Antibiotics Flashcards
Antibiotic Susceptibility Testing: Bactericidal Activity
- Level of antimicrobial activity that KILLS
- Lowest concentration of antibiotic that kills 99.9% = minimum bactericidal concentration (MBC)
Antibiotic Susceptibility Testing: Bacteriostatic Activity
- Level of antimicrobial activity that INHIBITS GROWTH
- Lowest concentration of antibiotic that inhibits growth = minimum inhibitory concentration (MIC)
Antibiotic
Isolated in NATURE
Antimicrobial
Synthesized in a LAB
Bacteriostatic
Inhibit growth
***Used when host defenses can be counted on
Bactericidal
Killing
***Used during invasive infection: bacteremia, meningitis, endocarditis
Broad-Spectrum Antibiotic (Definition and Advantages/Disadvantages)
Effective against a large variety of bacteria
Advantage: increased likelihood of effectiveness agaisnt bacterial infection of UNKNOWN etiology
Disadvantage: increased likelihood of disrupting normal biota
***Prescribed when you are unsure of the bacteria that is infection and want to start treatment immediately
Narrow-Spectrum Antibiotic (Definition and Advantages/Disadvantages)
Effective against only a small subset of bacteria
Advantage: avoids disruption of the normal microbiota
Disadvantage: Must have SPECIFIC DISEASE causing bacteria identified in order to choose abx
***Used in non-emergent cases
Do antibiotics cause antibiotic resistance?
No; they select against sensitive bacteria and for resistant bacteria, which allows for survival of bacteria that have gained a rare mutation/genetic acquisition
Empiric Therapy
Generally BROAD SPECTRUM
-Treatment while waiting for lab results
Targeted Therapy
NARROW SPECTRUM
-Refined treatment
Antibiotic resistance is ____ at an alarming rate; Antibiotic discovery is ____ at an alarming rate
Accelerating; Decelerating
Antibiotic Resistance (General Mechanisms)
- Breakdown of an antibiotic (e.g. Hydrolysis)
- Chemical modification of an antibiotic (e.g. Methylation or Phosphorylation)
- Alteration of the Target (Mutations and/or gene acquisition)
- Altered permeability, decreased influx, or increased efflux (e.g. pumps to pump out abx)
- Lack of target
Minimum Inhibitory Concentration (MIC) tests
- Disk-diffusion assay (e.g. Kirby-Bauer Test)
- Abx migrates out from disc from high concentration to low concentration; can measure zone of inhibition/clearing to get MIC - E-Test (same thing, except with strips that have a tapering of high to low concentration of abx)
- Broth Culture (measures both MIC and MBC; see subsequent slide)
Broth Culture
Measures both MIC and minimum bactericidal concentration (MBC)
-Measures DENSITY of bacteria based on how much light comes through the test tube
***MIC measures inhibition of growth via visualization in test tube
***MBC measures killing of bacteria via growth (or lack of growth) on an agar
Cell Wall Active vs Membrane Active Antibiotics
Cell Wall Active:
- Disrupts PEPTIDOGLYCAN synthesis
- ONLY effective against ACTIVELY DIVIDING bacteria
Membrane Active:
- Disrupts or interferes with MEMBRANE integrity/synthesis
- Effective against RESTING AND ACTIVELY DIVIDING bacteria
Beta-lactams
- Bactericidal*
- Inhibit cell wall synthesis
e.g. Penicillins,Cephalosporins, Cephamycins, Carbapenems, Monobactams
Beta-Lactams (Mechanism of Action)
Bind the active site transpeptidases (i.e. Penicillin Binding Proteins (PBP)), preventing them from crosslinking peptidoglycan together
Resistance to Beta-Lactams (4 mechanisms)
- Altered transpeptidases (e.g. mutation: decreased abx affinity)
- Altered outer-membrane permeability (e.g. mutation in porins)
- Presence of efflux pumps
- Chemical modificaiton of antibiotic (Beta-Lactamase)
Vancomycin (Sensitive Bacteria)
Bactericidal
- Vancomycin binds two D-ala residues on the end of the peptide chains, PREVENTING them from interacting with TRANSPEPTIDASE
- Cross-links cannot be formed = cell death
Vancomycin (Resistant Bacteria)
- The last D-ala has been REPLACED by a D-LACTATE, so Vancomycin cannot bind
- Cross-links are formed and cell wall is successfully made
Bacitracin
- Bactericidal*
- Interferes with dephosphorylation in cycling of lipid carier that transfers peptidoglycan subunits to the growing cell wall
Protein Synthesis Inhibitors (3 of them)
Tetracyclines, Aminglycosides, Macrolides
Tetracycline
- Bacteriostatic*
- Broad Spectrum
- Bind 30s subunit
e. g. Tetracycline, Doxycycline
Mnemonic: Both have cycline in the name
Aminoglycosides
- Bactericidal*
- Oxygen-dependent (INEFFECTIVE against intestinal pathogens)
- Bind 30s subunit
e. g. Gentamicin, Kanamycin
Macrolides
- Bacteriostatic*
- Used as an alternative for penicillin allergies
- Bind 50s subunit
e. g. Erythromycin, Azithromycin
Nucleic Acid Synthesis Inhibitors (3 of them)
Quinolones, Rifampin/Rifabutin, Metronidazole
Quinolones
- Bactericidal*
- WIDELY USED
- MOA: inhibits DNA replication, recombination, and repair via DNA topoisomerase type II (gyrase) or topoisomerase type IV
Rifampin/Rifabutin
- Bactericidal*
- MOA: binds to DNA-dependent RNA polymerase and inhibits initiation of RNA synthesis
Metronidazole
- Bactericidal*
- MOA reduced by bacteria = toxic compounds that damage DNA
Antimetabolites (MOA and examples)
Bacteriostatic
MOA: Target folate metabolism, preventing synthesis of purines and thymidine, and ultimately preventing DNA/RNA synthesis
e.g. Sulfonamides and Trimethoprim (***Work together SYNERGISTICALLY)
Sulfonamides prevent formation of ______
Dihydrofolic Acid (from Dihydropterate Diphosphate and PABA)
Trimethoprim prevents formation of ______
Tetrahydrofolic Acid (from Dihydrofolic Acid)
MIC vs MBC
MIC: lowest concentration of antibiotic that INHIBITS growth
MBC: lowest concentration of antibiotic that KILLS 99.9%
