complexty of antimicrobial therepy
DESCRIPTION
Complexty Of Antimicrobial TherepyTRANSCRIPT
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
www.freelivedoctor.com
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
www.freelivedoctor.com