Treatment of Bacterial Infections - Ch 87-93 Flashcards
(164 cards)
1
Q
What is Chemotherapy?
A
Drugs that are “selectively toxic” to invading microorganisms that have minimal effect on host
2
Q
Necrotizing fasciitis
A
“Flesh-eating disease”
Caused by variety of bacteria
3
Q
Infections
A
Invasion and multiplication of organisms
Infections may be caused by foreign bacteria or normal flora (e.g. in immunocompromized
patients)
4
Q
Colonization of the body by normal flora
A
Not usually harmful, can help in controlling growth of potentially pathogenic organisms
5
Q
What causes implications for the action of antibacterials?
A
Gram-positive or Gram-negative cell wall
6
Q
What are antibacterial drugs?
A
Either kill or slow down the growth of bacteria
7
Q
What are the 2 subgroups of antibacterial drugs?
A
Bactericidal
Bacteriostatic
8
Q
Bactericidal
A
Drugs are directly lethal to bacteria at clinically
achievable concentrations
9
Q
Bacteriostatic
A
Drugs can slow bacterial growth but do not cause
cell death
10
Q
What is critical in helping the body control and eliminate infections?
A
Immune system
11
Q
Host defences are especially important in what group of antibiotics?
A
Bacteriostatic
12
Q
Superinfection
A
new microbes take over when antibacterials kill normal flora
- eg respiratory, genitourinary tract and GI tract
microbe resistant to drug action = difficult to treat
13
Q
Opportunistic infections
A
Infections that would not normally harm an immunocompetent person
-Existing colonization becomes infections
-Can be viruses, fungi, bacteria or protozoa
14
Q
Who is affected by opportunistic infections?
A
Immunocompromised patients
15
Q
How many people die globally from antibacterial resistance?
A
5 million people
16
Q
What enhances selection of mutant bacteria (resistance)?
A
Improper choice of antibiotics
The dose is too low
Dosing not continued for long enough
Improper use of antibacterial, e.g, to treat a viral infection
Prophylactic use of antibacterials, e.g. in animal feed
17
Q
What host factors need to be taken into consideration when providing antibacterial therapy?
A
Host age, allergies, organ health, pregnancy, site of infection and person’s general health
18
Q
What are allergic reactions?
A
Immune response
-GI upset is not an allergic reaction
19
Q
What are the four common mechanisms of action of antibacterials?
A
- Disruption of critical metabolic reactions
- Interference with cell wall synthesis
- Interference with protein synthesis
- Interference with DNA replication
20
Q
What mechanism of action do sulfonamides use?
A
Inhibit metabolism
21
Q
What spectrum do Sulfonamides have?
A
Broad spectrum
(effective against gram-positive and gram-negative)
22
Q
What type of antibacterial are sulfonamides?
A
Bacteriostatic
23
Q
How do sulfonamides inhibit/disrupt metabolic reactions?
A
Prevent synthesis of folic acid
24
Q
Examples of sulfonamides
A
Sulfamethoxazole
Sulfadiazine
25
What are sulfonamides combined with?
trimethoprim
e.g, co-trimoxazole
Bactrim or Septra for UTI and otitis media
26
Where do sulfonamides reach effective concentrations?
Urinary tract
27
What are other clinical uses of sulfonamides?
Upper respiratory tract infections
others e.g, malaria, chlamydia
28
If someone is allergic to 1 sulfa-drug does that allergy applie to other reivatives of sulfa-life drugs?
Yes
e.g, anti diabetic agents sulfonylureas
thiazide and loop diuretics (increase urine)
29
Can pregnant women take sulfonamides and why?
No it is linked to birth defects in the 1st trimester and close to end of pregancy may increase fetal bilirubin (kernicterus brain damage)
30
It is advised to take sulfonamides during breastfeeding?
No also infants less than 2 months should not ingest
31
What are some adverse effects of sulfonamides?
Integumentary allergies
Blood adverse effects
GI adverse effects
32
What are some adverse effects affecting the skin caused by sulfonamides?
Stevens-johnson syndrome
Photosensensitivty
33
What are some blood adverse effects caused by sulfonamides?
(bone marrow depression)
Agranulocytosis, thrombocytopenia, aplastic anemia
34
What are GI adverse effects caused by sulfonamides?
Nausea and vomiting
35
Who discovered Beta-lactam antibacterials?
Sir Alexander Fleming (1928)
-Discovered Staphylococcus aureus was destroyed by the mold Penicillium notatu ---> penicillin
36
What percent of S. aureus is resistant to penicillin now?
95%
37
What mechanism of action do Beta-lactam antibacterials use?
