Exam 2 lecture 4 pt 2 Flashcards
What bacteria are aminoglycosides primarily active against
Primarily active against aerobic bacteria
What organisms should we be looking at for Aminoglycosides
Staph Aureus
Pseudomonas aeroginosa
enterococcus
MDR gram negatives
What is special about aminoglycosides
Group antibiotics that are dosed individually for each patient and require serum concentration monitoring
What are the most commonly used aminoglycosides
Gentamycin
Tobramycin
Amikacin
Are aminoglycosides polar or non polar? How does this affect their MOA
Are very polar
Polycationic
Water soluble
Incapable of crosiing lipid membrane
What bond holds aminoglycosides together?
glycosidic bond (oxygen between rings)
MOA of aminoglycosides? Bacteiostatic/cidal? why?Time/concentration?
Are one of the only protein synthesis inhibitors that are cidal in nature. This is bc it irreversibly bind 30S subunit.
Concentration dependent
Mechanism of resistance of aminoglycoside
- Synthesis of aminoglycoside modifying enzyme (most common)
- Plasmid mediated; enzyme modifies structure of aminoglycoside leading to poor uptake and ribosomal binding - Alteration in ribosomal binding sites
- Alteration in aminoglycoside uptake
Cross resistance of Aminoglycoside
Tobramycin and gentamycin have cross resistance
What drug do we primarily see alteration in ribosomal binding? Why?
Streptomycin only binds to a single site.
Genta, tobra, amika bind to multiple sites so they can still exert activity by binding other sites
spectrum of activity of aminoglycosides (what type of bacteria is it primarily active against?)
Primarily aerobic bacteria
For gram positives we ALWAYS use them in combinations
For gram negative we often use them in combination
What dose should aminoglycosides be used in in gram positive vs gram negative agents
Gram positive- low dose
Gram negative- high dose
What gram positive aerobes is aminoglycoside active against? What is the target organism?
Viridians streptococci (gent)
Enterococcus spp (gent or strepto)
most S aureus* (target organism)
What are gram negative aerobes aminoglycosides are used in? What is the target organism What drugs are used for gram negative aerobes
Gentamamycin, Tobramycin, amikacin and plazomycin
E coli, K pneumonia, proteus spp, Acinetobacter (not P), citrobacter, enterobacter spp, morganella, salmonella, providencia, serratia, shigella
Pseudomonas aeruginosa* (target organism)
PPPEEACKSSS
Do we use gent for monotherapy for MSSA or MRSA
No, always in combination
Which Aminoglycosides are the most effective for gram negative aerobes/ cover more strains
Amikacin and plazomycin
Does plazomycin have activity against acinetobacter?
no
Do aminoglycosides act against anaerobes?
Inactive against anaerobes
What is post antibiotic effect (PAE)? Do aminoglycosides have it?
PAE is suppression of bacterial growth after serum concentrations have fallen below MIC
What are aminoglycosides synergistic with? What does this synergism target?
Observed with AGs and cell wall active agents against enterococcus spp, staphylococcus spp, ciridians strep and gram negatives
WHat are soe cell wall active agents
B lactams and vancomycin
Can aminoglycosides be used as monotherapy for tx of infections due to gram positive aerobes
No, they should always ben used with cell wall active antibiotics in tx of infections to gram positive aerobes
Are aminoglycosides polar or non polar? How does this affect PK characteristics?
Highly polar
SO water soluble they are eliminated unchanged
Why do we individualize dosing of aminoglycosides
Interpatient variability exists in Vd and clearence
Are aminoglycosides concentration or time dependent? Cidal/static?
Concentration dependent bactericidal activity
What does the absorption look like for aminoglycosides? Preferred ROA?
Poorly absorbed from GI tract, must use parenteral administration
IM injection
Intermittent IV infusion preferred (G,t,a,p)
What are oral aminoglycosides
Oral neomycin and oral paramamycin
When not to use IM injection for aminoglycosides
Hypotensive pts
desscribe distribution of aminoglycosides (CSF, lungs, adipose) IBW or ADW for dosing?
Distribute poorly in CSF, lungs and adipose tissue
Use IBW (or ADW in obese patients) for dosing
What are factors we must take into account when calculating dose for aminoglycoside
Volume status must be taken into account to calculate appropriate dose
How are aminoglycosides eliminated? What does elimination half life depend on?
85-95% eliminated in kidneys
Elimination half life depends on renal function
What is necessary monitoring required in ALL patients receiving aminoglcosides
Serum concentration monitoring is necessary in ALL pts
Why do we monitor serum concentration for aminoglycoside
IT IS IMPERATIVE to achieve therapeutic concentrations quickly to decrease mortality
When dosing Aminoglycosides, What is standard dosing based on? What does gram positive dosing come out as? What does gram negative dosing come out as?
Lading dose and maintenance dose based on Vd, IBW or ADW and desired peak
Gram positive synergy- 1mg/kg gent
gram negative-
LD- 2-2.5 g/kg/dose gent, tobra
MD- 1.5-2 mg/kg/dose gent, tobra
What are the target peaks/troughs of gent and tobra for mod infection (UTI), mod-severe (SSTI, bacteremia), Severe (pneumonia, burn, life threat) Peak/trough for gram positive synergy (EXAM)
mod infection (UTI)- Peak= 4-6 mcg/ml, trough= 0.5-1.5 mcg/ml
Mod-severe (SSTI, bacteremia)- peak= 6-8, trough 1-1.5
Severe (pneumonia, burn, life threat)- Peak=8-10, trough=<2
Gram positive synergy- peak= 3-5 mcg/ml, Trough= 1 mcg/ml
How to dose aminoglycosides once daily? What type of patients can we use this in?
Gent/tobra= 7 mg/kg. Use IBW or ADW
Only in gram negative bacteria and patients with normal Crcl (>40-50)
target serum concentrations for QD dosing? (peak/trough) EXAM
Gent, tobra- Peak= 13-20, Trough <0.5
Amikacin- peak= 40-50, trough <8
clinical uses of aminoglycosides? Which aminoglycosides are used for gram negative aerobes? Which are used with gram positive aerobes
Used in combination with cell modifying agents to treat gram negative aerobes and gram positive aerobes
Gent, tobra, amikacin used in gram negative aerobes. including pseuomonas aerioginosa in combination with B lactams
Gentamicin and streptomicin used for synergy with cell wall wall active agent for gram positive aerobes
Streptomicin used for TB
What is plazomycin used for?
Complicated UTI due to MDR gram negative aerobes
What are gram positive aerobes that we use gentamicin/streptomycin for?
Endocarditis due to enterococci
Viridians strep
Staph aureua (including NRSA)
Adverse effects of aminoglycosides
Nephrotoxicity
Ototoxicity
Risk factors for aminoglycosides nephrotoxiciy? ototoxicity?
Prolonged high troughs, long duration of therapy (>2 wks), underlying renal dysfunction, elderly, hypovolemia
Same risk factors
Which of the following antibiotics does NOT have activity against pseudomonas aeruginosa. Cefepime, Ciprofloxacin, tobramycin, piperacillin, Ceftriaxone
Ceftriaxone
Which antibiotic does NOT cause nephrotoxicity Gentamicin, Televancin, Vancomycin, Azithromycin, Nafcillin
Azithro
