ANTIBIOTICS

CELL WALL INHIBITORS

 ANTIBIOTICS-CELL WALL INHIBITORS
Case-
A sixty eight year old man with type II diabetes presents with a unilateral swollen, red, and tender left foot that has
worsened over the last two days. He has had a fever and felt generally unwell. You suspect cellulitis. The most common
bacterial causes of cellulitis are staph and strep.

Penicillin and Flucloxacillin

V Benzylpenicillin
Oral phenoxymethylpenicillin (Penicillin V)

Case
• A GP is called to see a normally healthy twenty year old university student who has become rapidly unwell over a few
hours. On examination the GP notices signs of sepsis, including fever, tachycardia, sweating, and dry mucus membranes.
No rash or meningism is detected but the GP is concerned at the patient's degree of illness and suspects meningococcal
septicaemia. What is standard primary care management in suspected meningococcal sepsis?
• Give 1g penicillin V by mouth and transfer to hospital
• Give no antibiotics before blood cultures +/- lumbar puncture
• Give 1.2g IM or IV and transfer to hospital
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• If meningitis symptoms and signs are present the patient will be treated in hospital with intravenous antibiotics. As this will be
done before culture results are obtained this is called empirical treatment.
The choice of antibiotic is based on previous experience taking into account:
• The likely type of bacteria which have been sensitive to a specific agent before
• The tissue penetrance of the antibiotic
• The potency of the antibiotic
• The desirable absorption rate (e.g. an example of considering pharmacokinetics)

• The microbiologists at the Royal London Hospital have agreed that suspected
bacterial meningitis should be treated with a certain antibiotic.
• Using the above principles, what type of antibiotic out of the three, is the
treatment of choice?
Trimethoprim Phenoxymethylpenicillin (Penicillin V)
intravenous Cephlosporin
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Which of the following combination is correct?
a) Penicillin: inhibition of cell wall synthesis
b) Cephalosporin: inhibition of protein synthesis
c) Aminoglycoside: inhibition of cell wall synthesis
d) Fluoroquinolones: inhibition of cell wall synthesis

What is a common feature among the following group of antibiotics like

Penicillin, Cephalosporins, Carbapenems, and Monobactams?
a) They all bind penicillin-binding protein-1 and inhibit their transpeptidase activity
b) They all have a β-lactam ring as a part of their biological interaction
c) None of them can penetrate the central nervous system
d) All of the above
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Amoxycillin is similar to Ampicillin in different respects except in ………………
a) Antibacterial spectrum
b) Penicillinase resistance
c) Hypersensitivity reaction
d) Oral absorption
All of the following statements about Clavulanic acid, Sulbactam and Tazobactam
are true, except:
a) Antibiotic activity of beta-lactamases is inhibited by beta-lactamases
b) Inhibits beta-lactamases and can be administered with penicillinase sensitive
penicillins
c) Co-administered with carbapenems to block carbapenemase inactivation
d) Typically co-administered with the cephamycina.
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Amoxycillin is similar to Ampicillin in different respects except in ………………
a) Antibacterial spectrum
b) Penicillinase resistance
c) Hypersensitivity reaction
d) Oral absorption
All of the following statements about Clavulanic acid, Sulbactam and Tazobactam
are true, except:
a) Antibiotic activity of beta-lactamases is inhibited by beta-lactamases
b) Inhibits beta-lactamases and can be administered with penicillinase resistant
penicillins
c) Co-administered with carbapenems to block carbapenemase inactivation
d) Typically co-administered with the cephamycin.
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A 26-year-old male returns home from a holiday and complains of three days of dysuria and
a purulent urethral discharge. He is diagnosed to be a case of gonorrhea.
Which of the following is the appropriate treatment?
a) Ceftriaxone IM
b) Streptomycin
c) Gentamicin
d) Vancomycin IV

Redman syndrome is toxicity associated with

a) Amoxicillin
b) Cefazolin
c) Methicilin
d) Vancomycin
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Cilastatin is given along with Imipenem for the following reason:
a) Inhibition of beta-lactamases thus preventing inactivation of Imipenem
b) Blocking of bacterial transpeptidase and preventing degradation of Imipenem
c) Decreasing hydrolysis of Imipenem
d) Inhibition of renal tubular dipeptidase thus preventing hydrolysis of Imipenem
by renal tubular dipeptidase
Followings are the penicillinase-resistant penicillin, except:
a) Carbenicillin
b) Methicillin
c) Nafcillin
d) Cloxacillin
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Following cephalosporins can cross the blood-brain barrier and therefore can be used in
the treatment of meningitis except
a) Ceftazidime
b) Ceftriaxone
c) Cefotaxime
d) Cefixime

16) Random use of broad-spectrum antibiotics is contraindicated.

