Antibiotics and Synthetic Antimicrobial agents

Rinaldo John
Rinaldo JohnMedical Underwriter | Environmental Microbiotechnologist à Swiss Re
Antibiotics and Synthetic
Antimicrobial agents
2
Chloramphenicol was an early example
Antibiotics can be Bacteriostatic or Bactericidal
(static=stop; cidal=kill)
whilst humans (and all other eukaryotes) have 80S ribosomes
bacterial cells have 70S ribosomes, with a
smaller molecular weight and different shape
Antibiotics and Synthetic Antimicrobial agents
Definition
• An antibiotic refers to a substance produced by a
microorganism, or to a similar substance (produced wholly or
partly by chemical synthesis), which in low concentrations
inhibits the growth of other microorganisms.
• Chloramphenicol was an early example.
Sources
• 1. Microorganisms; Most antibiotics in current use have been
produced from Streptomyces spp.
• 2. Synthesis; Chloramphenicol is now usually produced by a synthetic
process.
• 3. Semisynthesis; part of the molecule is produced by a fermentation
process
• the product is then further modified by a chemical process. Many penicillins
and cephalosporins are produced in this way.
(Streptomyces venezuelae)
Antibiotics and Synthetic Antimicrobial agents
β-lactam
•Beta-lactam antibiotics kill bacteria that are
surrounded by a cell wall.
•Bacteria build cell walls by linking molecules
together—beta-lactams block this process.
• Without support from a cell wall, pressure
inside the cell becomes too much and the
membrane bursts.
There are several different types of β-lactam
antibiotics that are valuable, or potentially
important, antibacterial compounds.
penicillin and cephalosporin
Penicillins
Wonder Drug
• Dr. Fleming famously wrote about that red-letter date:
• “When I woke up just after dawn on September 28, 1928, I certainly
didn’t plan to revolutionize all medicine by discovering the world’s first
antibiotic, or bacteria killer. But I guess that was exactly what I did.”
Dr. Fleming
Dr. Howard Florey and Dr. Ernst Chain
Antibiotics and Synthetic Antimicrobial agents
The penicillins may be considered as being of
the following types.
• Naturally occurring. For example, those produced by
fermentation of moulds such as Penicillium notatum and P.
chrysogenum.
• examples are benzylpenicillin (penicillin G) and
phenoxymethylpenicillin (penicillin V).
• Semisynthetic. Example, Amoxicillin
• Several bacteria produce an enzyme, Beta-lactamase which may
inactivate a penicillin by opening the Beta-lactam ring,
• In general, the penicillins are active against Gram-positive
bacteria
• some members (e.g. ampicillin) are also effective against
Gram-negative bacteria though not Pseudomonas
aeruginosa
• whereas others (e.g. carbenicillin) are active against
Pseudomonas aeruginosa also.
Spectrum of Activity
Antibiotics and Synthetic Antimicrobial agents
Cephalosporins
• 1950s; species of Cephalosporium (now known as Acremonium)
produce the following antibiotics:
a) An acidic antibiotic, cephalosporin P (subsequently found to have a
steroid-like structure)
b) Another acidic antibiotic, cephalosporin N (later shown to be a
penicillin).
c) Cephalosporin C, obtained during the purification of cephalosporin
N; this is a true cephalosporin, and from it has been obtained 7-
aminocephalosporanic acid (7-ACA), the starting point for new
cephalosporins.
dihydrothiazine ring
Thiazolidine Ring
• Cephalosporins disrupt the synthesis of the peptidoglycan layer
forming the bacterial cell wall.
As a result, the bacteria die.
• First-generation cephalosporins are active predominantly against
Gram-positive bacteria, and successive generations have increased
activity against Gram-negative bacteria (though often with reduced
activity against Gram-positive organisms)
• They are less susceptible to β-lactamases
Antibiotics weaken the cell wall, and cause the cell to lyse.
The classification of cephalosporins into
"generations"
Generation 1
• Activity against Gram-positive: Activity against penicillinase-
producing, methicillin-susceptible staphylococci and streptococci. No
activity against methicillin-resistant staphylococci or enterococci.
• Activity against Gram-negative: Activity against Proteus mirabilis,
some E. coli, and Klebsiella pneumoniae ("PEcK"), but have no activity
against Bacteroides fragilis, Pseudomonas, Acinetobacter,
Enterobacter, indole-positive Proteus, or Serratia
• Cefadroxil (cefadroxyl; Duricef)
• Cephalexin (cefalexin; Keflex)
• Cefalotin (cephalothin; Keflin)
• Cefapirin (cephapirin; Cefadryl)
• Cefradine (cephradine; Velosef)
Some of the Members of Generation 1
Generation 2
• Activity against Gram-positive: Less than first-generation.
• Activity against Gram-negative: Greater than first-generation: HEN
Haemophilus influenzae, Enterobacter aerogenes and some Neisseria
+ the PEcK described before
