Antibiotics I Flashcards by Kyra Porter

minimal inhibitory concentration (MIC)

concentration of antimicrobial that inhibits growth of an organism

How well did you know this?

Not at all

Perfectly

minimal bacteriocidal concentration (MBC)

concentration that KILLS bacteria

How well did you know this?

Not at all

Perfectly

breakpoint

the MIC that is used to designate between sensitive and resistant; arbitrarily set by a committee

How well did you know this?

Not at all

Perfectly

if MIC > breakpoint, the organism is (resistant or sensitive?)

RESISTANT

How well did you know this?

Not at all

Perfectly

if MIC < breakpoint, the organism is (resistant or sensitive?)

SENSTITIVE (susceptible)

How well did you know this?

Not at all

Perfectly

pharmacodynamics for beta lactams

time above MIC
*needs to be > 50%
*continuous infusion is good for this

How well did you know this?

Not at all

Perfectly

pharmacodynamics for aminoglycosides

Cmax/MIC
*needs to be > 5
*high dosage once a day is good for this (gets the highest peak possible)

How well did you know this?

Not at all

Perfectly

pharmacodynamics for fluoroquinolones

area under the curve (AUC) / MIC
*needs to be > 35

How well did you know this?

Not at all

Perfectly

synergy

2 antibiotics work better together than either one of them could do alone
*ex. one inhibits cell wall and one inhibits ribosome

How well did you know this?

Not at all

Perfectly

antagonism

two antibiotics “get in each other’s way”
*usually when the 2 antibiotics are competing for the same target

How well did you know this?

Not at all

Perfectly

which antibiotic classes target cell wall synthesis

beta lactams, cephalosporins, carbapenems, vancomycin, bacitran

How well did you know this?

Not at all

Perfectly

subclasses of beta lactam antibiotics

penicillins, cephalosporins, carbapenems, monobactam (aztreonam)

How well did you know this?

Not at all

Perfectly

beta lactam antibiotics - target

*binds to penicillin binding proteins (PBPs) in cell wall

How well did you know this?

Not at all

Perfectly

beta lactam antibiotics - overview

*binds to PBPs in cell wall
*bactericidal
*spectrum dependent on subclasses
*generally good serum, urine, and tissue levels; CSF level variable
*time dependent pharmacodynamics (time above MIC > 50%)

How well did you know this?

Not at all

Perfectly

beta lactam ring - structure

amide bond - essential for the function of these antibiotics

How well did you know this?

Not at all

Perfectly

beta lactam antibiotics - mechanism of action

*act on penicillin binding proteins (PBPs; aka transpeptidases) to INHIBIT CROSS-LINKING of PEPTIDOGLYCAN via pentaglycine bridge
*causes osmotic dysregulation, which causes lysis

How well did you know this?

Not at all

Perfectly

beta lactam antibiotics - mechanisms of resistance

production of beta-lactamases (cleave the beta lactam ring)
alteration of PBPs (so the antibiotic cannot bind)
decreased permeability

How well did you know this?

Not at all

Perfectly

how do beta lactamases work in gram positive organisms

beta-lactamase diffuses away, leading to weak concentrations of the enzyme
*happens b/c there is only one cell membrane/wall

How well did you know this?

Not at all

Perfectly

how do beta lactamases work in gram negative organisms

beta-lactamase gets concentrated between the membranes
*leads to more potent activity of beta-lactamases

How well did you know this?

Not at all

Perfectly

beta-lactamase inhibitors

*bind to beta-lactamase irreversibly at the active site
*often given simultaneously with a beta lactam antibiotic, which “neutralizes” the beta-lactamases

what are the 4 beta lactamase inhibitors

-clavulanic acid
-sulbactam
-tazobactam
-avibactam

penicillin class antibiotics

penicillin
aminopenicillins
antistaphylococcal penicillin
extended spectrum (antipseudomonal penicillin)

