Aminoglycoside

Ahmad Noor, PharmD

Aminoglycosides are a group of antibiotics that are
effective against:
Aminoglycoside
(AGL)

Aerobic gram( - )bacteria
e.g.: pseudomonas,
Acinetobacter,
enterobacter


Some mycobacteria
e.g.:
bacteria that cause
tuberculosis
Some gram ( + ) bacteria
Mechanism of action & pharmacokinetic:
MOA : They bind to ribosomal units ( 30S-50S ) in bacteria
& inhibits protein synthesis

Pharmacokinetic :

PO poor absorption; IM or IV best

Distribution: hydrophillic, poor CSF, cross placenta

Metabolism :
Excreted unchanged, special dosing for renal failure
Aminoglycoside
(AGL)
Stretomyces
Suffix -mycin
Micromonospora
Suffix -micin
Streptomycin Paromomycin Gentamicin Amikacin
Neomycin Netilmicin Tobramycin
Use Drug
Second-choice medications: for
tuberculosis (TB)
streptococcal endocarditis (with B- lactam)
enterococcal endocarditis ( with penicillins )
Streptomycin
(Streptomycin Sulfate )
Intestinal infections
Ttt of hepatic encephalopathy
Ttt of amebiasis
Paromomycin
( Humatin )
prophylaxis GI surgery
prevention of hepatic encephalopathy &
hypercholesterolemia
Neomycin
( mycifrdish )
Ttt of systemic infection
respiratory tract infection
Tobramycin
( Nebcin ) , (Tobi)
Ttt of systemic infection
life threatening infection
eye infection
Gentamicin
( garamycin )
Respiratory tract infection
Skin infection
Urinary tract infection
Blood, abdomen or bones infection
Amikacin
( Amikin )
septicemia
Lower respiratory tract infection
Urinary tract infection
peritonitis and endometritis
Netilmicin
( NETROMYCIN )
Available dosage form
( all aminglycosides have very
poor absorption from G.I.T )
Dose regimen
(if creatinine clerance > 90ml/min)
Drug
I.V , I.M
I.V
25-30 mg/weak ( tuberculosis )

Streptomycin
(Streptomycin Sulfate )
Oral
Oral
500 mg po tid x7d
Paromomycin
( Humatin )
Oral , topical
It is not given intravenously, as it is
extremely nephrotoxic
Oral
For hepatic encephalopathy :
4-12 gm/d
As prophylactic in GI surgery :
1.0 gm po x3 with erythromycin

Neomycin
( mycifrdish )
I.V , I.M , inhalation
(Tobi)
I.V
5.1 ( 7 if critically ill ) mg/kg q24h
Tobramycin
( Nebcin )
I.V , I.M , Topical
I.V
5.1 ( 7 if critically ill ) mg/kg q24h

Gentamicin
( garamycin )
I.V , I.M
I.V
15mg/kg q24h
Amikacin
( Amikin )
I.V , I.M
The lowest ototoxic AGL
I.V
6.5 mg/kg q24h
Netilmicin
( NETROMYCIN )
Special concern in treatment:
Tobramycin is superior to gentamicin for ttt of
P.aeruginosa .
Gentamicin is the preferred AGL used in combination ttt
of enterococcal endocarditis ( with ampicillin or
vancomycin).
Streptomycin has the greatest activity of all the AGL
against M.tuberculosis.
Capreomycin is an AGL use as alternative drug to ttt
mycobacterial infection
Streptomycin & gentamicin are drugs of choice to ttt
tularemia
Streptomycin is drug of choice to ttt plague & brucellosis


Single Daily Dose (SDD) of AGL:
For Adult:
There are two main principles for the use of the SDD of AGL:
1. Since the AGL bactericidal effect is related to peak concentrations, higher doses
will achieve a higher peak concentration and ensure efficacy of therapy. With this
dosing, it is possible to achieve the desired peak:MIC ratio.
2. SDD may reduce the frequency of nephrotoxicity since low or undetectable trough
concentrations will be attained.
3. Dose ranges from 3 to 7mg/kg/day for gentamicin & tobramycin.
o For children:
The use of SDD of AGL in children has some limitation
because of:
1. Rapid AGL clearance.
2. Unknown duration of post-antibiotic effect.
3. Safety concerns.
4. Limited clinical and efficacy data.

Single Daily Dose of AGL: cont.

SDD relatively contraindications :
1. S.aureus or Enterococcal infection.
2. Bacterial pneumonia with pathogen having high MIC.
Toxicity with SDD:
1. Endotoxin like reactions with SDD AGLs therapy:
- many patients develop rigors, fever, tachycardia.
2. Ototoxicity: develop vestibular dysfunction with high dose.
3. Nephrotoxicity decreased with the use of SDD AGLs.
* N.B:
* SDD of AGL not for every infection, pathogen, or patient.
* Must have therapeutic goal based on pathogen susceptibility & location
of infection.
* PKs remain useful tool to screen patients & to establish desired Cpx:MIC
ratio.

Aminglycosides dosage :
AGL dose depend on IBW & cretinine clerance.

IMP. Formulae:
1. Creatinine clerance :
= (140-age)(IBW in kg) / (72)(Scr)=ml/min
x 0.85 for CrCl of women .
2. Ideal Body Weight (IBW) :
males: 50kg + 2.3kg per inch over 5= weight in kg
females: 45kg +2.3kg per inch over 5= weight in kg
3. Obesity adjustment :
use if Actual Body Weight (ABW) is >30% above IBW. To
calculate adjusted dosing weight in kg :
IBW+ 0.4 (ABW-IBW) = adjusted weight .



