Antibiotics and Vaccines Flashcards
(11 cards)
Mechanisms of Action for Cephalosporins, Glycopeptides, Fluoroquinolones, Lincosamides
Cephalosporins: Cell-Wall Active bind PBP
(Cefazolin, Cephalexin, Cefuroxime, Ceftriaxone, Ceftriazidime, Cefepime)
Glycopeptides: Cell-Wall Active bind terminal 2 AA residues prevent cross-links
(Vancomycin)
Fluoroquinolones: Inhibit DNA Gyrase, DNA Topoisomerase IV prevent replication
(Moxifloxacin, Levofloxacin, Ciprofloxacin)
Lincosamides: Protein Synthesis Inhibitor Inhibits 50S Subunit
(Clindamycin)
Mechanisms of Resistance (ESBL, MRSA, VRE, CRE)
ESBL: extended spectrum beta-lactamases – cleave/inactivate beta-lactams (Klebsiella)
MRSA: mutated PBP to PBP-2a – methicillin no longer binds
VRE: change D-ala-D-ala to D-ala-D-lactate – vancomycin no longer binds
CRE: carbapenemases (Klebsiella)
Major Abx Adverse Effects
Clostridiodes dificile: Gram positive, spore-forming rod, toxin producing
Acquired nosocomially from antibiotics (except metronidazole, especially clindamycin)
Pseudomembranes and profuse diarrhea
Taking more types of Abx and for longer times increases risk
Treat: stop the Abx and give oral vancomycin or oral metronidazole
MIC?
MIC: minimum concentration of Abx needed to inhibit growth
The further the MIC is below the breakpoint, the more effective it is
CDK vs. TDK
CDK: Increasing Cmax increases killing efficacy, Post Antibiotic Effect, Cmax/MIC
(Aminoglycosides, Fluoroquinolones)
TDK: Keeping C above MIC 40-50% of the time for good killing, NO PAE,
(Beta-Lactams, Linezolid)
Kirby-Bauer Susceptibility Test
Put disks of Abx on plated bacteria cultures, measure zone of inhibition,
Diameter of zone of inhibition correlates to MIC
TDM - what drugs, why? Rationale
Vancomycin and Gentamycin
Used to assure therapeutic levels achieved, toxic levels avoided
Useful in conditions that alter distribution/clearance (Renal dysfunction, obesity)
Rationale: direct relationship between drug dose and efficacy/toxicity
Interpatient variability exists, narrow TI
Clinical efficacy/toxicity is difficult to measure
Accurate Assay/way to do TDM is available
Antiretroviral Therapy Targets
Nucleoside Reverse Transcriptase Inhibitors: Abacavir (ABC), Emtricitabine (FTC),
Lamivudine (3TC), Tenofovir DF (TDF), Tenofovir AF (TAF)
Integrase Inhibitors: Dolutegravir (DTG), Bictegravir (BIC), other -tegravirs
Non-Nucleoside RT Inhibitors: -virenz/-virines
Protease Inhibitors: Darunavir, Ritonavir
Entry Inhibitors: Maraviroc (CCR5 inhibitor), Ibalizumab (gp120 mAb)
Antifungal Mechanisms of Action
Polyenes (Amphotericin B, nystatin) – Membrane Disruption
Binds ergosterol in fungal PM to disrupt fungal membrane
Due to similarities to cholesterol, may cause some toxicities
Azoles (Fluconazole, Voriconazole) – Sterol Synthesis Inhibitor
Inhibits ergosterol synthesis – fungi can’t form cell wall
Allylamines (Terbinafine) – Sterol Synthesis Inhibitor
Inhibits squalene epoxidase – earlier step in sterol synthesis
Echinocandins (Micafungins, -fungins) – Glucan Synthesis Inhibitor
Inhibit cell wall glucan synthesis – impairs cell wall stress tolerance
First line for empiric antifungal therapy
Herpes Zoster Vaccine
Shingrix: Newer, recombinant herpes zoster vaccine (subunit) – VZV glycoprotein E antigen with ASO1B adjuvant (enhances B/T cell response), 2 dose series, HIGH efficacy in adults 50-69, 70+, Recommended for people 50+, some pain at injection site, Cost-effective
Ebola Vaccine
VSV-ZEBOV Ebola Vaccine: (fractional vaccine in a live virus) recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing surface glycoprotein of Zaire Ebolavirus: 100% efficacy – currently in phase 3 efficacy trials in Guinea (live mild virus carrying other more virulent virus’ glycoprotein)