They............................................................................................
a) Are extremely nephrotoxic
b) Can produce dependency and psychogenic symptoms
c) Can induce anaphylactoid reactions
d) Can interfere with indigenous microbiota
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Which of the following group of antibiotics show bacteriostatic action?
a) Fluoroquinolones
b) Aminoglycosides
c) Macrolides
d) Monobactams

Which of the following group of antibiotics in accordance with the structure and
mode of action of penicillin?
a) Chloramphenicol
b) Polymyxins
c) Cycloserines
d) Cephalosporins :
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Which of the following antibiotics acts as a protein synthesis inhibitor?
a) Erythromycin, Chloramphenicol
b) Vancomycin, Cephamycin
c) Gentamicin, Tetracycline
d) Options a and c
e) Options b and c
Which of the following antibiotics works by blocking DNA replication?
a) Ofloxacin
b) Rifampin
c) Chloramphenicol
d) Tetracycline
e) cephalosporin
 ANTIBIOTICS-CELL WALL INHIBITORS
Which of the following penicillins has the best gram-negative spectrum?
a) Nafcillin
b) Ampicillin
c) Methicillin
d) penicillin V

All of the following are true statements about the antibiotic ampicillin, EXCEPT:
e) It is a member of the penicillin family of antibiotics
f) itacts by inhibiting biosynthesis of cell wall mucopeptide
g) givenorally, its absorption is adversely affected by food (should be taken on anempty
stomach)
h) It is available in combination with agents that inactivate beta-lactamase
i) It is resistant to penicillinase digestion
 ANTIBIOTICS-CELL WALL INHIBITORS
What is meant by antibiotic resistance?
a) It means our body has become resistant to the antibiotic
b) It means the bacteria have developed antibiotic resistance
c) Both (a) and (b)
d) None of the above

What type of side effect is most commonly observed in beta-lactam antibiotics?

a) Hearing loss
b) Aplastic anaemia
c) Allergic reaction
d) Yellowing of teeth
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What is meant by antibiotic resistance?
a) It means our body has become resistant to the antibiotic
b) It means the bacteria have developed antibiotic resistance
c) Both (a) and (b)
d) None of the above

What type of side effect is most commonly observed in beta-lactam antibiotics?

a) Hearing loss
b) Aplastic anaemia
c) Allergic reaction
d) Yellowing of teeth
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β-lactamases confer antibiotic resistance by
(A) Altering antibiotic permeability
(B) Altering penicillin-binding proteins
(C) Altering 70S ribosome structure
(D) Modifying cellular RNA polymerase
(E) Modifying antibiotic structure

Each of the following statements concerning penicillin is correct EXCEPT:

A. Penicillin inhibits transpeptidases, which are required for cross-linking peptidoglycan.
B. Penicillin is a bacteriostatic drug because autolytic enzymes are not activated.
C. An intact β-lactam ring of penicillin is required for its activity.
D. The structure of penicillin resembles that of a dipeptide of alanine, which is a component of peptidoglycan.
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Classification
Glycopeptide
 Vancomycin Disrupts peptidoglycan cross linkages
Indications
Bactericidal
1.
Serious allergies to penicillins
or β-lactams Spectrum of activity:
MRSA, S. aureus, S. epidermidis
2.
Serious infections caused by (gram +ve bacteria)
susceptible organisms
(MRSA, MRSE)
Orally: Clostridium difficle
Toxicity Resistance:
Red man syndrome (RMS, or Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM / NAG
VFS)
peptide) e.g. vancomycin resistant enterococcus (VRE)
Nephrotoxicity
NAM: N-acetyl muramic acid
Ototoxicity
ANTIBIOTICS-CELL WALL INHIBITORS
 ANTIBIOTICS-CELL WALL INHIBITORS
Classification
Glycopeptide
RESISTANCE TO VANCOMYCIN
 Vancomycin
ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action
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Mechanism of Action
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Mechanism of Action
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Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
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Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Resistance
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action
Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action
Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
 ANTIBIOTICS-CELL WALL INHIBITORS
Mechanism of Action

