Let’s take a quick glance at the pharmacology of cephalosporins – drugs which are used in the treatment of bacterial infections. They belong to the beta-lactam class of antibacterial drugs – the same group as penicillins, monobactams, and carbapenems. Cephalosporins are classed in accordance with the generation they belong to. For example, first generation cephalosporins include cefadroxil and cephalexin, whereas second generation cephalosporins include cefaclor and cefuroxime. Cephalosporins work by inhibiting cell wall synthesis – they are bactericidal in effect. While there is a risk of cross-reactivity with penicillins, this risk decreases with later generations. Unwanted effects with cephalosporins include nausea, skin rash, diarrhoea, and injection site reactions.
Pharmacology of Cephalosporins
Cephalosporins are drugs used in the treatment of a wide variety of bacterial infections. Like penicillins, cephalosporins have a beta-lactam ring – meaning they are also members of the beta-lactam group of antibacterial drugs. Cephalosporins work by interfering with bacterial cell wall synthesis, specifically by disrupting synthesis of peptidoglycan.
Cephalosporins have a diverse spectrum of activity, depending on which class the particular cephalosporin belongs to. Later generations have more activity against Gram negative bacteria than earlier generations, often at the expense of lower Gram positive activity. Fourth generation cephalosporins have, however, good activity against both Gram forms.
Cephalosporins are ineffective against Listeria, Atypicals (such as Mycoplasma), MRSA, and enterococci – which happens to form the mnemonic LAME (the only exception being fifth generation cephalosporins – such as ceftaroline – which are effective against MRSA). The classification scheme of cephalosporins is though, of limited clinical significance.
Some general rules with cephalosporins to keep in mind include:
- First generation oral cephalosporins – such as cefadroxil or cephalexin – are active against staphylococci and most streptococci, but are not effective against enterococci.
- Second generation oral cephalosporins – such as cefuroxime – have greater activity against some Gram negative organisms, such as Haemophilus influenza and Neisseria gonorrhoea. These drugs are also capable of traversing the blood brain barrier.
- Third generation oral cephalosporins can penetrate the cerebrospinal fluid. They also have greater stability against beta-lactamases compared with previous generations. And, as stated before, third generation cephalosporins have greater activity against Gram negatives when compared with the previous two generations. Ceftazidime demonstrates good activity against Pseudomonas
- Fourth generation cephalosporins are extended spectrum drugs, with similar activity against Gram positives as first generation cephalosporins. Fourth generation drugs also have greater beta-lactamase stability than their third generation equivalents. They are also effective in treating Pseudomonas aeruginosa
- Fifth generation cephalosporins – such as ceftaroline – are effective against MRSA. Other drugs in this class, like ceftolozane, can be used in the treatment of complicated urinary tract infections – a drug which is combined with the beta-lactamase inhibitor, tazobactam.
Again, there are no fixed rules regarding these classes – as exceptions do exist in some circumstances. Nonetheless, these general rules serve as a convenient starting point upon which your knowledge of the pharmacology of cephalosporins can be built. With this in mind, we can now turn our attention to the pharmacokinetics and unwanted effects of cephalosporins.
Just one quick note on bacterial resistance: earlier generations are more susceptible to beta-lactamases than later generations (however, resistance to third generations can occur via the extended-spectrum beta lactamase conferred by E. coli). In terms of pharmacokinetics, their ADME depends upon - you've guessed it - which class they belong to.
First generation cephalosporins are typically well absorbed from the gut. In contrast, some second generation cephalosporins – such as cefuroxime – are vulnerable to acidic environments - and so must be administered parenterally (though a prodrug version of this cephalosporin also exists for oral administration).
The vast majority of cephalosporins are eliminated via the kidney and most have relatively short half-lives (around or under the 3 hour mark). Some though, such as ceftriaxone, have longer half-lives (around the 8 hour mark) due to extensive protein binding. Cefixime, a third generation cephalosporin, is primarily eliminated via the biliary route.
Cephalosporins are generally well tolerated drugs. Though as with most drugs, cephalosporins come with their own range of potential unwanted effects. Common (<1%) unwanted effects include nausea, abdominal discomfort, skin rashes, and injection site reactions. Some patients also experience headache and diarrhoea.
It’s commonly reported that cephalosporins show cross-reactivity with penicillins at a rate of 10 percent. Research shows that the likely rate of cross-reactivity is significantly lower, with the risk of reactivity declining with succeeding generations. Nonetheless, cross-reactivity does remain a risk and should be considered. Fianlly, unlikely - but possible - alternative unwanted effects include dizziness, vomiting, fever, thrombocytopenia, neutropenia, and kidney dysfunction.
For more information about the generations of cephalosporins, please check the links below.
- First-Generation Cephalosporins
- Second-Generation Cephalosporins
- Third-Generation Cephalosporins
- Fourth-Generation Cephalosporins
- Fifth-Generation Cephalosporins
That's about it for this revision guide. Before you finish, check out our quiz on the pharmacology of cephalosporins to test your knowledge of just about everything covered in this article.