Treatment Of Bacterial Infections (87,93) Flashcards
1
Q
Prokaryotes vs eukaryotes
A
Pro- cell with NO nuclei (bacteria)
Eu- cells with nuclei (fungi, Protozoa, helminths)
2
Q
Prokaryotic cells
A
1-5 mm
-survive wide range of environments (extreme temp, anaerobic/aerobic)
-pathogenic or nonpathogenic
3
Q
Infections
A
Invasion and multiplication of organisms
-foreign bacteria/normal flora
4
Q
Colonization of body by normal flora
A
Not usually harmful, can help in controlling growth of potentially pathogenic organisms
5
Q
Gram positive/gram negative
A
Wether or not wall stains with gram stain
-implications for action of antibacterial
6
Q
Staphlococci vs streptococci
A
Staph- cocci in clumps
Strep- cocci in chains
7
Q
Bacterial cell wall located
A
Outside plasma membrane
-non stretchable string bag encoding bacterium
-internal osmotic pressure for suppprt
8
Q
Gram positive cell wall
A
Thick peptidoglycan layer
-gram strain (crustal violet) is trapped in peptidoglycan layer
-stains cells purple
9
Q
Peptidoglycan
A
Polymer of amino acids and sugars, not found in eukaryotes
10
Q
Gram negative cell wall
A
Contains a thin peptidoglycan layer
-outer membrane
-less gram stain is trapped
-LPS barrier to some antibacterial
11
Q
Antibacterial drugs
A
Medications used to react bacterial infections
-exploit the differences between human cells and bacteria
12
Q
Ideally one wants to identity what before initiating antibacterial therapy
A
Causative organism before beginning antibacterial therapy
-since there may be some antibacterial susceptibilities
13
Q
Antibacterial can be effective against
A
-gram positive bacteria (staphylococcus aureus)
-gram negative bacteria (e.coli)
14
Q
Narrow spectrum antibacterial
A
Are selective against one class of bacteria
15
Q
Broad spectrum antibacterial
A
Are affective against both classes of bacteria (negative and positive)
16
Q
Benefits of narrow spectrum antibacterial
A
Doesn’t harm your own bacteria, lowers risk of resistance
17
Q
Bactericidal
A
Drugs are directly lethal to bacteria at clinically achievable concentrations
18
Q
Bacteriostatic
A
Drugs can slow bacterial growth but do not cause cell death
19
Q
Immune system is important for
A
Bacteriostatic antibiotics
-as it helps control and eleminate the infections
20
Q
What is a superinfection?
A
New microbes take over when antibacterials kill normal flora
-this is normally a consequence of using antibiotics
-eg respiratory, genitourinary and GI tract
21
Q
A microbe resistant to drug action equals being
A
Difficult to treat
22
Q
What is an opportunistic infection?
A
Infections that would not normally harm an immunocompetent person
-but has occurred in an immunocompromised patient and will occur as fatal
23
Q
opportunistic infections can be..
A
Viruses, fungi, bacteria or Protozoa
24
Q
Globally __ ______ people die from antibacterial resistance
A
5 million
-but we still need antibiotics
25
Selection of mutant bacteria is enhanced by (things that increase drug resistant bacteria)
-improper choice/use of antibacterials
-dose of antibacterial is too low/continued too long
-prophylactic use of antibacterials
26
Examples of prophylactic use of antibacterials
In mass animal feed in order to improve meat (it barely does)
-an ongoing feed of antibiotics, where when needed it is okay to give animals drugs but when they don’t need them it creates drug resistance
27
Host factors for antibacterial therapy
Age, allergies, organ health, pregnancy, site of infection, general health
28
Allergic reactions are a
Immune response
29
Are GI upset’s a allergic reaction?
