Antibiotics By Dr. Humodi A. Saeed Associate Prof. of Medical Microbiology College of Medical Lab. Science Sudan University of Science and Technology E.

AntibioticsAntibiotics

ByBy

Dr. Humodi A. SaeedDr. Humodi A. SaeedAssociate Prof. of Medical MicrobiologyAssociate Prof. of Medical MicrobiologyCollege of Medical Lab. ScienceCollege of Medical Lab. ScienceSudan University of Science and TechnologySudan University of Science and TechnologyE mail address: Biotechsust@hotmail.comE mail address: Biotechsust@hotmail.com

Definition of Antibiotic

A substance of biological, semisyntheticor synthetic origin of low molecular weight

(on-protein) produced by a fungus or bacterium as secondary metabolites that inhibits or stop growth of other microorganisms in vitro and in vivo selectively, when it used in low concentration

Characteristics of AntibioticsCharacteristics of Antibiotics

It must be able to It must be able to reach the part of the reach the part of the human body where human body where

the infection is the infection is occurringoccurring..

Characteristics of AntibioticsCharacteristics of Antibiotics

It should not cause It should not cause the development of the development of resistant forms of resistant forms of

parasitesparasites..

Characteristics of AntibioticsCharacteristics of Antibiotics

It should not It should not produce undesirable produce undesirable side effects in the side effects in the host such as host such as allergic reaction, allergic reaction, nerve damage or nerve damage or irritation of the irritation of the kidneys and kidneys and gastrointestinal gastrointestinal tracttract..

Characteristics of AntibioticsCharacteristics of Antibiotics

It should be given It should be given orally without orally without inactivation by inactivation by

stomach acid, or by stomach acid, or by injection injection

(parenterally) (parenterally) without binding to without binding to the blood proteinsthe blood proteins..

Characteristics of AntibioticsCharacteristics of Antibiotics

Finally, it should Finally, it should have a high level of have a high level of

solubility in the solubility in the body fluids and be body fluids and be possible to achieve possible to achieve concentrations in concentrations in

the tissue or blood, the tissue or blood, which are which are

sufficiently high to sufficiently high to inhibit or kill the inhibit or kill the infectious agentinfectious agent..

Major groups of AntibioticsMajor groups of Antibiotics

11 . .Beta-lactam Beta-lactam antibioticsantibiotics

11 . .PenicillinsPenicillins

22 . .CephalosporinsCephalosporins

33 . .CarbapenemsCarbapenems

44 . .MonobactamsMonobactams

11 . .Beta-lactam antibiotics Beta-lactam antibiotics Toxicity ProblemToxicity Problem

The main toxicity The main toxicity problem with these problem with these

antibiotics is an allergic antibiotics is an allergic reaction that occurs reaction that occurs

because of formation of because of formation of beta-lactam/serum beta-lactam/serum

protein conjugate that protein conjugate that elicits an inflammatory elicits an inflammatory

immune responseimmune response..

11 . .Beta-lactam antibioticsBeta-lactam antibiotics Mode of ActionMode of Action

The beta-lactam The beta-lactam antibiotics inhibit antibiotics inhibit

the last step in the last step in peptidoglycan peptidoglycan

synthesissynthesis

11 . .Beta-lactam antibioticsBeta-lactam antibiotics SpectrumSpectrum

Some are effective Some are effective against both Gram-against both Gram-positive and Gram-positive and Gram-negative bacteria negative bacteria

whereas others are whereas others are more effective more effective against Gram-against Gram-

positive than Gram-positive than Gram-negative bacteria or negative bacteria or

vice versavice versa..

11 . .Beta-lactam antibioticsBeta-lactam antibiotics Example Example 1. ( Natural penicillins and 1. ( Natural penicillins and

cephalosporins )cephalosporins )

Penicillin G, Cephalothin Biological source Penicillium notatum Cephalosporium species Spectrum (effective against) Gram-positive bacteria Mode of action Inhibits steps in cell wall (peptidoglycan)

synthesis.

11 . .Beta-lactam antibioticsBeta-lactam antibiotics Example Example 2. ( Semisynthetic penicillin)2. ( Semisynthetic penicillin)

Ampicillin, AmoxycillinAmpicillin, Amoxycillin Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteriaGram-positive and Gram-negative bacteria Mode of actionMode of action   Inhibits steps in cell wall (peptidoglycan) Inhibits steps in cell wall (peptidoglycan)

synthesis. synthesis.

