classification , uses and adverse effects

1. By : Dr Mushahid Hasan

2. Introduction
These are a group of natural and semisynthetic
antibiotics having polybasic amino groups linked
glycosidically to two or more aminosugar.
Streptomycin was the first member discovered in
1944 by Waksman and his colleagues.

3. Classification
Systemic aminoglycosides
o Streptomycin
o Gentamicin
o Kanamycin
o Tobramycin
o Amikacin
o Sisomicin
o Netilmicin
Tropical aminoglycosides
o Neomycin
o Framycetin

4. MECHANISMOFACTION
A. Transport of aminoglycoside through the bacterial
cell wall and cytoplasmic membrane.
B. Binding to ribosomes resulting in inhibition of
protein synthesis.

6. The cidal action of aminoglycosides is conc dependent, i.e. rate of
bacterial cell killing is directly related to the ratio of the peak
antibiotic concentration to the MIC (minimum inhibitory conc)
value.
They also exert a long and concentration dependent ‘postantibiotic
effect’.
Therefore despite of their short t1/2 (2-4 hrs), single injection of
total dose of aminoglycoside may be more effective and possibly
less toxic than its conventional division into 2-3 doses

7. Mechanism Of Resistance
Resistance to aminoglycoside is acquired by one of
the following mechanism :-
a. Acquisition of cell membrane bound inactivating engymes
which phosphorylate / adenylate or acetylate the antibiotic.
b. Mutation decreasing the affinity of ribosomal proteins that
normally bind the aminoglycoside.
c. Decreased efficiency of the aminoglycoside transporting
mechanism : either the pores in the outer coat become less
permeable or the active transport is interfered.

9. Precaution And Interactions
 Avoid aminoglycosides during pregnancy : risk of foetal ototoxicity
 Avoid concurrent use of other ototoxic drugs, eg. Diuretics, minocycline.
 Avoids concurrent use of other nephrotoxic drugs , eg. Amphotericin B ,
vancomycin , cyclosporine.
 Cautious use in patients past middle age and in those with kidney damage.
 Cautious use of muscle relaxants in patients receiving an aminoglycoside
 Do not mix aminoglycoside with any drug in the same syringe / infusion
bottle.

10. Streptomycin
 It is the oldest antibiotic obtained from Streptomyces griseus .
 It is less potent than other aminoglycosides.
 The antimicrobial spectrum of streptomycin is relatively narrow ;
active primarily against aerobic gram negative bacilli , but potency is
low.
 Sensitive organisms are – Brucella , Nocardia , M. tuberculosis
 Only few stains of E.coli , H. Influenzae , V. cholera , shigella , and
some gram positive cocci are inhibited at high concentration

11. RESISTANCE
Many organism develop rapid resistance to streptomycin , either one-step mutation or
by acquisition of plasmid which codes for inactivating enzymes.

12. Adverse effects
• About 1/5 patients given streptomycin
1gm BD i.m. experience vestibulat
disturbances. Auditory disturbances are
less common.
• It has the lowest nephrotoxicity among
aminoglycosides ; probably because it is
not concentrated in the renal cortex.
• Hypersensitive reactions are rare;
rashes, eosinophilia, fever and
exfoliative dermatitis
• Anaphylaxis is very rare.
• Pain at injection site is common
Uses
1. Tuberculosis
2. Subacute bacterial
endocarditis (SABE)
3. Plague
4. Tularemia

13. Gentamicin
 It is obtained from Micromonospora Purpuraea in 1964 ; and has
become the most commonly used aminoglycoside for acute infections.
 Plasma t1/2 of 2-4 hrs
 It is more potent
 It has a broader spectrum of action : effective against Ps. Aeruginosa
and most stains of proteus , E. coli , Klebsiella , Enterobacter , Serratia .
 It is ineffective against M.tuberculosis , strep. Pyogens and strep.
Pneumoniae but inhibits many strep. Faecalis and some staph. Aureus.
 It is relatively more nephrotoxic.

