antibiotics and resistance Flashcards
Antibiotics
a class of chemotherapeuticagents • Chemotherapeutic agents are chemical compounds used to treat disease
• Antimicrobials
• Antimicrobials destroy pathogenic microbes or
inhibit their growth within host
• Antibiotics
• Antibiotics destroy or inhibit bacteria
• Most antibiotics are microbial products or their
derivatives
where do many antibiotics come from
many are derived from microbes as compounds produced to compete with other microbes
• 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
• 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: MIC and MBC
MIC
– minimal inhibitory concentration (MIC)
• lowest concentration of drug that inhibits growth of pathogen
MBC
minimal bacteriocidal concentration (MBC)
• lowest concentration of drug that kills pathogen
tests used to detemrine MIC/MBC
dilution susceptibility and disk diffusion
dilution susceptability
• 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
table for disk diffusion tests
radius of inhibiton zone: larger= able to inhibit at lower concentrations= lower MIC
may be resistant with smaller inhibition zone
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
Measurement of Drug
Concentrations in the Blood
when effective?
tests?
concentration of drug at infection site must be > MIC to be effective
• microbiological, chemical, immunological, enzymatic, or chromatographic assays can be used to determine concentration of drug in blood
Factors Influencing the Effectiveness of Antimicrobial Drugs
- ability to reach site of infection
- ability to exceed MIC of pathogen
- susceptibility of pathogen
Ability of drug to reach site of infection factors
• depends in part on mode of administration
– oral: some drugs destroyed by stomach acid
– topical
– parenteral routes: nonoral routes of administration
• drug can be excluded by blood clots or necrotic tissue
Factors influencing ability of drug to reach concentrations exceeding MIC
- amount administered
- route of administration
- speed of uptake
- rate of clearance (elimination) from body
Susceptibility of pathogen to drug factors
- Does a drug require bacterial cell growth to be effective? (can spores be targeted)
- Speed of action of a drug
concepts for Mechanism of Action of Antimicrobial Agents, how we target/ideally?
- can impact pathogen by targeting some function necessary for its reproduction or survival
- Ideally, targeted function is very specific to pathogen= high therapeutic index– Not always possible
Mechanisms of Action of Antimicrobial Agents
target bacterial cell wall
inhibition of protein synthesis
inhibition of NA synthesis
antimetabolites
Disruption of bacterial cell wall drug classes
b-lactams
Glycopeptides
Polypeptides
Others
how can we target the cell wall?
peptidoglycan unique to both +/- bacteria, most pathgens contain this
Peptidoglycan Synthesis basic steps and diagrammed
– peptidoglycan repeat unit forms incytoplasm
• involves use of uridine diphosphate (UDP) as a carrier
– repeat unit then transported across membrane by bactoprenol (“lipid”)
– repeat unit attached to growing peptidoglycan chain
– cross-links formed by transpeptidation
transpeptidation
how cross links form in peptidoglycan
exchange of one peptide bond for another
b-lactam function
b-lactam antibiotics inhibit transpeptidation
types of B lactams (names)
penicillins
cephalosporins
carbapenems
monobactams
different penicillins
many with different side chains modifications for variable properties