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Bacterial Cell Wall Synthesis Inhibitors Flashcards

1
Q

What are the examples of Gram +ve cocci?

A

Staphylococcus
Streptococcus
Enterococcus

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2
Q

What are the examples of Gram +ve Bacilli?

A 
Listeria monocytogenes
Bacillus
Clostridium species
Diptheria
Actinomyces
Mycobacterium
Corynebacterium
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3
Q

What are the examples of Gram -ve Cocci?

A 
Neisseria gonorrhoeae (gonococci)
Neisseria meningitides (meningococcus)
Moraxella catarrhalis
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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

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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

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6
Q

Name the 3 Penicillin G

A

P G Potassium
P G Procaine
P G Benzathine

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7
Q

ROA for Penicillin G Potassium

A

IV

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8
Q

ROA for Penicillin G Procaine and Benzathine

A

IM

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9
Q

ROA for Penicillin G

A

Parenteral

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10
Q

ROA for Penicillin V

A

Oral, better abs than Pen G as it is more acid stable

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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)

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12
Q

What are the main Gram +VE organisms that is targeted when using natural penicillins?

A

Streptococci, Bacillus diphtheriae

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13
Q

What are the main Gram -VE organisms that is targeted when using natural penicillins

A

Gram -ve (meningcocci and gonococci)

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14
Q

Which Penicillin is used to treat syphilis?

A

Pen G Benzathine

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15
Q

Which organism causes syphilis?

A

Spirochetes; Treponema pallidum

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16
Q

None of the penicillins are effective against _______

A

amoebae, plasmodia, rickettsiae, fungi, or viruses

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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.

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18
Q

Excretion of natural penicillins?

A

Renal, excreted unchanged in urine

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19
Q

Pen G procaine and benzathine can distribute into ____

A

storage tissues and released slowly (IM)

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20
Q

What are the names for Penicillinase-resistant penicillins?

A

Cloxacillin
Flucloxacillin
Methicillin (not in use)

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21
Q

ROA of Penicillinase-resistant penicillins?

A

IV, IM, Oral

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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.

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23
Q

Penetration into CSF for Penicillinase-resistant penicillins?

A

Doesn’t achieve therapeutic levels

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24
Q

Excretion of Penicillinase-resistant penicillins?

A

Renal clearance

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25
Q

Penicillinase-resistant penicillins are best taken on an ______

A

empty stomach.

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26
Q

The bulky side groups of b-lactamases-resistant penicillin confers protection from b-lactamases by _____

A

limiting accessibility to the catalytic site of action

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27
Q

Penicillinase-resistant penicillins =

A

Anti-staphylococcal penicilin

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28
Q

Aminopenicillins =

A

Broad spectrum penicillins

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29
Q

Names of Aminopenicillins

A

Ampicillin

Amoxicillin

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30
Q

ROA of ampicillin

A

Acid stable; Oral, IV

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31
Q

ROA of amoxicillin

A

Oral (better abs than ampicillin), IV

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32
Q

Aminopenicillins have additional ____ groups, allowing ______ via _______

A

Aminopenicillins have additional hydrophilic groups, allowing their penetration into Gram -ve bacteria via porins

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33
Q

Aminopenicillins are used for many ______

A

b-lactamases negative strains of many Gram -ve/+ve MO

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34
Q

Aminopenicillins doesn’t cover

A

Pseudomonas or Klebsiella

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35
Q

Penetration into CSF for Aminopenicillins

A

Parenteral ampicillin and amoxicillin can reach adequate CNS concentrations

Penetration is increased with inflamed meninges

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36
Q

Excretion of Aminopenicillins

A

Renal; Excreted unchanged in the urine.

Dose adjustment required for renal dysfunction.