11 . .Beta-lactam antibioticsBeta-lactam antibiotics Example 3. (Clavulanic Acid )Example 3. (Clavulanic Acid )

Clavamox is clavulanic acid plus Clavamox is clavulanic acid plus amoxycillinamoxycillin

Biological sourceBiological source Streptomyces clavuligerusStreptomyces clavuligerus Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteriaGram-positive and Gram-negative bacteria Mode of actionMode of action Suicide inhibitor of beta-lactamasesSuicide inhibitor of beta-lactamases

Example 4. (Monobactams )Example 4. (Monobactams )

AztreonamAztreonam Biological sourceBiological source Chromobacter violaceumChromobacter violaceum Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteriaGram-positive and Gram-negative bacteria Mode of actionMode of action Inhibits steps in cell wall (peptidoglycan) Inhibits steps in cell wall (peptidoglycan)

synthesis and murein assemblysynthesis and murein assembly

11 . .Beta-lactam antibioticsBeta-lactam antibiotics Example 5. ( Carboxypenems )Example 5. ( Carboxypenems )

ImipenemImipenem Biological sourceBiological source Streptomyces cattleyaStreptomyces cattleya Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteriaGram-positive and Gram-negative bacteria Mode of actionMode of action Inhibits steps in cell wall (peptidoglycan) Inhibits steps in cell wall (peptidoglycan)

synthesis. synthesis.

22 . .GlycopeptidesGlycopeptides

Another group of peptidoglycan Another group of peptidoglycan synthesis inhibitors is the synthesis inhibitors is the

glycopeptides, exemplified by glycopeptides, exemplified by vancomycin and teichoplaninvancomycin and teichoplanin..

22 . .GlycopeptidesGlycopeptides VancomycinVancomycin Biological sourceBiological source Streptomyces orientalesStreptomyces orientales Spectrum (effective against)Spectrum (effective against) Gram-positive bacteria, esp. Staphylococcus Gram-positive bacteria, esp. Staphylococcus

aureusaureus Mode of actionMode of action Inhibits steps in murein (peptidoglycan) Inhibits steps in murein (peptidoglycan)

biosynthesis biosynthesis

33 . .AminoglycosidesAminoglycosides

Members of this group contain sugars and consists Members of this group contain sugars and consists of streptomycin, dihydrostreptomycin, neomycin, of streptomycin, dihydrostreptomycin, neomycin, framycetin, gentamicin, kanamycin, paromycin, framycetin, gentamicin, kanamycin, paromycin,

tobramycin and amikacintobramycin and amikacin..

33 . .AminoglycosidesAminoglycosides

Example 1.Example 1. GentamicinGentamicin Biological sourceBiological source MicromonosporaMicromonospora species species Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteria esp. Gram-positive and Gram-negative bacteria esp.

PseudomonasPseudomonas Mode of actionMode of action Inhibit translation (protein synthesis)Inhibit translation (protein synthesis)

33 . .AminoglycosidesAminoglycosides

Example 2Example 2 StreptomycinStreptomycin Biological sourceBiological source Streptomyces griseusStreptomyces griseus Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteriaGram-positive and Gram-negative bacteria Mode of actionMode of action Inhibit translation (protein synthesis)Inhibit translation (protein synthesis)

44 . .TetracyclinesTetracyclines

Tetracyclines consist of eight members, and Tetracyclines consist of eight members, and may be considered as a group of antibiotics, may be considered as a group of antibiotics, obtained as byproducts from the metabolism obtained as byproducts from the metabolism

of various species of of various species of StreptomycesStreptomyces. .

44 . .TetracyclinesTetracyclines

Example 1.( Natural )Example 1.( Natural ) TetracyclineTetracycline Biological sourceBiological source Streptomyces Streptomyces speciesspecies Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteria, Gram-positive and Gram-negative bacteria,

RickettsiasRickettsias Mode of actionMode of action Inhibit translation (protein synthesis)Inhibit translation (protein synthesis)

44 . .TetracyclinesTetracyclines

Example 2. (Semisynthetic tetracycline)Example 2. (Semisynthetic tetracycline) DoxycyclineDoxycycline Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative Gram-positive and Gram-negative

bacteria, Rickettsias Ehrlichia, Borelliabacteria, Rickettsias Ehrlichia, Borellia Mode of actionMode of action Inhibit translation (protein synthesis)Inhibit translation (protein synthesis)

55 . .MacrolidesMacrolides

Macrolides are an ill-defined group Macrolides are an ill-defined group representing those antibiotics that have large representing those antibiotics that have large

ring structures containing oxygenring structures containing oxygen..

