Antibiotics!!! Flashcards
(31 cards)
What is Minimum Inhibitory Concentration (MIC)
Minimum Inhibitory Concentration (MIC) = lowest concentration of a drug that inhibits bacterial growth
Minimum Bactericidal Concentration (MBC)
lowest concentration that kills bacteria (usually a higher number)
MIC is used clinically over MBC because MIC is more easily determined
A lower number is better than a higher number (means it is more powerful!)
2 PHASES OF ANTIBIOTIC ADMINISTRATION?
Absorption phase (take it and reaches max concentration in your blood) and elimination phase (metabolized by liver or kidney so concentration in blood decreases)
Bacteriostatic
inhibits growth; prevents bacteria from spreading and immune system can catch up
Bacteriocidal
kills bacteria; decreases number of bacteria; needed for immunocompromised patients for which bacteriostatic is not enough
Beta lactams
Bacteriocidal
work on cell wall
Includes: Penicillins Cephalosporins Carbapenems Monobactams
all have a beta lactam central structure which looks just like the peptidoglycan cell wall precursor
Inhibit transpeptidase (PBP)- prevent crosslinkage of peptidoglycans; also called penicillin binding protein
Penicillin
Beta lactam ring
Works on GRAM POSITIVES and ANAEROBES (strep not staph)
many different types such as : Aminopenicillins Anti-staph penicillins Anti-pseudomonal penicillins PCN + beta-lactamase inhibitor (broadest coverage)
How does Beta lactamase lead to beta lactam resistance?
Bacteria produce it to break the beta lactamase ring of penicillin— due to this, a beta lactamase inhibitor is added (ex. clavulanate) to which beta lactamase binds instead of binding to and destroying penicillin and as a result penicillin can go into cell; this increases the spectrum of activity
Broad spectrum vs narrow spectrum
broad covers gram positive, negative and anaerobes; you use it when you don’t know what is going on with a patient.
Narrow spectrum is specific to organism
Penicillin Allergies
there is spectrum of allergic reactions (rash, hives, anaphylaxis)
NOT due to beta lactam ring, but more likely due to similarities in side chains
MRSA (Methicillin-resistant Staph aureus)
changed penicillin binding protein (transpeptidase) so no penicillin can bind
(PBP 2 –> PBP 2A)
Cephalosporins
have additional bond that makes it less susceptible to beta lactamases, and a different R-group side chain that allows for more spectrum of activity than the penicillins— 4th generation have the most coverage
Differences in coverage among cephalosporin classes
1st gen: (narrow)
+++ for S. aureus
+ for strep
+ gram negatives
2nd gen (aerobic cov)
++ for S. aureus
++ for strep
+ +gram negatives
3rd gen ( cov pseudomonas and good for CNS infections)
+ for S. aureus
+++for strep
+++ gram negatives
4th gen ( cefepime civers pseudomonas) *** best
+++ for S. aureus
+++for strep
++++ gram negatives
5th generation
+++ for S. aureus
+++ for strep
+ gram negatives
Carbapenems aka the biggest guns
” the biggest guns”
trans configuration makes it susceptible to beta lactamases
new r group side chain enhances antipseudomonal activity
**the broadest spectrum (gram +, -, anaerobes and even ESBLs)
achilles heels: MRSA(PBP 2A) and Mycoplasma (no cell wall so beta lactams can’t bind)
Aztreonam
Monobactam
Only covers gram-negative bacteria
Okay to use in those with penicillin allergy
Good Pseudomonas coverage
A Chromosomal Beta-lactamase: AmpC
Bacteria express AmpC to Induce resistance to 1st and 2nd generation cephalosporins, most penicillins, and β-lactamase inhibitor combinations
It is can be:
-Inducible (and by mutation)
- Constitutively expressed
- Transmissible plasmids
ESBLs (Extended Spectrum Beta-Lactamases)
Enzymes that confer resistance to penicillins AND cephalosporins AND monobactams
Found exclusively in gram-negative organisms
E. coli, Serratia, Klebsiella, etc
Use carbapenems to treat patients with infections that produce ESBLs
Mechanisms of Resistance
Efflux pumps
Inactivating enzymes
Target alternations
Decreased uptake
Vancomycin
-a glycopeptide
-inhibits transpeptidation, transglycosylation
-Bacteriocidal (except for Enterococcus for which is it bacteriostatic)
-gram positive coverage (MRSA)
-kidney damage
Red man syndrome- causes mast cells to release histamine and turn you red if you give it too fast
Binds to D-ALA-D-ALA of pentapeptide side chains, interferes sterically with formation of bridges between peptidoglycan chains
(works on CELL WALL!)
Aminoglycosides
Bacteriocidal & bacteriostatic
Covers gram negatives (pseudomonas)
Synergistic with penicillin (can’t penetrate thick cell wall of gram positives, but with penicillin it amino-glycosides can get in and bind 30s)
Binds 30S
Post-antibiotic effect (conc. dependent)- even when undetected in blood levels there is still bactericidal activity
Kidney damage, deafness and dizziness (can destroy hair cell in the inner ear, free radicals damage cells)
How they work: get through OM and disrupt magnesium bridges between adjacent lipopolysaccharide molecules–> bind to 30s ribosome irreversibly which disrupts peptide chain elongation by impairing proof reading process –> funky protein products –> alter permeability of cell membrane
Lincosemides (clindamycin)
Covers gram positives and anaerobes
Bacteriostatic (makes sense because it is inhibiting protein synthesis)
Can cause anti-biotic associated diarrhea
Dissociation of peptidyl-tRNA (50s)
How it works:
Binds to the 50S subunit of susceptible bacterial ribosomes close to the peptidyl transferase center and thereby inhibit protein synthesis. Clindamycin causes dissociation of peptidyl-tRNAs from the ribosome
DON’T SAY C DIFF
Macrolides
- bacteriostatic
- Cardiac side effects (rare)
- Dissociation of peptidyl-tRNA (50s) inhibit peptidyl transferase
- Covers atypicals (ex. mycoplasma), some Gram positives (Not strep pneumo!!)
can’t combine macrolides and clindamycin
CLEAN ( ANTIBIOTICS THAT WORK ON 50S subunit)
TAG ( work on 30s)
C = Clindamycin (lincosamides) L= Linezolid (oxazolidinones) E = Erythromycin (macrolides) A = Azithromycin (macrolides) N= nada
T = tetracyclines AG= aminoglycosides
*** BACTERIOSTATIC!!!! Except aminoglycosides
Tetracyclines
Bacteriostatic
Cover atypicals, some gram positives
Block amino-acyl tRNA binding (30s)
GI upset, teeth staining (binds to calcium ions), and photosensitivity (it is photoactivated and ribosomes may be site for phototoxic damage)
Good for intracellular bugs (Chlamydia, Rickettsia) + tickborne illnesses (Lyme, Ehrlichiosis, RMSF)
