Ch. 38 Cell Wall Inhibitors Flashcards
1
Q
cell wall is composed of
A
polymer called peptidogylcan that consists of glycan units joined to each other by peptide cross-links
2
Q
are among the most widely effective and the least toxic drug known , but increased resistance has limited their use
A
penicilins
3
Q
R substituent attached to the 6-aminopenicilanic acid residue
A
peniciilins
4
Q
interfere with the last step of bacterial cell wall synthesis (transpeptidation of cross -linkage)
A
penicilins
5
Q
cell lysis occurs after interference of the last step of bacterial cell wall synthesis, transpeptidation . describe cell lysis
A
osmotic pressure or activation of the autolysins
6
Q
penicilins are inactive against
A
mycobacteria, protozoa , fungi, and viruses
7
Q
bacterial enzymes involved in the synthesis of the cell, what are they called and what are they inactivated by?
A
they are peniciln binding protiens (PBPs) and they are inactivated by the penicilin
8
Q
what are the 3 mechanisms of action of penicilins
A
- penicillin-binding proteins
- inhibition of transpeptidas
- production of autolysins
9
Q
inhibition of transpeptidase-catalyzed reaction due to penicilins thus
A
hinder formation of the cross-links essential for the cell wall
10
Q
autolysins are from gram(+) or gram (-) ? what are autolysins?
A
gram(+)
degradative enzymes
11
Q
destruction of the existing cell wall caused by
A
autolysins thanks to penicilins
12
Q
determined in part by their ability to cross the bacterial peptidoglycan cell wall to reach the PBPs in the periplasmic space
A
antibacterial spectrum
13
Q
have cell walls that are easily traversed by penicillins , susceptible to the pencilin
A
gram (+) bacteria
14
Q
micro organism that have an outer lipopolysaccharide membrane surrounding the cell wall that presents a barrier to the water soluble penciillins
A
gram (-) bacteria
15
Q
how is transmembrane entrance permitted in gram(-) bacteria?
A
have proteins inserted in the lipopolysaccharide layer that act as water-filled channels (called porins) to permit transmembrane entry
16
Q
natural penicillins
A
penicillin G and penicillin V
-fermentations fo the fungus penicillium chrysogenum
17
Q
semisynthetic penicillins
A
amoxicillin and ampicillins (aminopenicillins)
-created by chemically attaching different R groups to the 6-aminopenicillanic acid nucleus
18
Q
cornerstone therapy for infectiinnns caused by gram(+) and gram(-) cocci , gram(+) bacilli, and spirochetes
A
penicillin G (benzyl-penicillin)
19
Q
resistant bacteria produce
A
inactivation of b-lactamases (penicillinases), thus making penicilins susceptible
20
Q
drug of choice for the treatment of gas gangrene (clostridium perfringens)
A
penicillins
21
Q
drug of choice for the treatment of syphilis (treponema pallidum)
A
penicillins
22
Q
not used for the treatment of bacteremia due to poor oral absorption
A
penicilin V
23
Q
penicilin V has a similar spectrum to which antiobiotic?
A
penicillin G
24
Q
penicillin V is more acid stable than penicillin G therefore
A
often employed orally
25
used to prevent gonoccoal ohthalmia in newborns
silver nitrate drops
26
cetriaxone with azithromycin or spectinomycin are used to treat
penicillinase-producing strains
27
B-lactamase (penicillinase)-resistant penicillins are
methicillin, nafcillin, oxacillin, and dicloxacillin
28
methicillin, nafcillin, oxacillin, and dicloxacillin are used to treat
infections cuased by pinicillinase-producing staphylococci, including methicillin-sensitive staphylococcus aureus (MSSA)
29
causes toxicity such as interstitial nephritis therefore no longer used clinically in the states, and used for laboratory testing to identify strains of S. aureus.
Methicillin
30
minimal to no activity against gram(-) infections
penicillinase resistant penicilllins
31
more effective against gram(-) bacilli
ampicillin and amoxicillin
| -antibacterial spectrum similar to penicillin G
32
Ampicillin is the drug of choice against
gram(+) Listeria monocytogenes
33
Ampicillin is susceptible to
eterococcal species
34
extended-spectrum penicllins are
ampicillins and amoxicillins
35
widely used in the treatment of respiratory infections
extended spectrum antibiotics (ampicillins/amoxicillins)
36
employed prophylactically be dentists to prevent high-risk patients for the prevention of bacterial endocarditis
amoxicillin
37
why is resistance to extended-spectrum antibiotics a major clinical problem?
-E. Coli and H. influenzae are resistant
inactivation by plasma-mediated penicillinases
38
-b-lactamase inhibitor
protects amoxicillin or ampicillin (extended-spectrum antibiotics) from enzymatic hydrolysis and extends their antimicrobial spectra.
