Understanding Antibiotics: Mechanisms of Action and Therapeutic Index

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LECTURE: ANTIBIOTIC 
IMPORTANT.
EXTRA INFORMATION.
D
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Objectives
Define antibiotic, chemotherapy and selective toxicity.
Describe the difference between bactericidal and bacteriostatic antibiotics
Recognize the narrow and broad spectrum antibiotics
Define the therapeutic index
Know the mechanism of action of antimicrobial agents
Recognize the various classes of antimicrobial agents (action, spectrum and side effects.)
Explain the criteria for an ideal antimicrobial.
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  ANTIMICROBIAL AGENTS
ANTIBIOTICS:
Natural compounds produced by
microorganism  which inhibit the
growth of other microorganism
.
Like :penicillin
SELECTIVE TOXICITY:
The 
ability to kill or inhibit the growth 
of a microorganism
without harming the host cells
.
CHEMOTHERAPY
:
Synthetic compound.
Antimicrobial agents
.
**صنع الشركات مش طبيعية**
Toxicity
Therapeutic Index:
The 
RATIO
 of the dose 
toxic
 to the host to the effective
therapeutic
 dose.
Examples
 
:
Penicillin
 
 
High
Aminoglycosides 
 
low
Polymyxin B 
 
the lowest
Low  
  less safety , more toxicity 
High 
 more safety , less toxicity
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Activity of antimicrobial agent
Spectrum of activity
BACTERICIDAL :
kills bacteria
100% will kill the
bacteria
BACTERIOSTATIC:
prevents multiplication 
And help our immune
system to overcome them
Broad spectrum :
Gram positive & Gram negative  bacteria
 
حتى الهوائية واللاهوائية
The best
Narrow spectrum:
 
selected organism
Activity:
Mechanisms of Action of antimicrobials
1)  Inhibition of 
cell wall synthesis.
2)  alteration of 
cell membrane
3)  Inhibition of 
protein synthesis
4)  Inhibition of 
nucleic acid synthesis
5)  
Anti-metabolite
 OR competitive antagonism.
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Mechanisms of Action of antimicrobials
Mechanisms of Action of antimicrobials
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Beta –Lactam
antimicrobial agents
Vancomycin
( Teicoplanin )
o
Penicillins
o
Cephalosporins
o
Cephamycin
o
Carbapenems
       (imipenem & meropenem)
o
Monobactams (aztreonam)
o
Beta-Lactamase inhibtors
Polymyxin B
Colistin
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Rifamycins
Quinolones
Metronidazole
Inhibit folate metabolism
Trimethoprim
Sulfamethoxazole
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1) Inhibition of cell wall synthesis 
1) Inhibition of cell wall synthesis 
Beta –Lactam antimicrobial agents 
Beta –Lactam antimicrobial agents 
*Contain: 
Beta-lactum ring 
and organic acid
*It can be natural or semi-synthetic
*
Bactericidal
*Bind to penicillin binding protein (PBP) and
interfere with trans-peptidation reaction.
*Toxicity: mainly
1/Hypersensitivity (allergy)
2/Anaphylaxis
3/Diarrhea
β- Lactam antibiotics 
 
Penicillins
Benzyl Penicillin :
Act mainly on 
gram +ve
Ex: Penicillin V
Benzathine Penicillin
Procaine Penicillin = Penicillin G
Isoxazolyl Penicillins :
Act on 
staphylococcus aureus
Ex: 
Cloxacillin
 
Amino-Penicillins :
Act on 
Enterobacteria
Ex : 
Ampicillin
Acylaminopenicillin :
Act on 
Psudomonas
Ex: 
Piperacillin
      Mezlocillin
1
st
 Generation :
Ex: Cephradine
Ceohalexine 
act on +ve
2
nd
 Generation :
Ex: 
Cefuroxime
Cephamycin (Cefoxitin)
3
rd
 Generation 
:
Expanded spectrum 
Ex : 
Ceftriaxone
       Ceftazidime
4
th
 Generation :
Ex : Cefepim
       Ceftobiprole
 
Cephalosporins
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1) Inhibition of cell wall synthesis 
1) Inhibition of cell wall synthesis 
Beta –Lactam antimicrobial agents 
Beta –Lactam antimicrobial agents 
 Beta-Lactamase inhibitors
 