No a GI upset is not an allergic reaction
30
Four common mechanisms of action
-disruption of critical metabolic reactions
-interference with cell wall synthesis
-interference with protein synthesis
-interference with DNA replication
31
Cell wall synthesis
PVC
-penicillins
-vancomycin
-cephalosporins
32
Protein synthesis
ATM
-aminoglycosides
-tetracyclines
-macrolides
33
Transcription mechanisms
F
-fluroquinolones
34
Metabolic pathways
S/T
-sulfamethoxazole/trimethoprim
35
Sulfonamides
-broad spectrum
-sulfa drug
36
Sulfonamides prevent
Synthesis of folic acid
37
Sulfonamides combined with trimethoprim (importance/drug names/treat)
Extremely good at their job as they both target two aspects of the bacterial folic acid cycle = greater chance of success
-Bactrim or Septra
-uti and middle ear infections
38
Sulfonamides: contraindicated (when will they never be given/used) conditions
-known allergies (sulfa allergy)
-pregnant women
-not advised during breast feeding
-infants less than 2 months of age
39
Sulfonamides treat
Urinary tract infections and upper respiratory tract infections
40
Sulfa allergies and sulfonamides
Make taking sulfonamides very dangerous depending on extent of allergy
-there are several derivatives of sulfa like drugs that can also put the person at risk
41
What does sulfonamides do during pregnancy
-linked to birth defects (first trimester)
-close to end of pregnancy may increase fetal bilirubin (which may lead to brain damage)
42
Adverse effects of sulfonamides
-integumentary allergies
-blood (by bone marrow depression)
-nausea and vomiting
43
What are the adverse effects of sulfonamides in integumentary allergies
-stevens johnson syndrome (toxic epidermal necrosis) **most severe
-photosensitivity
44
What are the adverse effects of sulfonamides in blood by bone marrow depression
-agranulocytosis (severely low neutrophil levels)
-thrombocytopenia (bone marrow doesn’t make enough platelets)
-aplastic anemia (bone marrow is damaged and you can’t make enough blood cells)
45
Sulfamethoxazole
Sulfonamide antibiotic
-bacteriostatic, disrupts folic acid
-for urinary tract and middle ear infections
46
B-Lactam Antibacterials were discovered by
Sir Alexander Fleming
-1928
47
Staph aureus was destroyed by
-but now..
The mold penicilium form fungus
-but now 95% of S. aureus now resistant to penicillin
48
B-Lactam Antibacterials function
Inhibit cell wall enzyme responsible for peptidoglycan synthesis
-causing lysis and cell death
-bactericidal
49
Four groups of B-Lactam Antibacterials
-penicillins
-cephalosporins
-monobactams
-carbapenems
50
B-Lactam Antibacterials are characterized by
The common B-Lactam ring in their structures
51
Which of the B-Lactam Antibacterials are commonly used in Canada?
-penicillins
-cephalosporins
-carbapenems
52
What are the two major types of penicillins? Explain them
Naturally occuring penicillin —> hasn’t been changed in any way, these are sensitive to b-lactamase
Sem synthetic penicillin —> has been modified in the lab to be useful but different, more broad spectrum
53
Narrow spectrum penicillins
Naturally occuring penicillin that is extremely narrow
-cannot target gram negative
-Penicillin G and penicillin V
54
Aminopenicillins (broader spectrum) +two examples
Semi synthetic penicillins, with a much greater range
-Amoxicillin (more acid stable so can be taken PO)
-ampicillin (IV/IM)
55
Antipseudomonal penicillins (extended spectrum)
Really broad spectrum
-even against pseudomonas aeruginoas (opportunistic infections)
56
Pseudomonas aeruginoas
Opportunist infection
-respiratory, ears, eyes, CNS, UTI, endocarditis
57
Penicillins mechanism of action
Enters the bacteria, where it binds to penicillin binding proteins disrupting normal cell wall synthesis
-bacteria cell ruptures
58
Penicillins do not
Kill other cells in the body
59
Penicillin targets…
Active against most gram positive bacteria, as well as some gram negative (depends on the penicillin)
-bactericidal
60
Penicillin is bactericidal (true or false)
TRUE!!!
61
Drug resistance to penicillins
Some bacteria produce enzymes capable of destroying penicillins called B-lactamases which destroy the B-lactam ring
62
B-lactamase inhibitors
Given in the tablet of penicillins in order to allow them to work
-clavulanic acid, used with amoxicillin
63
Which of the B-lactam antibacterials are resistant to B-lactamase
Monobactam and carbapenem
64
Broad and extended penicillins types kill..
Gram negative
65
Administration of penicillin
PO, IM, IV
-depends on the type of penicillin
66
Penicillins adverse effects
Generally well tolderated
-GI problems, disturbing normal gut flora
-allergic reactions: subcutaneous edema or rashes
-could be fatal
67
What are Cephalosporins?
Semisynthetic derivatives from a cephalosporins fungus
68
Cephalosporins are structurally and pharmacologically related to
Penicillins
69
Do cephalosporins have bactericidal action?
