Bacterial Cell Wall Synthesis Inhibitors Flashcards
1
Q
What are the examples of Gram +ve cocci?
A
Staphylococcus
Streptococcus
Enterococcus
2
Q
What are the examples of Gram +ve Bacilli?
A
Listeria monocytogenes Bacillus Clostridium species Diptheria Actinomyces Mycobacterium Corynebacterium
3
Q
What are the examples of Gram -ve Cocci?
A
Neisseria gonorrhoeae (gonococci) Neisseria meningitides (meningococcus) Moraxella catarrhalis
4
Q
What are the examples of Gram -ve Bacilli?
A
Pseudomonas aeruginosa
Enterobacteriaceae family (Includes Enterobacter species, Klebsiella pneumoniae, E.Coli, etc.)
Acinetobacter species
H. influenzae
5
Q
What is the MOA of b-lactams?
A
Interfere with the synthesis of the bacterial cell wall peptidoglycan
Bind to active site of PBP (transpeptidase enzyme), which catalyses the cross-linking of the terminal peptide components of the linear polymer chains.
Weakens cell wall structure, build up in the intracellular osmotic pressure and lysis of bacterial cells; bactericidal to actively growing cells
6
Q
Name the 3 Penicillin G
A
P G Potassium
P G Procaine
P G Benzathine
7
Q
ROA for Penicillin G Potassium
A
IV
8
Q
ROA for Penicillin G Procaine and Benzathine
A
IM
9
Q
ROA for Penicillin G
A
Parenteral
10
Q
ROA for Penicillin V
A
Oral, better abs than Pen G as it is more acid stable
11
Q
Natural penicillins are useful against
A
b-lactamase negative strains of selected Gram +Ve (Streptococci, Bacillus diphtheriae) and Gram -ve (meningcocci and gonococci)
12
Q
What are the main Gram +VE organisms that is targeted when using natural penicillins?
A
Streptococci, Bacillus diphtheriae
13
Q
What are the main Gram -VE organisms that is targeted when using natural penicillins
A
Gram -ve (meningcocci and gonococci)
14
Q
Which Penicillin is used to treat syphilis?
A
Pen G Benzathine
15
Q
Which organism causes syphilis?
A
Spirochetes; Treponema pallidum
16
Q
None of the penicillins are effective against _______
A
amoebae, plasmodia, rickettsiae, fungi, or viruses
17
Q
How is the penetration into CSF for natural penicillin G?
A
IV aqueous Pen G reaches higher conc than procaine/benzathine. Penetration is increased if the meninges are inflamed.
18
Q
Excretion of natural penicillins?
A
Renal, excreted unchanged in urine
19
Q
Pen G procaine and benzathine can distribute into ____
A
storage tissues and released slowly (IM)
20
Q
What are the names for Penicillinase-resistant penicillins?
A
Cloxacillin
Flucloxacillin
Methicillin (not in use)
21
Q
ROA of Penicillinase-resistant penicillins?
A
IV, IM, Oral
22
Q
Main organisms targeted in Penicillinase-resistant penicillins?
A
Staphylococci
Ineffective against Gram -ve
All are less effective against microorganisms susceptible to Pen G.
23
Q
Penetration into CSF for Penicillinase-resistant penicillins?
A
Doesn’t achieve therapeutic levels
24
Q
Excretion of Penicillinase-resistant penicillins?
A
Renal clearance
25
Penicillinase-resistant penicillins are best taken on an ______
empty stomach.
26
The bulky side groups of b-lactamases-resistant penicillin confers protection from b-lactamases by _____
limiting accessibility to the catalytic site of action
27
Penicillinase-resistant penicillins =
Anti-staphylococcal penicilin
28
Aminopenicillins =
Broad spectrum penicillins
29
Names of Aminopenicillins
Ampicillin
| Amoxicillin
30
ROA of ampicillin
Acid stable; Oral, IV
31
ROA of amoxicillin
Oral (better abs than ampicillin), IV
32
Aminopenicillins have additional ____ groups, allowing ______ via _______
Aminopenicillins have additional hydrophilic groups, allowing their penetration into Gram -ve bacteria via porins
33
Aminopenicillins are used for many ______
b-lactamases negative strains of many Gram -ve/+ve MO
34
Aminopenicillins doesn't cover
Pseudomonas or Klebsiella
35
Penetration into CSF for Aminopenicillins
Parenteral ampicillin and amoxicillin can reach adequate CNS concentrations
Penetration is increased with inflamed meninges
36
Excretion of Aminopenicillins
Renal; Excreted unchanged in the urine.
Dose adjustment required for renal dysfunction.