β
-Lactams with no antibacterial activity
Irreversibly bind to 
β
-lactamase enzyme
Ex : Clavulanic acid, Sulbactam, Tazobactam
Effective on staph. Penicillinases and broad spectrum 
β
-lactamases.
eg. 
amoxicillin/clavulanic acid, ticarcillin /clavulanic acid and
piperacillin /tazobactam.
Beta-Lactamase area enzymes in Bacteria act on
Beta –Lactam antimicrobial agents and destroy
Beta –Lactam antimicrobial agents and destroy
Beta-lactin ring  on them , so to solve these
problem we creative  Beta-Lactamase inhibitors 
To
To
inhibit these enzymes
inhibit these enzymes
Vancomycin
Vancomycin
Glycopeptides
Bactericidal
*inhibit cell wall synthesis.
Acts on 
Gram positive bacteria
only
 ( 
narrow
 
spectrum
).
Given by 
injection
 only.
Used for  (
MRSA
)
               S.epidemidis
             pseudomembranous colitis
Side effects:   
Red man syndrome
                               phlebitis,
                         nephrotoxic & ototoxic.
MRSA = methicillin resistant S.aureus systemic infections 
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  Classification of Antimicrobials
 
1) Inhibit 
cell wall 
synthesis
Beta –Lactam antimicrobial
agents
Penicillins 
Cephalosporins
Carbapenems
Monobactams (aztreonam)
Vancomycin
Vancomycin
 
( Teicoplanin )
Eg. 
Penicillin G
+ve, some anaerobes
       Ampicillin
Penicillin, +ve/-ve,
 anaerobes
       Pipracillin
Cover 
Pseudomonas
Inhibit 
peptoglycan
Side Effect =
Hypersensitivity
=anaphylaxis shock
Eg. 1
st
 generation
= 
Cephalexin
+ve
2
nd
 generation
= 
Cefuroxime 
+ve/-ve, Anaerobes
3
rd
 generation
= 
Ceftriaxone  
-ve
Eg. 
Vancomycin
Narrow
 spectrum
Cover 
Only +ve
Used as last option
As multidrug resistance
Gram +ve 
Can be given IV
Side Effect =
Red Man Syndrome
Allergy, when you give
Antihistamine 
= recover slowly 
Inhibit 
peptoglycan
Inhibit 
peptoglycan
Side Effect =
Hypersensitivity
=anaphylaxis shock
Note:  all antibiotic cause GIT Side effect
مهم   
Mechanism 
of action
*
*
*
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2) Inhibit of Cell Membrane
2) Inhibit of Cell Membrane
Polymyxin B :
 a Peptide active against 
Gram negative bacteria 
only.
Bactericidal
Only used locally due to serious 
nephrotoxicity
 when used systemically
 .
Colistin
 :
 a Peptide active against 
Gram negative bacteria 
only.
 
used for the treatment of 
multi-resistant organisms (MRO)
            such as  Pseudomonas and Acinetobacter infections.
Polymyxin B  Only used LOCALLY  (قطرة أذن – قطرة عين) وهذا كان قديماً أما الآن فليس فقط
جزئي
^وهو مضاد جديد يستخدم للحالات الصعبة جداً لفعاليته العالية , لكن مشكلته أن له نسبة سمومية كبيرة تقريباً
*
*
*
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3) Inhibit protein synthesis
3) Inhibit protein synthesis
 
Aminoglycosides
Bactericidal
Acts only on 
Gram –ve bacteria
      
( 
narrow
 spectrum)
Streptococci & anaerobes are
naturally resistant
Ex : Gentamicin
             Amikacin
             
Neomycin
            Tobramycin
Given by injection .
Side effects :
Nephrotoxic & Ototoxic
        dose related.
bacteriostatic
Broad spectrum
not used for children under 8 yrs.
or pregnant women.
Oral absorption.
Effective for Intracellular organisms
 Ex:  
Mycoplasma
, 
Chlamydia, 
Rickettsiae
,Brucella also for V. cholera & Nocardia
.
Side effects : teeth 
discoloration
                               GIT disturbance
Classes  
- 
Short acting
: Tetracycline
- 
Long acting: 
Minocycline
,Doxycycline  ( good CSF penetration).
- 
New tetracycline 
: Tigycycline
(covers MRSA,MSSA, some Gram
negative bacteria and anaerobes)
 
Tetracyclines
bactericidal
Broad spectrum
Side effects : 
it affects 
bone marrow
cells and cause aplastic
anemia
 
Used only for severe
infections not
responding to
treatment by other
antimicrobials , also
for the treatment of
Rickettsial diseases. 
Used also topically for
eye and ear infections
 