Transpeptidases
(Penicillin Binding
Proteins)
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Classification
Glycopeptide
RESISTANCE TO VANCOMYCIN
 Vancomycin
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MECHANISMS OF RESISTANCE TO PENICILLINS

1.
Bacteria produce β-lactamase (penicillinase) which hydrolyze β-lactam ring of penicillins.

2.
Loss or alteration of porin channels (gram –ve)

3.
Modification of Penicillin binding proteins (PBP)-low affinity
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Classification
1. Penicillins 2. Cephalosporins 4. Glycopeptide
 1st Generation Vancomycin
 Natural penicillins  2nd Generation
 3rd Generation
5. β-lactamase inhibitors
 Aminopenicillins  4th Generation
 Clavulanic acid
 Salbactum
 Penicillinase- 3. Carbapenems
resistant penicillins  Tazobactum
 Imipenam
 Merpenam 6. Monobactam
 Anti-pseudomonal  Aztreonam
 Doripenam
penicilins
 Irtapenam
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Classification
CEPHAOLSPORINS CEFALEXIN (oral) CEFADROXIL
 1st Generation CEFAZOLIN (i.v.) CEPHRADINE
*less susceptible to β-lactamase
 2nd Generation Toxicity:
• 10% cross reactivity of penicillin allergy
 3rd Generation • Nephrotoxicity
• Coomb’s positive anemia (3%)
 4th generation INDICATIONS (cefalexin)
Skin and soft tissue infections
Prevention of surgical site infections
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Classification
CEPHAOLSPORINS
Cepfamandole (bleeding problem) Cefoxitin (bleeding problem)

Cefmetazole (bleeding problem) Cefprozil-----oral

 1 Generation
st

Cefotiam Cefaclor
 2nd Generation Cefuroxime—oral and i.v. (GREATER POTENCY, SLOWER CLEARANCE, GREATER
SENSITIVITY THAN CEFACLOR)

 3rd Generation Cefotetan----

problem)
single dose (long t1/2 as compared to cefoxitin) (bleeding
Ceforanide Toxicity
 4th generation
Cefonicid • Disulfiram reaction
• Gram +ve weaker than 1st generation
• Gram –ve same as in 1st Gen, and includes anaerobe
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Cefotetan
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Classification
CEPHAOLSPORINS INDICATIONS
 1st Generation
Upper lower respiratory tract infections
 2nd Generation
NOT for bacteremia
soft tissue infections
 3rd Generation

 4th generation
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Classification
CEPHAOLSPORINS CEFTRIAXONE (single dose i.v. as compared to cefotaxime)
 1st Generation CEFOTAXIME
CEFTAZIDIME Toxicity
• Disulfiram reaction
CEFDINIR
 2 Generation
nd • 1% penicillin allergy cross
CEFIXIME (ORAL ONLY, not cross BBB) reactivity
CEFOPRAZONE
 3rd Generation
Spectrum: Same as in 2nd Gen
 4th generation + Gram “–ve” i.e., pseudomonas

Some have less activity against gram +ve bacteria.

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Ceftriaxone and cefotaxime

Ceftriaxone
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Classification
CEPHAOLSPORINS
INDICATIONS
 1st Generation Community acquired pneumonia (cefotaxime, ceftriaxone)
Community acquired bacterial meningitis (cefotaxime,
 2nd Generation ceftriaxone)
Gonorrhea (ceftriaxone only)
 3rd Generation Abdominal or pelvic infections (cefotaxime or ceftriaxone +
metronidazole)

 4th generation
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Classification
CEPHAOLSPORINS CEFEPIME
 1st Generation CEFPIROME
 2nd Generation
They can cross BBB and are effective in meningitis

 3rd Generation
Broad spectrum antibiotic for gram +ve and gram –ve.

 4th Generation
For empiric therapy of neutropenia
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Classification
CEPHAOLSPORINS CEFTAROLINE
 5th Generation CEFTOBIPROLE

Used to treat
• MRSA (methicillin-resistant Staphylococcus aureus),
• penicillin-resistant Streptococcus pneumoniae,
• Pseudomonas aeruginosa
• Enterococci.