Some of the Members of Generation 2
• Cefaclor (Ceclor, Distaclor, Keflor, Raniclor)
• Cefonicid (Monocid)
• Cefprozil (cefproxil; Cefzil)
• Cefuroxime (Zefu, Zinnat, Ceftin, Xorimax)
Generation 3
• Activity against Gram-positive: Some members of this group (in
particular, those available in an oral formulation, and those with
antipseudomonal activity) have decreased activity against gram-
positive organisms.
• Activity against Gram-negative: Third-generation cephalosporins have
a broad spectrum of activity and further increased activity against
gram-negative organisms.
Some of the Members of Generation 3
• Ceftriaxone (Rocephin)
• Cefotaxime (Claforan)
• Ceftazidime (Fortaz) (strong antipseudomonal activity)
• Able to penetrate the central nervous system, making them useful
against meningitis caused by
• pneumococci,
• meningococci,
• Haemophilus influenzae,
• and susceptible E. coli, Klebsiella,
• and penicillin-resistant Neisseria gonorrhoeae
Generation 4
• Activity against Gram-positive: They are extended-spectrum agents
with similar activity against Gram-positive organisms as first-
generation cephalosporins.
• Activity against Gram-negative: Fourth-generation cephalosporins are
zwitterions that can penetrate the outer membrane of Gram-
negative bacteria. They also have a greater resistance to β-
lactamases than the third-generation cephalosporins.
• Effective in meningitis.
Some of the Members of Generation 4
• Cefepime (Maxipime) antipseudomonal activity
• Cefpirome (Cefrom)
Generation 5
• has powerful antipseudomonal characteristics and appears to be less
susceptible to development of resistance
• Effective against MRSA (Methicillin-resistant Staphylococcus aureus)
• Ceftolozane (super antipseudomonal activity)
• Ceftaroline (only cephalosporin to treat MRSA)
Some of the Members of Generation 5
Clavams
• The clavams differ from penicillins in two respects, namely the
replacement of S in the penicillin thiazolidine ring with oxygen in the
clavam oxazolidine ring and the absence of the side-chain at position
6.
• Clavulanic acid
• Isolated from Streptomyces clavuligerus
• has poor antibacterial activity
• potent inhibitor of staphylococcal beta-lactamase and of most types
of Beta-lactamases produced by Gram-negative bacteria
1-oxacephems
• example latamoxef (moxalactam)
• the sulphur atom in the dihydrothiazine cephalosporin ring system is
replaced by oxygen.
• The introduction of the 7-a-methoxy group (as in cefoxitin), however,
stabilizes the molecule.
• Latamoxef is a broad-spectrum antibiotic with a high degree of
stability to most types of Beta-lactamases, and is highly active against
the anaerobe, B. fragilis.
1-carbapenems
• Comprise a new family of fused Beta-lactam antibiotics
• They are analogues of penicillins or clavams,
• the sulphur (penicillins) or oxygen (calvams) atom being replaced by
carbon.
• Examples are the olivanic acids, thienamycin and imipenem
1-carbacephems
• The sulphur in the six-membered dihydrothiazine ring of the
cephalosporins is replaced by carbon.
• Loracarbef is a new oral carbacephem which is highly active against
Gram-positive bacteria, including staphylococci.
Nocardicins
• The nocardicins (A to G) have been isolated from a strain of Nocardia
and comprise a novel group of Beta-lactam antibiotics.
• Nocardicin A is the most active member, and possesses significant
activity against Gram-negative but not Gram-positive bacteria.
Monobactams
• The monobactams are monocyclic Beta-lactam antibiotics produced
by various strains of bacteria.
• A novel nucleus, 3-aminomonobactamic acid (3-AMA), has been
produced from naturally-occurring monobactams.
• Several monobactams have been tested and one (aztreonam) has
been shown to be highly active against most Gram-negative bacteria
and to be stable to most types of Beta-lactamases.
Assignment
• Penicillanic acid derivatives
Penicillanic acid derivatives
• Penicillanic acid derivatives are synthetically produced /3-lactamase
inhibitors.
• Penicillanic acid sulphone protects ampicillin from hydrolysis by
staphylococcal /^-lactamase and some, but not all, of the ^-lactamases
produced by Gram-negative bacteria, but is less potent than clavulanic
acid.
• /3-bromopenicillanic acid inhibits some types of /^-lactamases.
• Tazobactam is a penicillanic acid sulphone derivative marketed as a
combination with piperacillin. Alone it has poor intrinsic antibacterial
activity but is comparable to clavulanic acid in inhibiting /J-lactamase
activity.
• Sulbactam is a semisynthetic 6-desaminopenicillin sulphone structurally
related to tazobactam. Not only is it an effective inhibitor of many /^-
lactamases but it is also active alone against certain Gram-negative
bacteria. It is used in combination with ampicillin for clinical use.
Hypersensitivity
• https://goo.gl/xFS1BM
1 sur 42