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37
Q

Incomplete oral abs of ampicillin results in higher incidence of ___

A

diarrhoea

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38
Q

Antipseudomonal penicillins =

A

Extended spectrum penicillins

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39
Q

Name of Antipseudomonal penicillins

A

Piperacillin (always in combi with tazobactam)

40
Q

Antipseudomonal penicillins have greater activity than other penicillins against __

A

Gram -ve bacteria, esp Pseudomonas and Proteus sp and some species of Klebsiells

41
Q

Antipseudomonal penicillins are used in treatment for ______

A

Pseudomonas infections

42
Q

Antipseudomonal penicillins has increased ____ coverage

43
Q

Antipseudomonal penicillins has been used against ___

A

non b-lactamase producing Gram +Ve strains of S. pyrogenes and Enterococcus

44
Q

Penetration into CSF for Antipseudomonal penicillins

A

Penetrated CSF fairly well in pts with inflamed meninges

45
Q

Excretion of Antipseudomonal penicillins

A

Primarily renal clearance; 70% excreted unchanged in urine

Dose adjustment required with renal dysfn

46
Q

What is the MOA of b-lactamase inhibitors?

A

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
Q

What are the 3 β-LACTAMASE COMBINATION DRUGS?

A

Clavulanic acid + Amoxicillin ; Augmentin
Sulbactam + Ampicillin ; Unasyn
Tazobactam + Piperacillin; Zosyn

48
Q

ROA for Clavulanic acid + Amoxicillin ; Augmentin

49
Q

ROA for Sulbactam + Ampicillin ; Unasyn

50
Q

ROA for Tazobactam + Piperacillin; Zosyn

51
Q

Clavulanic acid + Amoxicillin ; Augmentin is effective against which Main organisms?

A

Effective against βlactamase-producing strains
of staphylococci, H.
influenzae, gonococci, and E.
coli.

Used in skin, lower
respiratory tract infections
and UTI

52
Q

Sulbactam + Ampicillin ; Unasyn is effective against which Main organisms?

A 
Effective against β-lactamaseproducing strains of S.
aureus, GN aerobes, and 
anaerobes. Used in skin, intra 
abdominal and gynaecologic 
infections
53
Q

Tazobactam + Piperacillin; Zosyn is effective against which Main organisms?

A 
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
Q

Penetration

into CSF of Clavulanic acid and Tazobactam?

A 
Clavulanic acid
and tazobactam
have modest 
CSF penetration 
Their use in the 
treatment of 
CNS infections 
is discouraged.
55
Q

Penetration

into CSF of Sulbactam

A 
CSF 
penetration of 
sulbactam is 
variable, and 
depends on the 
presence of 
meningeal 
inflammation.
56
Q

Excretion of Augmentin and Unasyn?

A

Renal clearance; excreted
unchanged in the urine.
Dose adjustment is needed
with renal dysfunction

57
Q

Excretion of Tazobactam + Piperacillin; Zosyn

A 
Renal clearance; 
Tazobactam and its 
metabolites are excreted in 
the urine. Dose adjustment 
is needed with renal 
dysfunction
58
Q 
Clavulanic acid is a 
\_\_\_\_ inhibitor. 
\_\_\_\_\_bonds to the 
β-lactamase and
\_\_\_\_\_it, 
permanently \_\_\_\_\_\_
it.
A 
Clavulanic acid is a 
suicide inhibitor. 
Covalently bonds to the 
β-lactamase and
restructures it, 
permanently inactivating 
it.
59
Q 
Both sulbactam, and 
tazobactam \_\_\_\_
bind beta-lactamase at 
or near its active site.
This \_\_\_ other beta-lactam antibiotics from 
\_\_\_\_\_\_\_\_.
A 
Both sulbactam, and 
tazobactam irreversibly 
bind beta-lactamase at 
or near its active site.
This protects other betalactam antibiotics from 
beta-lactamase 
catalysis.
60
Q

MRSA

expresses ____, which has reduced _____for penicillins

A

MRSA

expresses PBP2a, which has reduced affinity for penicillins

61
Q

Production of β-lactamase resulting in ___of the β-lactam ring

A

Production of β-lactamase resulting in hydrolysis of the β-lactam ring

62
Q

Decreased ability of the antibiotic to reach the PBP when

bacteria decreases ____ production, resulting in a decrease in _____.

A

Decreased ability of the antibiotic to reach the PBP when
bacteria decreases porin production, resulting in a decrease in
the intracellular drug concentration.

63
Q

Presence of ____ also can resist penicillin

A

Presence of efflux pumps

64
Q

Which MO is resistant against the Penicillins class of antibiotics?