Chloramphenicol
Bacteriostatic
Erythromycin
 & Clindamycin
Good activity on :Legionella,
Camylobacter, 
Gram negative
and positive infections 
for
patients allergic to Penicillins
and Cephalosporins.
 Clindamycin acts on anaerobes
Side effects : GIT disturbance,
Pseudomembraneous colitis
       (mainly clindamycin).
New Macrolides :
Azithromycin & Clarithromycin 
 
Less side effects , better
penetration and longer half life
.
Macrolides
*Macrolides
50 Sub Unit of 23 r RNA
*Tetracycline
S30S ribosomal subunit
*Aminoglycosides
S30S ribosomal subunit
*Chloramphenicol
50 Sub Unit of 23 r RNA
** you don’t have to know them actually, just for your knowledge the
ribosome  is compose of two subunit the large is 50S and the smal is 30S
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3) Inhibit 
protein synthesis
 
Bone Marrow
Suppression 
8
th
 nerve effect ear and balance
Increase drug = effect bone nerve
No renal problems
*
*
*
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4) Inhibition of nucleic acid synthesis.
4) Inhibition of nucleic acid synthesis.
Bactericidal
Semi-synthetic
acts on 
Gram positive bacteria and selected Gram negative bacteria
.
Reserved for Tuberculosis 
(Anti TB)
Resistance develops quickly
Used in combination
Side effects : hepatotoxicity.  & discoloration of body fluids
Bactericidal
Synthetic, bactericidal
 inhibit DNA Gyrase and /or Topoisomerase.
Generations
:
o
1
st
 Generation: Nalidexic acid  locally acting
                              (
Broad spectrum)
o
2
nd
 Generation: 
Fluoroquinolones
 (
Narrow : Gram –ve
)
Ex. 
Ciprofloxacin
, Norfloxacin, Ofloxacin,Levofloxacin
o
3
rd
 Generation: Sparfloxacin, Gatifloxacin
o
 4
th
 Generation: 
Moxifloxacin
, Trovafloxacin 
(
Anaerobes
)
Side effects: affects cartilage & heart
 
Quinolones
Rifampicin
Metronidazole
Bactericidal
Nitroimidazole active on anaerobic bacteria and also parasite.
Causes DNA breakage.
Used for the treatment of infections due to  
B.fragilis
 , Trichomonas vaginalis
                                                                   and also for amoebiasis and giardiasis. (
Antiprotozoal
)
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4) Inhibition of 
nucleic acid 
synthesis.
الدكتور تكلم عنها بس ما ضللها بالجدول..
*
*
*
1
st
 Generation
2
nd
  Generation
4
th
 Generation
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5) Antimetabolites (Folate inhibition) 
5) Antimetabolites (Folate inhibition) 
Bacteriostatic
Trimethoprim-Sulfamethoxazole ( TMP-SMX)
Combination of TMP-SMX called 
:  Bactrim / Septrin
 
(اسم تجاري)   
Block sequential steps in 
folic acid synthesis
Used to treat :
 
Nocardia, Chlamydia, Protozoa & P.cranii infection.
Used for the treatment of: upper & lower respiratory tract infections ,
otitis media, sinusitis & infectious diarrhea.
Side effects:   GIT, hepatitis , bone marrow depression, hypersensitivity
5) Inhibit 
folate
 metabolism/
bacterial growth
Trimethoprim
Sulfamethoxazole
***
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Classification
Classification
 of 
Antimicrobials
Antimicrobials
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Beta –Lactam
antimicrobial agents
Vancomycin
o
Penicillins
o
Cephalosporins
o
Carbapenems
       (imipenem & meropenem)
o
Monobactams (aztreonam)
 
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Clindamycin
Oxazolidinones 
Streptogramins
(linezolid)
Quinupristin
dalfopristin
Rifamycins
Quinolones
Metronidazole
Inhibit folate metabolism
Trimethoprim
Sulfamethoxazole
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M
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Metronidazole
Daptomycin
Miscellaneous : including
 many thing of different kinds
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Bactericidal
   