Recommandé

Vitamin b12 par
Vitamin b12Vitamin b12
Vitamin b12Anushi Jain
85.3K vues20 diapositives
Antimicrobial chemotherapy par
Antimicrobial chemotherapyAntimicrobial chemotherapy
Antimicrobial chemotherapyfaraharooj
18.9K vues33 diapositives
Semisynthetic Penicillins par
Semisynthetic PenicillinsSemisynthetic Penicillins
Semisynthetic PenicillinsANUSHA SHAJI
2.5K vues14 diapositives
Bacterial cell wall synthesis par
Bacterial cell wall synthesisBacterial cell wall synthesis
Bacterial cell wall synthesisIrene Daniel
24.6K vues18 diapositives
Production of glutamic acid par
Production of glutamic acidProduction of glutamic acid
Production of glutamic acidvijaysrampur
7K vues9 diapositives
Industrial production of penicillin par
Industrial production of penicillinIndustrial production of penicillin
Industrial production of penicillinNischitha R
83.8K vues15 diapositives

Contenu connexe

Tendances

amylases enzymes production par
amylases enzymes productionamylases enzymes production
amylases enzymes productionNOMI KhanS
120.4K vues23 diapositives
Glutamic acid fermentation par
Glutamic acid fermentationGlutamic acid fermentation
Glutamic acid fermentationNOMI KhanS
48.6K vues24 diapositives
Antibiotics & mechanisms of actions par
Antibiotics & mechanisms of actionsAntibiotics & mechanisms of actions
Antibiotics & mechanisms of actionsabiola adeosun
130.8K vues37 diapositives
Antibiotic types and mechanism of action par
Antibiotic types and mechanism of actionAntibiotic types and mechanism of action
Antibiotic types and mechanism of actionHARINATHA REDDY ASWARTHA
1.7K vues46 diapositives
Streptomycin par
StreptomycinStreptomycin
StreptomycinSANDEEP MEWADA
22.8K vues13 diapositives
Industrial Microorganisms par
Industrial MicroorganismsIndustrial Microorganisms
Industrial MicroorganismsM Rakibul Islam
25K vues49 diapositives

Tendances(20)

amylases enzymes production par NOMI KhanS
amylases enzymes productionamylases enzymes production
amylases enzymes production
NOMI KhanS120.4K vues
Glutamic acid fermentation par NOMI KhanS
Glutamic acid fermentationGlutamic acid fermentation
Glutamic acid fermentation
NOMI KhanS48.6K vues
Antibiotics & mechanisms of actions par abiola adeosun
Antibiotics & mechanisms of actionsAntibiotics & mechanisms of actions
Antibiotics & mechanisms of actions
abiola adeosun130.8K vues
Citric acid production par Praveen Garg
Citric acid productionCitric acid production
Citric acid production
Praveen Garg7.8K vues
Biotransformation of steroids par sudha rajput
Biotransformation of steroidsBiotransformation of steroids
Biotransformation of steroids
sudha rajput74.6K vues
Antimicrobial agents par uptu
Antimicrobial agentsAntimicrobial agents
Antimicrobial agents
uptu22.3K vues
Production of vitamin B12 par Prathap H M
Production of vitamin B12Production of vitamin B12
Production of vitamin B12
Prathap H M22.6K vues
Pharmacology of Semi synthetic Penicillins par Vijay Kevlani
Pharmacology of Semi synthetic Penicillins Pharmacology of Semi synthetic Penicillins
Pharmacology of Semi synthetic Penicillins
Vijay Kevlani926 vues
Production of tetracyclin and cephalosporin par SamsuDeen12
Production of tetracyclin and cephalosporinProduction of tetracyclin and cephalosporin
Production of tetracyclin and cephalosporin
SamsuDeen1212.8K vues
Production of Penicillin by Fermentation par UBAID TARIQ
Production of Penicillin by FermentationProduction of Penicillin by Fermentation
Production of Penicillin by Fermentation
UBAID TARIQ49.7K vues
Production of vitamin B12 using fermentation par vijaysrampur
Production of vitamin B12 using fermentationProduction of vitamin B12 using fermentation
Production of vitamin B12 using fermentation
vijaysrampur11.2K vues

Similaire à Antibiotics and Synthetic Antimicrobial agents

Antibiotic par
AntibioticAntibiotic
Antibioticroya ghaderi
134 vues59 diapositives
Antimicrobial Agents and Resistance.pptx par
Antimicrobial Agents and Resistance.pptxAntimicrobial Agents and Resistance.pptx
Antimicrobial Agents and Resistance.pptxKrithikaaSekar
56 vues63 diapositives
Medicinal chemistry-beta lactam antibiotics par
Medicinal chemistry-beta lactam antibioticsMedicinal chemistry-beta lactam antibiotics
Medicinal chemistry-beta lactam antibioticsDHARMENDRA BARIA
69.3K vues49 diapositives
Cephalosporins antibiotics - Beta lactam antibiotics par
Cephalosporins antibiotics - Beta lactam antibioticsCephalosporins antibiotics - Beta lactam antibiotics
Cephalosporins antibiotics - Beta lactam antibioticsAkhil Nagar
614 vues39 diapositives
Cephalosporin.pptx par
Cephalosporin.pptxCephalosporin.pptx
Cephalosporin.pptxmdtaieb1
8 vues33 diapositives
medicinal chemistry of Antibiotic par
medicinal chemistry of Antibiotic medicinal chemistry of Antibiotic
medicinal chemistry of Antibiotic Ganesh Mote
105.4K vues91 diapositives

Similaire à Antibiotics and Synthetic Antimicrobial agents(20)