-najeeb concept: body gaurds that protect supermodels (amoxi and ampi)
Clavulanic acid or Sulbactam
| -beta-lactamase inhibitor
39
MSSA is resistant to ampicillin and amoxicillin due to
without administration of b-lactamase inhibitors
| Clavulanic acid or sulbactam
40
antipseudomonal penicillins
| -activity against psuedomonas aeruginosa
piperacillin
| -parental formation only
41
most potent of these antibiotics: natural penicllins, antistaphylococcal penicillin, extendend spectrum penicillins, antipseudomonal penicillins
piperacillin
42
what are piperacillin are effective against ?
what are piperacillin are not effective against ?
they are effective against gram(-) bacilli
ineffective against Klebsiella because of its constitutive penicillinase
43
extends the antimicrobial spectrum of these antibiotics to include penicillinase-producing organisms
-most enterobactericeae and bacteroides species
formulation of ticarcillin or piperacillin with clavulanic acid or tazobactam
44
how does natural resistance to the penicillins occur?
because they either lack a peptidoglyclan cell wall or have walls that are impermeable to the drugs
45
acquired resistance to the penicillins are
by plasma mediated B-lactamases
46
by obtaining resistance plasmids, bacteria may acquire on or more of the following properties , allowing survival in the presence of B-lactam antibiotics:
- B-lactamase activity
- decreased permeability to the drug
- altered PBPs
47
enzymes hydrolyzes the cyclic amide bond of the B-lactam ring which results
loss in bactercidal activity
48
where do betalactamases come from ?
| -constitutive
produced by bacterial chromosome or acquired by the transfer of plasmids
49
some of the B-lactam antibiotics can be
poor substrates for B-lactamases and resist hydrolysis, retaining their activity against B-lactamase-producing organisms.
50
organisms that secrete B-lactamases extracellularly
gram(+)
| - B-lactamase activity (resistance)
51
organisms that inactivate B-lactam drugs in the periplasmic space
gram(-)
| - B-lactamase activity (resistance)
52
prevents the drug from reaching the target PBPs
| - decreased permeability of the drug (resistance)
decreased penetration of the antibiotic through the outer cell membrane of the bacteria
53
the presence of what can reduce the amount of intracellular drug? what's an example?
presence of an efflux pump
| example is Klebsiella pneumoniae
54
have a lower affinity for B-lactam antibiotics
modified PBPs
55
explains MRSA resistance to most commercially available B-lactams
modified PBPs
56
determined by the stability of the drug to gastric acid and by severity of infection
B-lactam antibiotics
57
Administered IV or intramuscular
```
Ampicillin/sulbactam
ticarcillin/clavulanic acid
piperacillin/tazobactam
antistaphylococcal penicillins:
-nafcillin
-oxacillin
```
58
```
Ampicillin/sulbactam
ticarcillin/clavulanic acid
piperacillin/tazobactam
antistaphylococcal penicillins:
-nafcillin
-oxacillin
```
Administered IV or intramuscular
59
available only as oral preparations
Penicillin V, Amoxicillin, dicloxacillin
60
depot forms , administered IM
procain penicillin G and benzathin penicillin G
| -low levels over long periods of time
61
most penicillins should be taken on an empty stomach
food decreases the absorption of all the penicillinase-resistant penicillins
62
all the penicllins cross the placental barrier but
do none have teratogenic effects
63
imparied renal function reveals some metabolism of
penicillin G
64
primary excretion for most penicillins
organic acid (tubular) secretory system of the kidney
glomerular filtration
-also in breast milk
65
patients with impaired renal function must have dosage regimens adjusted EXCEPT
antistaphylococcal penicillins:
- nafcillin
- oxacillin
- primarily metabolized in the liver therefore do not require dose adjustment.
66
inhibits the secretion of penicillins by competting for active tubular secretion via organic acid transporto and thus can increase blood levels
probenecid
67
adverse reactions of penicillins
```
hypersensitivity
diarrhea
nephritiis
neurotoxicity
hematologic toxicities
```
68
hypersensititvity
5%
rashses
angioedema (lip swelling,tongue, periorbital area)
anaphylaxis
69
cross alergic reactions occur in
B-lactam antibiotics
70
to determins whether treatment with a B-lactam is safe when an allergy is noted
patient history regarding severity of previous reaction is essential
71
pseudomembranous colitis from clostridium defficile occurs
with penicillin use adverse effect
72
actute interstitial nephritis
methicillin
| -no longer in clinical use in the states
73
provokes seizures if injected intrathecally of if very high blood levels are reached
neurotoxicity caused by penicillins irritating neuronal tissue
74
in the sense of neurological toxicity , penicillins cause
GABAnergic inhibition
| -epileptic patients are at risk
75
hematological toxicities:
decreased coagulations observed with high doses of?