Yes they do
70
As the five generations progress of cephalosporins what increases
-better gram negative coverage
-better b lactamase resistance
71
Cephalosporins are divided based off
Into groups based according to their introduction to clinical use
Such as:
-inc permeability to gram negative cell
-increased stability against B-lactamase
72
Cephalosporins first generation: use for
Surgical prophylaxis, URIs, otitis media
73
Cephalosporins second generation: coverage
-good for gram positive
-better gram positive than first gen
74
Cephalosporins third generation
Broader spectrum
-better again gram negative than previous
75
Cephalosporins fourth generation: coverage
Broader spectrum of antibacterial activity than third Gen
-especially against gram positive bacteria
76
Cephalosporins fifth generation: drug
Ceftaroline
-MRSA infections
77
Adverse effects of cephalosporins
Similar to penicillins
-history of allergies (cross hypersensitivity, but does not exclude its use)
78
Carbapenems coverage
Broad spectrum antibacterial action
-gram negative, positive and anaerobic
79
Carbapenems are effective for…. And not for..
Effective for mixed infections, but not MRSA
80
How are carbapenems given?
Parentally given, not PO
81
Carbapenems are used for
reserved* for severe complicated body vanity and connective tissue infections
-last resort
-something that cannot be treated by a narrower drug
82
Imipenem-cilastatin
Carbapenems
-combination drug
-the cilastatin inhibits breakdown of imepenem in the kidney
83
Carbapenems drug resistance
-carbapenem resistant enterobasteriaceae (CRE)
-KPC (klebsiella pneumonias carbapenemase) and NDM (new delhi metallic-beta-lactamase)
-most antibacterial drugs
-opportunistic infections
84
Three Macrolides
-erythromycin
-azithromycin
-clarithromycin
85
Macrolides mechanism of action
Inhibits protein synthesis by binding to ribosomes
86
Macrolides coverage
Broad spectrum
-most gram positive, some gram negative
-bacteriostatic
87
Are macrolides bacteriostatic or bactericidal?
BOTH!!!!
-depends on concentration and bacterial suspectibilty
88
Macrolides are given to patients who are..
-allergic to b-lactamase antibacterials
-penicillin resistant infections (as they look nothing like penicillin)
Good alternative!!
89
Macrolides: azithromycin and clarithromycin example
Used in combination for people with HIV/AIDS for opportunistic infections
90
Macrolides are used primarily for
Infections of respiratory, skin, soft tissue
91
Adverse effects of macrolides
-nausea, vomiting, diarrhea
-provoke cardiac dysthymia (long Q-T)
92
Macrolides: azithromycin and clarithryomycin
-fewer drug drug interactions
-little to no inhibition of CYP enzymes
Azithromycin: does not affect liver enzymes, which is very important if people are taking multiple drugs to take the strain off of liver enzymes (advantage)
93
Tetracyclines coverage
Broad spectrum
-gram negative and positive
-bacteriostatic
94
Tetracyclines mechanism of action
Inhibit protein synthesis
95
Tetracyclines are
Bacteriostatic
96
Major tetracycline
Tetracycline
97
Tetracyclines bind to
Metal ions
-calcium, magnesium, iron, aluminum
-things like milk products, supplements, laxatives, antacids
-will form insoluble complexes
98
You cannot take tetracyclines with..
Dairy products, antacids and iron salts
-reduced absorption of tetracyclines
99
Never take tetracyclines
-if pregnant/breast feeding
-children less than 8 years old
100
Averse effects of tetracyclines
-strong affinity for calcium
-GI disturbance
-alteration in intestinal fora
-photosensivity
-antagonist to bactericidal antibacterials
101
Averse effects of tetracyclines: strong affinity for calcium
-discolouration of permanent teeth and tooth enamel in fetuses and children
-may retard fetal skeletal development during pregnancy
102
Averse effects of tetracyclines: Gi disturbances
-direct irritation
-gut flora disturbance
103
Averse effects of tetracyclines: the alteration in intestinal flora may result in
Is a broad spectrum drug so it will affect many bacteria including the good ones found in the GI tract
-leave risk for opportunistic infections (CDIFF)
Superinfections
104
Averse effects of tetracyclines: antagonistic to bactericidal antibacterials….
