Cephalosporins
The mechanism of action for cephalosporins involves disruption of bacterial cell wall synthesis.
Similar to penicillin, cephalosporins are beta-lactam antibiotics as they contain a beta-lactam ring in their molecular structure.
The beta-lactam ring binds to penicillin-binding proteins that would normally cross-link and strengthen bacterial cell walls, resulting in inhibition of cell wall synthesis and bacterial death.
Cephalosporins are grouped into 5 different generations based on their spectrum of coverage against gram-positive and gram-negative organisms.
First Generation = “FA/PHA”
First generation cephalosporins have coverage against most gram-positive cocci including staphylococcus and streptococcus species.
Although they have minimal coverage against gram-negative bacteria, they do cover Escherichia coli (E. coli), Proteus mirabilis, and Klebsiella pneumoniae.
Examples of first generation cephalosporins include cephalexin, cefazolin, cephalothin, cephapirin, cefadroxil, and cephradine.
First generation medications are commonly used for uncomplicated skin and soft tissue infections presumed to be caused by staphylococcal (methicillin-sensitive) and streptococcal species.
Other common uses include urinary tract infections, respiratory infections, otitis media, orthopedic injuries, and surgical prophylaxis.
The trick to remember first generation cephalosporins is “FA/PHA” as these medications contain “FA/PHA” in them.
Third Generation = “ONE/TEN/IME”
Third generation cephalosporins have less coverage against most gram-positive bacteria.
However, they have more extended coverage for gram-negative organisms compared to the first and second generation, having increased coverage for Enterobacteriaceae species, Neisseria species, and H. influenzae.
Examples of third generation cephalosporins include ceftriaxone, ceftibuten, cefixime, cefotaxime, ceftazidime, cefpodoxime, and cefdinir (an exception to the rule discussed later).
It is important to note that ceftriaxone is commonly used for meningitis as it can penetrate the blood-brain barrier and destroy bacteria in the cerebrospinal fluid.
Ceftriaxone is also commonly used to treat gonorrhea.
It is also important to note that ceftazidime has coverage for Pseudomas aeruginosa.
The trick to remember third generation cephalosporins is “ONE/TEN/IME” as they all end with one of those suffixes.
Fourth Generation = “PI”
Fourth generation cephalosporins have a similar profile as third generation cephalosporins.
The main difference is that they have additional coverage for beta-lactamase producing gram-negative bacteria.
Examples of fourth generation cephalosporins include cefepime and cefpirome.
These are broad-spectrum antibiotics, covering both gram-positive and gram-negative organisms, typically used in sepsis and serious infections.
Similar to ceftriaxone (third generation), cefepime can penetrate the blood-brain barrier and into cerebrospinal fluid.
Similar to ceftazidime (third generation), cefepime also has coverage for Pseudomas.
Some bacteria are resistant to beta-lactam antibiotics as they produce beta-lactamase, an enzyme that destroys the antibiotic beta-lactam structure.
Fourth generation cephalosporins can cover against beta-lactamase gram-negative organisms better than third generation medications can.
The trick to remember fourth generation cephalosporins is “PI” as they contain “PI” in their name.
Fifth Generation = “ROL”
Similar to fourth generation cephalosporins, fifth generation drugs are broad-spectrum antibiotics covering gram-positive and gram-negative organisms.
The main difference is fifth generation cephalosporins also have coverage against MRSA (methicillin-resistant Staphylococcus aureus).
Examples of fifth generation cephalosporins include ceftaroline and ceftobiprole.
It is important to note that although ceftaroline is a broad-spectrum antibiotic, plus covers MRSA, it does not cover for pseudomonas like ceftazidime or cefepime do.
The trick to remember fifth generation cephalosporins is “ROL” as they contain “ROL” in their name.
Second Generation = “Everything Else”
Now let’s go back to the second generation.
This generation was skipped because it contains “everything else” that does not fit any of the other patterns above.
Second generation cephalosporins have slightly less gram-positive coverage compared to first generation medications.
They do however, have increased gram-negative coverage compared to the first generation, including coverage against Haemophilus influenzae (H. influenzae), Moraxella catarrhalis, Bacteroides species, Enterobacter aerogenes, Neisseria species, and Serratia marcescens.
Examples of second generation cephalosporins include cefprozil, cefmetazole, cefotetan, cefoxitin, cefuroxime and cefaclor.
Cefuroxime and cefaclor are both exceptions to the “everything else” rule which you will see in the next section.
Indications and uses for the second generation are very similar to that of the first generation.
The trick to remember second generation cephalosporins is “Everything Else” as these medications do not fit any patterns or criteria used in the other generations.
Exceptions to the Rule
Like many rules, there are a few exceptions.
Although cefaclor contains “FA” within the word, it is a second generation medication and not a first.
Although cefuroxime ends in “IME”, it is a second generation rather than a third.
Lastly, cefdinir and moxalactam are third generation medications despite not having the “ONE/TEN/IME” ending.
Conclusion
Hopefully this gave you an easy way to remember the different cephalosporin generations.
Remember the following:
First generation = “FA/PHA”
Second generation = “Everything Else”
Third generation = “ONE/TEN/IME”
Fourth generation = “PI”
Fifth generation = “ROL”
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