Principles of Antibacterial Pharmacology Flashcards
What are the 6 Antibacterial drug classes?
- Often called antimicrobial drugs (AMDs)
- Hundreds of AMDs are available
- Most fall into 6 major groups
- Bela-Lactams (BL)
- Aminoclycosides (AG)
- Tetracyclines (TET)
- Sulfonamides (TMS)
- Macrolides (MAC)
- Fluoroquinolones
Miscellaneous others:
- Chloramphenicol, rifampin, metronidazole, clindamycin, etc.
Main AMD Mechanism of Action
Many antifungals - damage to plasma membrane
Beta-lactams - inhibition of cell wall synthesis
Aminoglycosides, tetracyclines, macrolides - inhibition of protein synthesis
Sulfonamides - inhibition of folic acid synthesis
Fluoroquinolones - damage to DNA
What is bactericidal and bacteriostatic?
Bactericidal: describes a drug that kills bacteria - can have more side effects
Bacteriostatic: describes a drug that inhibits bacterial growth and division - stop RNA synthesis of bacteria
- Drugs that are bactericidal at recommended concentrations may be bacteriostatic at low concentration; conversely some drugs that are normally bacteriostatic may kill bacteria if the concentration is high enough
Time-dependent AMDs
- Efficacy is associated with length of time drug concentration remains above MIC (minimum inhibitory concentration)
- Levels should remain above MIC throughout course of therapy - this is why we should never stop dose even if feel “cured”
- Most AMD groups:
- Beta-lactams
- Tetracyclines
- TMS
- Macrolides
Concentration-dependent AMD’s
- Efficacy depends on peak concentration
- May be well in excess of MIC
- Not necessary to maintain levels above MIC for the entire interval between doses
- Examples:
- Aminoglycosides
- Fluoroquinolones
How do we detemine which AMD to use?
- Most bacteria are benign or helpful to humans; one ~100 species are pathogenic
- bacteria will be classified into 4 types:
1. Gram + aerobes
2. Gram - aerobes
3. Anaerobes
4. Atypical bacteria
Antimicrobial sensitivity
- most drugs are effective against a mix of bacterial species and types (good susceptibility)
- Each class of antimicrobial drugs is usually more effective against certain types of bacteria than others, and these general patterns are useful to know
- good susceptibility, variable susceptibility, moderate susceptibility, or resistance
- resistance to any drug is. not an all or none characteristic of bacteria
- Different strains of the same bacterium from different patients may differ in sensitivity even in the same geographic area
- A single infection can contain a mix of bacteria of different sensitivities; therapy may leave the most resistant behind (different strains of same bacteria in infections can respond differently to treatment - some are/aren’t resistant)
How do we determine if bacteri is sensitive to an AMD?
- Serial dilution test
- test different AMDs of increasing concentration to determine if and at what dose the drug is bacteriostatic and/or bactericidal - Kirby-Bauer test
- spot test different drugs at commonly used concentrations to determine if the bacteria is resistant, intermediate or susceptible
antibacterial drug susceptibility testing: serial dilution
- Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) by serial drug dilution
- to determine MIC, serial 1:2 dilutions of an antimicrobial drug are added to tubes containing bacterial growth medium (μg/mL)
- Each tube is then seeded with a standard quantity of bacteria
- After a set time (usually 24h) the tubes are assessed for visible bacterial growth (turbidity of the growth medium)
- the tube is showing no turbidity at lowest drug concentration is designated the MIC (no visible growth, but bacteria may be alive)
- by culturing samples from each tube in drug-free medium, the MBC can be determined (the drug concentration that sterilized the tube, resulting in no growth in this step)
- Serial dilution MIC/MBC testing is labour intensive - not a practical process
- In routine testing, it is often replaced by the simpler Kirby-Bauer disk diffusion test
antibacterial drug susceptibility testing: Kirby-Bauer
Kirby-Bauer disk diffusion test - more practical
- Paper disks impregnated with drugs placed on plate uniformly swabbed with bacteria → drug diffuses from each disk into agar - drug conc is highest near disk, and falls as distance from disk increases
- Zone of inhibition around each disk measured after specified time
- Zone diameter is compared to a regression curve aqnd reported as sensitive, intermediate or resistant to the drug
Principles for Selecting and Administering AMDs - Step 1: If possible identify the organism
Scenario: Patient presents with symptoms consistent with a bacterial infection (i.e., a UTI)
- In non-critical infections, knowledge of the most common pathogens at the site warrants administration of a “first-line” drug (broad spectrum) without yet knowing the identity of the pathogen → C+S
- If first line treatment fails, pathogen identification becomes vitally important
- Quick and dirty method: Gram staining
- Slow and precise method: Culture and sensitivity (C&S)
Principles for Selecting and Administering AMDs - Step 2: Consider drug, host, and bacterium
Considerations:
- Bacterial sensitivity
- use narrow-spectrum drugs when possible, to avoid killing commensal (good/beneficial) bacteria
- Bacteriostatic vs. bactericidal
- want bactericidal drug if patient’s immune system is compromised or infection is life threatening
- Adverse effects
- the need for the drug should outweigh the likely adverse effects
- Distribution
- CNS and prostate both difficult for drugs to enter
- Cost?
Principles for Selecting and Administering AMDs - Step 3: Dosage
- Determined by commercial or government labs
- use label recommendations or consult a reference text
- adjust according to patients needs
Principles for Selecting and Administering AMDs - Step 4: in certain cases, initiate treatment ASAP
- With infections such as bacterial meningitis, septicaemia, septic arthritis, etc. delay may lead to potentially fatal or crippling outcomes
- send in sample for culture and sensitivity and treat empirically while awaiting results
- essentially an educated guess