37
Incomplete oral abs of ampicillin results in higher incidence of ___
diarrhoea
38
Antipseudomonal penicillins =
Extended spectrum penicillins
39
Name of Antipseudomonal penicillins
Piperacillin (always in combi with tazobactam)
40
Antipseudomonal penicillins have greater activity than other penicillins against __
Gram -ve bacteria, esp Pseudomonas and Proteus sp and some species of Klebsiells
41
Antipseudomonal penicillins are used in treatment for ______
Pseudomonas infections
42
Antipseudomonal penicillins has increased ____ coverage
anaerobic
43
Antipseudomonal penicillins has been used against ___
non b-lactamase producing Gram +Ve strains of S. pyrogenes and Enterococcus
44
Penetration into CSF for Antipseudomonal penicillins
Penetrated CSF fairly well in pts with inflamed meninges
45
Excretion of Antipseudomonal penicillins
Primarily renal clearance; 70% excreted unchanged in urine
Dose adjustment required with renal dysfn
46
What is the MOA of b-lactamase inhibitors?
Weak anti-bacterial properties
They work primarily by inactivating serine beta-lactamases, which are
enzymes that hydrolyze and inactivate the beta-lactam ring (especially in
gram-negative bacteria)
Strong affinity for β-lactamases. This allows them to either bind and
inactivate it or bind irreversibly thus protecting other β-lactam antibiotics
from being targeted by the β-lactamases
47
What are the 3 β-LACTAMASE COMBINATION DRUGS?
Clavulanic acid + Amoxicillin ; Augmentin
Sulbactam + Ampicillin ; Unasyn
Tazobactam + Piperacillin; Zosyn
48
ROA for Clavulanic acid + Amoxicillin ; Augmentin
Oral, IV
49
ROA for Sulbactam + Ampicillin ; Unasyn
IV
50
ROA for Tazobactam + Piperacillin; Zosyn
IV
51
Clavulanic acid + Amoxicillin ; Augmentin is effective against which Main organisms?
Effective against βlactamase-producing strains
of staphylococci, H.
influenzae, gonococci, and E.
coli.
Used in skin, lower
respiratory tract infections
and UTI
52
Sulbactam + Ampicillin ; Unasyn is effective against which Main organisms?
```
Effective against β-lactamaseproducing strains of S.
aureus, GN aerobes, and
anaerobes. Used in skin, intra
abdominal and gynaecologic
infections
```
53
Tazobactam + Piperacillin; Zosyn is effective against which Main organisms?
```
Broadest antibacterial
spectrum of the penicillins.
Coverage include βlactamase producing
organisms (most
Enterobacteriaceae and
Bacteroides species). Used in
appendicitis, moderate to
severe cases of nosocomial
pneumonia
```
54
Penetration
| into CSF of Clavulanic acid and Tazobactam?
```
Clavulanic acid
and tazobactam
have modest
CSF penetration
Their use in the
treatment of
CNS infections
is discouraged.
```
55
Penetration
| into CSF of Sulbactam
```
CSF
penetration of
sulbactam is
variable, and
depends on the
presence of
meningeal
inflammation.
```
56
Excretion of Augmentin and Unasyn?
Renal clearance; excreted
unchanged in the urine.
Dose adjustment is needed
with renal dysfunction
57
Excretion of Tazobactam + Piperacillin; Zosyn
```
Renal clearance;
Tazobactam and its
metabolites are excreted in
the urine. Dose adjustment
is needed with renal
dysfunction
```
58
```
Clavulanic acid is a
____ inhibitor.
_____bonds to the
β-lactamase and
_____it,
permanently ______
it.
```
```
Clavulanic acid is a
suicide inhibitor.
Covalently bonds to the
β-lactamase and
restructures it,
permanently inactivating
it.
```
59
```
Both sulbactam, and
tazobactam ____
bind beta-lactamase at
or near its active site.
This ___ other beta-lactam antibiotics from
________.
```
```
Both sulbactam, and
tazobactam irreversibly
bind beta-lactamase at
or near its active site.
This protects other betalactam antibiotics from
beta-lactamase
catalysis.
```
60
MRSA
| expresses ____, which has reduced _____for penicillins
MRSA
| expresses PBP2a, which has reduced affinity for penicillins
61
Production of β-lactamase resulting in ___of the β-lactam ring
Production of β-lactamase resulting in hydrolysis of the β-lactam ring
62
Decreased ability of the antibiotic to reach the PBP when
| bacteria decreases ____ production, resulting in a decrease in _____.
Decreased ability of the antibiotic to reach the PBP when
bacteria decreases porin production, resulting in a decrease in
the intracellular drug concentration.
63
Presence of ____ also can resist penicillin
Presence of efflux pumps
64
Which MO is resistant against the Penicillins class of antibiotics?
