Aminoglycosides

& Spectinomycin
linrong
Department of pharmacology
XI’AN JIAOTONG UNIVERSITY

Aminoglycosides are a
group of bactericidal
antibiotics obtained from
various streptomyces
species..

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 XI’AN JIAOTONG UNIVERSITY

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 Aminoglycosides

Aminoglycosides are used most widely

against gram-negative enteric bacteria,
especially in bacteremia and sepsis.

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 Aminoglycosides
General Properties
Mechanism of Action
Mechanism of Resistance
Spectrum of Activity
Clinic use
Adverse Effects

Streptomycin
Gentamicin
Tobramycin
Amikacin

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Aminoglycosides: General Properties

① The chemical structures of amino-

glycosides are similar.
All of them are organic alkalis with a high
dissociation and low lipid diffusion, and do
not easily transport across membranes.
② Their antimicrobial mechanisms are
similar.
inhibiting the synthesis of proteins
bactericidal action
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Aminoglycosides: General Properties

③ Their adverse effects are similar.

v hurt the structure of cochlea, resulting in the
hearing loss;
v hurt the structure of ear vestibule, resulting
in the loss of body’s balance.
v damage the renal function and cause
proteinuria, blood urine and renal failure
v block neuromuscular junction, causing
skeletal muscle relaxation
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Aminoglycosides: Mechanism of Action
Aminoglycosides binds to specific 30S-subunit
ribosomal proteins. Protein synthesis is
inhibited by them in at least three ways:
①They block the formation of initiation 70S
ribosomal mRNA complex;

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Aminoglycosides: Mechanism of Action
②They induce misreading of mRNA→ causes
incorporation of incorrect amino acids into peptide
→ resulting in a nonfunctional or abnormal protein
synthesis .
③ They inhibit the combination of the releasing
factor with the site A on ribosome → prevent
the synthesized peptide chain releasing from
the 70S ribosomal mRNA complex and the 70S
ribosomal mRNA complex dissociating into 30S
and 50S subunits.
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Aminoglycosides: Mechanism of Resistance

Up to now, at least three mechanisms of drug

resistance have been identified :
①production of transferase enzymes that
inactivate aminoglycosides by adenylylation,
acetylation, or phosphorylation.
②impaired penetration of aminoglycosides to
target site on the ribosome.
③modification of target site.
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 Aminoglycosides: Spectrum of Activity

Gram-Negative Aerobes (not streptomycin)

Ø enteric bacilli, E.coli, klebsiella, proteus, enterobacter are
highly susceptible;
Ø Pseudomonas aeruginosa is susceptible to some
aminoglycosides (e.g. gentamicin, amikacin, netilmicin,
and sisomicin), in particular tobramycin.
Gram-Positive Aerobes
staphylococci, including penicillin-resistant S.aureus
Mycobacteria
– M.tuberculosis - streptomycin, amikacin ,kanamycin

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 Aminoglycosides: Pharmacokinetics

Aminoglycosides are absorbed very poorly from

the intact gastrointestinal.
After intramuscular injection, minoglycosides
are well absorbed ,giving peak concentrations
in blood within 30-90 minutes.

Aminoglycoside toxicity in the patient is both

time-and concentration-dependent.
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 Aminoglycosides: Clinic use

Aminoglycosides are mostly used against gram-

negative enteric bacteria, especially when the
isolate may be drug-resistant and when there
is suspicion of sepsis.

Aminoglycosides are almost always used

incombination with a β-lactam Antibiotic.

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 Aminoglycosides: Adverse Effects

① Nephrotoxicity
– Aminoglycosides are mainly excreted by glomerular
filtration and can be stored up in kidney. It can cause
acute renal insufficiency and tubular necrosis.
– Neomycin is the most nephrotoxic drug, streptomycin
is the least one.
② Ototoxicity
– the cranial nerve damage - cochlea and ear vestibule
toxicity; irreversible
– vestibular: dizziness, vertigo, ataxia
– auditory: tinnitus, decreased hearing
– neomycin, kanamycin, and amikacin are the most
ototoxic drugs, Streptomycin and gentamicin are the
most vestibulotoxic. Netilmicin is the least ototoxic. 14
 Aminoglycosides: Adverse Effects

③ Neuromuscular junction blockade

– may take place at high doses or in
combination with curariform drugs .
④ Hypersensitivity reactions
– skin rash, fever, eosinophilia and
anaphylactic shock can be seen though
infrequetly.
– The special attention should be paid to the
anaphylactic shock caused by streptomycin

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 Aminoglycosides
Common characteristics
Mechanism of Action
Mechanism of Resistance
Spectrum of Activity
Clinic use
Adverse Effects

Streptomycin
Gentamicin
Tobramycin
Amikacin

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 Streptomycin
① Streptomycin was isolated from a strain of
Streptomyces griseus by Waksman and his
associates in 1944.
② It is the first drug used effectively for treatment
of tuberculosis, and nowadays streptomycin is
still used as a first-line drug.
③ At present, it is used alone to treat only two
infections: the tularemia caused by Francisella
tularensis and the plague caused by Yersinia
pestis.
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 streptomycin : Clinic use
① Mycobacterial Infections
Nontuberculous Infections
Mostly used to treat aerobic G- bacterial
infections: bacteremia, sepsis, meningitis,
pnumonia and other servere infective diseases,
especially caused by drug-resistant bacteria.

② Usually, they are used in combination with a

beta-lactam antibiotic in order to extend
coverage to include potential gram-positive
pathogens and to take advantage of the
synergism between these two classes of drugs.
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 Gentamicin
① Gentamicin is the most commonly used,
covering G- and G+ organism,and many of its
properties resemble those of those of other
aminoglyosides.
② Because of its cheaper price and excellent
effect, gentamicin is usually used as the first-
choice drug of aminolycosides for serious
infections (e.g. sepsis, bacteremia and
pneumonia) caused by G- bacteria
③ It is also used in antibiotic combination against
Staphylococcus aureus. 19
 Tobramycin
① Tobramycin is slightly more active against
pseudomonas, proteus and enterobacter,
whereas gentamicin is slightly more or as
same as active against other gram-negative
bacilli.
② Tobramycin and gentamicin are
interchangeable clinically.

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 Amikacin
① Of all aminoglycosides, amikacin is the drug
with the broadest antibacterial spectrum.
② the most prominent characteristic of amikacin
is that this drug is resistant to many enzymes
produced by gram-negative enteric bacilli,
P.aeruginosa and S.aureus.
③ Amikacin is mainly used for treatment of
infections caused by such bacteria that are
resistant to the other aminoglycosides.

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 Aminoglycosides
Common characteristics
Mechanism of Action
Mechanism of Resistance
Spectrum of Activity
Clinic use
Adverse Effects

Streptomycin
Gentamicin
Tobramycin
Amikacin

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