1.4 Flashcards
Antibiotics:
a class of chemotherapeutic agents
Chemotherapeutic agents are
chemical
compounds used to treat disease
Antimicrobials destroy
pathogenic microbes or
inhibit their growth within host
Antibiotics destroy or inhibit
bacteria
Most antibiotics are — products or their
derivatives
microbial
selective toxicity
– ability of drug to kill or inhibit pathogen while
damaging host as little as possible
therapeutic dose
– drug level required for clinical treatment
toxic dose
– drug level at which drug becomes too toxic for patient
i.e., produces side effects
therapeutic index
– ratio of toxic dose to therapeutic dose
Bacteriocidal antibiotics
– kill bacteria
Bacteriostatic antibiotics
– inhibit growth of bacteria
Broad-spectrum antibiotics
– attack many different bacteria (Gram + and Gram -)
Narrow-spectrum antibiotics
– attack only a few different bacteria
Determining the Level of
Antimicrobial Activity
• effectiveness expressed in two ways
– minimal inhibitory concentration (MIC)
– minimal bacteriocidal concentration (MBC)
– minimal inhibitory concentration (MIC)
• lowest concentration of drug that inhibits growth of pathogen
– minimal bacteriocidal concentration (MBC)
• lowest concentration of drug that kills pathogen
Dilution Susceptibility Tests
• involves inoculating media containing different
concentrations of drug
– broth or agar with lowest concentration showing no
growth is MIC
– if broth used, tubes showing no growth can be
subcultured into drug-free medium
• broth from which microbe cannot be recovered is MBC
Disk Diffusion Tests
• disks impregnated with specific drugs are
placed on agar plates inoculated with test
microbe
• drug diffuses from disk into agar,
establishing concentration gradient
• observe clear zones (no growth) around
disks
Kirby-Bauer method
• standardized method for carrying out disk
diffusion test
• sensitivity and resistance determined using tables
that relate zone diameter to degree of microbial
resistance
• table values plotted and used to determine if
concentration of drug reached in body will be
effective
Kirby-Bauer method (steps)
Inoculate plate evenly with bacteria whose susceptibility is being studied Place discs containing antibiotics or control solutions onto the plates Incubate a defined amount of time at a defined temperature Measure zone of inhibition
Measurement of Drug
Concentrations in the Blood
• concentration of drug at infection site must
be > — to be effective
MIC
microbiological, chemical, immunological,
enzymatic, or chromatographic assays can
be used to determine
concentration of
drug in blood
Factors Influencing the
Effectiveness of Antimicrobial
Drugs (3)
• ability of drug to reach site of infection
• ability of drug to reach concentrations in body
that exceed MIC of pathogen
• susceptibility of pathogen to drug
Ability of drug to reach site of
infection
• depends in part on mode of administration (3)
– oral
– topical
– parenteral routes
– oral
• some drugs destroyed by stomach acid
– parenteral routes
• nonoral routes of administration
drug can be excluded by (2)
blood clots or necrotic
tissue
Factors influencing ability of drug
to reach concentrations
exceeding MIC (4)
- amount administered
- route of administration
- speed of uptake
- rate of clearance (elimination) from body
Mechanism of Action of
Antimicrobial Agents
• can impact pathogen by targeting some
function necessary for its (2)
reproduction or
survival
Ideally, targeted function is very specific to
pathogen =
high therapeutic index.
– Not always possible
b-lactams (4)
penicillins
cephalosporins
carbapenems & monobactams
(+ b-lactamase inhibitors)
Glycopeptides (2)
vancomycin & teichoplanin
Polypeptides (2)
bacitracin & polymixins
Others (3)
cycloserine
isoniazid & ethionamide
ethambutol
- Disruption of bacterial cell wall (2)
– Peptidoglycan is unique to bacteria
– Most pathogens contain peptidoglycan