Aminoglycoside antibiotics

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Structure of the aminoglycoside streptomycin

Aminoglycoside antibiotics , shortly aminoglycosides are carbohydrates related oligomers and consist of amino sugar - and nitrogenous Cyclitol building blocks. They form a large, growing group of around 200 water-soluble antibiotic substances, many of which are used medicinally.

Streptomycin was the first aminoglycoside antibiotic that was discovered in 1944 by the group around Selman Waksman . Many similar active substances were subsequently isolated from actinomycetes , especially from the genera Streptomyces and Micromonospora .

By convention, the aminoglycoside antibiotics from the genus Streptomyces are named with the suffix -mycin , while those from the genus Micromonospora are named with the suffix -micin .

Mechanism of action

The act aminoglycoside antibiotics pronounced concentration-dependent strong bactericidal by inhibiting protein synthesis with him dividing and non-dividing pathogens by binding to the 30 S - subunit of the ribosome to couple and reading errors of the mRNA cause. This leads to the formation of defective proteins that lose their biological function. As a consequence, z. B. defective proteins built into the cell membrane of the bacterium, which leads to lysis of the pathogen.

Important representatives

Application and administration

The spectrum of activity mainly includes the gram-negative enterobacteria and Pseudomonas aeruginosa as well as the gram-positive staphylococci . Aminoglycosides are ineffective against anaerobic bacteria because they are absorbed into the cell through an oxygen-consuming process. Nor are they effective against streptococci and Haemophilus species.

They are used, for example, for serious infections such as meningitis ( meningitis ) and heart inflammation ( endocarditis ), as well as often against lung infections ( Pseudomonas aeruginosa , see above) in the context of existing cystic fibrosis .

Aminoglycosides are not absorbed and must therefore be administered parenterally in systemic infections . They achieve a good distribution in the extracellular space and cross the placenta, but they hardly pass the cell walls of the host organism and are therefore poor in tissue penetration; if meningitis is present , they are moderately cerebrospinal . Excretion occurs mainly via the kidneys with a short half-life of around two hours .

The problem is the rapid development of resistance that can occur during aminoglycoside therapy. They are therefore usually given in combination with other antibiotics (esp. Β-lactam antibiotics ).

Because of the toxic side effects (see below), the serum levels of aminoglycosides must be monitored during antibiotic therapy, with the trough levels being important for the toxic side effects and the peak levels for antibacterial activity. Examples of guideline values ​​for aminoglycoside levels (here at 8-hour intervals):

  • Amikacin: peak level 20-30 mg / L, trough level 5-10 mg / L
  • Gentamicin, tobramycin, and netilmicin: 6-10; under 2.

Side effects

Because of their narrow therapeutic range , systemic aminoglycosides must be dosed very carefully and are therefore typical intensive care antibiotics. Aminoglycosides are particularly concentrated in the kidneys and inner ear and are highly toxic there ( nephrotoxicity , ototoxicity ). It is assumed that the ototoxicity of the aminoglycosides arises through several mechanisms. Aminoglycosides enter the cell interior via a specific transduction channel on the cilia of the hair cells in the inner ear. Due to electrical charges on the side of the channel facing the cell interior, they can no longer leave the cells in this way and accumulate. Inside the cell, the aminoglycosides can form chelate complexes with metal ions , which catalyze the formation of reactive oxygen species (ROS), which cause oxidative damage to various cell structures and ultimately cause cell death. The result is irreversible damage, which can range from mild hearing loss in the upper frequency ranges to complete deafness. Further mechanisms based on the interactions of the aminoglycosides with various ion channels and receptors have not yet been clarified in detail.

Other possible side effects are respiratory paralysis , allergies or blood formation disorders . When given once a day, the ratio of desirable to undesirable effects is particularly favorable. This is due to the fact that the aminoglycosides are concentration-dependent antibiotics, which work well when the peak levels are well above the minimum inhibitory concentration of the pathogen , but the trough levels are very low (<1μg / ml). The side effects, on the other hand, increase when high trough levels occur, as would be the case with more frequent administration. This is due to the fact that the active substance accumulates in the organs that are mainly affected, the kidneys and inner ear, and is only released back into the blood when the peripheral levels are low; if this is not the case because the trough levels are high, the active substance remains in the organs and damage them. It is therefore important to determine the trough level before giving another dose.

Apart from exceptional cases, a single dose of aminoglycosides is not permitted in children and pregnant women, endocarditis, meningitis, severe sepsis, pronounced ascites, severe burns, dialysis or haemofiltration.

Some aminoglycosides (neomycin, kanamycin) are only indicated for the treatment of local infections (skin, mucous membrane, eye) because of their nephro- and ototoxicity.

Individual evidence

  1. ^ Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , pp. 334.
  2. ↑ Entry on aminoglycoside antibiotics. In: Römpp Online . Georg Thieme Verlag, accessed on June 15, 2014.
  3. ↑ a b c Mutschler , drug effects, 9th edition, Wissenschaftliche Verlagsgesellschaft Stuttgart, 2008 ISBN 978-3-8047-1952-1
  4. ↑ Marianne Abele-Horn (2009), p. 334.
  5. ^ F. Maurer: Danger to ear and balance . Pharmaceutical newspaper, edition 22/2016.
  6. ↑ Marianne Abele-Horn (2009), p. 334.