Cephalosporin Coverage: The Arrow Trick
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Cephalosporin Antibiotics
In the previous lecture, you were shown a simple memory trick to remember the different cephalosporin generations.
You were also provided a way to remember which generation each cephalosporin medication belongs to.
This lecture will now focus on cephalosporin coverage against bacteria.
Each cephalosporin drug class has different coverage against bacteria, including gram-positive organisms, gram-negative organisms, pseudomonas, and MRSA.
As with every EZmed lecture, you will learn a simple memory trick to remember the material.
And for this lecture, you can use the arrow trick below to memorize the bacterial coverage for each cephalosporin generation!
We will also review the mechanism of action (MOA) for cephalosporins.
So let’s get right into it!
Cephalosporin Mechanism of Action
Let’s quickly recap the mechanism of action of cephalosporins.
Cephalosporins work by disrupting bacterial cell wall synthesis.
Similar to penicillin, cephalosporins are beta-lactam antibiotics.
This means cephalosporins contain a beta-lactam ring in their molecular structure.
The beta-lactam ring binds to penicillin-binding proteins, which would normally cross-link and strengthen bacterial cell walls.
This disrupts bacterial cell wall synthesis and results in bacterial death (bactericidal).
Cephalosporins are categorized into 5 different generations based on their spectrum of coverage against gram-positive and gram-negative organisms.
Let’s look at a trick to remember what types of bacteria each generation covers!
Cephalosporin Coverage
The trick to remember cephalosporin coverage is to first draw 3 arrows as depicted below.
Then label the arrows 1st-5th generation as shown.
The first arrow will cover generations 1-3, the second arrow will cover the 4th generation, and the final arrow will cover the 5th generation.
Next, label the first arrow gram-positive on the left and gram-negative on the right.
Label the second arrow pseudomonas.
Finally, label the third arrow MRSA.
Arrow 1: First-Third Generations
The first arrow covers generations 1-3.
The arrow starts off with gram-positive and ends with gram-negative.
This is to help you remember that generally speaking the first generation cephalosporins have strong gram-positive coverage and minimal gram-negative coverage.
Then as you progress down the arrow, the gram-positive coverage weakens but gram-negative coverage improves significantly.
Let’s break down each generation below.
1st Generation
First generation cephalosporins have coverage against most gram-positive cocci including staphylococcus and streptococcus species.
For this reason, they are commonly used for uncomplicated skin and soft tissue infections presumed to be caused by staphylococcal (methicillin-sensitive) and streptococcal species.
They have less coverage against gram-negative bacteria, but do cover Escherichia coli (E. coli), Proteus mirabilis, and Klebsiella pneumoniae.
Examples of first generation cephalosporins include cephalexin, cefazolin, cephalothin, cephapirin, cefadroxil, and cephradine.
Other common uses for fist generation medications include urinary tract infections, respiratory infections, otitis media, orthopedic injuries, and surgical prophylaxis.
First generation medications are labeled at the beginning of the arrow to help you remember strong gram-positive coverage and minimal gram-negative coverage.
2nd Generation
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.
As a result, second generation cephalosporins are further down the arrow (to indicate less gram-positive coverage and increased gram-negative coverage).
Gram-negative coverage includes Haemophilus influenzae (H. influenzae), Moraxella catarrhalis, Bacteroides species, Enterobacter aerogenes, Neisseria species, and Serratia marcescens.
Indications and uses for the second generation are very similar to that of the first generation.
Examples of second generation cephalosporins include cefprozil, cefmetazole, cefotetan, cefoxitin, cefuroxime and cefaclor.
Second generation medications are labeled in the middle of the arrow to help you remember less gram-positive and more gram-negative coverage compared to first generation.
3rd Generation
Third generation cephalosporins have less gram positive coverage compared to the previous two generations.
However, the gram negative coverage continues to improve which is why it is further down the arrow.
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.
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.
Third generation medications are labeled at the end of the arrow to help you remember poor gram-positive coverage and strong gram-negative coverage.
Arrow 2: Fourth Generation
Fourth generation cephalosporins have a similar gram-positive and gram-negative profile as third generation cephalosporins.
The main difference, however, is fourth generation cephalosporins generally cover pseudomonas as well.
That is why the second arrow is labeled “pseudomonas” to help you remember fourth generation drugs have coverage against this.
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.
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.
Fourth generation medications are labeled pseudomonas to help you remember coverage against this. The gram-positive and gram-negative coverage is fairly strong.
Arrow 3: Fifth Generation
Fifth generation cephalosporins continue to have similar gram-positive and gram-negative coverage as the fourth generation.
The main difference, however, is fifth generation cephalosporins also have coverage against MRSA (methicillin-resistant Staphylococcus aureus), which is why the final arrow is labeled to reflect this.
Examples of fifth generation cephalosporins include ceftaroline and ceftobiprole.
It is important to note that although ceftaroline is a broad-spectrum antibiotic including MRSA coverage, it does not cover against pseudomonas like ceftazidime or cefepime do.
Fifth generation medications are labeled MRSA to help you remember coverage against this. The gram-positive and gram-negative coverage is fairly strong.
Summary
Hopefully the arrow trick gave you an easy way to remember cephalosporin coverage for the different generations.
Use the following to help you remember the general coverage:
1st Generation: Good Gram-Positive; Poor Gram-Negative
2nd Generation: OK Gram-Positive; OK Gram-Negative
3rd Generation: Poor Gram-Positive; Good Gram-Negative
4th Generation: Pseudomonas + Good gram-positive and negative
5th Generation: MRSA + Good gram-positive and negative
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https://www.ncbi.nlm.nih.gov/books/NBK551517/