A

MRSA is resistant against the Penicillins class of antibiotics

65
Q

5-6 Adverse Reactions to Penicillins

A
  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
Q

What are the Allergy/hypersensitivity when using penicillins?

A

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
Q

4 mechanisms of resistance to penicillin

A

PBP2a, B-lactamase, decreased porin production, efflux pumps

68
Q

which generation of cephalosporins have excellent CSF penetration

A

3rd,4th,5th

69
Q

which generations of cephalosporins are given usually in the oral form? (with one exception)

A

first and second gen (exception is first gen cefazolin = IV)

70
Q

cefazolin is used as an alternative for

A

anti-staphylococcal (penicillase-resistant) penicillins in patients with mild allergic reactions to penicillins

71
Q

what are the first gen cephalosporins and they are active against?

A

cefazolin, cephalexin; gram +ve = strep (except for penicillin-resistant strains) and stap (except for MRSA)

72
Q

second gen cephalo names and against what?

A

cefuroxime

useful against e.coli, klebsiella, proteus, H.influenzae (gram -ve ONLY)

73
Q

Third gen cephalo names and against what?

A

cefotaxime, ceftriaxone, ceftazidime

enterobacteriaceae, N.gonorrhoeae, Stap aureus, S.penumonia and S.pyogenes

cefotaxime = most active against S.aureus and S.pyogenes

74
Q

which third gen is effective against P.aeruginosa

A

ceftazidime = only gram -

75
Q

fifth gen cephalo names and cover

A

ceftaroline = LAME, VRSA, S.pneumoniae, H.inluenzae, Moraxella catarrhalis, MRSA

ceftobiprole = LAME, e.coli, enterobacter, Klebsiella, and P.aeruginosa, MRSA

76
Q

fourth gen name and against?

A

Cefepime; covers Pseudomonas

77
Q

which drug is cleared via hepatic

A

third gen ceftriaxone

78
Q

3 characteristic of cephalosoprins as it goes from first to 4/5th gen?

A

higher activity against gram -ve bacteria, greater resistance to b-lactamases, better distribution to cerebrospinal fluid

79
Q

ROA for 3rd/4/5th gen cephalosporins

80
Q

what are the atypicals

A

mycoplasma, chlamydia, legionella spp

81
Q

adverse rxn to cephalosporins

A

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
Q

when have pencillin allergy, what sub can we give?

A

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
Q

imipenem (+ cilastatin) active against

A

streptococci (including penicillin-resistant s.pneumoniae), enterococci, staphyloccoci (including penicillinase-producing strain)

gram -ve: pseudomonas, anaerobes, bacteriodes fragilis

84
Q

which carbapenem lacks activity against p-aeruginosa and enterococcus spp

85
Q

can aztreonam used in B-lactamase producing gram -ve bacteria?

86
Q

vancomycin resistance (2 emergence)

A

enterococcal (reducing binding affinity by sub terminal D-alanine for D-lactate/D-serine) and s.aureus

87
Q

which cephalosporins cover P.aeruginosa?

A

3rd gen: Ceftazidime
4th gen: Cefepime
5th gen: Ceftobiprole

88
Q

aztreonam is indicated for what infections?

A

UTI, lower resp tract infection

  • septicemia and intra-abdominal infections
89
Q

how is Aztreonam administered

90
Q

indications for vancomycin?

A

(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
Q

adverse effect of carbapenems

A
  1. GIT (N/V/D)
  2. Neurotoxicity
  3. Cross-Hypersensitivity with penicillins
  4. Rashes
92
Q

Preg cat for vancomycin

A

Parenteral (IV): Cat C

Oral: Cat B

93
Q

Adverse effect of vancomycin?

A

Nephrotoxicity, Ototoxicity

Red man/ Red neck syndrome

Thrombophlebitis, fever/chills

94
Q

Adverse effect of cephalosporins?

A
  1. GIT (CDAD)
  2. Thrombophlebitis (minimise risk by giving slowly, diluted form, rotating infusion site)
  3. Cross-hypersensitivity with penicillins
95
Q

ROA of carbapenems

96
Q

ROA of piperacillin

PT (19 decks)

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