Antibiotics Flashcards
What is prophylactic therapy?
No s/sx of infection, trying to avoid it
Make the best choice of antimicrobial that will reduce the pathogen at the potential site of infection
What is empiric therapy?
Clinical s/sx present
Requires knowledge of the most likely pathogens
Infection is known and/or clinically apparent (ex. most likely pathogen in a UTI is E. coli)
Make the best choice of antimicrobial that will help eradicate the pathogen at the site of infection and take host factors into account
What is definitive therapy?
Site of infection usually known, bacterial susceptibilities known
The data on the pathogen(s) and susceptibility pattern(s) to antimicrobials is already known
Narrow (de-escalate) from initial empiric therapy
What is minimum inhibitory concentration (MIC)?
Drug concentration at which organism’s growth is inhibited
What is minimum bactericidal concentration (MBC)?
Drug concentration at which organism death occurs, will exceed MIC
How is susceptibility determined?
MIC value + clinically achievable drug concentrations at the site of infection
BOTH must be taken in to account
What are the ideal antibiotic properties?
Selective toxicity
Easily classified
No acquired resistance
What is a superinfection? How do they develop?
A new infection that appears during the treatment of a primary infection
Develop when Abx kill microbiota that normally inhibit pathogens –> dysbiosis
Superinfections are most likely to occur as a result of what type of antibiotics?
Broad spectrum Abx
Natural vs Acquired Resistance:
Natural
- the organism has an inherent trait that makes it resistant to the drug
Acquired
- Enzymes that modify/inactivate the drug
- Altered ability to accumulate the drug
- Modified site of action
- Altered cell surface permeability to drug
How does acquired resistance occur?
Spontaneous genetic mutations during DNA replication (vertical transfer)
Acquisition of genetic mutations in horizontal transfer
Vertical transfer vs. Horizontal transfer
Vertical transfer:
- Once the mutated genes conferring resistance have been created, they are transferred directly to all the bacteria’s progeny during reproduction/binary fission
Horizontal transfer:
- Conjugation
- Transformation
- Transduction
Describe the three types of horizontal transfer
- Conjugation: cell-to-cell contact results in the direct transfer of small pieces of DNA called plasmids
- Transformation: DNA is taken up by the bacteria from the external environment. This DNA is normally present due to the death and lysis of another bacterium
- Transduction: Bacteria-specific viruses transfer DNA between two closely related bacteria
What are beta-lactam antibiotics? How can they be inactivated?
Antibiotics that contain a beta-lactam ring
They are highly susceptible to the enzyme beta-lactamase, which breaks the beta-lactam ring and renders the drug inactive
Describe the relationship between MRSA and PBPs
MRSA (certain strains of S. aureus have acquired genes that code for PBPs that have a very low affinity for penicillins and cephalosporins
Low affinity PBPs –> penicillins and cephalosporins cannot bind to those PBPs and exert their antibacterial effects
What clinical presentation does MRSA have?
Can commonly cause skin and soft tissue infections, such as furuncles and carbuncles, including necrotizing fasciitis
What are antibiotic stewardship programs?
Programs that are coordinated interventions designed to improve and measure the appropriate use of antibiotic agents
Promotes the selection of the optimal antibiotic drug regimen (dosing, duration of therapy, and route of administration)
What are the 4 general MOA of antibacterial agents?
- Cell wall active antibacterials
- Interfere with protein synthesis
- Interfere with nucleic acids
- Anti-metabolite antibacterial, such as those interfering with synthesis of a derivative of folic acid
Describe the role of transpeptidase in antibiotics that destroy the cell wall
Transpeptidase creates cross bridges between strands of peptidoglycan polymers, which add strength to the cell wall
Abx (penicillin) inhibits transpeptidases, which prevents cross-bridge formation and weakens the cell wall
Which class of antibiotics interrupt DNA replication and transcription?
Fluoroquinolones
Bactericidal vs Bacteriostatic
Bactericidal: kill bacteria outright
Bacteriostatic: prevent bacterial growth
What does it mean when an antibiotic is concentration-dependent?
As the concentration of the drug increases, the rate and extent of bacterial killing increases
What does it mean when an antibiotic is time-dependent?
The duration of exposure above the MIC is key
Once the abx reaches a certain concentration, there is not an increased rate of bacterial killing with increasing concentrations of antibiotic
What is the post-antibiotic effect of a concentration-dependent antibiotic vs. a time-dependent antibiotic?
Time-dependent: shorter post-antibiotic effect
Concentration-dependent: longer post-antibiotic effect