Antimicrobial Agents and Resistance.pptx par KrithikaaSekar
Antimicrobial Agents and Resistance.pptxAntimicrobial Agents and Resistance.pptx
Antimicrobial Agents and Resistance.pptx
KrithikaaSekar56 vues
Medicinal chemistry-beta lactam antibiotics par DHARMENDRA BARIA
Medicinal chemistry-beta lactam antibioticsMedicinal chemistry-beta lactam antibiotics
Medicinal chemistry-beta lactam antibiotics
DHARMENDRA BARIA69.3K vues
Cephalosporins antibiotics - Beta lactam antibiotics par Akhil Nagar
Cephalosporins antibiotics - Beta lactam antibioticsCephalosporins antibiotics - Beta lactam antibiotics
Cephalosporins antibiotics - Beta lactam antibiotics
Akhil Nagar614 vues
Cephalosporin.pptx par mdtaieb1
Cephalosporin.pptxCephalosporin.pptx
Cephalosporin.pptx
mdtaieb18 vues
medicinal chemistry of Antibiotic par Ganesh Mote
medicinal chemistry of Antibiotic medicinal chemistry of Antibiotic
medicinal chemistry of Antibiotic
Ganesh Mote105.4K vues
Beta-Lactam Antibiotics par KayhanNajar
Beta-Lactam Antibiotics Beta-Lactam Antibiotics
Beta-Lactam Antibiotics
KayhanNajar774 vues
Antimicrobial agents 2 wafaa par wafaa ahmed
Antimicrobial agents 2 wafaaAntimicrobial agents 2 wafaa
Antimicrobial agents 2 wafaa
wafaa ahmed1.5K vues
Beta-lactam antibiotics.pptx par yogesh532361
Beta-lactam antibiotics.pptxBeta-lactam antibiotics.pptx
Beta-lactam antibiotics.pptx
yogesh53236185 vues
Cephalosporin and aminoglycoside par nikhil k
Cephalosporin and aminoglycosideCephalosporin and aminoglycoside
Cephalosporin and aminoglycoside
nikhil k211 vues
6 beta lactum drugs dental par IAU Dent
6  beta lactum drugs dental6  beta lactum drugs dental
6 beta lactum drugs dental
IAU Dent3.6K vues
Cephalosporins & other β lactam antibiotics & cell wall destructors par FarazaJaved
Cephalosporins & other β lactam  antibiotics & cell wall destructorsCephalosporins & other β lactam  antibiotics & cell wall destructors
Cephalosporins & other β lactam antibiotics & cell wall destructors
FarazaJaved5.5K vues
Antibiotics and analgesics par Firas Kassab
Antibiotics and analgesicsAntibiotics and analgesics
Antibiotics and analgesics
Firas Kassab2.7K vues

Plus de Rinaldo John

Virtual machine par
Virtual machineVirtual machine
Virtual machineRinaldo John
1.1K vues9 diapositives
Handling fermenters and troubleshooting par
Handling fermenters and troubleshootingHandling fermenters and troubleshooting
Handling fermenters and troubleshootingRinaldo John
203 vues13 diapositives
Fermenter designs and setup par
Fermenter designs and setupFermenter designs and setup
Fermenter designs and setupRinaldo John
260 vues11 diapositives
Bioprocessing and its significance par
Bioprocessing and its significanceBioprocessing and its significance
Bioprocessing and its significanceRinaldo John
741 vues30 diapositives
Luke 18:18-30 par
Luke 18:18-30Luke 18:18-30
Luke 18:18-30Rinaldo John
130 vues14 diapositives
Lost in communication par
Lost in communicationLost in communication
Lost in communicationRinaldo John
18 vues5 diapositives

Plus de Rinaldo John(20)

Handling fermenters and troubleshooting par Rinaldo John
Handling fermenters and troubleshootingHandling fermenters and troubleshooting
Handling fermenters and troubleshooting
Rinaldo John203 vues
Fermenter designs and setup par Rinaldo John
Fermenter designs and setupFermenter designs and setup
Fermenter designs and setup
Rinaldo John260 vues
Bioprocessing and its significance par Rinaldo John
Bioprocessing and its significanceBioprocessing and its significance
Bioprocessing and its significance
Rinaldo John741 vues
Role of Environmental Biotechnology par Rinaldo John
Role of Environmental BiotechnologyRole of Environmental Biotechnology
Role of Environmental Biotechnology
Rinaldo John2.5K vues
Molecular analysis of Microbial Community par Rinaldo John
Molecular analysis of Microbial CommunityMolecular analysis of Microbial Community
Molecular analysis of Microbial Community
Rinaldo John769 vues
Journal Club Presentation PPT Format par Rinaldo John
Journal Club Presentation PPT FormatJournal Club Presentation PPT Format
Journal Club Presentation PPT Format
Rinaldo John99 vues
Distribution of microbes in aquatic environment par Rinaldo John
Distribution of microbes in aquatic environmentDistribution of microbes in aquatic environment
Distribution of microbes in aquatic environment
Rinaldo John1.4K vues
Microbial contamination par Rinaldo John
Microbial contamination Microbial contamination
Microbial contamination
Rinaldo John911 vues
Soil as microbial habitat par Rinaldo John
Soil as microbial habitatSoil as microbial habitat
Soil as microbial habitat
Rinaldo John2.2K vues

Dernier

Gold Nanoparticle as novel Agent for Drug targeting (1).pptx par
Gold Nanoparticle as novel Agent for Drug targeting (1).pptxGold Nanoparticle as novel Agent for Drug targeting (1).pptx
Gold Nanoparticle as novel Agent for Drug targeting (1).pptxsakshijadhav9843
18 vues13 diapositives
POSTER IV LAWCN_ROVER_IUE.pdf par
POSTER IV LAWCN_ROVER_IUE.pdfPOSTER IV LAWCN_ROVER_IUE.pdf
POSTER IV LAWCN_ROVER_IUE.pdfSOCIEDAD JULIO GARAVITO
8 vues1 diapositive
Physical Characterization of Moon Impactor WE0913A par
Physical Characterization of Moon Impactor WE0913APhysical Characterization of Moon Impactor WE0913A
Physical Characterization of Moon Impactor WE0913ASérgio Sacani
42 vues12 diapositives
plasmids par
plasmidsplasmids
plasmidsscribddarkened352
7 vues2 diapositives
RemeOs science and clinical evidence par
RemeOs science and clinical evidenceRemeOs science and clinical evidence
RemeOs science and clinical evidencePetrusViitanen1
26 vues96 diapositives
application of genetic engineering 2.pptx par
application of genetic engineering 2.pptxapplication of genetic engineering 2.pptx
application of genetic engineering 2.pptxSankSurezz
6 vues12 diapositives

Dernier(20)

