Talk:Cephalosporin
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Anybody got any idea how this antibiotic (Cephalosporin) is related to immunosuppressant?
- No, but there is a immunosuppressant called cyclosporin. Daevatgl 09:56, 25 September 2005 (UTC)
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[edit] Help needed
The classes of Cephalosporins are complicated.
- Structure Activity Relationships "Antibacterial Agents; Structure Activity Relationships," André Bryskier MD; beginning at pp83
This article does a superb job of elucidating the structural activity relationships. It utilizes a different grouping than the traditional generations, that should also be reflected in the article, though the generations should be retained. Farseer 07:46, 24 December 2005 (UTC)farseer
The first generation Cephalosporins are clearly derivitives of the natural antibiotic, based on the core shown. Second generation members seem to have come about from modification of the first to increase the activity against gram negative bacteria and anaerobes.
[edit] Cephamycins (cephems)
In searching for these, the cephamycins turned up, which replace a hydrogen on the four membered ring with a methoxy group. All or nearly all are anti-anaerobes.
[edit] Third generation
As newer compounds were prepared, the spectrum was improved significantly and a new generation was recognized - the third. Most of the these have a five membered ring.
3rd generation core structure 8-[2-(2-amino-1,3-thiazol-4-yl)acetyl]amino- in the eight position off the main cephalosporin stucture (the group to the right of the four member cephalosporin core ring).
But not all do. This aminothiazolyl moeity is a hallmark of third generation cephs. And either it or the aminothiadiazolyl variant seem to be hallmarks of the fourth generation.
[edit] Fourth generation
Fourth generation members also often have this same moeity, and generally add a positively charged aromatic with a charged nitrogen seeming to be the hallmark.
For example: cefipime and cefpirome have the two major charged moeities that seem to be the hallmark of fourth generation cephalosporins:
cefepime
cefpirome
Not all sources agree on which generation each member belongs to. Some members assigned as first generation have the charged moeity that is a hallmark of fourth generation, while lacking the five member ring. Some fourth generation cephalosporins also lack the five member ring.
Cefalonium and cephaloridine (classed as 1st generation), ceftazidime (classed as 3rd generation) and the as yet unclassified cefempidone have a similar structure that appears to be more appropriately classified as fourth generation. Cefalonium and cephaloridine lack the aminothiadiazolyl or aminothiazolyl moeity that are hallmarks of most third and fourth generation cephalosporins and that provide their antipseudomonal character.
Can anyone point to a definitive source for classifying the cephalosporins by generation? In other words, who defined what constitutes each generation.
[edit] "New generation"
Ceftobiprole and ceftobiprole medocaril are strong anti-MRSA antipseudomonal antibiotics currently in phase III trials. They are asserted to be a "new generation" of anti-MRSA cephalosporins. Ceftobiparole contains the aminothiadiazolyl moiety and lacks the charged moeity typical of 4th generation. So, should it be classed as 3rd generation, or 4th?
ceftobiprole
ceftobiprole medocaril
[edit] Oxacephems
To add the confusion, the new oxacephems (rarely called oxycephems) substitute an oxygen for the sulfur in the main six member ring. They so far also include the methoxy group that demarks a cephamycin. However, it seems likely that will change and an oxacephalosporin will be produced.
flomoxef
[edit] Sulfoxy/sulfoxa/sulfoxyl cephalosporins
Two new members substitute a sulfoxy group for the sulfur in the six memebr main ring. They seem to provisionally be fourth generation members. But lacking a spcecific definition, that remains unclear.
cefmepidium chloride
[edit] Other categorization schemes
There is also a second major categorization scheme that refers to the cephalosporins and cephems by group (Groups 1 to 7). The groupings overlay the generations and also separate the parenteral members from the oral members. I have found a good reference for this, however, for many members, classification is still not obvious.
[edit] Other issues
It may be that classification into generations depends on the spectrum that each member displays. Given the large variation in member properties, there is an equally large diversity in the antibiotic spectrum.
Then lastly, the antipseudomonal designation seems to change rapidly as resistance develops in use. Individual members that were considered antipseudomonal a few years ago, are no longer of much use in that regard and in many sources are no longer considered to by antipseudomonal.
So how should these be designated and grouped?
Farseer 21:20, 19 December 2005 (UTC)farseer
[edit] Cross-reactivity
In light of the article in the Journal of Family Practice[1] I put a note advising that the cross-reactivity may not be as high as the widely quoted 10% - the article, looking at ~3400 penicillin allergic patients compares the reaction rate with those of non-penicillin allergic patients (N=35,450) and shows similar rates for many of the 2nd generation and all 3rd generation cephalosporins reported on. My background however is neuroscience, not pharmacology, so others may wish to examine the article, which goes on to suggest use of a table of side-chain similarities to predict cross-reactivity.
