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The basic concepts of resistance in Gram-negative bacteria

Step explaining how some common antibiotics work and the mechanisms by which resistance to them occurs.
Black tarmac with white question marks painted on it
© BSAC
In Step 2.2 you were introduced to the danger that antimicrobial resistance, especially among Gram-negative bacteria, poses for clinical treatment globally.
Since their introduction, cephalosporins, beta-lactam/beta-lactamase inhibitor combinations and carbapenems have been the standard of care for the treatment of infections due to Gram-negative bacteria.
Because of their importance, a basic understanding of the concepts frequently used to address the problem of resistant Gram-negative bacteria is necessary.
In the table below you will find a summary of these key concepts. You should familiarise yourself with these before moving on.
You will also find these terms in the Glossary.
Table adapted from those in Emerging Issues in Gram-Negative Bacterial Resistance.Table adapted from those in Emerging Issues in Gram-Negative Bacterial Resistance. (Click to take a closer look)
As we have learned, antimicrobial resistance can be acquired by different routes. Expression of beta-lactamases – enzymes capable of rendering beta-lactam antibiotics ineffective – is one of the most important mechanisms of resistance among Gram-negative bacteria.
The table below provides an overview of this classification scheme, as well as common enzymes belonging to each class, and the beta-lactam antibiotic they inactivate. It has been modified from the article “Emerging issues in Gram-Negative Bacterial Resistance”.
Ambler table: Title row - ESBL enzyme activity ESBL, Ambler class A Serine is the active residue, Plasmid is the resistant gene location and the ß-lactams are inactivated with 1st generation to 4th generation cephalosporins, aztreonam and older BLBLs; AmpC Activity is Cephalosporins, Ambler Class c, Residue Serine, Resistant gene location is Chromosomal and ß-lactams are inactivated with 1st generation to 3rd generation cephalosporins, and older BLBLs and carbapenems, KPC is Ambler class A, Serine residue, Plasmid is the resistant gene location and ß-lactams are inactivated with 1st generation to 4th generation cephalosporins, aztreonam and older BLBLs, carbapenems, NDM; activity is Carbapenemases, Ambler class B, Residue Serine, Resistant gene location is Plasmid, ß-lactams are inactivated with 1st generation to 4th generation cephalosporins, and older BLBLs, carbapenems, OXA- 48 group, Ambler class D, ß-lactams are inactivated with 1st generation to 4th generation cephalosporins, carbapenems, however, may have variable or diminished hydrolisis of 3rd generation and 4th generation cephalosporins. The Ambler classification is a scheme used to group these enzymes based on their particular molecular characteristics. (Click to take a closer look)
You may also find this video Mechanisms of Resistance in Gram-negative Bacteria to Beta-Lactam Antibiotics by Cubist Pharmaceuticals useful to watch.
© BSAC
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Challenges in Antibiotic Resistance: Gram Negative Bacteria

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