Lecture 20: Inhibitors of Cell Wall Synthesis Flashcards
1
Q
What is the major difference between bacterial and mammalian cells
A
Presence of rigid cell wall
2
Q
The cell wall in bacterial cells protects cells from ____
A
Osmotic rupture
3
Q
What structure in the bacterial cell wall is particularly important for rigidity and resistance to osmotic lysis
A
Peptidoglycan
4
Q
Gram ___bacteria have a thick peptidoglycan layer and no outer membrane
A
Positive
5
Q
Gram ___bacteria have a thin peptidoglycan layer and an outer membrane
A
Negative
6
Q
Penicillin, cephalosporins, monobactams, and carbapenems are what type of antibiotics
A
B-lactams
7
Q
What is the mechanism of action for b-lactams
A
Prevent the crosslinking/ transpeptidation
8
Q
What antibiotic is a glycopeptide
A
Vancomycin
9
Q
Are Cell wall inhibitors bacteriocidal or bacteriostatic
A
Bacteriocidal
10
Q
Cell wall inhibitors eventually result in cell death due to ___
A
Osmotic lysis
11
Q
Protein synthesis inhibitors prevent the action of ___, therefore should not be used together
A
Cell wall inhibitors
12
Q
Natural penicillin is extracted from culture of ___and semisynthetic penicillins are manufactured from ____
A
Penicillium chrysogenum, penicillin nucleus (6-amino penicillanic acid- 6-APA)
13
Q
What is the chief structural requirement for the biological activity of penicillin
A
Penicillin nucleus
14
Q
The antibacterial activity of penicillin resides in the ___
A
Intact b-lactam ring
15
Q
___can split the B-lactam ring by enzymes or acids and result in loss of antibacterial action
A
B-lactamases
16
Q
Natural penicillins have the highest antibacterial activity against ___
A
Gram positives
17
Q
Natural penicillins cover what bacteria
A
- Gram positive
- Some gram negative
- Some anaerobes
18
Q
Do natural penicillins have antipseudomonas activity
A
No
19
Q
How are natural penicillins eliminated
A
Via kidney
20
Q
Natural penicillins have poor ___penetration, unless their is inflammation
A
CNS
21
Q
What natural penicillin has a short half life ~2hrs and is administered IV, IM
A
Penicillin G potassium
22
Q
What natural Pencillin has a low concentration for 30days and is used prophylactically, administered IM
A
Penicillin G benzathine
23
Q
What natural penicillin is used for everyday practice, longer half life ~10-20hrs, given IM
A
Penicillin G procaine
24
Q
What natural penicillin is relatively acid resistant and therefore orally useful
A
Penicillin V
25
Natural penicillins are the drug of choice for what 4 bacteria
1. Group A beta hemolytic streptococci
2. Spirochetes
3. Many Gram positive anaerobes
4. Gram negative aerobic cocci
26
Penicillinase resistant penicillins (antistaphylococcal penicillins) have lower activity against what bacteria
Gram positive
27
Penicillinase resistant penicillins have coverage against what bacteria
1. Some gram negative
2. Some anaerobe
3. Less gram positive
28
Penicillinase resistant penicillins is the drug of choice against ___
Penicillinase producing S. Aureus
29
Penicillinase resistant penicillins have ___metabolism and ___excretion
Hepatic, renal
30
What are the 3 examples of penicillinase resistance penicillins
1. Oxacillin
2. Cloxacillin
2. Methicillin
31
What is methicillin used for
Diagnostic tool to determine if organism is resistant to methicillin which is a change in penicillin binding protein or if B-lactamase activity
32
What is oxacillin used for
Treatment of bone, soft tissue, and skin infections by penicillinase producing staphylococci
33
Oxacillin is used in what species
Dogs and horses
34
What is cloxacillin used for
Intramammary administration in dry and lactating dairy cattle
35
Extended spectrum penicillins have lower coverage of what bacteria
Gram positive
36
What bacteria do extended spectrum penicillins cover
1. Gram negative bacteria
2. Anaerobic coverage when combined with penicillinase inhibitor
37
Do extended spectrum penicillins have antipseudomonal activity