Inhbit cell wall enzyme responsible for peptidoglycan synthesis
38
What kind of antibacterial are Beta-lactams?
Bactericidal
39
What are the 4 groups of Beta-lactam antibacterials?
Penicillins
Cephalosporins
Monobactams
Carbapenems
40
What do all Beta-lactam antibacterials have in common?
Beta-lactam ring in their structures
41
What groups of Beta-lactams are commonly used in Canada?
Penicillins
Cephalosporins
Carbapenems
42
What are the 2 min subgroups of penicillins?
Naturally occurring
Semi-synthetic
43
What are Naturally occurring penicillin sensitive to?
Beta-lactamase
44
What are semi-synthetic penicllin resistant to?
Beta-lactamase
45
What kind of spectrums do semi synthetic penicillin have?
Broad or extended
46
What are broad spectrum semi-synthetic penicillins called?
Aminopenicillins
47
What are extended semi-synthetic penicillins called?
Anti-pseudomonal penicillins
48
What are the 2 narrow-spectrum (natural) penicillins that are still commonly used?
Penicillin G and Penicillin V
49
Example of beta-lactamase-resistant penicillin?
Cloxacillin
50
Examples of aminopenicillins (broader-spectrum)
Amoxicillin (more acid-stable), ampicillin
51
Examples of anti-pseudomonal penicillins (extended-spectrum)
Ticarcillin, piperacillin
52
Anti-pseudomonal penicillins can even be used against which bacteria?
Pseudomonas aeruginoas
-affects mostly ill people e.g, immunocompromized, cystic fibrosis
53
Pseudomonas aeruginosas opportunistic infections?
Respiratory tract
Ears
Eyes
CNS
UTI
Endocarditis
54
Describe the mechanism of action of Penicillins
- Penicillins enter the bacteria
- Inside the cell they bind to penicillin- binding proteins
- Normal cell wall synthesis is disrupted
- Bacteria cells rupture
- Penicillins do not kill other cells in the body
55
What kind of antibacterial are penicillins?
Bactericidal
56
Depending on which type of penicllin, penicillins are active against most of which type of bacteria?
Most gram-positive
-Only some gram-negative
57
Why is there resistance to Penicillins?
Some bacteria produce enzymes capable of destroying penicillins
58
What enzyme do bacteria produce that causes resistance?
Beta-lactamases which splits the Beta-lactam ring
59
What is used in combination with penicillins?
Beta-lactamase inhibitors
(helps with resistance)
60
Examples of Beta-lactamase inhibitors
Clavulanic acid (amoxicillin + clavulanic acid)
Tazobactam (piperacillin + tazobactam)
61
How can Penicillins be administered?
PO, IM, IV
62
Penicillin G administration
IV or IM
63
Penicillin V administration
PO
64
Adverse effects of Penicillin
GI problems
-Nausea, vomiting, diarrhea, pain
(generally well tolerated)
Allergic reactions
65
What is the most common cause of drug allergy?
Penicillin
66
What reaction do people with allergies to penicillin display?
Skin rashes
Subcutaneous edema (e.g, lips)
Also can be fatal
67
Cephalosporins are derivatives of what?
Semisynthetic derivatives from Cephalosporium fungus
68
Cephalosporins are structurally and pharmacologically related to what?
Penicillins
69
What kind of antibacterial are cephalosporins?
Bactericidal
70
How are cephalosporins named?
Based on generations
1st gen ---> 5th gen
(introduction to clinical use)
71
With the newer generations of cephalosporins, what happens?
Better gram-negative coverage
Better Beta-lactamase resistance
72
First Generation cephalosporins examples?
Cefazolin
Cephalexin
Cefadroxil
used for Surgical prophylaxis, URIS, otitis media
73
How is cefazolin administered?
IV
74
Cefazolin is excellent on which kind of bacteria?
Gram-positive
75
How is cephalexin administered?
PO
76
Second genration cephalosporins are good against which kind bacteria?
Gram-positive
Better gram-negative coverage than first gen
77
Second generation cephalosporins examples?
Cefuroxime
Cefoxitin
78
How is cefuroxime administered?
PO
-For surgical prophylaxis
79
How is cefoxitin administered?
IV and IM
80
THird-gen cephalosporins are better against which bacteria than previous generations?
Gram-negative
81
Examples of third-gen cephalosporins?
Cefotaxime
Cefixime
82
How does cefotaxime work?
Easily passes meninges and diffuses into CSF to treat CNS infections
e.g, meningitis
83
How is Cefotaxime administered?
IV and IM
84
How is Cefixime administered?
