Microbiology- Chapter 12 (Antimicrobial Drugs)

Front 1

What are antimicrobial drugs?

Back 1

Antimicrobial Drugs are:

-Chemical substances used for treatment of infectious diseases – chemotherapy
-Antimicrobial drugs have selective toxicity (harmful against microbes and not the host)
-Antibiotic- substance produced by one microorganism that is inhibitory or toxic against other Microorganism

Front 2

What was the first discovered antibiotic?

Back 2

The first discovered antibiotic was penicillin –Alexander Fleming in 1928
-Mold – Penicillin notatum
-It’s commercial use stated in 1945
-New antibiotics are being discovered by screening large number of microbes (400,000 screened; 3 useful drugs)

Front 3

What is the spectrum of antibacterial activity?

Back 3

-An antibiotic can be effective against a
-narrow group of microbes (ex. penicillin G – against Gram positive bacteria)
-broad-spectrum antibiotic
-disadvantage- eliminates also the normal microflora

Front 4

What are the two ways a antimicrobial drug can act?

Back 4

Bactericidal- kills the microbes

Bacteriostatic – inhibits the growth

Front 5

How does a antimicrobial drug work?

Back 5

-Inhibition of:

-Cell wall synthesis
-cytoplasmic membrane synthesis
-protein synthesis
-DNA synthesis
-Synthesis of essential metabolites

Front 6

What are the inhibitors of cell wall synthesis?

Back 6

Inhibitors of Cell Wall Synthesis

-Penicillins and cephalosporins interfere with the formation of peptidoglycan layer in the cell wall of bacteria (not present in eukaryotic cells). Bactericidal.

Penicillins/Cephalosporins:

-These drugs block the enzymes that cross-link N-actylglucosamin and N-acetyl muramic acid
-Less effective against Gr negative bacteria – do not penetrate the outer membrane

Front 7

Describe penicillins.

Back 7

Penicillins:

-Natural penicillin (Penicillin G)
-It has a narrow spectrum (staphylococci, streptococci, and spirochetes)
-It is rapidly excreted from the body
-More efficient when injected than when taken orally
-It is susceptible to penicillinases (enzymes that cleave the penicillin molecule)

Front 8

what are Semisynthesic Penicillins ?

Back 8

Semisynthesic Penicillins

-Partially produced by the mold Penicillin and partially by a chemical process
-The change of the shape of the molecule makes it more difficult to break up by penicillinase

Front 9

How does B-Lactamase (penicillinase) work?

Back 9

B-Lactamase (penicillinase) action
-bacteria resistant to penicillin have the enzyme b-lactamase
-It breaks the Lactam ring

Front 10

Describe cephalosporins.

Back 10

-Cephalosporins

-Similar to penicillin, resistant to B-lactamase
-Oral administration possible

Front 11

What is another cell wall inhibitor other than penicillins and Cephalosporins?

Back 11

Bacitracin
-Polypeptide antibiotic effective against Gr + bacteria
-Major ingredient of Neosporin – used for skin infections

Front 12

What are the protein synthesis inhibitors?

Back 12

-Aminoglycosides (Streptomycin)

-Chloramphenicol

-Tetracyclin

-Erythromycin

Front 13

Describe Aminoglycosides (Streptomycin) and how it works.

Back 13

-Aminoglycosides (Streptomycin)
-Change in the 30S ribosome shape; mRNA misread
-Isolated from Streptomyces

Front 14

Describe Chloramphenicol.

Back 14

Chloramphenicol

-Inhibits formation of polypeptide chain
-Bacteriostatic
-The use is restricted- suppresses formation of blood cells

Front 15

Describe Tetracyclin

Back 15

Tetracyclin

Interferes with attachment of tRNA to mRNA
-Effective against Gr + and Gr –
-Bacteriostatic

Front 16

Describe Erythromycin

Back 16

Erythromycin
-Binds to ribosome and prevents its movement along the mRNA
-Not effective against Gr negative bacteria
-Bacteriostatic

Front 17

What causes injury to plasma membrane?

Back 17

Polymixin B


-changes the permeability of plasma membrane
-Effective against Gr- bacteria – Pseudomonas
-Bactericidal effect

Front 18

what is the inhibitor of Nucleic Acid Synthesis.

Back 18

Riframpin:

-inhibits the synthesis of mRNA
-Used for treatment of mycobacterial infections (tuberculosis)
-Good penetration of tissues
-Cannot penetrate the cell envelope of Gr negative bacteria
-Bactericidal

Front 19

what are the Competitive Inhibitors of the Synthesis of Essential Metabolites?