No
38
Extended spectrum penicillins are susceptible to ___
B-lactamase (why combine with penicillinase inhibitors to provide anaerobic coverage)
39
Can you give extended spectrum penicillins orally
Yes- acid resistant
40
Extended spectrum penicillins have ___excretion
Urinary
41
What are the two examples of extended spectrum penicillins
Amoxicillin and ampicillin
42
What are ampicillin and amoxicillin used for
Tx sensitive bacterial infections, particularly respiratory infections
43
Which has better absorption: ampicillin or amoxicillin
Amoxicillin
44
Ampicillin and amoxicillin are FDA approved for what species
Dog, cats, cattle
45
What coverage do antipseudomonal penicillins provide
1. Extended spectrum penicillins (gram negative, anaerobes if combined with penicillinase inhibitors)
2. Enteric gram negative bacilli (not Klesibella)
46
Antipseudomonal penicillins major use is the treatment of ___
Pseudomonas aeruginosa
47
Antipseudomonal penicillins are susceptible to ___
B-lactamase
48
Can you give antipseudomonal penicillins orally
No-acid sensitive
49
Antipseudomonal penicillins have ___excretion
Renal
50
What are the two examples of antipseudomonal penicillins
Piperacillin
Ticarcillin
51
Which has better antipseudomonal activity, piperacilin or ticarcilin
Piperacillin
52
What are the 3 beta-lactamase inhibitors that can be combined with other products
1. Clavulanic acid
2. Sulbactam
3. Tazobactam
53
B-lactamase inhibitors are not active against
Methicillin resistant, penicillinase-producing staphylococci- because change in PBP not B-lactamase activity
54
What are some mechanisms of resistance to penicillin (5)
1. B-lactamase
2. Decreased permeability
3. Alteration in PBPs
4. Autolytic enzymes not being activated- tolerance
5. Lack of peptidoglycan cell wall- mycoplasma and chlamydia
55
90% of penicillin is excreted via the __
Tubular system
56
Tubular secretion of penicillins can be partially blocked by ___ which can provide ___systemic level of penicillin in severe infections
Probenecid, higher
57
What is the major penicillin toxicity
Allergies- hypersensitive rxn- anaphylaxis
58
Are first generation cephalosporins narrow or broad spectrum
Narrow
59
What do first generation cephalosporins have activity against
1. Good activity against gram positive
2. Moderate activity against gram negative
60
First generation cephalosporins have good activity against some gram positive cocci except ___ and ___
Enterococci, methicillin resistant S. Aureus
61
Which generation of cephalosporins have good activity against E. Coli, Klebsiella pneumonia, and Proteus mirabilis
First
62
What are the 4 example of first generation cephalosporins
1. Cefazolin
2. Cefadroxil monohydrate
3. Cephalexin
4. Cephapirin
63
What is cefazolin used for
Surgical prophylaxis
64
What is cefadroxil monohydrate used for
Susceptible infections of skin, soft tissue, and GU in dogs and cats
65
What is cephalexin used for
Susceptible skin infections in dogs
66
What is cephapirin used for
Mastitis in lactating and dry cows
67
What spectrum are second generation cephalosporins
Intermediate
68
Second generation cephalosporins have increased activity against ___
Gram negative
69
What are the two examples of second generation cephalosporins
1. Cefoxitin
2. Cefaclor
70
Are third generation cephalosporins narrow or broad spectrum antibiotics
Broad
71
Third generation cephalosporins are less active than first generation against __, but much more active against ___, including ___ producing strains
Gram positive cocci, enterobacteriaecae, including penicillinase producing strains
72
What are the 4 examples of third generation cephalosporins
1. Ceftiofur
2. Cefovecin
3. Cefixime
4. Cefpodoxime
73
What is ceftiofur used for
Respiratory infections for cattle, swine, and horses
74
What is cefovecin used for
Cats and dogs with skin and soft tissue infections
75
What is cefixime used for