PO
-Best oral cephalosporin against gram-negative
85
What drug is the only PO 3rd generation?
Cefixime
86
How do fourth gen antibacterials compare to 3rd gen?
fourth generation have a broader spectrum, especially against gram-positive
87
Example of fourth gen cephalosporins?
Cefepime
88
Example of fifth gen cephalosporin
Ceftaroline
-MRSA infections
89
What are the adverse effects of cephalosporins?
Similar to penicillins (GI)
Patients with a history of allergy to penicillin have cross-hypersensitivity to cephalosporins
90
Describe the spectrum of Carbapenems?
Broad-spectrum
Work against gram-positive, gram-negative and anaerobic
91
Carbapenems are effective against which infections?
Mixed infections
-NOT MRSA
92
How are all carbapenems administered?
Parentally
-Not PO
93
Examples of Carbapenems
Imipenem
Meropenem
94
Whata re carbapenems reserved for?
Severe, complicated body cavity and connective tissue infections
-Last resort antibacterial when something can't be treated by a narrower drug
95
What is the name of a combination carbapenem drug?
Imipenem-cilastin
96
What does cilastin do in combination with imipenem?
Inhibits breakdown of imipenem in kidney
97
What is the type of bacteria that are resistant to Carbapenems?
Carbapenem-resistant Enterobacteriaceae (CRE)
-Resistant against most antibacterials
-Cause difficult to treat oppurtunistic infections
98
What are the enzymes called that break down Carbapenems?
KPC: Klebsiella pneumoniae carbapenemase
NDM: New Delhi Metallo-beta-lactamase
99
What is the class of drugs that are large in size?
Macrolides
100
Examples of Macrolides?
Erythromycin (protypical)
Azithromycin
Clarithromycin
101
What are macrolides mechanisms of action?
Inhibits protein synthesis by binding to 50S portion of the ribosome
102
Describe the spectrum of macrolides?
broad spectrum
-Most Gram-positive, some gram-negative
103
What group of antibacterials are macrolides?
Both bacteriostatic and bactericidal
-Depends on concentration and bacterial susceptibility
104
Macrolides are used as alternatives to what when an allergic reaction occurs?
Beta-lactam allergies
105
Macrolides are used an alternatives to what when resistance forms?
Penicillin resistance
106
Are macrolides ever used in combination?
Yes
e.g, azithromycin and clarithromycin
used in combination for people with HIV/AIDS for opportunistic infections
107
What infections are Macrolides used to treat?
- Respiratory, skin and soft tissue
- Strep infections
- Streptococcus pyogenes (group A beta-hemolytic streptococci)
- Mild to moderate URI (upper respiratory infections)
- Haemophilus influenzae
- Spirochetal infections
- Syphilis and Lyme disease
- Gonorrhea, Chlamydia, Mycoplasma
108
What are the adverse effects of macrolides?
GI disturbances (nausea, vomiting, diarrhea)
Cardiac dysrhythmia (Long Q-T)
109
Adverse effects of azithromycin and clarithromycin specifically?
Fewer drug-drug interactions (theophylline, warfarin, cyclosporine)
Little to no inhibition of CYP enzymes
110
Describe the spectrum of Tetracyclines?
Broad-spectrum
-Gram positive, gram-negative
111
What is the mechanism of action of tetracyclines?
Inhibits protein synthesis
-Binds to 30S portion
112
What group of antibacterials is Tetracyclines?
Bacteriostatic
113
Examples of Tetracyclines?
Tetracycline
Doxycycline
Minocycline
Demeclocycline
114
What specific bacteria can Tetracycline be used to treat?
Mycoplasma, Rickettsia, Chlamydia, Syphilis
Protozoa
115
What do Tetracyclines bind to?
Metal ions
Ca 2+, Mg 2+, iron and aluminum
found in, milk products, supplements, some laxatives most antacids
116
What happens when Tetracyclines bind with metal ions?
Insoluble complexes form called Chelation
117
What happens if Tetracyclines are taken with dairy products, antacids and iron salts?
Reduces absorption of tetracyclines
118
Do NOT use Tetracyclines in which populations?
Children less than 8 years old
Pregnancy/breast feeding
119
Why should young kids/pregnant women not take Tetracyclines?
Have a strong affinity for calcium which causes...
-Discoloration of permanent teeth and enamel in fetuses and kids
-Retards fetal skeletal development during pregnancy
120
What other adverse effects do tetracyclines have?
GI disturbances (direct irritation, distrubs gut flora)
Photosensitivity
121
Alteration in intestinal flora caused by tetracyclines may result in what?
