Lecture 3: Antiboitics Flashcards
Definition of an antibiotic according to Waksmann
A chemical substance that is produced by microorganisms and that has the capacity in dilute solution to selectively inhibit the growth or kill other microorganisms
Modern definition of an antibiotic
any substance of natural, semisynthetic or synthetic origin that kills or inhibits the growth of microorganisms/bacteria but causes little or no damage to the host
Relationship between antibiotics and antimicrobials
All antibiotics are antimicrobials but not all antimicrobials are antibiotics
4 types of usage of antimicrobials in animals
Therapeutic
Prophylactic
Metaphylactic
Growth promotion
Therapeutic use
when diseased animals are treated to cure infection
Prophylactic use
when healthy herds or animals are treated to prevent infection
Metaphylactic use
when diseased herds are treated to cure infection in some individuals and prevent infection in others
Growth promotion use
when healthy animals are treated with low (sub-therapeutic) concentrations in feed to improve growth rate and efficiency of feed utilization, and improve reproductive performance
Most of the antimicrobial use in the US is for
Growth promotion use in livestock
6 Ways to Classify antibacterial agents
- Chemical structure
- Origin
- Effect on bacteria
- Spectrum of activity
- Mode of action
- PK/PD index
Three kinds of beta lactams
- Penicillins
- Cephalosporins
- Carbapenems
Three origins
Natural
Semi-synthetic
Synthetic
Natural
- Produced by fungi and bacteria
- Most common
Semi-synthetic
- Chemically altered natural compounds
- Modified to enhance activity of the drug
- Either to increase or decrease toxicity
Synthetic
Chemically designed by man
Bactericidal
kills bacteria
Bacteriostatic
inhibits growth of colonies but does not kill the cells
Three determinants of whether a drug may be bacteriostatic or bactericidal
- Drug concentration
- Presence of other drugs
- Bacterial species
Narrow spectrum durgs
have activity restricted to few bacterial groups
Broad spectrum drugs
have activity against a wide range of different bacterial organisms
Spectrum assessment
- Assessed before drug marketing in the Summary of Product Characteristics (SPC)
- May change over time as a consequence of drug use and resistance development
Three main ways to classify according to mode of action
- Cell wall synthesis
- Folic acid metabolism
- Protein synthesis inhibitors
Three PK/PD indices
- Time over MIC
- Cmax/MIC
- AUC/MIC
Time over MIC
The time that the drug concentration at the site of infection is higher than the minimal inhibitory concentration
Cmax/MIC
The ratio of the peak drug concentration at the site of infection to the MIC
AUC/MIC
The ratio of the “area under the (concentration-time) curve” over 24 hours to the MIC
MIC
The lowest concentration of the drug that inhibits the bacteria completely
Time dependent antibiotics
- Index: Time over MIC
- Most effective if their concentration is maintained above the MIC as long as possible (at least 50% of dosing interval for beta-lactams).
- An increase in concentration more than 4 times MIC does not influence efficacy
Concentration-dependent antibiotics
Most effective if they reach a high concentration compared to the MIC at the site of infection, while the time they maintain this concentration is less important
In order to maximize clinical efficacy, what dose do you use for concentration-dependent drugs?
High
In order to maximize clinical efficacy, what dose do you use for time-dependent drugs?
Regular dose intervals