-cytopenias have been associated with therapy of greater than 2 weeks
-blood counts should be monitored
piperacillin, ticarcillin, and nafcillin
| -to some extent penicillin G
76
7-aminocephalosporanic acid
- produced semisynthetically
- B-lactam antibiotics similar to penicillins
cephalosporins
77
antibacterial spectrum of cephalosporins:
| -based largely on their bacterial susceptibility patterns an resistance to B-lactamases
1rst generation
2nd generation
3rd generation (more potent as the generation moves on)
4th generation
78
ineffective against MRSA, L. monocytogenes, C. difficile, and the enterococci
commercially available cephalosporins
79
activity against proteus mirabilis, e. coli, K. pneumoniae
1rst generation cephalosporins
80
resistant to the staphylococcal penicillinase ( that is , they cover MSSA)
1rst generation cephalosporins
81
act as penicillin G substitutes
1rst generation cephalosporins
82
greater activity against three additinal gram(-) organisms:
| H. influenzae, Enterobacter aerogenes, Neisseria species
2nd generation cephalosporins
83
activity against gram(+) organisms is weaker
2nd generation cephalosporins
84
cephamycins?
| antimicrobial coverage of cephamycins include ?
Cefotetan and cefoxitin
includes anaerobes (bacteroides fragilis)
85
less potent than first-generation cephalosporins against MSSA, but have enhanced activity against gram(-) bacilli, as well as most other enteric organisms plus Serratia marcescens?
3rd generation cephalosporins
86
agents of choice of treatment of meningits
ceftriaxone and cefotaxime
| -3rd generation cephaolosporin
87
activity against P. aeruginosa
ceftazidime
| -3rd generation cephalosporin
88
assoiciated with "colloteral damage"
3rd generation cephalosporins
| -flororquinolone as well
89
- must be administered parentallly
- wide antibacterial spectrum , with activity against streptococci, and staphylococci (only those that are methicillin suceptible)
4th generation cephalosporins
| cefepime
90
effeective against gram (-) organisms such as :
| Enterobacter species, E. Coli, K. pneumoniae, P. mirabilis, and P aueruginosa
cefepime
| 4th generation cephalosporin
91
Iv as a prodrug, broad-spectrum
Ceftaroline fosamil
| -advanced generation
92
only commercially available B-lactam in the states with activity against MRSA and is indicated for the treatment of complicated skin and skin structure infections and community acquired pneumonia
Ceftaroline
| -advanced generation
93
the unique structure allows this cephalosporin to bind to PBP2a found with MRSA and PBP2x found with streptococcus pneumoniae
Ceftaroline
| -advanced generation
94
in addition to its broad gram(+) activity it also has similar gram(-) activity to the 3rd generation cephalosporin ceftriaxone
ceftaroline
| -advanced generation
95
coverage includes P. aeruginosa, extended-spectrum B-lactamase (ESBL)-producing enterobactericeae, and Acintobacter baumannii
ceftaroline
| -advanced generation
96
twice-daily dosing regimen also limits its use outside of an instiutional setting
ceftaroline
| -advanced generation
97
Cephalosporins are suceptible to
ESBLs
- E. coli
- K. pneumoniae
98
most cephalosporins are administered via
IV or IM due to poor oral absorption
99
ceftriaxone and cefotaxime are effective in the treatment of
neonatal and childhood meningits caused by H. influenzae
100
used as a single prophylaxis dose prior to surgery because of its 1.8-hour V1/2
cefazolin
101
active against penicillinase-producing S. aureus
cefazolin
102
effective in most surgical procedures including orthopedic surgery due to its ability to penetrate bone
cefazolin
103
all cephalosporins cross
the placenta
104
doses adjusted in cases of renal dysfunction
cephalosporins
105
elimination of ceftriaxone
| -employed for patients with?
through bile into the feces
| -for patients with renal insufficiency
106
patients who should not recieve cephalosporins?