Back 19

Sulfanamides"

-Bacteria require PABA (para-aminobenozoic acid) for synthesis of folic acid (essential for synthesis of nucleic bases)
-A sulfanil amid drug mimics the PABA and acts as competitive inhibitor

Front 20

What are the antifungal drugs?

Back 20

-Restricted use – target the same mechanisms as those found in higher animals (protein and nucleic acid synthesis)

-Amphotericin B: is the most commonly used antifungal antibiotic

-Produced by Streptomyces
-It combines with sterols – components of fungal plasma membrane causing an increase of permeability
-The drug is toxic to kidneys


Griseofulvin:

-Produced by Penicillin
-Effective against fungi infecting hair and nails
-Interferes with mitosis (reproduction)
-Binds to keratin

Front 21

What are antiviral drugs?

Back 21

-Viruses cause 60% of infectious diseases
-There is a limited number of antiviral drugs because viruses are endocellular pathogens

Front 22

What are the modes of actions of antiviral drugs?

Back 22

~Inhibition of virus entry
-Fuzeon – prevents binding of viral (HIV) receptor to cell receptor
-Amantidine – prevents entry of influenze virus into cell
~ Inhibition of nucleic acid synthesis
-Acyclovir – Purine analog –terminates DNA replication
-Zidovudin –reverse transcriptase inhibitor (HIV)
~ Inhibition of viral assembly
-Indinavir – protease inhibitor – prevents maturation of virus particles

Front 23

what is an analog of viral DNA and RNA components?

Back 23

-Acyclovir
-Effective against herpesvirus (genital herpes)
-The drug has a structure similar to guanosisne nucleotide (component of DNA)

Front 24

How *does* bacteria evade the action of antibiotics?

Back 24

-Inactivation of the drug (B-lactamase)
-Prevention of penetration
-Efflux – pumping the drug out of the cell
-Alteration of the drug’s target sites (mutation in a single amino acid in the ribosome)

Front 25

Natural Selection and Drug Resistance .. Where does it come from?

Back 25

-Any microbial population contains individual cells with a prior mutation (drug resistance)
-If the population is exposed to a drug – the resistant cells will eventually become dominant

Front 26

what are the reasons for the rise of drug resistance?

Back 26

The Rise of Drug Resistance
-The reasons:

-Use of antibiotitcs for cold or influenza
-Patient’s failure to follow the prescribed treatment
-Long-term, low-dose treatment of acne
-Use of antibiotics in animal feed (antibiotics promote growth and weight gain in farm animals)

Front 27

What is MRSA and describe its resistance?

Back 27

MRSA (methicilin resistant Staphylococccus Aureus)
-Methicillin – the first semisynthetic penicillin
-Designed to evade the action of penicillinase
-Staphylococci developed resistance
-Methicillin discontinued in the US

Front 28

Microbes are becoming resistant to antibiotic : What now?

Back 28

-Look for novel antibiotics from sources other than microbial (plants, animals)
-To target in the iron-scavenging capabilities of bacteria (Staphylococcus aureus takes iron from erythrocytes through a special pathway)

Front 29

What is the probiotic approach?

Back 29

-Probiotic approach – desirable bacteria are included in animal’s feed; this could prevent development of harmful bacteria

Front 30

What are the side effects of antibiotics?

Back 30

Side Effects of Antibiotics

-Hearing impairment
-Liver and kidney damage
-Toxic effect when taken with other drugs
-Diarrhea
-Allergies
-Candida Albicans vaginal infections
-Clostridium difficile large intestine infections (pseudomembranous colitis)

Front 31

what is Suppression of Normal Microbiota?

Back 31

-Beneficial bacteria colonize human body
-Broad-spectrum antibiotics targets the infectious agent but also the normal microflora
-Complication called superinfection

Front 32

how do you test an antibiotics effectiveness?

Back 32

-The treatment of bacterial infection is based on estimation which antibiotic is the most effective

-If the case of bacterial resistance, the isolated strain should be tested against different antibiotics

Front 33

What is the Diffusion method?

Back 33

-The surface of agar medium is uniformly inoculated with a test organism
-The filter paper discs impregnated with different antibiotics
-The effective antibiotic will inhibit the growth of bacteria- clear zone will occur
-The diameter of zone indicates the effectiveness of the antibiotic

Front 34

What is Minimal Bactericidal concentration? MBC

Back 34

Minimal Bactericidal concentration
(MBC) is the minimal concentration of antibiotic that kills the bacteria (not only inhibits)

Front 35

What is the broth dilution test?

Back 35

Broth Dilution Test:

-Broth containing different antibiotic concentrations is inoculated with the test bacterium
-A minimal concentration of antibiotic that prevents a visible growth is called minimal inhibitory concentration (MIC)