Aminoglycosides Flashcards
Gram (-) moderate infections
UTIs
Gentamicin and Tobramycin
- Peak–> 4-6
- Trough–> 0.5-1.5
Gram (-) moderate to severe infections
Soft-tissue, bacteremia
Gentamicin and Tobramycin
- Peak–> 6-8
- Trough–> 1-1.5
Gram (-) severe infections
Pneumonia, burns, life-threatening
Gentamicin and Tobramycin
- Peak–> 8-10
- Trough–> < 2
MOA
Inhibits protein synthesis by binding irreversibly to the 30S ribosomal subunit
Bactericidal–>concentration dependent
MOR
Alteration in aminoglycoside uptake
Synthesis of aminoglycoside-modifying enzymes
Alteration in ribosomal binding sites (only for streptomycin)
Spectrum of activity
Gram (+) aerobes–>NEVER USED ALONE, always use in LOW DOSES with cell-wall active agents
Gram (-) aerobes–> often used with cell-wall active agents; HIGHER doses are used
- Pseudomonas aeruginosa
Mycobacteria:
- Streptomycin is active against mycobacterium tuberculosis
Pharmacology
Highly polar cations
Interpatient variability exists in the PK parameters of VD and clearance
Absorption
Poorly absorbed in the GI tract–> IV or IM
Drug absorption after IM injection may be decreased in patients with hypotension and should not be used in critically ill patients
Distribution
Distributed primarily in the extracellular fluid compartment
Poor penetration in CSF
IBW should be used for dosing
Elimination
Eliminated unchanged by kidneys
Decreased renal function–>increased half-life
Serum concentration monitoring
Because of the interpatient variability in PK parameters and the narrow therapeutic index of aminoglycosides, serum concentration monitoring is necessary in ALL patients
Must achieve therapeutic concentration within 24 hours as studied show increased mortality with sub-therapeutic levels
Adverse effects
Nephrotoxicity–>reversible
- Prolonged high trough concentrations, prolonged therapy > 2 weeks, renal insufficiency, advanced age, use of concomitant nephrotoxins
Ototoxicity–> irreversible
- Prolonged high trough concentrations, prolonged therapy > 2 weeks, renal insufficiency, advanced age, vancomycin and loop diuretics
Factors affecting dosing
Volume status must be taken into account
Normal Vd= 0.25L/kg
Large Vd= 0.3-0.35L/kg–>Ascites, CHF, pregnancy
Small Vd=0.15-0.2L/kg–>Dehydration
Gram (+) peak and trough
Peak: 3-5
Trough: 1
Extended dosing interval–> only gram (-)
Gent, tobra= 5-7 mg/kg q24h
Amikacin= 15-25 mg/kg q24h
Caution in immunocompromised, large/small vd, high/low clearance
Peak and trough extended dosing interval
intraabdominal infections, urosepsis, skin/soft tissue infection
Gent, tobra
Peak= 13-20
Trough= < 0.5