Superinfection (overgrowth of new, non-susceptible organisms such as Candida)
Diarrhea
Pseudomembraneous colitis (C. Diff) colon infection
122
Tetracyclines are antagonistic to which bacterials?
Bacteriocidal antiacterials so must be times for use usually at least an hour apart
123
What are the 2 forms of Aminoglycosides?
Natural and semisynthetic
124
What are Aminoglycosides produced from?
Streptomyces
125
Aminoglycosides were the first antibacterial effect against what?
Gram-negative bacteria
126
What group of antibacterials are Aminoglycosides?
Bactericidal
127
What mechanism of action do Aminoglycosides use?
Prevents protein synthesis
(or causes abnormal protein synthesis)
128
Aminoglycosides are used against which bacteria?
Mostly gram-negative and some gram-positive
129
Examples of Aminoglycosides?
Gentamicin
neomycin
streptomycin
tobramycin
amikacin
130
What are some examples of gram-negative bacteria that aminoglycosides are effective against?
Pseudomonas spp
E. coli
Proteus spp
Klebsiella spp
Serratia spp
131
Are aminoglycosides used in combination?
Yes with other antibacterials for synergistic effect
132
Where are aminoglycosides poorly absorbed?
Through GI Tract
133
How are aminoglycosides administered?
Parenterally (IV or IM)
134
When are aminoglycosides given PO?
To decontaminate the GI tract before surgical procedures or enema
135
Aminoglycosides are drugs with _________ __________!!
Serious toxicities
136
What types of toxic effects do aminoglycosides cause?
Ototoxicity
Nephrotoxicity
137
Ototoxicity
Affects the ear
Auditory impairment e.g, Tinnitus, deafness
Vestibular impairments e.g, balance problems, dizziness, vertigo
138
Is Ototoxicity reversible?
No it is irreverisble
139
How is aminoglycosides Ototoxicity made worse?
If other ototoxic drugs are given e.g, Loop diuretics
140
Nephrotoxicity
Affects the kidney
Causes kidneys to detriorate
141
Who is extremely affected by nephrotoxicity?
Neonates
People with pre-existing renal conditions
-measure proteinuria, serum creatinine levels, BUN
142
Is Nephrotoxicity reversible?
Yes it is reversible
143
You must monitor what to prevent toxicities caused by aminoglycosides?
Plasma drug levels
144
Theres is an additive effect for nephrotoxicity if used with what?
Vancomycin
Cyclosporine (immunosuppressant)
Amphotericin B (antifungal)
145
What mechanism of action do Quinolones/Fluroquinolones use?
Affect DNA replication
Alters DNA of bacteria by preventing proper supercoiling
146
Examples of Quinolones?
Ciprofloxacin
Norfloxacin
gemifloxacin
levofloxacin
gatifloxacin
147
What is a very effective and most commonly used quinolone?
Ciprofloxacin
148
How is Ciprofloxacin administered?
PO
149
What group of antibacterials are quinolones?
Bactericidal
150
Describe the spectrum of Quinolones?
broad spectrum
-Gram-negative (major use)
-Some gram-positive
151
Do quinolones affect human DNA?
NO
152
What infectiosn are treated with quiniolones?
UTI
Lower resp. tract infections
Bone and joint infections
Infectious diarrhea
Skin infections
STDs
Anthrax!!!!!!!!!!!!
153
What adverse effects do quinolones have?
GI distrubances (nausea, vomiting, diarrhoea)
Skin (rashes)
CNS (headache, dizziness)
154
What drugs do quinolones have interactions with that cause CYP inhibition?
Theophylline (asthma drug)
Warfarin
155
What reduces oral absorption of Quinolones?
Antacids
Iron, zinc, calcium-containing preparations
-Drugs should be given 1-2 hours before consuming those preparations
156
What is the mechanism of action of Vancomycin?
Inhibits cell wall syntehsis
157
What group of antibacterials is Vancomycin?
Bactericidal
158
Vancomycin have a different what to Beta-lactams?
Different protein targets
159
How is Vancomycin administered?
IV and PO
160
Iv administration of Vancomycin is used to treat what?
MRSA and other gram-positive infections
161
Oral administration of Vancomycin is used to treat what?
Pseudomembranous colitis (C. diff)
162
What is increasing in regards to Vancomycin use?
Vancomycin resistance
163
What infusion rate (over 1 hour ) related adverse effects does Vancomycin have?
Flushing syndrome possible
164
What adverse effects does Vancomycin have?
Fever, chills and phlebitis (inflamed vein at injection)
Ototoxicity
Nephrotoxicity
