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Aminoglycosides
• Gentamicin
• Tobramycin
• Amikacin
• Streptomycin
• Neomycin
Aminoglycosides MOA
• Inhibit protein synthesis
• Diffuse through porin
channels of gramnegative
pathogens and
then are transported
across cell membrane
via an oxygen
dependent transport
mechanism
• Bind to 30S ribosomal
subunit
• Concentration
dependent killing
– Enhanced effect with
increasing drug conc
• Postantibiotic effect
– Bacterial killing
continues after serum
concentrations fall below
MIC of organism
Aminoglycoside Spectrum of Activity
• Aerobic bacterial only
• Gram-positive
– Streptococcus
– Staphylococcus
– Enterococcus
• Gram-negative
– Most aerobic gram-negatives including
Pseudomonas
• Synergistic with β-lactam antibiotics
Methods of Resistance of aminoglycoside
• Decreased uptake
• Altered 30S ribosomal subunit with decreased
affinity for aminoglycoside
• Aminoglycoside modifying enzymes
Absorption of Aminoglycosides
– Poor oral absorption
– Neomycin – oral
Distribution of Aminoglycosides
– Limited to extracellular
fluid
– Highly polar – do not
readily enter cells
– Poor CSF penetration
Renal elimination of Aminoglycosides
– Rapidly excreted by glomerular filtration
– Accumulates in patients with impaired renal function
– Must dose adjust in renal impairment
Adverse Effects of Aminoglycosides
• Ototoxicity
– Auditory
– Vestibular
• Nephrotoxicity
• Neuromuscular blockade
Antimycobacterials Treatments
– Always combination therapy
– Initially 4 drug regimen which may be narrowed to a minimum of 2 drugs if the isolatedem onstrates no resistance
– Duration:
• 6 - > 24 months
Antimycobacterials Methods of Resistance
– Single drug
• Usually rifampin or isoniazid
– Multidrug
– Degree of resistance determines:
• Number of antimycobacterial agents
• Duration of therapy
Isoniazid Method of Action
– Inhibits synthesis of
mycolic acids
– Prodrug
– Bactericidal
• Rapidly dividing
organisms
– Bacteristatic
• Resting organisms
Isoniazid Pharmacokinetics
– Well absorbed
– Widely distributed
including into CSF
– Metabolized in liver
– CYP450 inhibitor
– Metabolites excreted in
urine
– No dosage adjustment in
renal impairment
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