Aminoglycosides

Question 1

Aminoglycosides

Answer 1

Gentamicin
Tobramycin
Amikacin

Streptomycin
Spectinomycin

Have narrow therapeutic window
Improper dosing can cause significant toxicities (nephrotoxicity and ototoxicity)

Retain good activity against many problem pathogens (Pseudomonas, Acinetobacter)

Excellent at synergizing with beta lactams and glycopeptides to improve efficiency of bacterial killing

Gent, Tobra are most widely used
Amik reserved for pathogens resistant to the first two
Streptomycin has limited uses (Enterococcus, Tuberculosis, Plague)

Question 2

Aminoglycosides

MOA

Answer 2

Bind to bacterial ribosome (30s subunit) causing misreading of genetic code leading to incorrect protein formation and interruption of protein synthesis

Question 3

Gent/Tobra/Amik Spectrum

Answer 3

Good
Gram- (E. coli, Klebsiella, Pseudomonas, Acinetobacter, most others)

Moderate
In combo with beta lactam or glycopeptide (staph including MRSA, Viridans strep, Enterococci (gent and streptomycin are best)

Poor
Atypicals
Anaerobes
Gram+ as monotherapy

Question 4

Aminoglycosides Adverse Effects

Answer 4

Nephrotoxicity
Oliguric acute renal failure preceded by a rising serum creatinine (dose related)
Can reduce risk by correct dosing (including using extended interval dosing); avoidance of coadministration of other nephrotoxins (cyclosporine, cisplatin, foscarnet, etc)

Ototoxicity
Dose related cochlear and vestibular toxicity
Need baseline and follow up audiology of planning > 2 weeks of therapy
Monitor for hearing loss or balance problems; not reversible and can seriously affect quality of life

Neurologic
Neuromuscular blockade can occur, especially in high doses to patients who are receiving therapeutic paralysis

Question 5

Aminoglycosides Important Facts

Answer 5

Once daily / extended interval dosing leverages their concentration dependent killing to create an equally effective, more convenient and possibly safer regimen
Has not been extensively studied in these populations (pregnant, critically ill, significant renal dysfunction, morbidly obese)
Pregnancy category D; avoid if possible

For traditional dosing, draw peak 30 minutes AFTER the END of infusion; draw trough within 30 minutes of next dose
For once daily dosing, there are published nomograms for potential monitoring points

Have relatively poor distribution to many tissues (including lungs and CNS)
Less optimal as monotherapy for more serious infections
Dosing should be based on patient’s ideal or adjusted body weight, rather than total body weight

Minor difference in activity
For Pseudomonas: Amik > Tobra > Gent
For Klebsiella: Amik = Gent > Tobra

Older references list Streptomycin as first line for TB; was the first TB drug available; safer and more effective drugs now available
Still an alternative in resistant TB

Question 6

Aminoglycosides Good For

Answer 6

Serious documented or suspected Gram- infections (Febrile neutropenia, Sepsis, Exacerbations of CF, VA pneumonia)

Primarily Gent used in combo with beta lactam or glycopeptide for serious Gram+ infections (endocarditis, osteomyelitis, sepsis)

Drug resistant Mycobacterium tuberculosis or other mycobacteria (Streptomycin and Amik)