Aminoglycosides

Dr Salman
Ami nogl ycosi des
• Chemically they consist of a
glycoside and an amino-sugar.
Gentamicin is produced by
Micromonospora Purpurea while
other are produced by
Streptomyces griseus.Cognition
• Useful primarily in the treatment
of infections caused by ‘aerobic
gram-negative Bacteria’
Cl assi fi cati on
• Streptomycin:
• Gentamicin
• Tobramycin:
• Amikacin:
• Neomycin:
• Netilmicin:
• Spectinomycin:
Aminoglycosid es: Mechanism
of A ction
• Aminoglycosides are bactericidal. They irreversibly
inhibit protein synthesis. Initially they passively diffuse
via porin channels across the outer membrane of gram
negative bacteria to enter the periplasmic space.
• Then the drug is actively transported across the
cytoplasmic membrane (inner) into cytoplasm by an
oxygen dependant electron transport process.
Therefore they have no activity against anaerobic
bacteria. Penicillins and Vancomycin which are cell
wall active drugs, enhance the transport of
aminoglycosides hence they are synergistic.
• After entering into the cell-wall, the aminoglycosides
bind to specific 30S-subunits\ ribosomal proteins.
Protein synthesis is inhibited in the following ways:
Mechani sm of Act ion
Mechani sm Conti nued…
After entering into the cell-wall, the
aminoglycosides bind to specific
30S-subunits\ ribosomal proteins.
Protein synthesis is inhibited in
the following ways:
• They block the formation of “initiation complex” of
peptide formation.
• They cause miscoding of amino-acids in the emerging
peptide chain due to miscoding of the code of mRNA
template.
• They block translocation on mRNA
• They block the movement of ribosome after formation
of a single initiation complex, resulting in an mRNA
chain, with only a single ribosome on it, a so-called
monosome. In other words they disrupt polysomal
structure.
Mechani sm conti nued…
• The aberrant protein produced
may be inserted in the cell
membrane, leading to altered
permeability and influx of more
drug “Energy Dependant Phase II”
(EDP2 )
Spectrum of Acti vi ty
• Citrobacter Freundii
• Enterobacter
• E-coli
• Klebsiella pneumoniae
• Proteus mirabilis
• Providencia staurtii
• Serratia (nosocomial)
• Enterococcus Faecalis
• Staphylococcus Aureus
• Mycobacterium TB (Kenamycin, Amikacin,
streptomycin)
Spectrum wi th Peni ci lli ns
• Gram +ve Cocci
– Streptococcus viridans: endocarditis
bacteremia and dental caries
– Streptococcus agalactiae: bacteremia,
meningitis, neonatal abscess
– Enterococcus faecalis: endocarditis,
bacteremia
• Gram +ve bacilli
– Corynaebacterium species: Diphtheroids
causing endocarditis and bacteremia
– Listeria monocytogenes: meningitis,
bacteremia
Conti nued
• Gram negative Bacilli:
– E-coli: UTI Traveler’s diarrhea, bacteremia,
meningitis
– Proteus: UTI, other infections
– Pseudomonas aeroginosa: pneumonia
– Klebsiella pneumonae: pneumonia
– Serratia: Pneumonia, Bacteremia &
nosocomial infections
– Acinetobacter: nosocomial infection
– Campylobacter fetus: bacteremia,
meningitis
– Enterobacter
Toxi ci ties
• Ototoxicity – auditory or vestibular damage
or both, and may be irreversible. Auditory
damage is more likely with Amikacin and
Kenamycin. Vestibular damage is more
likely with Gentamicin and Tobramicin.
Ototoxicity may be increased with the use
of Loop-Diuretics
• Nephrotoxicity – Usually acute tubular
necrosis occurs. Nephrotoxicity is more
common in elderly patients and in those
concurrently receiving Amphotericin B,
Cephalosporins or Vancomycin. Gentamicin
and Tobramicin are most nephrotoxic
Cont inued
• Neuromuscular blockade – at high doses of
aminoglycosides, a curare-like block may
occur (inhibit the prejunctional release of
acetylcholine and postsynaptic sensitivity to
the neurotransmitter) and may result in
respiratory paralysis. It may be treated with
calcium and Neostigmine.
• Skin rashes: Allergic skin reactions and
contact dermatitis may occur. Neomycin is
more likely to cause contact dermatitis.
• Other Effects on CNS:
– Streptomycin( in particular) – dysfunction
of optic nerve
– Paresthesia (perioral) other areas of face
may be involved , occurs after 30-60mins
after injection, remains for several hours.
 • Streptomycin:
• Tuberculosis – as a second line agent
• Plague, Tularemia, Brucellosis
• With penicillins used for Enterococcal Endocarditis
• Gentamicin:
• With penicillins it has a synergistic action against:
• Pseudomonas, Proteus, Enterobacter, Klebsiella, Serratia,
Stenotrophomonas
• It is given I/M, for severe infections (Sepsis, pneumonia)
caused by gram negative bacteria such as pseudomonas,
Enterobacter, Serratia, Proteus, Acinetobacter and Klebsiella.
Gentamicin is combined with penicillins or cephalosprins fro
life threatening infections.
• It has been used intrathecally for meningitis caused by gram
negative bacteria but 3rd generation cephalosprins are
preferred.
• Topically it is used for infected burns, wounds and skin
lesions.
• For ocular infections it can be injected sub-conjunctively.
 • Tobramycin:
• Spectrum: As compared to gentamicin, tobramycin is
more active against Pseudomonas.
• Enterococcus faecium is resistant to tobramycin.
• Amikacin:
• It is resistant to many enzymes that inactivate
gentamicin or Tobramicin. Many gram negative enteric
bacteria, including Proteus, Pseudomonas,
Enterobacter and Serratia are susceptible. Strains of
Multidrug-resistant Mycobacterium Tuberculosis are
also susceptible.
• Neomycin:
• Only used topically and locally for example in GIT
• Netilmicin:
• Serious infections caused by organisms resistant to
other aminoglycosides.
• Spectinomycin:
• It is an amino cyclitol related to aminoglycosides.
Given intra-muscularly for Gonorrhea.