Ceph /fad ⇒ Uro’s/Aclor ⇒ Cef’s ⇒ Cefepime ⇒ ceftaroline & ceftobiprole
I. FIRST GENERATION CEPHALOSPORINS
They are active against aerobic gram-positive cocci and some aerobic gram-negative bacilli. - They do not cross the meninges and are therefore not used in treatment of meningitis.
They are B-lactamase sensitive
Examples of this class include:
For parenteral administration: Cephalothin , and Cephradine. For oral administration: Cephalexin, Cephradine and Cefadroxil .
II. SECOND GENERATION CEPHALOSPORINS
They have extended spectrum including few anaerobes and gram-negative bacilli especially Proteus, Enterobacter and H. influenza.
They are relatively resistant to B-lactamases. - Doesn’t cross meninges.
For parenteral administration: Cefuroxime For oral administration: Cefuroxime and cefaclor
III. Third GENERATION CEPHALOSPORINS
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They cover gram negative organisms including Pseudomonas and anaerobic microorganisms with diminished gram positive activity. These are broad-spectrum agents that have many different uses.
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Highly resistant to B-lactamase & high cross to meninges
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Penetrate blood brain barrier and attain high concentrations in CSF, therefore they are used in gram-negative bacterial meningitis except cefoperazone.
For parenteral administration: ceftriaxone, cefotaxime, ceftazidime, Cefoperazone, cefixime*
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Cefoperazone (third generation) are primarily excreted in bile and its serum level is not greatly influenced by renal failure.
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Ceftriaxone has the characteristic of having dual modes of elimination via both renal and biliary excretion. It does not need to be adjusted for renal dysfunction, but it does effectively treat UTIs. can be used with typhoid Typhoids Medications))
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Cefotaxime dose adjustment needed in renal insufficiency as its excreted by kidney
Ceftriaxone has two problems that make its use in neonates problematic:
- It interacts with calcium-containing medications to form crystals that can precipitate in the lungs and kidneys, which has led to fatalities,
- and it can lead to biliary sludging with resultant hyperbilirubinemia. Avoid ceftriaxone for neonates—cefotaxime is a safer drug for these young patients.
IV. FOURTH GENERATION CEPHALOSPORINS
- Like 3rd generation but more resistant to B lactamases
- Highly active against Haemophilus, Pseudomonas, and anaerobes.
- There is only one fourth-generation cephalosporin: cefepime.
- Cefepime is the broadest spectrum cephalosporin, with activity against both gram-negative organisms, including Pseudomonas, and gram-positive organisms. One way to remember its spectrum is to think that cefalothin (1st) + ceftazidime (3rd) = cefepime (4th).
Adverse Effects
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Generally, similar to those of other beta-lactams, but cefepime may be associated with more neurotoxicity (non convulsive status epilepticus).than most other beta-lactams.
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A person allergic to penicillin, about 10% chance of being allergic
V. FIFTH GENERATION CEPHALOSPORINS :
Ceftaroline & ceftobiprole - ANTI-MERSA
Agent: ceftaroline
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It is sometimes called a “fifth generation cephalosporin,” or “anti-MRSA cephalosporin,”
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What makes this agent unique is activity against MRSA. Its structure has been engineered to bind to the penicillin-binding protein 2a of MRSA, Unlike other beta-lactams, ceftaroline can bind to penicillin-binding protein 2a, a type that is expressed by MRSA. This characteristic is responsible for its anti-MRSA activity. which has low affinity for other beta-lactams. It is often used as an alternative to vancomycin or daptomycin for MRSA infections.
Adverse Effects Similar to those of other beta-lactams, with possibly a higher incidence of neutropenia seen with prolonged administration.
6th SIDEROPHORE CEPHALOSPORIN
Cefiderocol is a unique drug. It has the basic structure of a cephalosporin and works to prevent peptidoglycan cross-linking, as other beta-lactams do. But it has a side chain that complexes with iron and is recognized by bacteria as a siderophore, which bacteria actively uptake.
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Bacteria need iron to grow. Siderophores are substances that many bacteria secrete into their environment to complex with free iron, then actively transport across their cell walls to the interior of the cell. When cefiderocol complexes with iron, bacteria recognize it as a siderophore and actively transport the complex into the cell, where it can work to prevent cell wall synthesis.
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Cefiderocol’s siderophore side chain allows for active uptake into bacteria, avoiding some mechanisms of resistance, such as porin changes.
- Cefiderocol is an expensive antibiotic that has utility against many of the most resistant gram-negative organisms in practice, including those resistant to Carbapenems.
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Cefiderocol used for treatment of complicated UTIs and hospital acquired pneumonia. However, it is used off-label for the treatment of many types of infections caused by resistant gram-negative infections.
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Cefiderocol should be used only in patients with resistance to other antibiotics.
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Of course, cefiderocol resistance occurs. Those bacteria never quit, so susceptibility testing still needs to be performed.