Penicillin
Cephalosporins
Carbapenems
Monobactams
Vancomycin
Aminoglycosides
Fluoroquinolones
Metronidazole
Rifampin
Isoniazid
Bacteriostatic
Tetracyclines
Doxycycline
Macrolides
Sulfonamides
***
Antibiotic for Anaerobic
 Metronidazole
Moxifloxacin
Clindamycin
Antibiotic for +ve gram only
Vancomycin
Cephalexin
Antibiotic for -ve gram only
Colistin & 
Polymyxin B 
Aminoglycosides
Fluoroquinolones
Sulfadiazine
Narrow spectrum
Can cause Nephrotoxicity as side effect
Aminoglycosides
Colistin & 
Polymyxin B
Can cause hepatotoxicity as side effect
Rifampin
Can cause Hypersensitivity as side effect
Penicillins
Cephalosphorins
We can not use it with pregency women
Tetracyclines
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Antituberculous agents:
First line
:
o
 Isonlazide (inh)
o
Rifampicin
o
Ethambutol
o
Pyrazinamide
second line
:
o
streptomycin
o
PASA
o
cycloserine,
o
capreomycin
If the 1
st
 line does not work,
they use the 2
nd
 line
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Antibiotic Resistance in Bacteria
Cross resistance 
:
Resistance to one group confer resistance to  other drug of the same group .
eg. Resistance to 
erythromycin
 and 
clindamycin
Dissociate resistance
:
 resistance to 
gentamicin
 does not confer resistance to 
tobramycin
 .
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Long term:
Tuberculosis, rheumatic fever
recurrent urinary tract infections,
Short term:
Meningitis
Antibiotic Resistance in Bacteria
#
#
 
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^
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Antibiotics play a crucial role in combating microbial infections by either killing or inhibiting bacteria. This lecture covers important topics such as the difference between bactericidal and bacteriostatic antibiotics, spectrum of activity, and the therapeutic index. It also explores the mechanisms of action of antimicrobial agents and the importance of selective toxicity in antibiotic treatment.


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  1. microbiology microbiology LECTURE: ANTIBIOTIC *** Imp IMPORTANT. EXTRA INFORMATION. DOCTOR S NOTE

  2. Objectives Define antibiotic, chemotherapy and selective toxicity. Describe the difference between bactericidal and bacteriostatic antibiotics Recognize the narrow and broad spectrum antibiotics Define the therapeutic index Know the mechanism of action of antimicrobial agents Recognize the various classes of antimicrobial agents (action, spectrum and side effects.) Explain the criteria for an ideal antimicrobial.

  3. Toxicity ANTIMICROBIAL AGENTS SELECTIVE TOXICITY: The ability to kill or inhibit the growth of a microorganism without harming the host cells. Therapeutic Index: The RATIO of the dose toxic to the host to the effective therapeutic dose. Examples: Penicillin High Aminoglycosides low Polymyxin B the lowest High more safety , less toxicity CHEMOTHERAPY: Synthetic compound. Antimicrobial agents. ** ANTIBIOTICS: Natural compounds produced by microorganism which inhibit the growth of other microorganism. Like :penicillin Low less safety , more toxicity **

  4. Mechanisms of Action of antimicrobials Activity: 1) Inhibition of cell wall synthesis. Activity of antimicrobial agent 2) alteration of cell membrane BACTERICIDAL : kills bacteria 100% will kill the bacteria BACTERIOSTATIC: prevents multiplication And help our immune system to overcome them 3) Inhibition of protein synthesis 4) Inhibition of nucleic acid synthesis Spectrum of activity The best 5) Anti-metabolite OR competitive antagonism. Broad spectrum : Gram positive & Gram negative bacteria Narrow spectrum: selected organism

  5. Mechanisms of Action of antimicrobials 5 5) ) Anti Anti- -metabolite metabolite OR OR Competitive antagonism Competitive antagonism. . 4 4) ) Inhibition Inhibition of nucleic acid nucleic acid synthesis synthesis of 1 1) Inhibition of ) Inhibition of cell wall cell wall synthesis synthesis 2 2) ) alteration alteration of of Cell Cell membrane membrane 3) Inhibition of 3) Inhibition of protein protein synthesis synthesis Inhibit folate metabolism Aminoglycosides Beta Lactam antimicrobial agents Rifamycins Polymyxin B Trimethoprim Tetracyclines o o o o (imipenem & meropenem) o Monobactams (aztreonam) o Beta-Lactamase inhibtors Penicillins Cephalosporins Cephamycin Carbapenems Colistin Quinolones Chloramphenicol Sulfamethoxazole Macrolides Metronidazole Vancomycin ( Teicoplanin )