Gold Nanoparticle as novel Agent for Drug targeting (1).pptx par sakshijadhav9843
Gold Nanoparticle as novel Agent for Drug targeting (1).pptxGold Nanoparticle as novel Agent for Drug targeting (1).pptx
Gold Nanoparticle as novel Agent for Drug targeting (1).pptx
Physical Characterization of Moon Impactor WE0913A par Sérgio Sacani
Physical Characterization of Moon Impactor WE0913APhysical Characterization of Moon Impactor WE0913A
Physical Characterization of Moon Impactor WE0913A
Sérgio Sacani42 vues
application of genetic engineering 2.pptx par SankSurezz
application of genetic engineering 2.pptxapplication of genetic engineering 2.pptx
application of genetic engineering 2.pptx
SankSurezz6 vues
Ethical issues associated with Genetically Modified Crops and Genetically Mod... par PunithKumars6
Ethical issues associated with Genetically Modified Crops and Genetically Mod...Ethical issues associated with Genetically Modified Crops and Genetically Mod...
Ethical issues associated with Genetically Modified Crops and Genetically Mod...
PunithKumars618 vues
Distinct distributions of elliptical and disk galaxies across the Local Super... par Sérgio Sacani
Distinct distributions of elliptical and disk galaxies across the Local Super...Distinct distributions of elliptical and disk galaxies across the Local Super...
Distinct distributions of elliptical and disk galaxies across the Local Super...
Sérgio Sacani30 vues
CSF -SHEEBA.D presentation.pptx par SheebaD7
CSF -SHEEBA.D presentation.pptxCSF -SHEEBA.D presentation.pptx
CSF -SHEEBA.D presentation.pptx
SheebaD710 vues
himalay baruah acid fast staining.pptx par HimalayBaruah
himalay baruah acid fast staining.pptxhimalay baruah acid fast staining.pptx
himalay baruah acid fast staining.pptx
HimalayBaruah5 vues
Metatheoretical Panda-Samaneh Borji.pdf par samanehborji
Metatheoretical Panda-Samaneh Borji.pdfMetatheoretical Panda-Samaneh Borji.pdf
Metatheoretical Panda-Samaneh Borji.pdf
samanehborji16 vues
ENTOMOLOGY PPT ON BOMBYCIDAE AND SATURNIIDAE.pptx par MN
ENTOMOLOGY PPT ON BOMBYCIDAE AND SATURNIIDAE.pptxENTOMOLOGY PPT ON BOMBYCIDAE AND SATURNIIDAE.pptx
ENTOMOLOGY PPT ON BOMBYCIDAE AND SATURNIIDAE.pptx
MN6 vues
How to be(come) a successful PhD student par Tom Mens
How to be(come) a successful PhD studentHow to be(come) a successful PhD student
How to be(come) a successful PhD student
Tom Mens422 vues
Conventional and non-conventional methods for improvement of cucurbits.pptx par gandhi976
Conventional and non-conventional methods for improvement of cucurbits.pptxConventional and non-conventional methods for improvement of cucurbits.pptx
Conventional and non-conventional methods for improvement of cucurbits.pptx
gandhi97616 vues
MSC III_Advance Forensic Serology_Final.pptx par Suchita Rawat
MSC III_Advance Forensic Serology_Final.pptxMSC III_Advance Forensic Serology_Final.pptx
MSC III_Advance Forensic Serology_Final.pptx
Suchita Rawat10 vues