55 . .MacrolidesMacrolides

ExampleExample ErythromycinErythromycin Biological sourceBiological source Streptomyces erythreusStreptomyces erythreus Spectrum (effective against)Spectrum (effective against) Gram-positive bacteria, Gram-negative Gram-positive bacteria, Gram-negative

bacteria not enterics, Neisseria,Legionella, bacteria not enterics, Neisseria,Legionella, MycoplasmaMycoplasma

Mode of actionMode of action Inhibits translation (protein synthesis)Inhibits translation (protein synthesis)

66 . .LincosamidesLincosamides

Lincosamides are a family of antibiotics that Lincosamides are a family of antibiotics that bind to bacterial 50S ribosomal subunit. They bind to bacterial 50S ribosomal subunit. They

differ considerably from macrolides in differ considerably from macrolides in structurestructure..

66 . .LincosamidesLincosamides

ExampleExample ClindamycinClindamycin Biological sourceBiological source Streptomyces lincolnensisStreptomyces lincolnensis Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteria Gram-positive and Gram-negative bacteria

esp. anaerobic Bacteroidesesp. anaerobic Bacteroides Mode of actionMode of action Inhibits translation (protein synthesis)Inhibits translation (protein synthesis)

77 . .QuinolonesQuinolones

Quinolones are a family of antibiotics that Quinolones are a family of antibiotics that interferes with DNA replication.interferes with DNA replication. Quinolones Quinolones

are bactericidal antibioticsare bactericidal antibiotics..

Nalidixic acidNalidixic acid

CiprofloxacinCiprofloxacin

NorfloxacinNorfloxacin

OfloxacinOfloxacin

88 . .RifampinRifampin

Rifampin (or Rifampicin) is an antibiotic that Rifampin (or Rifampicin) is an antibiotic that inhibits bacterial RNA polymerase by binding inhibits bacterial RNA polymerase by binding

to its ß-subunit. Rifampin is a bactericidal to its ß-subunit. Rifampin is a bactericidal antibioticantibiotic..

99 . .PolypeptidesPolypeptides

Example 1Example 1 PolymyxinPolymyxin Biological sourceBiological source Bacillus polymyxaBacillus polymyxa Spectrum (effective against)Spectrum (effective against) Gram-negative bacteriaGram-negative bacteria Mode of actionMode of action Damages cytoplasmic membranesDamages cytoplasmic membranes

99 . .PolypeptidesPolypeptides

Example 2Example 2 BacitracinBacitracin Biological sourceBiological source Bacillus subtilisBacillus subtilis Spectrum (effective against)Spectrum (effective against) Gram-positive bacteriaGram-positive bacteria Mode of actionMode of action Inhibits steps in murein (peptidoglycan) Inhibits steps in murein (peptidoglycan)

biosynthesis. biosynthesis.

1010 . .PolyenesPolyenes

Example 1.Example 1. AmphotericinAmphotericin Biological sourceBiological source Streptomyces nodosusStreptomyces nodosus Spectrum (effective against)Spectrum (effective against) FungiFungi Mode of actionMode of action Inactivate membranes containing sterolsInactivate membranes containing sterols

1010 . .PolyenesPolyenes

Example 2.Example 2. NystatinNystatin Biological sourceBiological source Streptomyces nourseiStreptomyces noursei Spectrum (effective against)Spectrum (effective against) Fungi (Candida)Fungi (Candida) Mode of actionMode of action   Inactivate membranes containing sterolsInactivate membranes containing sterols

. .Rifamycins11Rifamycins11 ExamplesExamples RifampicinRifampicin Biological sourceBiological source Streptomyces mediterraneiStreptomyces mediterranei Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteria, Gram-positive and Gram-negative bacteria,

Mycobacterium tuberculosisMycobacterium tuberculosis Mode of actionMode of action Inhibits transcription (eubacterial RNA Inhibits transcription (eubacterial RNA

polymerase)polymerase)

1212 . .PhenolsPhenols

ExampleExample ChloramphenicolChloramphenicol Biological sourceBiological source Streptomyces venezuelaeStreptomyces venezuelae Spectrum (effective against)Spectrum (effective against) Gram-positive and Gram-negative bacteriaGram-positive and Gram-negative bacteria Mode of actionMode of action Inhibits translation (protein synthesis)Inhibits translation (protein synthesis)

Resistance to AntibioticsResistance to Antibiotics

Resistance to AntibioticsResistance to Antibiotics

Resistance to AntibioticsResistance to Antibiotics

Resistance to AntibioticsResistance to Antibiotics

Resistance to AntibioticsResistance to Antibiotics

Antibiotics Susceptibility TestsAntibiotics Susceptibility Tests