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Info


A. Overview [1]

  1. Bind to bacterial ribosomes and inhibit protein production
  2. Aerobic gram negative coverage is excellent
  3. Synergistic for Staphylococci and Enterococci when given with ß-lactam or vancomycin
  4. Most rapid cell kill compared with other antibiotics for susceptible organisms
  5. A minimum of one dose should be given to most sepsis patients
  6. Agents
    1. Streptomycin
    2. Gentamicin
    3. Tobramycin
    4. Amikacin
    5. Netilmycin
    6. Neomycin / Kanamycin
    7. Paromomycin
  7. Administration
    1. All aminoglycosides are IV but can be given IM
    2. However, only streptomycin is FDA approved for IM injection
    3. Serum peak (1 hour post-dose) and trough (30 minutes pre-dose) levels are measured and doses of drug adjusted accordingly
    4. High peak levels correlate with efficacy (and possibly toxicity in elderly persons)
    5. High trough levels correlate best with renal injury and ototoxicity
    6. Single daily dosing in patients with normal kidneys leads to reduction in trough levels

B. Gentamicin (Garamycin® and others) [2]

  1. First choice aminoglycoside for (suspected) gram negative rods in most patients
  2. Activity against hospital acquired organisms varies
  3. If Pseudomonas is highly suspected, gentamicin should not be used as first line
  4. Standard Dosing
    1. Dosing: load 2mg/kg x 1, then 1.5mg/kg q8-24 hours depending on renal function
    2. Alternatively, 1.7mg/kg can be given q8 hours with normal renal function
    3. Interval between doses should be prolonged or dose reduced for renal insufficiency [2]
    4. May be given intramuscularly (IM) if intravenous (IV) access not available
  5. Once Daily (Extended Interval) Dosing [1,2]
    1. Once daily dosing 5mg/kg has less toxicity q8-12 hour dosing with equal efficacy [3]
    2. Once daily dosing does not reduce efficacy in any detectable fashion [4]
    3. Dose must be adjusted for patient's renal function [2,3]
    4. For <40mL/min creatinine clearance, lower doses given multiple times may be used
    5. Elderly patients (implied renal dysfunction) may do better with q12 hour dosing [5]
    6. Avoid once daily dosing in serious burns, ascites, severe sepsis, dialysis, neonates
    7. Single daily dosing may be combined safely with multiple other agents
  6. Topical application of gentamicin in patients with cystic fibrosis and CFTR stop codons causes suppression of stop codons by ribosomes and expression of CFTR protein [6]

C. Tobramycin

  1. Excellent Pseudomonas and Enterobacter coverage
  2. More expensive than gentamicin
  3. Should be used if hospital acquired organisms may be gentamicin resistant
  4. Dosing identical to gentamicin
  5. Inhaled Tobramycin (Tobi®) [7,8]
    1. Very effective in patients with cystic fibrosis (CF)
    2. Eradicates Pseudomonas aeruginosa and prevents recolonization in CF patients [8]
    3. Dose is 80mg bid for colonization in 2mL saline by inhalation
    4. Dose is 300-600mg tid for treatment of establishedf Pseudomonas infection

D. Amikacin (Amikin®)

  1. Far more expensive than other agents
  2. Reserved only for highly resistant organisms
  3. Standard Dosing: 8mg/kg load x 1, then 4-6mg/kg q8-24 hours
  4. Once daily dosing 15mg/kg is also acceptable [1]
  5. Dose must be adjusted for renal function

E. Streptomycin

  1. First aminoglycoside ever discovered for human use
  2. Useful for only a subset of organisms
  3. Specific mycobacterial infections and plague are highly susceptible
  4. Active against tularemia 15mg/kg bid intramuscularly (IM)

F. Neomycin / Kanamycin

  1. Sometimes used orally for bowel decontamination
  2. Neomycin is a common component of topical antibiotic ointments

G. Paromomycin (Humatin®)

  1. Topical or parenteral available
  2. Activity against cryptosporidium, ameba, leishmaniasis
  3. Parenteral non-inferior to and better tolerated than amphotericin B (~94% cure rate) for visceral leishmaniasis [10]
  4. Dose for leishmaniasis is 15mg/kg paromycin sulfate intramuscular (deep gluteal)

H. Toxicity

  1. Nephrotoxic
    1. Correlates with high trough (not peak) levels
    2. Careful dosing in pre-existing renal disease: diabetes, hypertension, myeloma
    3. Once daily dosing reduces risk of nephrotoxicity [1,2,3]
  2. Vestibular Dysfunction and Ototoxicity [9]
    1. May correlate with high peak as well as high trough levels
    2. Toxic effects on vestibular sensory epithelial hair cells is major problem
    3. Drug appears to accumulate in these areas and remain with long half-life
    4. Vestibular damage is much more common than hearing loss
    5. Once daily dosing reduces risk of ototoxicity [3]
  3. Avoid concomitant use of other nephrotoxic or ototoxic agents [1]
    1. Amphotericin
    2. Cis-platinum
    3. Loop Diuretics, especially ethacrynic acid
    4. ACE (angiotensin converting enzyme) inhibitors
    5. Nonsteroidal antiinflammatory agents (NSAIDs)

References

  1. Gerberding JL. 1998. Am J Med. 105(9):256
  2. Gilbert DN, Lee BL, Dworkin RJ, et al. 1998. Am J Med. 105(9):182
  3. Hatala R, Dinh T, Cook DJ. 1996. Ann Intern Med. 124(8):717 abstract
  4. Barza M, Ioannidis JP, Cappelleri JC, Lau J. 1996. Brit Med J. 21:338
  5. Wilschanski M, Yahav Y, Yaacov Y, et al. 2003. NEJM. 349(15):1433 abstract
  6. Minor LB. 1998. JAMA. 279(7):541 abstract
  7. Ramsey BW, Pepe MS, Quan JM, et al. 1999. NEJM. 340(1):23 abstract
  8. Ratjen F, Doring G, Nikolaizik WH. 2001. Lancet. 358(9286):983 abstract
  9. Koo J, Tight R, Rajkumar V, Hawa Z. 1996. Am J Med. 101(2):177 abstract
  10. Sundar S, Jha TK, Thakur CP, et al. 2007. NEJM. 356(25):2571 abstract