{"id":1,"date":"2023-05-09T11:57:52","date_gmt":"2023-05-09T10:57:52","guid":{"rendered":"http:\/\/microregistrar.com\/?p=1"},"modified":"2023-05-11T18:43:56","modified_gmt":"2023-05-11T17:43:56","slug":"hello-world","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=1","title":{"rendered":"Cefiderocol"},"content":{"rendered":"\n

Class and Chemical Structure<\/h2>\n\n\n\n

 It is a Siderophore cephalosporin<\/strong>, a synthetic conjugate of a cephalosporin moiety and a siderophore moiety. Siderophore moiety binds to the iron and helps the antibiotic to gain entry into bacterial cells using active iron transporters (e.g. CirA and Fiu in E coli, PiuA in P. aeruginosa)<\/em>\u2013 a \u201cTrojan horse\u201d like approach.<\/p>\n\n\n\n

\"Active<\/figure>\n\n\n\n

 <\/p>\n\n\n\n

The chemical structure is similar to both ceftazidime and cefepime.<\/p>\n\n\n\n

 It has high stability against beta-lactamase, including ESBL, ampC and carbapenemases. Modifications of C-7 (a carboxypropanoxyimino group, like ceftazidime) and C-3 ( pyrrolidinium group, like cefepime) side chains lead to the stability against \u03b2-lactamases, including carbapenemases.<\/p>\n\n\n\n

Mechanism of action of cefiderocol<\/h2>\n\n\n\n

Cefiderocol\u2019s mechanism of action is similar to other beta-lactams \u2013 It binds to the Penicillin-binding proteins (PBP)  to prevent cell wall formation. It has a high affinity for PBP3.<\/p>\n\n\n\n

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The main component of the bacterial cell wall is peptidoglycan, which helps bacteria retain stability against osmotic pressure and maintain shape and morphology. Peptidoglycan comprises two amino sugars: N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). A pentapeptide structure is attached to NAM (see picture: L-ala to D-ala), with two terminal D-ala<\/p>\n<\/div>\n<\/div>\n\n\n\n

PBP, an enzyme, helps to establish a cross-link between L-lys and the 4th D-ala. This cross-link provides structural strength to the cell wall. Bata-lactams, with a similar alanyl-alanine structure, binds to the PBP and prevent the cross-linking and hence, cell wall formation.<\/p>\n\n\n\n

Mechanism of resistance of cefiderocol<\/h2>\n\n\n\n

Some mutations, especially in iron transporters, are associated with an increase in minimum inhibitory concentration (MIC). Some beta-lactamase enzymes may also have a similar effect.<\/p>\n\n\n\n