14. Uses :
1) For preventing and treating respiratory infections in critically ill
patients ; in those with impaired host defence (receiving anticancer
drugs or high dose corticosteroid; AIDS)
2) Pseudomonas , proteus or klebsiella infections : burns , UTI ,
pneumonia , lung abscesses , osteomyelitis , middle ear infection ,
septicaemia , etc.
3) Meningitis caused by gram-negative bacilli
4) SABE
Dose : According to body weight and level of renal function. For an average adult
with normal renal function (creatinine clearance >=100ml/min) 3-5mg/kg/day i.m.
either as single dose or divided in three 8hourly doses is recommended

15. kanamycin
o Obtained from S. kanamycetius (in 1957) , it was the second
systemically used aminoglycoside.
o It is similar to streptomycin in all aspects including efficacy
against M. tuberculosis and lack of activity on Pseudomonas.
o It is more toxic , both to cochlea and to kidney.
o Hearing loss is more common than vestibular disturbance.
o It is occasionally used as second line of drug in resistant
tuberculosis.
Dose :
0.5g i.m. BD-TDS

16. Tobramycin
o It is obtained from S. tenebrarius in the 1970s.
o The antibacterial and pharmacokinetic properties , as well as
dosage are almost identical to gentamicin , but it is 2-4 times more
active against Pseudomonas and Proteus , including those resistant
to gentamicin.
o Ototoxicity and nephrotoxicity is probably lower than gentamicin.
Dose :
3-5 m/kg day in 1-3 doses

17. Amikacin
o It is semisynthetic derivative of kanamycin to which it resembles in
pharmacokinetics , dose and toxicity .
o It has the widest spectrum of activity , including many organisms
resistant to other aminoglycosides.
o However , relatively higher doses are needed for Pseudomonas , Proteus
and Staph. Infections.
o It is recommended as a reserve drug for hospital acquired gram-
negative bacillary infections where gentamicin / tobramycin resistance is
high.
Dose :
15mg/kg/day in 1-3 doses ; urinary tract infection 7.5mg/kg/day.

18. Sisomicin
o Introduced in 1980s , it is a natural aminoglycoside from
Micromonospora inyoensis that is chemically and
pharmacokinetically similar to gentamicin but somewhat more
potent on Pseudomonas , a few other gram-negative bacilli and b-
haemolytic streptococci.
o It is moderately active on faecal streptococci – can be combine for
SABE.
o It can be used interchangeably with gentamicin for the same
purposes in the same doses.

19. Netilmicin
o This semisynthetic derivative of sisomicin has a broader spectrum
of activity than gentamicin.
o It is more active against Klebsiella , Enterobactor and Staphylococci
, but less active against Ps. Aeruginosa.
o Pharmacokinetic characteristics and dosage of netilmicin are
similar to gentamicin.
o It is less ototoxic , than gentamicin and tobramycin .
Dose :
4-6 mg/kg/day in 1-3 doses.

20. Neomycin
o Obtained from S. fradiae , it is a wide spectrum aminoglycoside ,
active against most gram-negative bacilli and some gram-positive
cocci .
o Neomycin is highly toxic to the internal ear and to kidney. It is
therefore, not used systemically.
Dose :
0.25-1 g QID oral , 0.3-0.5% topical

21. Uses
1. Topically for infected
wound , ulcers , burn ,
external ear infections ,
conjunctivitis .
2. Orally for : Preparation of
bowel before surgery: (3
doses of 1.0g along with
metronidazole 0.5g on day
before surgery) may reduce
postoperative infections.
Adverse effects
1. Topically applied neomycin
has low sensitizing potential.
However , rashes do occur.
2. Oral neomycin has a
damaging effect on intestinal
villi – prolonged treatment can
induce malabsorption
syndrome with diarrhea .
3. Due to marked suppression of
gut flora , super infection by
candida can occur.

22. Framyetin
o Obtained from S. lavendulae , it is very similar to neomycin.
o It is too toxic for systemic administration and is used topically on
skin , ear , eye in the same manner as neomycin.
o 1% skin cream , 0.5% eye drops or ointment.