Aminoglycosides

Question 1

Aminoglycosides

Answer 1

Gentamicin - MC
Tobramycin - MC
Amikacin - MC
Streptomycin - MDR TB
Neomycin - topical

Question 2

Aminoglycoside MOA

Answer 2

Binds to 30S ribosomal subunit to inhibit bacterial synthesis
Bactericidal
Creates fissure in outer bacterial membrane = leakage of intracellular contents and enhanced abx uptake
Drug actively transported across cell membrane

Question 3

Aminoglycoside Resistance Mechanism

Answer 3

Transferase enzyme inactivates Aminoglycoside - plasmid mediated
Changes binding site to the 30S ribosome
impaired entry of Aminoglycoside into the cell
Amikacin = 1 locus so less resistance
Tobra/Gent = 6 loci so more resistance
Anaerobes are resistant because they cant transport abx across membrane

Question 4

Aminoglycoside PK/PD

Answer 4

Parental administration due to poor GI absroption
Freely distributed in ECF
Excreted unchanged in kidneys
Half-life = 1-3 hours –> 30-60 hrs with reduced GFR
Concentration-dependent killing
Post-Abx effect: ABx activity persists despite low concentrations

Question 5

Aminoglycoside SOA

Answer 5

Aerobic, Gm neg: E. coli, Klebsiella, Proteus, enterobacter, acinetobacter, pseudomonas
Moderate gram pos cocci: staph, enetro, strept
Certain mycobacteria: streptomycin for MDR TB - give IM

Question 6

Aminoglycoside Clinical Uses

Answer 6

Gram negative infections
Use in combo with cell wall active agent: PCN, cephalosporins or vanco for synergy in treating Gm +
Monotherapy not recommended: ampicillin + gent
Negligible anaerobic coverage

Question 7

Aminoglycoside Tx

Answer 7

Severe abdominal or UTIs
Severe bacteremia, endocarditis, sepsis, pneumonia
Drug resistant HA infx like P. aureginosa = tobra, gent, amikacin
Tobra = ocular infections
Streptomycin = TB or tularemia

Question 8

Aminoglycoside Distribution

Answer 8

Wide distribution in ECF - pleural, synovial, peritoneal, abscesses
Poor distribution in bile, aqueous humor, bronchial secretion, sputum, or CSF

Question 9

Tobramycin DOC for?

Answer 9

DOC to treat chronic pulmonary infection with pseudomonas and burkholderia
Nebulized solution or powder
Daily for 28 days then off for 28 days
CF patients

Question 10

Gentamicin

Answer 10

IV use - MC also IM, topical, ophthalmic

Gm neg and Gm + –> use with beta lactam

Question 11

Tobramycin

Answer 11

Better pseudomonas coverage than gentamicin

IV, IM, inhaled

Question 12

Amikacin - Amikin

Answer 12

for gent or tobra resistant bacteria

IV or IM

Question 13

Streptomycin

Answer 13

2nd line for TB in combo with other agents
IM, off-label IV
Sulfite Sensitivity: may cause allergy, anaphylaxis, or asthma

Question 14

Neomycin (Mycifradin)

Answer 14

Topical and oral use before poor bioavailability
Bowel prep for surgery with erythromycin for Gm + coverage
Only use topical as last resort
Too toxic for IV use - lethal

Question 15

Aminoglycoside Special Populations

Answer 15

Pregnancy Cat D

Lactation: probably safe - not well absorbed orally even if in breast milk

Question 16

Aminoglycoside CI

Answer 16

allergy or hypersensitivity to Aminoglycoside
Neuromuscular blockade = high risk, antagonizes calcium to decrease ACh release
Myasthenia gravis, Parkinson’s, recent muscle relaxants, recent anesthesia
Respiratory paralysis if given in < 30 min
Reversible with calcium gluconate

Question 17

Aminoglycoside AE and BBW

Answer 17

BBW: nephrotoxicity, ototoxicity, neuromuscular blockade
Nephrotoxicity: accumulation of drug in PCT = increased trough levels
Ototoxicity: vestibular and cochlear - related to peak level
2/3 vestibular - vertigo, ataxia, loss of balance, tinnitus
1/3 cochlear - high frequency hearing loss
Amikacin is the most ototoxic

Question 18

Aminoglycoside Dosing

Answer 18

Multiple times daily or once daily
Peak: 30 minutes after infusion
Troughs: 30 minutes before infusion
Once daily dosing: check levels 10-12 hours post infusion