci and the organisms causing atypical pneumonia and therefore can be used in the treatment of community-acquired pneumonia.
105
What is Metronidazole effective against?
Anaerobes, both gram positive (e.g., Clostridia) and gram negative (e.g., Bacteroides spp.)
Resistance amongst anaerobes is virtually unknown, while it has no useful activity against aerobes.
It is widely used in any situation which may involved anaerobic infection e.g. intra-abdominal sepsis.
106
What is Fusidic acid effective against?
Fusidic acid is used only as an anti-staphylococcal drug.
Staphylococcus aureus can develop resistance very readily to this agent and thus it should always be used in combination with other anti-staphylococcal drugs such as flucloxacillin.
It diffuses well into bone and tissues and so is useful in staphylococcal osteomyelitis and pneumonia.
107
What are tetracyclines used against?
Tetracyclines are broad spectrum agents which inhibit bacterial protein synthesis and have a few limited applications nowadays.
They are useful for some genital tract (chlamydia) and respiratory tract infection (e.g. psittacosis, Mycoplasma pneumoniae).
108
Why are tetracyclines not used in children and pregnant women?
They should not be given to pregnant women or children under 12 years of age as they are deposited in teeth and bone.
109
What is the only lincosamide antibiotic in common use and what is it used against?
Clindamycin has good activity against gram positive organisms such as staphylococci and streptococci. It also has good activity against anaerobes.
110
What are the advantages and disadvantages of clindamycin?
Advantages of clindamycin are that it has very good tissue penetration – e.g. into bone – and can be taken orally.
The disadvantage is that it is a common cause of pseudo-membranous colitis
111
What agents are only used in the treatment of urinary tract agents?
Nalidixic acid
Nitrofurantoin
112
What are allergic reactions associated with?
These may occur following the administration of any antimicrobial, but are most commonly associated with the β-lactam group of drugs (penicillins and cephalosporins).
113
Is true penicillin hypersensitivity rare or common?
Rare - approximately 10% of truly penicillin allergic patients will also be allergic to cephalosporins.
114
What is an immediate hypersensitivity?
Anaphylactic shock is an extreme life-threatening form of this and usually follows parenteral administration of the antibiotic.
This is IgE mediated and occurs within minutes of administration.
Characterised by itching, urticaria, nausea, vomiting, wheezing and shock.
115
What is delayed hypersensitivity?
This 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
116
What are GI side effects?
Nausea and vomiting are common
117
What is C. difficile?
Anaerobic gram positive bacillus which can be carried asymptomatically in the GI tract, especially in the very young and very old.
118
How is C. diff diagnosed?
Detection of toxin in the stool by an enzyme immunoassay (EIA)
119
What is the treatment for C. diff?
Oral metronidazole or oral vancomycin.
120
What causes thrush?
Therapy with broad spectrum penicillins or cephalosporins for example may be complicated by overgrowth of the yeast Candida albicans, resulting in oral and/or vaginal candidiasis.
121
When is liver toxicity seen?
These side effects are more common in patients with pre-existing liver disease and in pregnancy.
Tetracycline, the anti-tuberculous drugs isoniazid (INH), rifampicin and flucloxacillin can cause this.
122
What is the most important route of drug excretion?
The kidney is the most important route of drug excretion.
123
When is kidney toxicity seen?
Nephrotoxicity is dose related and is more common in patients with pre-existing renal disease.
It is most commonly seen with the aminoglycoside group of antibiotics (e.g. gentamicin, netilmicin and amikacin) or with vancomycin.
124
When is Ototoxicity seen?
This is most often seen following aminoglycoside or vancomycin use.
125
When is Optic Neuropathy seen?
With use of ethambutol (an anti-tuberculous drug)
Regular monitoring of optic nerve function during therapy is recommended
126
When is Encephalopathy and convulsions seen?
High dose penicillin and cephalosporin use, or with aciclovir (see anti-viral section), especially if the dose is not reduced in the presence of renal impairment.
127
When is Peripheral neuropathy seen?
Metronidazole and nitrofurantoin may produce a reversible peripheral neuropathy of uncertain mechanism.
128
How do antimicrobials have a toxic effect on bone marrow and what does it result in?