2 important aminopenicillins

*ampicillin (IV)
*amoxicillin (PO)
note - augmentin = amoxicillin/clavulanate

2 important antistaphylococcal penicillins

-methicillin (IV)
-dicloxacillin (PO)

important extended spectrum (antipseudomonal) penicillin

piperacillin

penicillin G

*"prototype" of penicillin *used for strep, enterococci, and spirochetes *resistance is NOT a concern in group A and group B strep *resistance occurs (through altered PBPs) for pneumococcus, enterococci, and viridans strep

benzathine penicillin

*used for direct observed therapy for syphilis *has a LONG half-life, so one injection lasts for about 3 weeks

resistance mechanism for staph aureus (MRSA)

***resistance through altered PBPs** *resistance **transferred via MecA operon** *causes resistance to ALL beta-lactams

benefit of anti-staphylococcal penicillins

bactericidal to staph (NOTE - developing resistance [MRSA] via altered PBPs)

benefit to aminopenicillins

*extend the spectrum to include more gram negative rods *good drug for head/neck and respiratory tract infections

benefits to antipseudomonal penicillins (piperacillin)

extends activity to **include pseudomonas** & gram negative rods *downside: must be given IV

type 1 beta lactam allergy (immediate hypersensitivity)

*IgE/mast cell mediated *urticaria (hives) and anaphylaxis *most serious

type 2 beta lactam allergy (innocent bystander)

*adherence of drug as a hapten to a cell (attaches to RBC membrane and IgG attacks, lysing the cell) *hemolytic anemia

type 3 beta lactam allergy ("Arthus" immune complex)

*serum sickness: fever, glomerulonephritis, arthritis, adenopathy (not all at the same time) *the penicillin clumps into a ball and antibodies attach; the complex gets stuck in joints, kidneys, etc

type 4 beta lactam allergy (delayed hypersensitivity)

*most common beta lactam allergy ***T cell mediated *usually after 7-10 days of antibiotic** *rash, usually with fever *eosinophilia

cephalosporins

***subclass of beta lactam antibiotics (bind to PBPs)** *more stable to beta lactamases than other subclasses *examples: **"-CEFs":** ceftriaxone, cefepime, etc

benefits of cephalosporins

*SAFE (high therapeutic to toxicity ratio) *3rd generation cephalosporin **(ceftriaxone) has good CNS penetration**

1st generation cephalosporins

*active against gram positive organisms (Staph and Strep) 1. cefazolin** (IV) 2. cephalothin (IV and PO)

2nd generation cephalosporins

*active against gram positive and some gram negative organisms (Haemophilus, enterobacteriaceae) 1. cefoxitin (IV) 2. cefuroxime (IV and PO)

3rd generation cephalosporins

*broader spectrum 1. ceftriaxone (broad spectrum but not pseudomonas; CROSSES BLOOD-BRAIN BARRIER) 2. ceftazadime (good against pseudomonas and other GNRS; loses potency against gram positives)

ceftriaxone

*3rd generation cephalosporin *crosses the blood-brain barrier (for bacterial meningitis) *not effective against pseudomonas

4th generation cephalosporins

1. cefepime (broad, GP, GN, includes pseudomonas)

5th generation cephalosporins

*enhanced antipseudomonal activity 1. ceftolozane (given with tazobactam)

MRSA active cephalosporin

ceftaroline

cefiderocol (new cephalosporin)

*uses the bacterial active iron transport channels to penetrate in the periplasmic space of gram negative bacteria *overcomes many resistance mechanisms because it can cross the outer membrane, even if there is a loss of porins

aztreonam

*monobactam (beta lactam) *active ONLY against gram negative AEROBES *no cross reaction with type 1 hypersensitivity

carbapenems

***subclass of beta lactams (bind to PBPs)** *one of the broadest spectrums of antibiotics *can NOT kill MRSA, enterococci, listeria *examples: **"-penems:"** imipenem, meropenem, ertapenem

carbapenems - mechanism of resistance

*reduced permeability of gram negative rod outer membrane (loss of porins [D2 porin] - antibiotic can't get in) *carbapenemases increasing in incidence

3 examples of carbapenems

1. imipenem 2. meropenem 3. ertapenem