anaphylactic response, stevens-johnson syndrome, toxic epidermal necrolysis to penicillins
-people who have penicillin alergy (avoid or cautionary use)
107
the highest rate of allergic cross sensitivity is between
penicillin and 1rst generation cephalosporins
108
other B-lactam antibiotics
carbapenems
109
sythetic B-lactam antibiotics
| -sulfur atom of the thiazolidine ring has been externalized and replaced by a carbon atom
carbapenems
110
carbapenem group
impenem, meropenem, doripenem , ertapenem , imipenem
111
compounded with cilastatin to protect it from metabolism by renal dehydropeptidase
carbapenem
112
resists hydrolysis by most B-lactamases but not the metallo-B-lactamases
imipenem
113
active against B-lactamase-producing gram(+) and
| gram(-) organisms, anaerobes, and P. aeruginosa
imipenem
114
lacks coverage against P. aeruginosa, enterococcus species, and acinetobacter species
ertapemen
115
IV and penetrates into CSF when there is meningitis
imipenem/cilastatin and meropenem
116
cilastatin with imipenem prevents the
prevents the formation of toxic metabolite that causes nephrotoxicity
117
only carbapenem that requires coadministration of cilastatin
imipenem
118
iv or im once daily , carbapenem
ertapenem
119
adverse effects of impenemim/cilastatin
nausea, vomiting, diarrhea
120
high levels of which carbapenem provokes siezures?
imipenem
121
a monobactam that distrupt bacterial cell wall synthesis
| -unique because B-lactam ring is not fused to another ring
aztreonam
122
primarily against gram(-) pathogens including enterobacteriaceae and P. aeruginosa
Aztreonam
123
lacks activity against gram poistive organisms and anerobes
aztreonam
124
resistant to the action of most B-lactamases with the exception of the ESBLs
Aztreonam
125
administered IV or IM
-relatively nontoxic but may cause
phlebitis, skin rash and occasionally abnormal liver function tests
aztreonam
126
safe alternative for patientes allergic to other penicillins, cephaolsporins or carbapenems
aztreonam
127
destroys the antimicrobial activity of a B-lactam antibiotic
hydrolyis of the B-lactam ring
128
calvulanic acid sulbactam and tazobactam are
b-lactamase inhibitors
| -protects anitbiotics
129
tricyclic glycopeptide, important in treating life threatening MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE) as well as enteroccal infections
Vancomycin
130
used in individuals with prosthetic heart valves and in patients undergoing implantation of prosthetic devices especially in hospitals with rates of MRSA or MRSE
vancomycin
131
not absorbed after oral administration
vancomycin
132
bacericidal concentration-dependent cyclic lipopeptide antibiotic that is an alternative to other agents such as linezolid and quinupristin/dalfopristin, for treating infections caused by resistant gram (+) organisms , including MRSA and vancomycin resistant enterococci (VRE)
Daptomycin
133
treatment of complicated skin and skin structure infections bacteremia caused by S. aureus, including those with right-sided infective endocarditis
daptomycin
134
inactivated by pulmonary surfactants
| -should never be used in treatments of pneumonia
daptomycin
135
bactercidad concentration-dependendent smeisynthetic lipoglycopeptide antibiotic that is a synthetic derivative of vancomycin
telavancin
| -inhibits bacterial cell wall synthesis
136
alternative to vancomycin, daptomycin and linezolid in treating complicated skin and skin structure infections caused by resistant gram(+) organisms (including MRSA)
telavancin
137
last choice for hospital-acquired and ventilator-associated bacterial pneumonia when alternative treatments are not suitable
telavancin
138
adverse effects of telavancin
teratogenic, interactions with medications that can prolong the QT interval (flouroquinolones, azole antifungals, macrolides)
139
bactercidal synthetic derivative of phosphonic acid
fosfomycin
140
blocks cell wall synthesis by inhibiting the enzyme
| UDP-N-acetylglucosamine enolpyruvyl transferase, which catalyzes the 1rst step in peptidoglycan synthesis
fosfomycin
141
fosfomycin dosage and treatments
1 time dose
| urinary tract infections caused by E. coli and E. faecalis
142
rapidly absorbed after oral administration and distributes well to kidneys, bladder, and prostate
fosfomycin
143
excretion of fosfomycin
feces/urine in active form
144
adverse effects of fosfomycin
diarrhea , vaginitis, nausea, and headache
145
cation polypeptides that bind to phospholipids on vacterial cell membrane of gram(-) bacteria
polymyxins
146
detergent like effect that distrupts cell membrane integrity leading to leakage of cellular components and ultimately cell death
polymyxins
147
activity against gram(-) bacteria , including P. aeruginosa, E. coli, K. pneumoniae, Acinetobacter species, and enterobacter species
polymyxins
148
allos may species of proteus and serratia to be intrinsically resistant
polymyxins
149
polymyxins in clinical use today
polymyxins B and colistin (polymyxin E)
150
available in parenteral, ophthalmic, otic , and topical preparations
Polymyxin B
151
Colistin only available as a prodrug
colistimethate sodium, administered via IV or nebulizer (inhaled)
152
increases risk of nehprotoxicity and neurotoxicity (slurred speech, muscle weakness) when used systematically
Colistimethate sodium (prodrug of colistin)
153
salvage therapy for patients with multidrug-resistant infections
colistimethate sodium (prodrug of colistin)
