Aminoglycoside antibiotics are natural or semi-synthetic derivatives of compounds produced by soil actinomycetes that contain amino sugars linked to an aminocyclitol ring. Some key aminoglycoside antibiotics are streptomycin, gentamicin, and amikacin. They are bactericidal, act by interfering with bacterial protein synthesis, and are primarily effective against aerobic gram-negative bacilli. While they have a narrow safety margin, aminoglycosides are used to treat various infections due to their synergistic effects in combination therapy and activity against multidrug-resistant organisms. However, they can cause ototoxicity, nephrotoxicity, and neuromuscular blockade as adverse effects.

1. Aminoglycoside antibiotics
Dr. Anant Khot

2. Introduction
 Aminoglycosides are natural or semi-
synthetic derivatives of compounds
produced by a variety of soil actinomycetes
 These agents contain amino sugars linked
to an aminocyclitol ring by glycosidic bonds

3.  Streptomycin (1944-Waksman) was first
isolated from Streptomyces griseus
 Gentamicin & netilmicin- derived from
species of Micromonospora.

4. Drugs
 Systemic- Streptomycin, Amikacin,
Gentamicin, Sisomicin, Kanamycin,
Tobramycin, Netilmicin, paromomycin
 Topical- Neomycin, Framycetin

5. Common properties
 AGA are used as sulfate salts, which are
highly water soluble; solutions are stable for
months.
 They ionize in the solution; are not absorbed
PO; distribute only extracellularly; do not
penetrate brain or CSF.

6.  All are excreted unchanged in urine by GF
 Are bactericidal & more active at alkaline pH
 They act by interfering with bacterial protein
synthesis.
 All are active primarily against aerobic gram-
negative bacilli & do not inhibit anaerobes

7.  Partial cross resistance is seen among them
 Have relatively narrow margin of safety
 All exhibit ototoxicity & nephrotoxicity

8. Mechanism of action
 Irreversible inhibitors of protein synthesis
 AGA Periplasmic space
Porin channel Cytoplasm
Transmembrane electrochemical
gradient & transport is coupled
to proton pump

9.  Inside the cell, AGA bind to specific 30S-
subunit ribosomal proteins
 Interference with the initiation complex of
peptide formation.
 Misreading of mRNA incorporation of
incorrect AA’s into the peptide

10.  Breakup of polysomes into nonfunctional
monosomes
 Altered integrity of cytoplasmic membrane
Leakage of ions, AA & proteins
Cell death

11. Resistance to the Aminoglycosides
 Production of a transferase enzyme or
enzymes inactivates the AGA by adenylation,
acetylation or phosphorylation.
 Impaired entry of AGA into the cell
 The receptor protein on the 30S ribosomal
subunit may be deleted or altered

12. PK
 ROA- IV/IM, Inhalation & Topical
 Vd ~ECV, they cross the placenta but not
BBB. High concentrations are found only in
the renal cortex & the endolymph
 Plasma t1/2 ~2-3 hrs, elimination is virtually by
glomerular filtration

13. Uses
 Combination therapy- HAP or sepsis, where
MDR gram-negative organisms such as P.
aeruginosa, Enterobacter, Klebsiella &
Serratia are involved
 UTI esp.. due to E.coli- Complicated or UC
 Bacterial Endocarditis- Synergistic

14.  Tularemia- DOC
 Brucellosis- IM Streptomycin + Doxycycline
 Severe forms of plague
 Mycobacterial Infections
 Cystic Fibrosis- Recurrent infections due to
Pseudomonas species- Tobramycin
 Neomycin & paromomycin : Skin and
mucous membrane infections
 PO- “Bowel preparation” prior to surgery
or selective digestive decontamination

15. Adverse Effects
 Ototoxicity- Irreversible, B/L , high-
frequency hearing loss or vestibular
hypofunction
 Audiometric data – Incidence ~20-25%
 Strepto & gentamicin- Vestibular effects
 Amikacin, kanamycin & neomycin- Auditory

16. Nephrotoxicity
 Reversible, mild rise in plasma creatinine
 ~ 8%–26% of patients who receive an AGA for
several days develop mild renal impairment
 Neomycin is highly nephrotoxic
 Streptomycin is the least nephrotoxic
 High-dose, extended-interval dosing

17.  Acute neuromuscular blockade & apnea
 Patients with myasthenia gravis are
particularly susceptible (N-M>T-L blockade)
 Mech: Inhibit the prejunctional release of
Ach & also reducing postsynaptic sensitivity
 Rx- IV calcium salts & Neostigmine

18.  Rare- hypersensitivity reactions including
skin rashes, eosinophilia, fever, blood
dyscrasias, angioedema, exfoliative
dermatitis, stomatitis & anaphylactic shock

19.  Pregnancy: Fetal ototoxicity
 With other ototoxic drugs: furosemide, minocycline
 With nephrotoxic drugs: vancomycin ,cisplatin
 Elderly patients & those with kidney disease
 Cautious use of muscle relaxants
 Do not mix with any other drug in same syringe
Precautions / Contraindications

20. Thank you