L20: Antibiotics Flashcards
Antibiotic vs antimicrobial
- Antibiotic: produced in nature
- Antimicrobial: synthetic
Bacteriostatic vs bactericidal. In which pt groups are each best suited?
- Bacteriostatic: inhibit growth of bacteria, but don’t kill – used in pts with good immune system when host defenses can be counted on
- Bactericidal: kill bacteria – used during invasive infections (bacteremia, meningitis, endocarditis etc.) and in pt who is immunocompromised
What is antibiotic synergism?
- Combination of antibiotics with enhanced bactericidal activity when used together
What is antibiotic antagonism?
- Combination of antibiotics in which one interferes with the activity of the other
Advantages and disadvantages of broad and narrow-spectrum antibiotics
- ) Broad-spectrum: effective against large variety of bacteria
- Advantage: increased likelihood of effectiveness against bacterial infection of unknown etiology
- Disadvantage: increased likelihood of disrupting pts normal microbiota - ) Narrow-spectrum: effective against only a small subset of bacteria
- Advantage: avoid disruption of normal microbiota
- Disadvantage: must have disease causing bacterium(a) identified
Spectrum of antibiotic activity
- Narrow spectrum, expanded, broad, extended
Do antibiotics cause resistance?
- No!!!! They select against selective bacteria and for resistant bacteria, allowing for survival of bacterial that have gained rare mutation/genetics
From a clinical lab, what are ranges of antibiotic resistance that will show up on a lab report
- ) S: sensitive – treat with dosage of antimicrobial recommended
- ) I: intermediate – treat directly in body sites where drug are physiologically concentrated or when high dosage can be used
- ) R: resistant – not inhibited by usually achieved concentration
Empiric vs targeted antibiotic therapy. What is the difference?
- Empiric: treatment while waiting for lab results (broad spectrum)
- Targeted: treatment as lab results dictate (narrow spectrum)
Mechanisms of antibiotic resistance by bacteria
- ) Breakdown of antibiotic
- ) Chemical modification of antibiotic
- ) Alteration of target
- ) Altered permeability (decreased influx / increased efflux)
- ) Lack of target
What is MIC/MBC in terms of antibiotic testing?
- MIC = minimum inhibitiory concentration – level of antimicrobial concentration that inhibits growth (bacteriostatic)
- MBC = minimum bactericidal concentration – level of antimicrobial concentration that kills 99.9% of bacteria
How to determine MIC?
- Disk-diffusion assay (Kirby-Bauer test)
- E-test (newer)
- Broth culture (determines MIC and MBC)
Difference between a cell wall active and membrane active antibiotic
- Cell wall active: disrupts peptidoglycan synthesis and therefore is only active against dividing bacteria
- Membrane active: disrupts membrane integrity/synthesis and therefore is active against resting and actively dividing bacteria
Classes of antibiotics (and examples) targeting cell wall synthesis. Are these effective against static bacterial infections?
- ) Beta-lactams: penicillins, cephalosporins, cephamycines, carbapenems, monobactams
- ) Glycopeptides: vancomycin
- ) Polypeptides: bacitracin, polymixins
- ineffective against static bacterial infections, only against actively dividing bacteria
Classes of antibiotics/specific examples targeting protein synthesis.
- ) Aminoglycosides: gentamicin, kanamycin
- ) Macrolides: erythromycin, azithromycin (z-pak)
- ) Tetracyclines/doxycycline
- ) Chloramphenicol
Classes of antibiotics/specific examples targeting nucleic acid synthesis
- ) Quinolones: ciprofloxacin, levofloxacin
- ) Rifampin (specific), rifabutin (specific)
- ) Metronidazole
Classes of antibiotics/specific examples targeting folic acid synthesis
- ) Sulfonamides
2. ) DHFR inhibitor: trimethoprim
Mechanism of beta-lactam action – bacteriostatic or bactericidal?
- Beta-lactams bind to transpeptidases (penicillin binding proteins-PBPs) covering reactive serine site and prevent cross-linking of peptidoglycan sheets
- Bacteriostatic
How can bacteria become resistant to beta-lactams?
- ) Alter transpeptidase (eg. To have decreased affinity for antibiotic)
- ) Alter outer-membrane permeability
- ) Presence of efflux pumps
- ) Chemical modification of antibiotic (eg. Via beta-lactamase)
Someone is being treated with penicillin, which is not combatting his or her infection. The patient is switched to a cephalosporin medication. Is this good or bad?
- Resistance to a specific antibiotic typically confers resistance to that entire class. Pt should be placed on a different class of antibiotic
Mechanism of vancomycin (a glycopeptide class of antibiotic) – bacteriostatic or bactericidal?
- Binds to two D-ala residues on end of pentapeptide chain in peptidoglycan and prevents them from interacting with transpeptidase that cross-links them causing cell death. Will only work on cells that are actively dividing.
- Bacteriostatic
How can bacteria become resistant to vancomycin?
- 5th D-ala residue is replaced with D-lactate so vancomycin cannot bind
Mechanism of action of bacitracin (a polypeptide class of antibiotic) – bactericidal or bacteriostatic?
- Interferes with dephosphorylation of bactoprenol, which is the lipid carrier that transfers peptidoglycan subunits to growing cell wall. This prevents it from recycling to inner membrane leaflet
- Bacteriostatic
Mechanism of action of tetracycline/doxycycline – is it bacteriostatic/bactericidal? Broad or narrow spectrum?
- Bacteriostatic, broad spectrum, binds 30S subunit
Mechanism of action of macrolides – is it bacteriostatic/bactericidal?
- binds 50S subunit – good alternative to individuals with penicillin allergy
- bacteriostatic
Mechanism of action of quinolones – bactericidal or bacteriostatic?
- inhibits DNA replication, recombination and repair by affecting bacterial topoisomerase/aka gyrase
- bactericidal
Mechanism of action of rifampin/rifabutin – is it bactericidal or bacteriostatic?
- binds to DNA-dependent-RNA polymerase and inhibits initiation of RNA synthesis
- bactericidal
Mechanism of action of metronidazole – is it bactericidal or bacteriostatic?
- reduced by bacteria to form toxic compound that damages DNA
- bactericidal
Mechanism of action of sulfonamides – bacteriostatic or bactericidal?
- Blocks step in folic acid synthesis, folic acid used for purine and thymidine synthesis
- Bacteriostatic
Mechanism of action of DHFR inhibitor (trimethoprim) – bacteriostatic or bactericidal?
- blocks step in folic acid synthesis, folic acid used for purine and thymidine synthesis
- bacteriostatic
