Professional Documents
Culture Documents
Controlling
Microbial
Growth in
the Body:
Antimicrobial
Drugs
2012 Pearson Education Inc.
Antimicrobial agents
Drugs that treat infections
Paul Ehrlich
Magic bullets
Arsenic compounds that killed microbes
Alexander Fleming
Penicillin released from Penicillium
Gerhard Domagk
Discovered sulfanilamide
Selman Waksman
Antibiotics
Antimicrobial agents produced naturally by
organisms
2012 Pearson Education Inc.
Staphylococcus
aureus
(bacterium)
Penicillium
chrysogenum
(fungus)
Zone where
bacterial growth
is inhibited
Semisynthetics
Chemically altered antibiotics that are more
effective than naturally occurring ones
Synthetics
Antimicrobials that are completely
synthesized in a lab
Inhibition of pathogens
attachment to, or
recognition of, host
Arildone
Pleconaril
Inhibition of cell
wall synthesis
Penicillins
Cephalosporins
Vancomycin
Bacitracin
Isoniazid
Ethambutol
Echinocandins
(antifungal)
Inhibition of
protein synthesis
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Human
cell membrane
Inhibition of DNA
or RNA synthesis
Actinomycin
Nucleotide
analogs
Quinolones
Rifampin
Disruption of
cytoplasmic membrane
Polymyxins
Polyenes (antifungal)
Inhibition of general
metabolic pathway
Sulfonamides
Trimethoprim
Dapsone
Growth
Normal bacterial
cell wall
NAM
NAG
Cross-link
NAG-NAM
chain
Figure 10.3b A scanning electron micrograph of bacterial cells with normal cell walls
-lactam ring
Penicillin G (natural)
Cephalothin (semisynthetic)
Aztreonam (semisynthetic)
Cephalosporin
Monobactam
Methicillin (semisynthetic)
Penicillins
Growth
New NAM-NAM
cross-links
inhibited by
penicillin
Previously formed
cross-links remain
unchanged
Bacitracin
Blocks secretion of NAG and NAM from cytoplasm
Tenofovir
Adefovir
Adenosine arabinoside
Dideoxyinosine (ddl)
Ribavirin
Penciclovir
Adenosine
Guanosine
Acyclovir (ACV)
Ganciclovir
Dideoxycytidine (ddC)
Lamivudine
Valaciclovir
NUCLEOSIDES
Stavudine
(d4T)
Azidothymidine
(AZT)
Thymidine
Iododeoxyuridine
Trifluridine
Cytidine
Readily available
Inexpensive
Chemically stable
Easily administered
Nontoxic and nonallergenic
Selectively toxic against wide range of pathogens
Spectrum of Action
Number of different pathogens a drug acts
against
Narrow-spectrum effective against few organisms
Broad-spectrum effective against many
organisms
May allow for secondary or superinfections to
develop
Killing of normal flora reduces microbial
antagonism
Efficacy
Ascertained by
Diffusion susceptibility test
Minimum inhibitory concentration test
Minimum bactericidal concentration test
Bacterial lawn
Zone of inhibition
Turbid tubes
Clear tubes
Clear
MIC tube
8 g/ml
Bacterial colonies
16 g/ml
No colonies
Drug-free media
25 g/ml
No colonies
Routes of Administration
Topical application of drug for external infections
Oral route requires no needles and is selfadministered
Intramuscular administration delivers drug via
needle into muscle
Intravenous administration delivers drug directly to
bloodstream
Know how antimicrobial agent will be distributed to
infected tissues
Figure 10.13 The effect of route of administration on blood levels of a chemotherapeutic agent
Administration method
Relative concentration of drug in blood
Oral
Intramuscular
(IM)
Continuous
intravenous
(IV)
Time (hours)
Allergies
Allergic reactions are rare but may be life
threatening
Anaphylactic shock
2012 Pearson Education Inc.
Figure 10.14 Some side effects resulting from toxicity of antimicrobial agents-overview
Mechanisms of Resistance
At least seven mechanisms of microbial resistance
Produce enzyme that destroys or deactivates drug
Slow or prevent entry of drug into the cell
Alter target of drug so it binds less effectively
Alter their metabolic chemistry
Pump antimicrobial drug out of the cell before it
can act
Biofilms retard drug diffusion and slow
metabolic rate
Mycobacterium tuberculosis produces MfpA protein
2012 Pearson Education Inc.
Lactam ring
Penicillin
-lactamase (penicillinase)
breaks this bond
Inactive penicillin
Superbugs
Cross resistance
Retarding Resistance
Maintain high concentration of drug in patient
for sufficient time
Kills all sensitive cells and inhibits others so
immune system can destroy
Retarding Resistance
Use antimicrobials only when necessary
Develop new variations of existing drugs
Second-generation drugs
Third-generation drugs