complexty of antimicrobial therepy

Complexity of Antimicrobial Therapy(Antimicrobic Drug =antibiotic or synthetic drug)

Drug DeliveryProblems

Oral (destruction/poor uptake), Intravenous

or Intramuscular(inconvenient),

Topical, Poor Tissue Uptake, Injection into

Body Cavity

Wrong DrugWrong Spectrum

of Activity (informed best guess),

Few Targets on Pathogen

(fungi, protozoa, viruses)

Drug RetentionProblems

Elimination from Host,Inactivation by Host

Side EffectsToxicity to Host,

Allergic Reaction,Normal Flora

Disruption(superinfection)

Antimicrobial Administration

Selective Toxcity & Successful Deliverywww.freelivedoctor.com

Complexity of Antimicrobial Therapy

ToxinsExotoxins,Endotoxins

(in Gram-negative septicemia

antibiotic treatment can make situation

even worse)

Development ofResistance

Evasion,Mutation-Mediated,

Acquired (R plasmids)

Prevention of Growth

Bactericidal,Bacteriostatic,Host Defenses(elimination of

pathogen from body)

Prevent Resistance by Using…

Only as Necessary, At sufficiently high

doses for sufficiently long periods, In

Combination

Selective Toxcity & Successful Delivery

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Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the hostwww.freelivedoctor.com

Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

www.freelivedoctor.com

Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

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Ant

ibio

tics

Sou

rces

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Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines

Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin

Causes misreading of mRNA: binds to 30S ribosmal subunit

Sulfonamides

Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

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Site

s of

Ant

ibio

tic A

ctio

n Site of Action Antibiotic Examples

Cell wall (peptidoglycan) synthesis

•Glycopeptides•B-lactams

Replication or transcription of genetic material

•Quinolones•Nitroimidazoles•Rifampicin

Protein synthesis •Aminoglycosides•Chloramphenicol•Macrolides

Cell membrane functions (fungi)

•Polymixins

Antimetabolites •Diaminopyrimidines

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Antibiotic Modes of Action

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Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

www.freelivedoctor.com

Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

www.freelivedoctor.com

Spectrum of Activity

Narrow Spectrum Wide Spectrumwww.freelivedoctor.com

Info

rmed

Bes

t Gue

ss

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Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

www.freelivedoctor.com

Dis

tingu

ishi

ng A

ntib

iotic

sAntibiotics differ in terms of…

…their chemical structure

…the organism they are or were isolated from

…their site of action in bacterial cells

…bacteriostasis versus bacteriostatic

…the spectrum of bacteria they are active against

…the degree to which susceptible organisms are capable of evolving resistance

…toxicity to the host

www.freelivedoctor.com

Var

ious

Ant

ibio

tics

Antibiotic Mode Spectrum of Activity Side Effects

Ampicillin C Gram+, some neg. (broad)

Allergic (diarrhea, anemia)

Bacitracin C Gram+ (narrow) If injected: renal injury

Clindamycin S Gram+ anaerobes (narrow)

Diarrhea

Erythromycin S Gram+ mycoplasma (narrow)

Gastrointestinal upset, hepatic injury

Isoniazod C Mycobacteria (narrow) Allergic, gastrointestinal upset, hepatic injury

Penicillin C Gram+ (narrow) Allergic (nausea, anemia)

Rifampin S Gram+ & mycobacteria (broad)

Allergic, nausea, hepatic injury

Streptomycin C Gram+, Gram-, & mycobacteria (broad)

Allergic, nausea, renal injury, loss of hearing

Sulfonamides S Gram+, Gram- (broad) Allergic (hepatic and renal injury, anemia)

Tetracyclines S Gram+, Gram-, rickettsia, chlamydia

Teeth discoloration, gastrointestinal upset (hepatic and renal injury)

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Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Cephalosporins Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Chloramphenicol Interferes with protein synthesis by binding to the bacterial ribosome

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Erytrhomycin Reversibly binds to ribosome, interfering with protein synthesis

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

www.freelivedoctor.com

Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

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Blo

ckin

g R

ibos

ome

Fun

ctio

n

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Ant

ibio

tic M

odes

of A

ctio

n Drug Mode of Action

Vancomycin Binds to D-Ala-D-Ala terminus; inhibits transpeptidation

Penicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Carbenicillin Inhibits transpeptidation enzymes. Activates lyctic enzymes of cell wall

Rifampin Blocks RNA synthesis: binds to, inhibits DNA-dependent RNA polymerase

Ciprofloxacin Inhibits bacterial DNA gyrase; interferes with DNA-involved activities like DNA replication

Tetracyclines Interfere with aminoacyl-tRNA binding: binds to 30S ribosomal subunit

Streptomycin Causes misreading of mRNA: binds to 30S ribosomal subunit

Sulfonamides Interferes with synthesis of folic acid by competition with p-aminobenzoic acid

Polymyxin B Disrupts structure and permeability of plasma mambrane by binding with it

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