  6. 1) Inhibition of cell wall synthesis Beta Lactam antimicrobial agents Penicillins Benzyl Penicillin : Act mainly on gram +ve Ex: Penicillin V Benzathine Penicillin Procaine Penicillin = Penicillin G Isoxazolyl Penicillins : Act on staphylococcus aureus Ex: Cloxacillin Cephalosporins - Lactam antibiotics *Contain: Beta-lactum ring and organic acid *It can be natural or semi-synthetic 1st Generation : Ex: Cephradine Ceohalexine act on +ve 2nd Generation : Ex: Cefuroxime Cephamycin (Cefoxitin) *Bactericidal *Bind to penicillin binding protein (PBP) and interfere with trans-peptidation reaction. 3rd Generation : Expanded spectrum Ex : Ceftriaxone Ceftazidime *Toxicity: mainly 1/Hypersensitivity (allergy) 2/Anaphylaxis 3/Diarrhea Amino-Penicillins : Act on Enterobacteria Ex : Ampicillin Ex : Cefepim Ceftobiprole 4th Generation : Acylaminopenicillin : Act on Psudomonas Ex: Piperacillin Mezlocillin

  7. 1) Inhibition of cell wall synthesis Vancomycin Beta Lactam antimicrobial agents Beta-Lactamase inhibitors -Lactams with no antibacterial activity Glycopeptides Bactericidal *inhibit cell wall synthesis. Irreversibly bind to -lactamase enzyme Acts on Gram positive bacteria only ( narrowspectrum). Ex : Clavulanic acid, Sulbactam, Tazobactam Effective on staph. Penicillinases and broad spectrum -lactamases. Given by injection only. eg. amoxicillin/clavulanic acid, ticarcillin /clavulanic acid and piperacillin /tazobactam. S.epidemidis pseudomembranous colitis Used for (MRSA) Beta-Lactamase area enzymes in Bacteria act on Beta Lactam antimicrobial agents and destroy Beta-lactin ring on them , so to solve these problem we creative Beta-Lactamase inhibitors To inhibit these enzymes nephrotoxic & ototoxic. Side effects: Red man syndrome phlebitis, MRSA = methicillin resistant S.aureus systemic infections

  8. *** Classification of Antimicrobials Mechanism of action Penicillins Glycopeptides 1) Inhibit cell wall synthesis Cephalosphoeins Beta Lactam antimicrobial agents Penicillins Cephalosporins Carbapenems Monobactams (aztreonam) Vancomycin Eg. Penicillin G +ve, some anaerobes Ampicillin Penicillin, +ve/-ve, anaerobes Pipracillin Cover Pseudomonas Eg. 1st generation = Cephalexin +ve 2nd generation = Cefuroxime +ve/-ve, Anaerobes Eg. Vancomycin Narrow spectrum Cover Only +ve Used as last option As multidrug resistance Gram +ve Can be given IV Vancomycin ( Teicoplanin ) 3rd generation = Ceftriaxone -ve Inhibit peptoglycan Inhibit peptoglycan Inhibit peptoglycan Side Effect = Red Man Syndrome Allergy, when you give Antihistamine = recover slowly Side Effect = Hypersensitivity =anaphylaxis shock Note: all antibiotic cause GIT Side effect Side Effect = Hypersensitivity =anaphylaxis shock

  9. 2) Inhibit of Cell Membrane 2) Inhibit of Cell Membrane Polymyxin B : a Peptide active against Gram negative bacteria only. Bactericidal Only used locally due to serious nephrotoxicity when used systemically . Eg. Colistin & Polymyxin B , ) ( Polymyxin B Only used LOCALLY ^ *Narrow Spectrum *Gram ve Colistin : a Peptide active against Gram negative bacteria only. used for the treatment of multi-resistant organisms (MRO) such as Pseudomonas and Acinetobacter infections. *Used as multidrug resistance gram -ve Side Effect *** = Nephrotoxicity

  10. 3) Inhibit protein synthesis Aminoglycosides Bactericidal Macrolides Tetracyclines Chloramphenicol Bacteriostatic bacteriostatic bactericidal Erythromycin & Clindamycin Broad spectrum not used for children under 8 yrs. or pregnant women. Acts only on Gram ve bacteria ( narrow spectrum) Broad spectrum Good activity on :Legionella, Camylobacter, Gram negative and positive infections for patients allergic to Penicillins and Cephalosporins. it affects bone marrow cells and cause aplastic anemia Side effects : Oral absorption. Streptococci & anaerobes are naturally resistant Effective for Intracellular organisms Ex: Mycoplasma, Chlamydia, Rickettsiae Amikacin Neomycin Tobramycin Ex : Gentamicin ,Brucella also for V. cholera & Nocardia . Side effects : teeth discoloration GIT disturbance Classes - Short acting: Tetracycline Used only for severe infections not responding to treatment by other antimicrobials , also for the treatment of Rickettsial diseases. Clindamycin acts on anaerobes Side effects : GIT disturbance, Pseudomembraneous colitis (mainly clindamycin). Azithromycin & Clarithromycin Less side effects , better penetration and longer half life. Given by injection . New Macrolides : - Long acting: Minocycline ,Doxycycline ( good CSF penetration). - New tetracycline : Tigycycline (covers MRSA,MSSA, some Gram negative bacteria and anaerobes) Nephrotoxic & Ototoxic dose related. Side effects : Used also topically for eye and ear infections *Macrolides 50 Sub Unit of 23 r RNA *Chloramphenicol 50 Sub Unit of 23 r RNA *Aminoglycosides S30S ribosomal subunit *Tetracycline S30S ribosomal subunit ** you don t have to know them actually, just for your knowledge the ribosome is compose of two subunit the large is 50S and the smal is 30S