Antibiotics and Synthetic Antimicrobial agents

  • 2. 2 Chloramphenicol was an early example
  • 3. Antibiotics can be Bacteriostatic or Bactericidal (static=stop; cidal=kill) whilst humans (and all other eukaryotes) have 80S ribosomes bacterial cells have 70S ribosomes, with a smaller molecular weight and different shape
  • 5. Definition • An antibiotic refers to a substance produced by a microorganism, or to a similar substance (produced wholly or partly by chemical synthesis), which in low concentrations inhibits the growth of other microorganisms. • Chloramphenicol was an early example.
  • 6. Sources • 1. Microorganisms; Most antibiotics in current use have been produced from Streptomyces spp. • 2. Synthesis; Chloramphenicol is now usually produced by a synthetic process. • 3. Semisynthesis; part of the molecule is produced by a fermentation process • the product is then further modified by a chemical process. Many penicillins and cephalosporins are produced in this way. (Streptomyces venezuelae)
  • 8. β-lactam •Beta-lactam antibiotics kill bacteria that are surrounded by a cell wall. •Bacteria build cell walls by linking molecules together—beta-lactams block this process. • Without support from a cell wall, pressure inside the cell becomes too much and the membrane bursts.
  • 9. There are several different types of β-lactam antibiotics that are valuable, or potentially important, antibacterial compounds. penicillin and cephalosporin
  • 11. Wonder Drug • Dr. Fleming famously wrote about that red-letter date: • “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.” Dr. Fleming Dr. Howard Florey and Dr. Ernst Chain
  • 13. The penicillins may be considered as being of the following types. • Naturally occurring. For example, those produced by fermentation of moulds such as Penicillium notatum and P. chrysogenum. • examples are benzylpenicillin (penicillin G) and phenoxymethylpenicillin (penicillin V). • Semisynthetic. Example, Amoxicillin
  • 14. • Several bacteria produce an enzyme, Beta-lactamase which may inactivate a penicillin by opening the Beta-lactam ring,
  • 15. • In general, the penicillins are active against Gram-positive bacteria • some members (e.g. ampicillin) are also effective against Gram-negative bacteria though not Pseudomonas aeruginosa • whereas others (e.g. carbenicillin) are active against Pseudomonas aeruginosa also.
  • 18. Cephalosporins • 1950s; species of Cephalosporium (now known as Acremonium) produce the following antibiotics: a) An acidic antibiotic, cephalosporin P (subsequently found to have a steroid-like structure) b) Another acidic antibiotic, cephalosporin N (later shown to be a penicillin). c) Cephalosporin C, obtained during the purification of cephalosporin N; this is a true cephalosporin, and from it has been obtained 7- aminocephalosporanic acid (7-ACA), the starting point for new cephalosporins.
  • 20. • Cephalosporins disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. As a result, the bacteria die. • First-generation cephalosporins are active predominantly against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (though often with reduced activity against Gram-positive organisms) • They are less susceptible to β-lactamases
  • 21. Antibiotics weaken the cell wall, and cause the cell to lyse.
  • 22. The classification of cephalosporins into "generations"
  • 23. Generation 1 • Activity against Gram-positive: Activity against penicillinase- producing, methicillin-susceptible staphylococci and streptococci. No activity against methicillin-resistant staphylococci or enterococci. • Activity against Gram-negative: Activity against Proteus mirabilis, some E. coli, and Klebsiella pneumoniae ("PEcK"), but have no activity against Bacteroides fragilis, Pseudomonas, Acinetobacter, Enterobacter, indole-positive Proteus, or Serratia
  • 24. • Cefadroxil (cefadroxyl; Duricef) • Cephalexin (cefalexin; Keflex) • Cefalotin (cephalothin; Keflin) • Cefapirin (cephapirin; Cefadryl) • Cefradine (cephradine; Velosef) Some of the Members of Generation 1
  • 25. Generation 2 • Activity against Gram-positive: Less than first-generation. • Activity against Gram-negative: Greater than first-generation: HEN Haemophilus influenzae, Enterobacter aerogenes and some Neisseria + the PEcK described before
  • 26. Some of the Members of Generation 2 • Cefaclor (Ceclor, Distaclor, Keflor, Raniclor) • Cefonicid (Monocid) • Cefprozil (cefproxil; Cefzil) • Cefuroxime (Zefu, Zinnat, Ceftin, Xorimax)
  • 27. Generation 3 • Activity against Gram-positive: Some members of this group (in particular, those available in an oral formulation, and those with antipseudomonal activity) have decreased activity against gram- positive organisms. • Activity against Gram-negative: Third-generation cephalosporins have a broad spectrum of activity and further increased activity against gram-negative organisms.
  • 28. Some of the Members of Generation 3 • Ceftriaxone (Rocephin) • Cefotaxime (Claforan) • Ceftazidime (Fortaz) (strong antipseudomonal activity)
  • 29. • Able to penetrate the central nervous system, making them useful against meningitis caused by • pneumococci, • meningococci, • Haemophilus influenzae, • and susceptible E. coli, Klebsiella, • and penicillin-resistant Neisseria gonorrhoeae
  • 30. Generation 4 • Activity against Gram-positive: They are extended-spectrum agents with similar activity against Gram-positive organisms as first- generation cephalosporins. • Activity against Gram-negative: Fourth-generation cephalosporins are zwitterions that can penetrate the outer membrane of Gram- negative bacteria. They also have a greater resistance to β- lactamases than the third-generation cephalosporins. • Effective in meningitis.
  • 31. Some of the Members of Generation 4 • Cefepime (Maxipime) antipseudomonal activity • Cefpirome (Cefrom)
  • 32. Generation 5 • has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance • Effective against MRSA (Methicillin-resistant Staphylococcus aureus) • Ceftolozane (super antipseudomonal activity) • Ceftaroline (only cephalosporin to treat MRSA) Some of the Members of Generation 5
  • 33. Clavams • The clavams differ from penicillins in two respects, namely the replacement of S in the penicillin thiazolidine ring with oxygen in the clavam oxazolidine ring and the absence of the side-chain at position 6.
  • 34. • Clavulanic acid • Isolated from Streptomyces clavuligerus • has poor antibacterial activity • potent inhibitor of staphylococcal beta-lactamase and of most types of Beta-lactamases produced by Gram-negative bacteria
  • 35. 1-oxacephems • example latamoxef (moxalactam) • the sulphur atom in the dihydrothiazine cephalosporin ring system is replaced by oxygen. • The introduction of the 7-a-methoxy group (as in cefoxitin), however, stabilizes the molecule. • Latamoxef is a broad-spectrum antibiotic with a high degree of stability to most types of Beta-lactamases, and is highly active against the anaerobe, B. fragilis.
  • 36. 1-carbapenems • Comprise a new family of fused Beta-lactam antibiotics • They are analogues of penicillins or clavams, • the sulphur (penicillins) or oxygen (calvams) atom being replaced by carbon. • Examples are the olivanic acids, thienamycin and imipenem
  • 37. 1-carbacephems • The sulphur in the six-membered dihydrothiazine ring of the cephalosporins is replaced by carbon. • Loracarbef is a new oral carbacephem which is highly active against Gram-positive bacteria, including staphylococci.
  • 38. Nocardicins • The nocardicins (A to G) have been isolated from a strain of Nocardia and comprise a novel group of Beta-lactam antibiotics. • Nocardicin A is the most active member, and possesses significant activity against Gram-negative but not Gram-positive bacteria.
  • 39. Monobactams • The monobactams are monocyclic Beta-lactam antibiotics produced by various strains of bacteria. • A novel nucleus, 3-aminomonobactamic acid (3-AMA), has been produced from naturally-occurring monobactams. • Several monobactams have been tested and one (aztreonam) has been shown to be highly active against most Gram-negative bacteria and to be stable to most types of Beta-lactamases.
  • 41. Penicillanic acid derivatives • Penicillanic acid derivatives are synthetically produced /3-lactamase inhibitors. • Penicillanic acid sulphone protects ampicillin from hydrolysis by staphylococcal /^-lactamase and some, but not all, of the ^-lactamases produced by Gram-negative bacteria, but is less potent than clavulanic acid. • /3-bromopenicillanic acid inhibits some types of /^-lactamases. • Tazobactam is a penicillanic acid sulphone derivative marketed as a combination with piperacillin. Alone it has poor intrinsic antibacterial activity but is comparable to clavulanic acid in inhibiting /J-lactamase activity. • Sulbactam is a semisynthetic 6-desaminopenicillin sulphone structurally related to tazobactam. Not only is it an effective inhibitor of many /^- lactamases but it is also active alone against certain Gram-negative bacteria. It is used in combination with ampicillin for clinical use.

