Aminoglycosides

Aminoglycosides

 Description:

Aminoglycosides are antibiotics that are highly effective against gram-negative and to a lesser extent gram-positive bacteria. Neomycin, among others, is effective against Enterobacter, Salmonella and Shigella. Neomycin, is not effective against Pseudomonas aeruginosa as opposed to Gentamicin, which is. Aminoglycosides are ineffective against fungi and yeast. Neomycin consists of a mixture of Neomycin A, B and C, which differ in the side chains attached to the amino sugars. Neomycin A is a degradation product of Neomycin B and C, and has no antimicrobial activity. Aminoglycosides consist of a central hexose or diaminohexose molecule to which two or more amino sugars are attached by a glycosidic bond. Neomycin is an aminoglycoside antibiotic. It consists of 78-88 % Neomycin B and 10-16 % Neomycin C.
Neomycin, had better activity than streptomycin against aerobic gram-negative bacilli.

 

Mechanism of action: The bactericidal effect of these antibiotics is based on the inhibition of protein synthesis. Aminoglycosides bind to the 30S subunit of the bacterial ribosome, interfering with the binding of fMet-tRNA and therefore the formation of the initiation complex. Attachment to the 30S subunit results in stagnation of the initiation phase during translation. Because of this stagnation elongation can no longer take place and protein synthesis stops.

 

Source:  
Neomycin Streptomyces fradiae

 

Streptomycin Streptomyces griseus
Spectinomycin Streptomyces spectabilis
Gentamicin Micromonospora purpurea

 

Indications: Gentamcin: Its extended stability and slow development of bacterial resistance allow long-term virus and tissue culture studies.
 
  Gentamicin is also indicated for turkey egg dipping. A concentration of 500 ppm is recommended.
Neomycin: Treatment of enteric infections.

 

Dosage:
Chickens:
Turkeys:
Pigeons:
Neomycin
70-140 g/ ton feed
22 mg/kg/day water medication
ND
     
       
Streptomycin
20 mg/kg; 2.5-5.0 mg per chick
ND
ND
     
Spectinomycin
50-100 mg/kg bw
ND
ND
Gentamicin sulphate
5.5 mg/kg IM
5 mg/kg IM
ND
  Chicks: 0.2 mg/chick    

 

Pharmacokinetics: Aminoglycosides are poorly absorbed from the gastrointestinal tract. After parenteral administration, aminoglycosides are primarily distributed within the extracellular fluid. Penetration of biologic membranes is poor because of the drug's polar structure, and intracellular concentrations are usually low, with the exception of the proximal renal tubule.

 

Gentamicin levels after IM injection
Avian

Lungs

µg/g

Muscle

µg/g

Liver

µg/g

Kidneys

µg/g

Plasma

µg/g

Pigeons
0.0
0.0
25.0
530
0.1
Injection of 10 mg/kg bw. Values 6 h after inj
 
Gentamicin
Avian
Dosage (IM) mg/Kg
t 1/2
(Hrs)
Tmax
(Hrs)
F (%)
Turkeys
5
2.57±0.79
0.81±0.34
102±21
3.92±1.51
1.13±0.41
97.2±31.41
Chickens
5
4.17±1.96
0.79±0.19
ND
10
1.8
ND
ND
Geese/Ducks
10
2.3
ND
ND
Pigeons
10
0.9
ND
ND
20
1.0
ND
ND

 

Neomycin
Avian
Dosage (IM) mg/Kg
t 1/2
(Hrs)
Tmax
(Hrs)
Chickens
20
2.16
0.5

 

                           Spectinomycin 

Avian

Dosage

mg/Kg

t 1/2
(Hrs)

Tmax
(Hrs)

F

%

Chicken

50 (IM)

1.65±1.07

0.25

136.1

50 (SC)

2.03±1.06

0.25

128.8

50 (PO)

3.74±1.07

2.00

11.8

100 (PO)

8.93±1.13

2.00

26.4

 

Residues: IM Injection of Neomycin 20 mg/Kg bw
Values 6 Hrs p.i.
Avian

Lungs

µg/g

Liver

µg/g

Kidneys

µg/g

Plasma

µg/g

Chickens
0.92
12.86
219.2
1.09

4 wks p.i. the Neomycin level in kidneys was 0.65 micro-g/g

 

Contra-indications:

Gentamycin is highly basic compound, it can damage cell-associated Marek's vaccine if used at too high dose (greater than 0.2mg/chick) or improperly mixed with the vaccine. 

 

Toxicity: Repetitive dosing may result in renal accumulation and toxicity. Nephrotoxicity results from renal cortical accumulation resulting in tubular cell degeneration and sloughing.
Proximal acute tubular necrosis (ATN) result in decrease GFR.
The use of gentamicin or neomycin (Inj) has been associated with polyuria, polydipsia and nephrotoicity.

 

Resistance

Via plasmid-mediated aminoglycoside-modifying enzymes. Bacterial inactivation by intracellular enzymes.

 

Combinations Synergistic in combination with beta-lactams and glycopeptides.
Spectinomycin can be combined with colistin or lincomycin.
   
Drug-Drug Interctions There is an in vitro interction between aminoglycoside antibiotics and penicillins leading to a significant loss of aminoglycoside antibacterial activity if these antibiotics are mixed in the same bottle. The extend of inactivation depends on the penicillin concentration, the contact time, and the temperature. Aminoglycosides should not be mixed with penicillins or cephalosporines in the same bottle.

 

Comments: The antimicrobial effect of the antibiotic depends on the extracellular pH. Antimicrobial activity decreases significantly at pH levels of 6.5 and lower. The presence of divalent cations (Ca+2 and Mg+2) in the medium also decreases the antimicrobial activity.