MRSA is resistant against the Penicillins class of antibiotics
65
5-6 Adverse Reactions to Penicillins
1. Allergy/Hypersensitivity
2. Clostridium difficile-associated diarrhoea (CDAD)
3. Neurotoxicity
4. Hepatotoxicity
5. Anosmia
6. In patients with renal failure, high doses of penicillins can cause seizures
66
What are the Allergy/hypersensitivity when using penicillins?
Stevens Johnson syndrome
(SJS)
toxic epidermal necrolysis (TEN).
Penicillins are contraindicated in patients with previous anaphylactic reactions
or serious skin reactions, for example, SJS and TEN
67
4 mechanisms of resistance to penicillin
PBP2a, B-lactamase, decreased porin production, efflux pumps
68
which generation of cephalosporins have excellent CSF penetration
3rd,4th,5th
69
which generations of cephalosporins are given usually in the oral form? (with one exception)
first and second gen (exception is first gen cefazolin = IV)
70
cefazolin is used as an alternative for
anti-staphylococcal (penicillase-resistant) penicillins in patients with mild allergic reactions to penicillins
71
what are the first gen cephalosporins and they are active against?
cefazolin, cephalexin; gram +ve = strep (except for penicillin-resistant strains) and stap (except for MRSA)
72
second gen cephalo names and against what?
cefuroxime
| useful against e.coli, klebsiella, proteus, H.influenzae (gram -ve ONLY)
73
Third gen cephalo names and against what?
cefotaxime, ceftriaxone, ceftazidime
enterobacteriaceae, N.gonorrhoeae, Stap aureus, S.penumonia and S.pyogenes
cefotaxime = most active against S.aureus and S.pyogenes
74
which third gen is effective against P.aeruginosa
ceftazidime = only gram -
75
fifth gen cephalo names and cover
ceftaroline = LAME, VRSA, S.pneumoniae, H.inluenzae, Moraxella catarrhalis, MRSA
ceftobiprole = LAME, e.coli, enterobacter, Klebsiella, and P.aeruginosa, MRSA
76
fourth gen name and against?
Cefepime; covers Pseudomonas
77
which drug is cleared via hepatic
third gen ceftriaxone
78
3 characteristic of cephalosoprins as it goes from first to 4/5th gen?
higher activity against gram -ve bacteria, greater resistance to b-lactamases, better distribution to cerebrospinal fluid
79
ROA for 3rd/4/5th gen cephalosporins
IM/IV
80
what are the atypicals
mycoplasma, chlamydia, legionella spp
81
adverse rxn to cephalosporins
hypersensitivity (similar to penicillin), GIT (diarrhoea esp with oral cephalo; CDAD, thrombophlebitis (minimise risk by giving slowly and in diluted form, rotating infusion site)
82
when have pencillin allergy, what sub can we give?
monobactam and vancomycin, cefazolin (cef is an alternative for anti-stap penicillins in pt with mild allergic rxn to penicillin; BUT not given due to cross-allergy)
83
imipenem (+ cilastatin) active against
streptococci (including penicillin-resistant s.pneumoniae), enterococci, staphyloccoci (including penicillinase-producing strain)
gram -ve: pseudomonas, anaerobes, bacteriodes fragilis
84
which carbapenem lacks activity against p-aeruginosa and enterococcus spp
ertapenem
85
can aztreonam used in B-lactamase producing gram -ve bacteria?
yes
86
vancomycin resistance (2 emergence)
enterococcal (reducing binding affinity by sub terminal D-alanine for D-lactate/D-serine) and s.aureus
87
which cephalosporins cover P.aeruginosa?
3rd gen: Ceftazidime
4th gen: Cefepime
5th gen: Ceftobiprole
88
aztreonam is indicated for what infections?
UTI, lower resp tract infection
- septicemia and intra-abdominal infections
89
how is Aztreonam administered
IM/IV
90
indications for vancomycin?
(1) CDAD/ C.D. associated diarrhoea
(2) MSSA/MRSA
(3) Strep (including resistance)
(4) enterococcus
(5) osteomyelitis, endocarditis
(6) prophylaxis treatment in pneumonia where MRSA is expected and meningitis caused by PCN-R S.pneumoniae
91
adverse effect of carbapenems
1. GIT (N/V/D)
2. Neurotoxicity
3. Cross-Hypersensitivity with penicillins
4. Rashes
92
Preg cat for vancomycin
Parenteral (IV): Cat C
Oral: Cat B
93
Adverse effect of vancomycin?
Nephrotoxicity, Ototoxicity
Red man/ Red neck syndrome
Thrombophlebitis, fever/chills
94
Adverse effect of cephalosporins?
1. GIT (CDAD)
2. Thrombophlebitis (minimise risk by giving slowly, diluted form, rotating infusion site)
3. Cross-hypersensitivity with penicillins
95
ROA of carbapenems
IV
96
ROA of piperacillin
IV