Notes de l'éditeur

  1. 1928 that penicillin, the first true antibiotic, was discovered by Alexander Fleming
  2. An antibiotic was originally defined as a substance, produced by one microorganism, which inhibited the growth of other microorganisms. An antibiotic refers to a substance produced by a microorganism, or to a similar substance (produced wholly or partly by chemical synthesis), which in low concentrations inhibits the growth of other microorganisms.
  3. DNA replication Enzyme substrate interaction Protein formation In the latter method, antibiotics make use of the fact that cell structures in bacterial cells are different to cell structures in human cells, so whilst humans (and all other eukaryotes) have 80S ribosomes (organelles in the cell that are responsible for protein synthesis), bacterial cells have 70S ribosomes, with a smaller molecular weight and different shape. These ribosomes are different enough for antibiotics to be able to recognise bacterial ribosomes as separate to eukaryotic ribosomes, Attack the peptidoglycan layer
  4. An antibiotic was originally defined as a substance, produced by one microorganism, which inhibited the growth of other microorganisms.
  5. bacitracin and polymyxin are obtained from some Bacillus species; streptomycin, tetracyclines, etc. from Streptomyces species; gentamicin from Micromonospora purpurea; griseofulvin and some penicillins and cephalosporins from certain genera (Penicillium, Acremonium) of the family Aspergillaceae; and monobactams from Pseudomonas acidophila and Gluconobacter species. Most antibiotics in current use have been produced from Streptomyces spp. Chloramphenicol was originally derived from the bacterium Streptomyces venezuelae, isolated by David Gottlieb, and introduced into clinical practice in 1949
  6. There are several different types of /3-lactam antibiotics that are valuable, or potentially important, antibacterial compounds.
  7. Examples of beta-lactams include penicillin and cephalosporin, which are used to treat many types of bacterial infections.
  8. Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming Penicillium notatum Thiazolidine Ring
  9. Dr Florey; 50 mice; streptococcus But the problem remained: how to produce enough pure penicillin to treat people. In spite of efforts to increase the yield from the mold cultures, it took 2,000 liters of mold culture fluid to obtain enough pure penicillin to treat a single case of sepsis in a person. 1940 police constable In the summer of 1941, shortly before the United States entered World War II, Florey and Heatley flew to the United States Penicillium chrysogeum; yielded 200 times the amount of penicillin 1945 Nobel Prize; Fleming, Florey, and Chain; Fleming presciently warned that the overuse of penicillin might lead to bacterial resistance.
  10. In contrast to narrow spectrum penicillin G and V, amoxicillin has got a wide antibiotic spectrum and is effective against some gram negative rods too but, it is still susceptible to beta lactamase enzymes. Penicillin V is an antibiotic that fights bacteria in your body. Penicillin V is used to treat many different types of infections caused by bacteria, such as ear infections Penicillin G : intravenous or intramuscular use.  Penicillin V :is a more acid stable and can be administered orally.  Both Penicillin G and V are indicated as therapy for mild-to-severe infections caused by susceptible organisms including (but not limited to) streptococcal infections and pneumonia, enterococcal and non-enterococcal endocarditis, diphtheria, anthrax, bacterial meningitis, Lyme disease, gonorrhea, syphilis, actinomycosis, botulism and others.
  11. However, some penicillins are considerably more resistant to this enzyme than are others, and consequently may be extremely valuable
  12. To test the sensitivity of microorganisms in the presence of antibiotics i.e. “Microbial Inhibition Spectrum” (MIS).
  13. The purified culture is then tested to find what types of microorganisms are sensitive in the presence of these the antibiotics i.e. “Microbial Inhibition Spectrum” (MIS).
  14. Cephalosporins consist of a six-membered dihydrothiazine ring fused to a /3-lactam ring. Thus, the cephalosporins (A3-cephalosporins) are structurally related to the Penicillins *these medicines are usually prescribed for patients undergoing dialysis and for patients with cystic fibrosis. Steroids can be divided into sex steroids, corticosteroids, and anabolic steroids. All three are used as medical aids in different kinds of illnesses or dysfunction. Sex steroids, testosterones for instance, are widely employed in reproductive regulation like contraception and correction of hormonal imbalances. Anabolic steroids, the most popular type, aid in muscle and bone synthesis and boost strength. Lastly, corticosteroids regulate metabolism, immune function, blood volume, and renal excretion of electrolytes.
  15. Cephalosporins consist of a six-membered dihydrothiazine ring fused to a /3-lactam ring. Thus, the cephalosporins (A3-cephalosporins) are structurally related to the penicillins
  16. The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their antimicrobial properties. The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended-spectrum cephalosporins were classified as second-generation cephalosporins. Each newer generation has significantly greater Gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against Gram-positive organisms. Fourth-generation cephalosporins, however, have true broad-spectrum activity.
  17. having a lower osmotic pressure than a particular fluid
  18. The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their antimicrobial properties. The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended-spectrum cephalosporins were classified as second-generation cephalosporins. Each newer generation has significantly greater Gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against Gram-positive organisms. Fourth-generation cephalosporins, however, have true broad-spectrum activity.