Antimicrobials may have a toxic effect on the bone marrow resulting in selective depression of one cell line (eg, neutropenia) or unselective depression of all bone marrow elements (ie, pancytopenia).
129
How can adverse reactions be minimised?
Antimicrobials should be used only when indicated and in the minimum dose and duration necessary to achieve efficacy.
130
What should you do when working with antimicrobials with low theraputic margin?
Antimicrobials with a low therapeutic margin (ie, those where the difference between an effective and a toxic dose is small) should be monitored to ensure maximal efficacy and minimal toxicity.
131
Who should adverse reactions be reported to?
Committee on Safety of Medicines
132
What patient characteristics need to be considered when prescribing medicine?
Age
Renal funciton
Liver function
Pregnancy
133
What is prophylaxis?
Administration of antimicrobials to prevent the future occurrence of infection.
134
What are indications for prophylaxis?
Where the patient has been exposed to other patients with highly communicable disease or is shortly about to be subjected to surgical procedures associated with high post-operative infection rates.
135
What is an important principle of prophylaxis?
Dosage should cover the period of risk only (usually one dose pre-operatively) and should not be extended beyond this to avoid selecting out resistant organisms.
136
What is an example of where prophylaxis is needed?
Most abdominal operations in which the bowel is opened and organisms potentially released.
137
What is monotherapy?
Use of one antibiotic, usually the best option
138
When is it necessary to use antimicrobials in combination?
* To cover mixed infection by more than one organism.
* Because two antimicrobials sometimes have an enhanced effect together (see ‘synergy’ below).
* To minimise the development of resistant strains to any one agent (especially in the treatment of TB or HIV).
139
What are the possible outcomes when antimicrobials are used in combination?
* 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.
140
What is the general rule about the combination of antimicrobials?
As a general rule, the combination of two cidal drugs or of two static drugs is additive or synergistic.
The combination of one static and one cidal drug may result in antagonism.
141
What is the most common yet overlooked consideration of antimicrobial combination?
Penetration to site of infection
142
Who might need reducded dosage os come agents?
Children and patients with renal failure may require a reduced dosage of some agents.
143
What is the standard course of therapy for many infections?
Seven days, but patients with osteomyelitis or endocarditis may require several weeks of anti-bacterial therapy.
144
What therapy is now recommended for patients with Staph aureus bacteraemia?
At least 14 days of intravenous therapy
145
What is the course of treatment for simple urinary tract infections?
Short courses e.g. 3 days of trimethoprim.
146
What are the two main reasons for monitoring serum levels of an antimicrobial?
1. To ensure that therapeutic levels have been achieved.
2. To ensure that levels are not so high as to be toxic.
147
What are the ways to test suseptibility?
Automated methods
E test
148
How is organism considered sensitive or resistant?
There are nationally agreed “cut-offs” for MIC values below which an organism is considered “sensitive” and above which it is “resistant”.
149
What is the simplest way to measure MIC?
A test strip such as the E-test.
150
What is the simplest way to measure MIC?
A test strip such as the E-test.
151
How is an E test used?
Uses 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.
152
How can fungi be subdivided?
Yeast
Filamentous fungi (mould)
153
What are the types of anti-fungal drugs?
Polyenes
Azoles
Allylamines
Echinocandins
154
What do polyene drugs do?
Polyene drugs bind to ergosterol, which is present in the fungal cell wall but not in the bacterial cell wall, and this results in an increase in the permeability of the cell wall.
155
What do polyene drugs do?
Polyene drugs bind to ergosterol, which is present in the fungal cell wall but not in the bacterial cell wall, and this results in an increase in the permeability of the cell wall.
156
What are polyenes active against?
They are active against both yeasts and filamentous fungi.
157
What is the only polyene available for use?
Amphotericin B is the only such drug available for intravenous use and is used for the treatment of serious systemic fungal infection.
158
What is the disadvantage of Amphotericin B?
It is extremely toxic, however, with a wide range of side effects including renal, hepatic and cardiac toxicity.
159
What drug, other than amphotericin B, is common in clinical use?
Nystatin is the other polyene drug in regular clinical use.
160
How is nystatin administered?