Aminglycosides dosage : cont.
SARUBBI-HULL NOMOGRAM FOR AMINOGLYCOSIDES:











General dosing information: The following dosing chart by Sarubbi-Hull
(Ann Intern Med 1978; 89: 612-8) may be used to provide the clinician
with an initial loading dose and maintenance dose regimen in adult
patients. Further dosage adjustments should be individualized and
based on peak/trough serum concentrations, which should be drawn
after the 3rd maintenance dose.

Drug Therapeutic
concentration
Max. peak conc. Max. trough
conc.
Amikacin 15-25 g/mg 35 g/mg 5 g/mg
Gentamicin 4-10 g/mg 10 g/mg 2 g/mg
Tobramycin 4-10 g/mg 10 g/mg 2 g/mg
Aminglycosides dosage : cont.
1- Select loading dose ( based on IBW ) to provide peak serum
concentration in the range listed below for the desired AGL:

AGL Usual loading dose Expected peak serum
conc.
Gentamicin, Tobramycin 1.5-2 mg/kg 4-10 g/ml

Amikacin 5-7.5 mg/kg 15-30 g/ml
Aminglycosides dosage : cont.
2- Select maintenance dose ( as % of loading dose ) to maintain peak serum conc. Indicated above
according to desired dosing interval & the patient corrected CrCl:
CrCl ( ml/min ) Half-life ( hours ) % of loading dose required for dosage interval selected *

8 hours 12 hours 24 hours
90 3.1 84 % - -
80 3.4 80 91 % -
70 3.9 76 88 -
60 4.5 71 84 -
50 5.3 65 79 -
40 6.5 57 72 92 %
30 8.4 48 57 81
20 11.9 37 50 75
17 13.6 33 46 70
15 15.1 31 42 67
12 17.9 27 37 61
10 20.4 24 34 56
7 25.9 19 28 47
5 31.5 16 23 41
2 46.8 11 16 30
0 69.3 8 11 21
* This chart is not applicable to children & neonate.
Side effects:

Nephrotoxicity
Risk of Nephrotoxicity with Cyclosporine , Vancomycin ,
Ampho B , Radiocontrast & NSAIDs .
Risk of nephrotoxicity by once-daily dosing method.
Ototoxicity , deafness
Risk of ototoxicity with loop diuretic .
Risk of nephro/ototoxicity with Cis platinum .
Pseudomembrane colitis
Neuromuscular toxicity
Other drug-drug interactions:
Neuromuscular blocking agents apnea or respiratory paralysis
Non-polarizing muscle relaxant apnea
Oral anticoagulants prothrombin time
Note: there is no known method to eliminate risk of AGL
nephro/ototoxicity .proper Rx attempts to the % risk.
Follow up & monitoring :
Monitor patient for ototoxicity : tinnitus, vertigo,
hearing loss
the drug should be stopped if tinnitus occurs.
Monitor patient for nephrotoxicity periodically .if serum
creatinine increases by more than 50% over baseline value
it may be advisable to discontinue drug ttt & use less
nephrotoxic agent.
Monitor neuromuscular function when administering the
drug IV. Too rapid administration may cause paralysis &
apnea. Have Ca gluconate or pyridostigmine available to
reverse such effect
Monitor patient's neurologic status if the drug is given for
hepatic encephalopathy .

Contraindications:

Hypersensitivity to AGL


Pregnancy
(AGL is class D during pregnancy )


Myasthenia gravis
Parkinsonism
(AGL may cause neuromuscular blockade, resulting in
further skeletal muscle weakness )

Fetal eight nerve damage
( AGL may cause auditory and vestibular toxicity )





Patient counseling :
Do not take AGL if you are pregnant or could become
pregnant during treatment.


Do not take AGL if you are breast-feeding a baby.

Take each dose with a full glass of water.

Take AGL with food.

Store AGL at room temperature away from moisture,
heat, and direct light.
References :
1. Joel Hardman, Lee Limbird, Alferd Goodman Gilman,
eds. The Pharmacological Basis Of Theraputics.10
th
ed.
Mcgraw-hill;2001;p1219-1238.
2. Seymour Ehrenpreis, Eli Ehrenpreis, eds. Clinicians
Handbook Of Prescription Drugs.1
st
ed. McGraw-hill;
2001;p959-960.
3. David Gilbert, Robert Moellering, George Eliopulos, Merle
Sande, eds. The Sanford Guide To Antimicrobial therapy.
35
th
ed. Antimicrobial Therapy, Inc;2005;p47-53.
4. Simeon Marglis, Rodney Friedman, Thomas Dickey,
Jermy Birch, eds. The Johns Hopikins Consumer Guide
to Drugs.1
st
ed. Medletter associates, Inc;2005;p766.
5. Frederic Vagnini, Barry Fox, eds. The Side Effects
Bible.1
st
ed. Random House, Inc;2005;p499-500.
6. http://health.yahoo.com/drug/d00014a1.
7. http://www.rxlist.com/cgi/generic2/streptomycin.htm.
8. http://www.medscape.com/viewarticle/448281_print.
9. http://bmj.bmjjournals.com/cgi/content/full/312/7027/338.
10. http://depts.washington.edu/druginfo/Formulary/Aminogl
ycosides.pdf#search='aminoglycosidenomogram.




Thank You
Ahmad Noor , PharmD