Extra label for skin, soft tissue and urinary infections in dogs and cats
76
What is cefpodoxime used for
Labeled for skin and soft tissue infections in dogs
77
Fourth generation cephalosporins are more resistant to ___
B-lactamases
78
What is the 1 example of fourth generation cephalosporins
Cefepime
79
What is cefepime used for
Potentially used for treating neonatal foals and dogs with severe infections
80
What 4 organisms do cephalosporins have no activity against
1. MRSA
2. Listo. Monocytogenes
3. Enterococci
4. Atypical- Myocplasma and chlamydia
81
What two organisms do cephalosporins have no effect against but penicillin does
Listo. Monocytogenes
Enterococci
82
Most cephalosporins are excreted by the ___
Kidney
83
What is the mechanism of action of polymixin B
Produces a detergent that disrupts the cell membrane
84
What are the uses for polymixin B
1. Topically to treat gram negative bacterial infections of skin, eye and ear in all species
2. Combined with bacitracin for broad spectrum effects
3. Administered orally to cattle and swine to tx gram negative enteric infections
85
What are some adverse effects of polymixin B
Nephrotoxicity if given parenterally
86
Monobactams: Aztreobam are drugs with ___ring
Monocyclic beta-lactation
87
Aztreonam is relatively resistant to ___
B-lactamases
88
What is Aztreonam active against
Gram negative rods, including pseudomonas
89
Aztreonam have no activity against ___and ___
Gram positive and anaerobes
90
What are some side effects of Aztreonam
Phlebitis, skin rash, abnormal liver function
91
Aztreonam has not cross sensitivity with ___derivatives
Pencillin
92
What class do imipenem; cilastatin and meropenem belong to
Carbapenems, B-lactam antibiotics
93
Imipenem is rapidly inactivated by ___ and must be given with ___
Dehydrogenase, cilastatin (dehydrogenase inhibitor)
94
Are carbapenems broad or narrow spectrum
Broad
95
What do carbapenems: imipenem; cilastatin and meropenem have activity against
1. Anaerobes
2. Gram positive
3. Gram negative rods
96
What carbapenem can cause seizures at high levels
Imipenem
97
What is the mechanism of action of vancomycin
Inhibits cell wall synthesis by:
1. Binding to D-Ala-D-Ala terminus of peptidoglycan and prevents crosslinking
2. Inhibits transglycosylation which inhibits elongation of peptide chain
98
How does resistance develop to vancomycin
D-Ala-D-Ala mutation replaced by D-Ala-D-lactate
99
Gram ___are resistant to vancomycin and can be combined with ___for synergistic effect
Negative, Aminoglycosides
But also has synergistic toxicity
100
What antibiotic is very useful in MRSA and gram positive infections in Pencillin allergic patients
Vancomycin
101
T or F: vancomycin is absorbed orally
False
102
What are some adverse reactions with vancomycin
1. Hypersensitivity
2. Nephro and ototoxicty
3. Uremia after high dose can be fatal
103
What antibiotic is very useful for susceptible Gram positive systemic life threatening infections
Vancomycin
104
T or F: vancomycin can be used in food producing animals
False, banned
105
What is the mechanism of action of Bacitracin
Interferes with final dephosphorylation step of lipid carrier so can’t transport peptidoglycan to outer cell wall
106
Bacitracin is active against what bacteria
Gram positive
107
Parenteral bacitracin use is rare due to risk of ___
Nephrotoxicity
108
Bacitracin is commonly used topically in addition with ___ and ___ to prevent ___
Neomycin and polymixin
Prevent superficial skin and eye infections following minor injuries
109
Which antibiotic has the properties in series A
A. Imipenem/Cilastatin
B. Vancomycin
C. Pencillin
D. Ampicillin
E. Cefazolin
D. Ampicillin
110
Which antibiotic has properties in series C:
A. Imipenem/ Cilastatin
B. Vancomycin
C. Penicillin G
D. Ampicillin
E. Cefazolin
B. Vancomycin
111
Which antibiotic has the properties in series A
A, Aztreonam
B. Vancomycin
C. Penicillin G
D. Cefixime
E. Oxacillin
C. Penicillin G