  11. 3) Inhibit protein synthesis *** Macrolides & Lincosamides Aminoglycosides Tetracyclines Chloramphenicol Eg. Gentamicin Spectrum of activity Eg. Erythromycin & Clindamycin Amikacin Broad Spectrum the treatment of Rickettsial diseases Tobramycin = Broad spectrum neomycin Spectrum of activity All are gram ve Side Effect Eg. Clindamycin = Rickettsiae Bactericidal = bone marrow = spectrum acts on anaerobes Mycoplasma Narrow spectrum a plastic anemia Clamydia Side Effect Side Effect New Macrolides : Azithromycin Clarithromycin = Discoloration in children = Otoxicit and Nephrotoxicity Pregnant = destruct bone of baby Bone Marrow Suppression Side Effect 8th nerve effect ear and balance Increase drug = effect bone nerve No renal problems = GIT pseudo- membranous Colitis

  12. 4) Inhibition of nucleic acid synthesis. Rifampicin Quinolones Bactericidal Semi-synthetic acts on Gram positive bacteria and selected Gram negative bacteria. Reserved for Tuberculosis (Anti TB) Resistance develops quickly Used in combination Side effects : hepatotoxicity. & discoloration of body fluids Bactericidal Synthetic, bactericidal inhibit DNA Gyrase and /or Topoisomerase. Generations: o 1st Generation: Nalidexic acid locally acting (Broad spectrum) o 2nd Generation: Fluoroquinolones (Narrow : Gram ve) Metronidazole Ex. Ciprofloxacin, Norfloxacin, Ofloxacin,Levofloxacin Bactericidal o 3rd Generation: Sparfloxacin, Gatifloxacin Nitroimidazole active on anaerobic bacteria and also parasite. o 4th Generation: Moxifloxacin, Trovafloxacin (Anaerobes) Causes DNA breakage. Side effects: affects cartilage & heart Used for the treatment of infections due to B.fragilis , Trichomonas vaginalis and also for amoebiasis and giardiasis. (Antiprotozoal)

  13. 4) Inhibition of nucleic acid synthesis. *** Quinolones Metronidazone Rifampicin .. Eg. Nalidixic acid Eg. Nitroimidazoles Anti-TB 1st Generation =Broad spectrum Anaerobes Gram +ve/-ve Gram +ve/ ve, anaerobes Flouroquinolones Used with other drug NOT alone. Eg. Ciprofloxacin Bactericidal; anaerobes 2nd Generation =Narrow spectrum Also Antiprotozoal Because it will create resistance immediately Gram ve Eg. Moxifloxacin Side Effect Side Effect 4th Generation Anaerobes = GIT = Hepatotoxicity Side Effect = Cartilage damage

  14. 5) Antimetabolites (Folate inhibition) Bacteriostatic 5) Inhibit folate metabolism/ bacterial growth Trimethoprim Sulfamethoxazole Sulfonamides Trimethoprim-Sulfamethoxazole ( TMP-SMX) ) ( Combination of TMP-SMX called : Bactrim / Septrin Eg. Sulfadiazine Block sequential steps in folic acid synthesis Used to treat : Nocardia, Chlamydia, Protozoa & P.cranii infection. Blocks folic acid synthesis Used for the treatment of: upper & lower respiratory tract infections , otitis media, sinusitis & infectious diarrhea. Bacteriostatic Side effects: GIT, hepatitis , bone marrow depression, hypersensitivity Grame ve Used a lot in hospital http://upload.wikimedia.org/wikipedia/en/e/e9/THFsynthesispathway.png Side Effect = GIT ***