Nystatin is used topically or in oral suspension and is not an intra-venous agent for serious fungal infection
161
What do azoles do?
Inhibit ergosterol synthesis
Can be divided into the older imidazoles (miconazole and ketoconazole) and the more recent triazoles (fluconazole, itraconazole and voriconazole).
162
What is an example of an azole used to treat yeast?
Fluconazole is used to treat yeast (not filamentous fungal) infection but has no activity against filamentous fungi such as Aspergillus spp.
163
Is Fluconazole toxic?
Fluconazole does not appear to have serious toxicity problems, but resistance among some Candida species is emerging.
164
What is an azole that is active against both yeasts and filamentous Fungi?
Itraconazole is a similar drug which is active against both yeasts and filamentous fungi, including Aspergillus spp. and dermatophytes.
165
What is used to treat aspergillosis?
Voriconazole and itraconazole are used to treat aspergillosis.
166
How do allyamines work?
Suppress ergosterol synthesis, but act at a different stage of the synthetic pathway from azoles.
167
What is the only allyamine in common use and what is it used for?
Terbinafine - used for fungal infection of skin and nails
Mild infections are treated topically and more serious infections (including onychomycosis) orally.
168
What is terbinafine used for?
This drug is active primarily against derma- tophytes, and its clinical use is restricted to dermatophyte infections of the skin (eg, ringworm, athlete’s foot) and nails (onychomycosis).
169
How do enchinocandins work?
Inhibit the synthesis of glucan polysaccharide in several types of fungi.
170
What are enchinocandins used for?
Echinocandins are used for serious Candida and Aspergillus infections
171
What are examples of herpes viruses?
Herpes Simplex virus (HSV), Varicella-Zoster virus (VZV) , Epstein-Barr virus (EBV), and Cytomegalovirus (CMV).
172
When should treatment be started in herpes?
Treatment is most effective if started early, but does not eradicate any of these viruses.
173
How does Aciclovir work?
Before it can work, it must first be converted into its active form by an enzyme (thymidine kinase) coded for by the virus genome. Thus, it is specific for virus- infected cells and has very low toxicity for uninfected host cells.
174
What is Aciclovir active against?
Herpes Simplex virus
Varicella zoster virus
175
What herpes treatment is toxic?
Ganciclovir, also a nucleoside analogue, is active against CMV.
However, it is toxic and given by IV infusion. Its use is largely restricted to treating life or sight threatening infections in the immunocompromised
176
What is an oral alternative to ganciclovir?
Valganciclovir, a pro-drug of ganciclovir, is an oral alternative to ganciclovir for some CMV situations, both treatment and prophylaxis.
177
What is a nephrotoxic drug used in the treatment of HSV, VZV and CMV?
Foscarnet is a different type of drug which can be used for some HSV, VZV and CMV infections resistant to the nucleoside analogues.
It is highly nephrotoxic and can only be given intravenously.
178
How are drugs for HIV selected?
Drugs that are active on at least two different stages of HIV replication (nevirapine, efavirenz) or a protease inhibitor which inhibits viral protease enzymes (saquinavir, darunavir)
179
What drug is used for chronic Hep B and Hep C?
Interferon-α which is a protein that forms part of the host immune response
180
What has limited the clinical use of Interferon-α?
Low response rate, serious side effects and the high cost of treatment have limited its us
181
What is the common initial treatment for chronic hep C?
Combination therapy with weekly pegylated interferon-α given by subcutaneous injection and daily oral ribavarin
182
What is an example of a drug used for selected patients with Hep B and what is its advantage?
Tenofovir.
An advantage over interferon-α is that these drugs are given orally.
183
What drugs can be used for influenza A or B within 48 hours of the onset of symptoms and post-exposure prophylaxis?
Zanamavir and Oseltamivir
184
What drug is used for Respiratory Syncytial Virus (RSV) infections?
Ribavarin
185
Why is administration for ribavarin difficult?
It must be inhaled as a fine spray to reach the site of infection in the lungs
186
What is genotypic analysis and what can it help with?
Sequencing of part of the viral genome, may help in choosing rational treatment in selected patients - HIV infection, where the viral load is rising despite adherence to treatment