So must be timed for use usually at least an hour apart
105
Aminoglycosides
Natural and semisynthetic
-produced from streptomyces
106
Aminoglycosides were the first antibacterial effective against
Gram negative bacteria
107
Aminoglycosides mechanism of action
Bactericidal
-preventing abnormal protein synthesis
108
Aminoglycosides coverage
Mostly gram negative and some gram positive
109
Aminoglycosides (5)
-gentamicin
-neomycin
-streptomycin
-to army in
-amikacin
110
Aminoglycosides are active against
Gram negative bacteria
111
Aminoglycosides are often used in combination with
Other antibacterials for synergistic effect
112
How are Aminoglycosides administered
Given parenterally IV or IM
-as they are poorly absorbed
113
Then why would aminoglycosides used orally?
They are given orally to decontaminate the GI tract before surgical procedures
-or if the infection is in GI lumen
114
Unfortunately aminoglycosides have…
Serious toxic effects
-ototoxicity
-nephrotoxicity
115
Ototoxicity of aminoglycosides
-auditory impairment (ringing, tinnitus, deafness)
-vestibular (balance problems, dizziness, vertigo)
116
Ototoxicity is made worse if
Other ototoxic drugs are given
-loop diuretics
117
Nephrotoxicity from aminoglycosides
Extreme in neonates and pre existing renal conditions
-must monitor plasma drug levels to prevent toxicities
118
Is nephrotoxicity reversible?
Yes!!!!!!!!!!
119
aminoglycosides has increased risk for nephrotoxicity if used with
-vancomycin
-cyclosporine
-amphotericin B
120
Quinolones mechanism of action
Alters DNA of bacteria
-prevents proper super coiling
-does not affect human DNA
-bactericidal
121
Ciprofloxacin
Very effective and most common quinolones used
-PO
122
Quinolones coverage
Gram negative organisms and some gram positive organisms
-broad spectrum
123
Quinolones are used for
-urinary tract infections
-anthrax
-lower resp infections
-bone, joint infections
-diarrhea
-skin infections
-STD
124
Adverse effects of quinolones
-nausea, vomiting, diarrhea
-skin rashes
-CNS (headache, dizziness)
125
Interactions of quinolones
drug to drug —> very good at CYP inhibition
-if other drugs are metabolized by CYP then there is a problem…
126
Quinolones oral absorption is reduced by
-antacids
-iron, zinc, calcium containing preparations (so drugs need to be given 1-2 hours before)
127
Vancomycin mechanisms of actions
Inhibits cell wall synthesis
-bactericidal
-a different protein target to B-lactams
128
Vancomycin is administered by
IV
-given orally for pseudomembranous colitis/ C diff
-because it is such a large molecule!!!
129
Vancomycin is the treatment of choice for
MRSA and other gram positive infections
130
Adverse effects of vancomycin
-flushing syndrome (need to infuse over 1 hour)
-fever chills and phlebitis
-ototoxicity
-nephrotoxicity
131
Flushing syndrome
Subjective sensation of warmth accompanied by visible skin erythema
-face mostly
132
Antimircrobials covers what categories of drugs?
-antiboiodics
-antifungals
-antivirals
133
What is the rising worry with last resort drugs?
That they too are becoming at risk for drug resistance
-bad because the whole idea of last resort is using these drug less so that they have less chances of becoming resistant
134
How do bacteria resist drugs?
They mutant and are able to gain selective advantages
-such as a pump that gets rid of the antibiotics, or enzymes that break down antibiotics and render them useless
-essentially survival of the fittest
135
What is a common adverse effect of antibacterials?
GI upset
-almost every antibacterial has risk of GI upset of some sort
136
What was the first drug group to be discovered
Sulfonamides
137
How were B-lactam antibiotics discovered
Alexander Fleming left the petriy disc out by a window and both fungus and bacteria were colonized, but around the fungus there was a circle of space with no bacteria formed which lead to him hypothesizing the poitential for fungus to create something that kills bacteria -> penicillin
138
Which two B-lactam antibacterials are very similar?
Penicillins and cephalosporins
139
How do sulfonamides destroy folic acid?
They are very similar in structure to PABA (precursor to folic acid) and are able to bind with the enzyme that PABA normally does which reduces the amount of folic acid made = less DNA/RNA in a bacteria
140
Penicillin G is given…
IV or IM
141
Penicillin V is given…
PO
142
Patients with a history of allergy to penicillin may indicate an allergy towards what types of drug?
Cephalosporins
-since they are so similar
143
How are the toxic effects of aminoglycosides monitored
Since these are given IV after a dump of drugs is administered patients are given a blood test to monitor the level of toxins in blood and give a break to hold off more severe symptoms as a result of the drug
144
Is ototoxicity reversible?
No because it is killing the hair cells in the ear which do not grow back
-this is why when you age your hearing can get worse