  15. Classification of Antimicrobials *** 4 4) Inhibition of ) Inhibition of nucleic acid synthesis acid synthesis nucleic 5 5) ) Anti Anti- -metabolite metabolite OR Competitive antagonism. Competitive antagonism. OR 3 3) Inhibition of ) Inhibition of protein synthesis synthesis protein 1 1) Inhibition of ) Inhibition of cell wall synthesis synthesis cell wall Miscellaneous Miscellaneous Aminoglycosides Beta Lactam antimicrobial agents Inhibit folate metabolism Tetracyclines Metronidazole Rifamycins o o o (imipenem & meropenem) o Monobactams (aztreonam) Penicillins Cephalosporins Carbapenems Trimethoprim Chloramphenicol Daptomycin Macrolides Quinolones Sulfamethoxazole Clindamycin Miscellaneous : including many thing of different kinds Oxazolidinones (linezolid) Vancomycin Metronidazole Streptogramins Quinupristin dalfopristin ) ( ###

  16. Bactericidal and Bacteriostatic ### *** Narrow spectrum Bactericidal Antibiotic for Anaerobic Metronidazole Moxifloxacin Clindamycin Penicillin Cephalosporins Carbapenems Monobactams Vancomycin Aminoglycosides Fluoroquinolones Metronidazole Rifampin Isoniazid Can cause Nephrotoxicity as side effect Aminoglycosides Colistin & Polymyxin B Can cause hepatotoxicity as side effect Rifampin Can cause Hypersensitivity as side effect Penicillins Cephalosphorins Antibiotic for +ve gram only Vancomycin Cephalexin Antibiotic for -ve gram only Colistin & Polymyxin B Aminoglycosides Fluoroquinolones Sulfadiazine We can not use it with pregency women Tetracyclines Bacteriostatic Tetracyclines Doxycycline Macrolides Sulfonamides

  17. Antituberculous agents: First line: o Isonlazide (inh) o Rifampicin o Ethambutol o Pyrazinamide Side Effect ### second line: o streptomycin Anti TB Elhambiotd Pyrazinamide o PASA cycloserine, isoniazide (INH) o o capreomycin Side Effect Side Effect Side Effect = Hepatotoxicity peripheral neuropathy = Optic neurititis If the 1st line does not work, they use the 2nd line = Hepatitis, arthraglia (gout) (color blindness) + turn urine and tears into red/pink + Hepatotoxicity *** Antibiotics class ACTION USE S/E Hepatotoxicity Bacteriocidal All lung tissue T.B treatment and prophylaxis peripheral neuropathy (pyridoxine (vitamin B6)) Anti TB isoniazide (INH) bactericidal Elhambiotd concentrated lung alveoli phagolysosome Acid environment of macrophages TB treatment Optic neurititis Pyrazinamide TB treatment Hepatitis, arthraglia (gout)

  18. Antibiotic Resistance in Bacteria Types of Resistance Innate resistance (primary resistance) Acquired resistance (primary resistance) Selective pressure resistance o Naturally resistance. Called Constitutive resistance. 1) Mutation: 2) Gene Transfer: Bacteria Mutant (like 1 in 10000) And when Antibiotic used lead to kill all sensitive stray Ex: Mycobacterium Resistance to Streptomycin . Acquired from other bacteria Called Horizontal o Eg: Streptococcus & anaerobes are resistant to gentamicin. Resulting in survival of resistance stray o Called Vertical Either Plasmid mediated using sex pilli (resistance transferred within same species) o Mutation during replication in DNA formation Or through Transposons (can transfer resistance from gram +ve to ve) o Mother to child Cross resistance : Resistance to one group confer resistance to other drug of the same group . eg. Resistance to erythromycin and clindamycin Dissociate resistance: resistance to gentamicin does not confer resistance to tobramycin .

  19. Antibiotic Resistance in Bacteria Mechanisms of resistance Principles of antimicrobial therapy Criteria for ideal antimicrobial agent Indication Choice of drug Route Dosage Duration Distribution Excretion Toxicity Combination use as in tuberculosis (SYNERGISTIC, ANTAGONISTIC or ADDIDITIVE) 1- Permeability changed Has selective toxicity Causes no hypersensitivity 2- Modification of site of action, e.g. Mutation. Penetrate tissues quickly Resistance does not develop quickly 3- Inactivation by enzymes . E.g. Beta- Lactamase & aminoglycoside inactivating enzymes. Has no effect of normal flora Broad spectrum 4- Passing blocked metabolic reaction e.g. PABA ( para amino benzoic acid) folic acid , and is plasmid mediated. USE (PROPHYLAXIS, EMPIRIC or DEFINITE) Long term: Tuberculosis, rheumatic fever recurrent urinary tract infections, Short term: Meningitis ^^ ##

