Cephalosporins

Cephalosporins are a large group of antibiotics derived from the mold Acremonium (previously called Cephalosporium). Cephalosporins are bactericidal (kill bacteria) and work in a similar way to penicillins. They bind to and block the activity of enzymes responsible for making peptidoglycan, an important component of the bacterial cell wall. They are called broad-spectrum antibiotics because they are effective against a wide range of bacteria.

Since the first cephalosporin was discovered in 1945, scientists have been improving the structure of cephalosporins to make them more effective against a wider range of bacteria. Each time the structure changes, a new "generation" of cephalosporins are made. So far there are five generations of cephalosporins. All cephalosporins start with cef, ceph, or kef. Note that this classification system is not used consistently from country to country.

What are cephalosporins used for?

Cephalosporins may be used to treat infections caused by susceptible bacteria, such as:

• Bone infections
• Ear infections (eg, otitis media)
• Skin infections
• Upper respiratory tract infections
• Urinary tract infections.

Cephalosporins are not usually used as a first-choice antibiotic. They tend to be reserved for use when other antibiotics (often penicillins) cannot be used.

What are the differences between cephalosporins?

There are currently five “generations” of cephalosporins, with each generation differing slightly in their antibacterial spectrum (ie, how effective they are at killing certain types of bacteria). Within each generation, there are differences in terms of administration (such as oral or intravenous administration), absorption, excretion, and how long the activity of the cephalosporin lasts for in the body.

First generation cephalosporins

First generation cephalosporins refer to the first group of cephalosporins discovered. Their optimum activity is against gram-positive bacteria such as staphylococci and streptococci. They have little activity against gram-negative bacteria.

Cephalexin and cefadroxil can be given by mouth, whereas cefazolin can only be given by injection (IV/IM). There are also differences with regards to how frequently the different first-generation cephalosporins need to be dosed.

Second generation cephalosporins

Second-generation cephalosporins are more active against gram-negative bacteria, with less activity against gram-positive bacteria.

Third generation cephalosporins

Third generation cephalosporins followed the second-generation cephalosporins. No one third-generation cephalosporin treats all infectious disease scenarios.

Cefotaxime and ceftizoxime (discontinued) offer the best gram-positive coverage out of all the third-generation agents; ceftazidime and cefoperazone (discontinued) are unique in that they provide antipseudomonal coverage.

Ceftriaxone has a long half-life which allows for once daily dosing and may be used for the treatment of gonorrhea, pelvic inflammatory disease, and epididymo-orchitis. It is also an alternative to penicillins for suspected meningitis.

All the third-generation cephalosporins except for cefoperazone (discontinued) penetrate cerebrospinal fluid.

Fourth generation cephalosporins

Fourth generation cephalosporins are structurally related to third-generation cephalosporins but possess an extra ammonium group, which allows them to rapidly penetrate through the outer membrane of gram-negative bacteria, enhancing their activity. They are also active against β-lactamase producing Enterobacteriaceae which may inactivate third-generation cephalosporins.

Some fourth-generation cephalosporins have excellent activity against gram-positive bacteria such as methicillin-susceptible staphylococci, penicillin-resistant pneumococci, and viridans group streptococci.

Cefepime is the only fourth generation cephalosporin available in the United States. Cefpirome is available overseas.

Next (fifth) generation cephalosporins

Ceftaroline is currently the only next-generation cephalosporin available in the United States. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and gram-positive bacteria. It also retains the activity of the later-generation cephalosporins and is effective against susceptible gram-negative bacteria.

Are cephalosporins safe?

Cephalosporins are generally safe, with low toxicity and good efficacy against susceptible bacteria.

Allergic reactions have been reported with cephalosporins and symptoms may include a rash, hives (urticaria), swelling, or rarely, anaphylaxis. Up to 10% of people with a history of penicillin allergy will also be allergic to cephalosporins.

Rarely, seizures have been reported with some cephalosporins; the risk is greatest in those with kidney disease.

Cephalosporins have also been associated with a reduced ability of the blood to clot leading to prolonged bleeding times. People with kidney or liver disease, nutritionally deprived, taking cephalosporins long-term, or concurrently receiving anticoagulant therapy are more at risk.

For a complete list of severe side effects, please refer to the individual drug monographs.

What are the side effects of cephalosporins?

Cephalosporins generally cause few side effects. The most common side effects reported include abdominal pain, diarrhea, dyspepsia, headache, gastritis, and nausea and vomiting. Transient liver problems have also been reported.

Rarely, some people may develop a super-infection due to overgrowth of a naturally occurring bacterium called Clostridium difficile, following use of any antibiotic, including cephalosporins. Symptoms may include severe diarrhea.

Uncommonly, an overgrowth of the yeast, Candida albicans, may occur following cephalosporin use, resulting in the symptoms of thrush.

For a complete list of side effects, please refer to the individual drug monographs.