Antibiotics And Anti microbials Flashcards
Define differential toxicity
Based on the concept that the drug is more toxic to the infecting organism than the host
Define minimum inhibitory concentration
Minimum concentration of an antibiotic require to INHIBIT THE GROWTH of the test organism
Definite minimum bactericidal concentration
Minimum concentration of antibiotic required to KILL the test organisms
Describe concentration dependent killing
Goal is to maximize concentration
Host can be dosed less frequently
Describe time dependent killing
Goal is to maximize exposure of drug to host. Dosed more frequently
Define prophylaxis
Anti microbial agents are administered to PREVENT infection
Ex. Dose of antibiotics BEFORE surgery to reduce chance of infection
Describe empiric therapy
With rapidly acting diseases you must treat quickly. Make an educated guess based on the knowledge you already have to start treatment while waiting for lab results. Based on epidemiology
What are advantages of combination therapy
Testing polymicrobial infections, broad coverage empirical therapy, synergy (1+1=4) and may prevent the emergence of resistance
What are disadvantages of combination therapy?
Antagonism (drug drug reaction), cost, increased risk of side effects, usually not necessary for maximal efficacy
Define resistance
The inability to kill or inhibit the organism with clinically achievable drug concentrations. Resistance may be innate or acquired
What are the three mechanisms of resistance
Transformation
Conjugation
Transduction
What may accelerate the development of resistance
Inadequate levels of antibiotics at site of infection Duration of treatment Overwhelming # of organisms Overuse/misuse of antibiotics Counterfeits Animal husbandry Over the counter medication Frequent exposure
Define anti microbial stewardship
Limit use of broad spectrum antibiotics to patients that absolutely require them
Proper administration of antibiotics !!! Not all bugs need drugs
Describe penicillin binding proteins (PBP)
Target of betalactam drugs, inhibits transpeptidases, the cross linking reaction of bacterial cell wall, weakened cell wall = cell death
Define transpeptidases
Involved in the stages of assembling the cell wall by cross linking the peptidoglycan lager and reshaping cell wall during division
Target of betalactan drugs is to inhibit this PBP
What causes beta lactam resistance
Production of beta lactamase (enzyme that destroys betalactam drugs)
Altered PBP
Novel PBP (MRSA)
Altered permeability (gram negative outer membrane=drug can’t get in)
What are the most common betalactamase inhibitors
Clavulanic acid and tazobactam
Define glycopeptides
Cell wall active agents
Only work on gram POSITIVE agents only
Bind to terminal D-ala of nascent cell wall peptides to prevent cross linking
Makes D-ala TOO big to fit and form cell wall
Describe glucopeptide (vancomycin) resistance
D-ala target altered to d-lac therefore vancomycin can NOT bind and becomes resistant to drug
When is vancomycin used? (Spectrum of activity)
Gram positive cocci & gram positive rods
C.difficile must be given ORALLY otherwise it is usually IV administered
Describe Fosfomycin
Cell wall synthesis inhibitor. An old drug used to treat e.Coli induced UTI
Works in the cell wall and has less damage to kidney
Describe the evolution of fluroquinolones
Gets more effective as generations increase
3rd generation uses in treating complicated respiratory diseases as it has enhanced gram positive -/+ anaerobic activity
Describe floroquinolones mechanism of action
Inhibit 2 enzymes (topoisomerase & gyrase) involved in Bacterial dna synthesis enabling these agents to be specific and bactericidal
Describe development of resistance for fluroquinolones
Spontaneous mutation of parC and gyrA (most common) produces reduced affinity
Over expression of Efflux pumps which leads to drug being pumped out of the cell
Down regulation of porin channels which leads to topoismerase protection
What are some adverse events in fluoroquinolones
Hyper/hypo glycemia
Cartiledge toxicity/tendon rupture in pediatric useage
What are some inhibitors of protein synthesis
Macrolides
Tetracyclines
Aminoglycosides
Linezolid
Describe macrolides
Bind to 50s subunit of bacterial ribosomes to inhibit protein synthesis
What are some mechanisms of resistance in macrolides?
Efflux pump and target site modification (erm site)
When are macrolides typically used
Community acquired pneumonia
Pertussis (whooping cough)
Atypical pathogens (no cell wall)
What are potential adverse reactions of macrolides
GI upset
Ventricular arrhythmia
Cyto p-450 interactions (drug drug interaction)
Describe clindamycin
The antibiotic most commonly associated with C.diff colitis
Used in anaerobic infections
Gram positive infections
Binds to ribosomes to shut down proteins synthesis therefore shutting down toxin production
Usually avoided as a medication
Describe tetracycline mechanism of action
Bind reversibly to 30s ribosomal unit
Where is tetracyclines useful
Treating atypical bacteria, animal borne diseases and most gram positive infections and CA-MRSA
What are potential adverse events of tetracyclines
Discolouration of teeth, photo sensitivity, depression of skeletal growth
Not prescribed to children under 8
Describe Aminoglycosides
Natural/semi synthetic antibiotics with excellent gram NEGATIVE activity and good gram positive activity
Describe Aminoglycosides mechanism of action
Binds IRREVERSIBLY to 30S ribosomal subunit, bacteria must actively transport drug into the cell. This step is rate limiting and blocked by divalenf cations and anaerobiosis
These drugs DO NOT work in anaerobic environments (abscess)
What are mechanisms of resistance with Aminoglycosides
Enzymatic modification, modify the drug to render it inactive
What are some adverse effects with Aminoglycosides
Ototoxic (affect hearing)
Nephrotoxic (kidney damage)
Long term use requires therapeutic drug monitoring
Describe inhibitors of metabolic pathways
TMP/SMX prescribed together
Good gram NEGATIVE some gram positive
Block folic acid synthesis at 2 different points
Inhibits folic pathway
Describe TMP/SMX
Resistance now high as often used for UTIs
Management of PCP pneumonia and GI infections
Describe metronidazole (flagyl)
Inhibits nucleic acid synthesis by distrupting/damaging DNA
Go to for ANAEROBIC organisms
Very little resistance
Describe adverse effects of Metronidazole
Antabuse effect (can not mix with alcohol)