  19. methicillin, is a narrow-spectrum β-lactam antibiotic of the penicillin class
  20. Oral 1st-generation cephalosporins are commonly used for uncomplicated skin and soft-tissue infections, which are usually due to staphylococci and streptococci. Cefacetrile (cephacetrile) Cefaloglycin (cephaloglycin) Cefalonium (cephalonium) Cefaloridine (cephaloradine) Cefatrizine Cefazaflur Cefazedone Cefroxadine Ceftezole
  21. Proteus mirabilis, E. coli, and Klebsiella pneumoniae
  22. often used for polymicrobial infections that include gram-negative bacilli and gram-positive cocci Cephems are a sub-group of β-lactam antibiotics including cephalosporins and cephamycins The following cephems are also sometimes grouped with second-generation cephalosporins: Carbacephems: Loracarbef (Lorabid) Cephamycins: Cefbuperazone Cefmetazole (Zefazone) Cefminox Cefotetan (Cefotan) Cefoxitin (Mefoxin) Cefotiam (Pansporin)
  23. useful in treating hospital-acquired infections (used for skin and soft-tissue infections, should be restricted to uncomplicated infections due to streptococci.) They are also able to penetrate the central nervous system, making them useful against meningitis caused by pneumococci, meningococci, Haemophilus influenzae, and susceptible E. coli, Klebsiella, and penicillin-resistant Neisseria gonorrhoeae (Meningitis is an inflammation (swelling) of the protective membranes covering the brain and spinal cord known as the meninges. This inflammation is usually caused by an infection of the fluid surrounding the brain and spinal cord.) Tending to destroy bacteria of the genus pseudomonas (gram –ve)
  24. They are also able to penetrate the central nervous system, making them useful against meningitis caused by pneumococci, meningococci, Haemophilus influenzae, and susceptible E. coli, Klebsiella, and penicillin-resistant Neisseria gonorrhoeae (Meningitis is an inflammation (swelling) of the protective membranes covering the brain and spinal cord known as the meninges. This inflammation is usually caused by an infection of the fluid surrounding the brain and spinal cord.) For clinically acquired pnemonia Lung No anaerobic coverage Extended spectrum beta lactamase
  25. (Meningitis is an inflammation (swelling) of the protective membranes covering the brain and spinal cord known as the meninges. This inflammation is usually caused by an infection of the fluid surrounding the brain and spinal cord.) Streptococcus pneumoniae; gram +ve; anaerobes Neisseria meningitidis; gram –ve grane-ve; facultatively anaerobic K pneumoniae; Gram-ve; non motile
  26. Gram-ve; outer layer of phospholipids and lipopolysaccharides They are also used against Pseudomonas aeruginosa. In chemistry, a zwitterion, formerly called a dipolar ion, is a neutral molecule with both positive and negative electrical charges
  27. Fourth-generation cephalosporins as of March, 2007, were considered to be "a class of highly potent antibiotics that are among medicine's last defences against several serious human infections" according to the Washington Post No anaerobic coverage Serious infections; fever of unknown origin
  28. Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body. It's tougher to treat than most strains of staphylococcus aureus -- or staph -- because it's resistant to some commonly used antibiotics (methicillin, amoxicillin, penicillin, oxacillin) Because it's hard to treat, MRSA is sometimes called a "super bug.“ They took the structure of ceftazidime and made it better. Most antipseudomonal cephalosporin we currently have
  29. Penams contain a β-lactam ring fused to a 5-membered ring, where one of the atoms in the ring is a sulfur and the ring is fully saturated. H =Methly group COOH =Carboxyl group CH2OH =hydroxymethyl group
  30. Clavulanic acid, a naturally occurring clavam isolated from Streptomyces clavuligerus, has poor antibacterial activity but is a potent inhibitor of staphylococcal jft-lactamase and of most types of Beta-lactamases produced by Gram-negative bacteria
  31. Sulphur atom in Clavams This would tend to make the molecule chemically less stable and more susceptible to inactivation by Beta-lactamases. Its because sulfur is large in size compared to oxygen. So for the same charge it has less electron density in its electron cloud. Because of large size, electron cloud is loosely bound to nucleus and more shared as compared to oxygen which makes that negative charge more stable. Bacteroides fragilis =is an obligately anaerobic, Gram-negative, rod-shaped bacterium. It is part of the normal flora of the human colon
  32. Analogues =a compound with a molecular structure closely similar to that of another. community-acquired intra-abdominal infections of mild-to-moderate severity The spectrum of activity of the carbapenems imipenem, doripenem, and meropenem includes most Enterobacteriaceace species, including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, and Serratia marcescens. Activity is maintained against most strains of E. coli and K. pneumoniae that are resistant to cephalosporins due to the production of extended spectrum beta-lactamases. The spectrum of activity of the carbapenems against gram-positive bacteria is fairly broad, but not as exceptionally so as in the case of gram-negative bacteria. Good activity is seen against methicillin-sensitive strains of Staphylococcus species, but many other antibiotics provide coverage for such infections. Good activity is also observed for most Streptococcus species, including penicillin-resistant strains
  33. It is not destroyed by staphylococcal /3-lactamases but is inactive against all strains of Staph, aureus tested.