  20. Antibiotics class Examples Mechanisms Spectrum of Activity S/E INHIBITION OF CELL WALL Bactericidal-most active against gram +; synthetic and potentiated penicillin have improved gram coverage Penicillin G +ve, some anaerobes Ampicillin Penicillin, +ve/-ve, anaerobes Pipracillin Cover Pseudomonas Natural; penicillin G Semi- synthetic: oxacillin, ampicillin- clavulanic acid, ampicillin- sulbactam Pipracillin Penicillins 1ST generation: cephalothin, cephalexin, 2nd generation: Cefuroxime 3rd generation: ceftriaxone, ceftazidime 4th generation: cefepime Inhibit peptoglycan synthesis necessary for cell-wall formation Bactericidal Hypersensitive, anaphylaxis GIT 1st gen: Gram +, limited Gram - 2nd gen: Gram+, improved Gram and some anaerobes. 3rd gen: limited Gram+, excellent Gram- and anaerobes CEPHALOSPHORINS Inhibit Red man syndrome Nepro and ototoxicity Glycopeptides Vancomycin Peptidoglycan synthesis Bacteriocidal; Gram+ve bacteria only MRSA Inhibition of cell Membrane Alter cell memnrano permeability Polymyxin Colistin Bacteriocidal; Gram-ve bacteria Nephrotoxicity

  21. Antibiotics class Examples Mechanisms Spectrum of Activity S/E Inhibition of protein synthesis (Ribosome) Aminoglycosides Gentamicin, amikacin, tobramycin, neomycin Bind 30S ribosomal subunit; inhibit peptide elongation Bactericidal; Gram-, includingPseudomonas and Mycobacterium, Streptococcus and anaerobes are resistant Ototoxicity snd Nephrotoxicity Tetracyclines Tetracyclines, doxycycline Bind 30S subunit; inhibit RNA function Bacteriostatic; Gram+ and Gram -; Rickettsiae, Mycoplasma, Clamydophila Teeth discoloration GIT photosensitivity Chloramphenicol Chloramphenicol Bind 50S subunit, inhibit protein synthesis Bacteriostatic; broad Gram+ and Gram- spectrum BM a plastic anemia Macrolides and Erythromycin Azithromycin Clarithromycin Bind 50S subunit; inhibit protein synthesis Bacteriostatic; Gram+, Legionella, Camphylobacter, Mycoplasma, Chlamydophila, Ricketstsiae, good anaerobic spectrum GIT pseudo-membranous colitis lincosamides Clindamycin

  22. Antibiotics class Examples Mechanism Spectrum of Activity S/E INHIBITION OF NUCLEIC ACID SYNTHESIS Bactericidal; Gram +ve and gram -ve, INCLUDING Pseudomonas at a higher dosage Inhibits DNA gyrase, preventing supercoiling DNA degradation Nalidixic acid, Ciprofloxacin, Gatifloxacin Moxifloxacin Flouroquinolones Cartilage damage Metabolized by anaerobes to intermediates that prevent DNA synthesis Bactericidal; anaerobes (Also antiprotozoal) Nitroimidazoles Metronidazole GIT Bactericidal; Gram +ve and gram ve bacteria Discoloration of body fluid hepatotoxicity Rifampicin Rifampicin DNA degradation INHIBITION OF BACTERIAL GROWTH Competitive analogue of para-aminobenzoic acid (PABA) inhibits dihydrofolate reductase blocks folic acid synthesis Bacteriostatic bactericidal when combined. Gram ve Chlamydia, nocardia, protozoa and pneumocystic Trimethoprim-sulfadiazine, ormethoprim sulfa Sulfonamides GIT

  23. Contact us : THE TEAM : THE TEAM : 436microbiologyteam@gmail.com Waleed Aljamal Ibrahim Fetyani Meshal Eiaidi Khalid Alhusainan Hussam Alkhathlan Faisal Alqumaizi Abdulaziz Alangari Khalid Alshehri Nasir Aldosarie Mohammad Al-Kahil Shrooq Alsomali Rawan Alqahtani Hanin Bashaikh Jawaher Alkhayyal Reem Alshathri Ohoud Abdullah Ghadah Almazrou Lama Al-musallm Twitter : @microbio436

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