β-lactam antibiotics

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Basic structure of penicillins (above) and cephalosporins (below). The β-lactam ring is marked in red .

The β-lactam antibiotics , also azetidin-2-ones , are a group of antibiotics / antibacterial anti-infectives , all of which have a four-membered lactam ring in their structural formula . They go back to the penicillin that the Scottish bacteriologist Alexander Fleming extracted in 1928 from cultures of the mold Penicillium notatum , which is also the most important and best-known representative of this group. They all have a bactericidal effect by inhibiting peptidoglycan synthesis during cell division . Differences in effectiveness are mainly due to different affinity and penetration ability. Nowadays, β-lactam antibiotics are mainly produced semi-synthetically.


Azetidin-2-one group of substances
Azetidin-2-ones
Azetidin-2-one
(β-lactam)
Azetidin-2-one
Azetidin-2-one

At the same time, the azetidin-2-ones form a group of substances in organic chemistry .

history

Around 1940, Howard Walter Florey and Ernst Boris Chain developed drugs based on penicillin, which were used therapeutically for the first time a year later. For this, Fleming received the Nobel Prize for Medicine in 1945, together with the two other scientists . At that time, penicillin preparations were often used incorrectly, especially against pathogens that are naturally resistant to β-lactam antibiotics. Several times, originally sensitive pathogens developed antibiotic resistances to the β-lactam preparations used. In the course of time, various “generations” of β-lactam preparations have therefore already been developed, as the preparations previously used no longer showed a reliable effect.

biosynthesis

Beta-lactam closure routes.png

effectiveness

All β-lactam antibiotics are ineffective against mycoplasma , chlamydia and legionella . In addition, there are also acquired resistances in some other bacteria that are based on a β-lactamase . At high concentrations of bacteria, β-lactam antibiotics lead to a decrease in their effect , which is known as the Eagle effect .

Side effects

β-lactam antibiotics are generally well tolerated by humans, which is due to the mechanism of action. They intervene in the cell wall synthesis of dividing bacteria - this metabolic process does not occur in humans. However, there are now many allergies to penicillin and related substances, which can range from mild skin reactions to anaphylactic shock in all degrees of severity. Also must be cross reactions are expected between the β-lactam antibiotics.

Classification

Today a distinction is made between the following four groups of β-lactam antibiotics: penicillins , cephalosporins , β-lactamase inhibitors and other β-lactam antibiotics.

Penicillins

Cephalosporins

β-lactamase inhibitors

Others

Resistance and Mechanisms

During the use of β-lactam preparations, resistance to the respective preparations develops only rarely and slowly . Overall, however, resistance to β-lactam preparations has now become a serious problem. A distinction must be made between three resistance mechanisms:

  • insensitive penicillin binding proteins
  • Membrane changes
  • Formation of β-lactamases
β-lactamases are enzymes produced by bacteria that open the β-lactam ring in the preparations. The β-lactam preparations are thus ineffective. The genetic information for the formation of β-lactamases is inherited chromosomally or plasmid . Depending on the group of β-lactam preparations rendered ineffective, the β-lactamases are referred to as penicillinases , cephalosporinases or carbapenemases .

In order to obtain penicillins stable to β-lactamase, bulky groups are introduced into the penicillin molecule. These newly introduced parts of the penicillin molecule hinder the opening of the β-lactam ring due to the changed spatial structure of the entire molecule ( sterically ). The use of β-lactamase inhibitors such as clavulanic acid , sulbactam or tazobactam is also possible .

β-Lactam antibiotics not only block the division of bacteria, including cyanobacteria , but also the division of cyanelles, the photosynthetically active organelles of glaucocystaceae and the chloroplasts of bladder moss , liverwort ( Marchantia polymorpha ) and moss fern ( Selaginella nipponica .). However , they have no effect on the division of the plastids in more highly developed vascular plants such as tomatoes . This is an indication that in higher plants due to evolutionary changes in the plastid division, β-lactam antibiotics no longer have any effect on chloroplasts.

literature

  • Claus Simon, Wolfgang Stille: Antibiotic therapy in clinics and practices . 10th edition. Schattauer, Stuttgart 2001, ISBN 3-7945-1970-1 .
  • Peter Imming: How does the fungus make penicillin? Current research, trends in β-lactam antibiotics. Biosynthesis of penicillins and cephalosporins. Pharmazie in our time 18 (1), pp. 20-24 (1989).

Individual evidence

  1. ↑ a b Kasten, Britta and Reski, Ralf (1997): β-lactam antibiotics inhibit chloroplast division in a moss (Physcomitrella patens) but not in tomato (Lycopersicon esculentum) . In: J. Plant Physiol. 150 , 137-140; PDF ( Memento of the original dated February 4, 2012 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (free full text access). @1@ 2Template: Webachiv / IABot / www.plant-biotech.net
  2. ↑ Tounou, E. et al . (2002): Ampicillin Inhibits Chloroplast Division in Cultured Cells of the Liverwort Marchantia polymorpha . In: Cytologia 67 ; 429-434; doi : 10.1508 / cytologia.67.429 .
  3. ↑ Izumi, Y. et al . (2003): Inhibition of plastid division by ampicillin in the pteridophyte Selaginella nipponica Fr. et Sav. In: Plant Cell Physiol . 44 (2): 183-189; PMID 12610221 ; PDF (free full text access)