Next generation cephalosporins

Other names: fifth generation cephalosporins, next-generation cephalosporins

What are Next generation 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.

After the first cephalosporin was discovered in 1945, scientists improved the structure of cephalosporins to make them more effective against a wider range of bacteria. Each time the structure changed, a new “generation” of cephalosporins were made. There are five generations of cephalosporins. Next generation cephalosporins were the fifth generation of cephalosporins to be developed.

The other analgesics, such as acetaminophen or ibuprofen, typically found in narcotic analgesic combinations mainly work by inhibiting enzymes called cyclo-oxygenase (COX) enzymes that produce prostaglandins. Prostaglandins promote inflammation, pain and fever.

Cefiderocol is the latest novel 5th–6th generation cephalosporin to be approved by the FDA in November 2019 for the treatment of complicated urinary tract infections (UTIs) and pyelonephritis, and in September 2020 it was approved for hospital-acquired and ventilator-associated bacterial pneumonia (HAP/VAP).

Next generation antimicrobials (NGAs) are compounds that target bacterial virulence factors to disrupt pathogenic potential without impacting bacterial viability.

What are next generation cephalosporins used for?

Next generation cephalosporins have activity against multi-resistant Staphylococcus aureus (MRSA), gram-positive bacteria and some gram-negative bacteria. Ceftaroline is the only next-generation cephalosporin available in the United States. In adults and children aged two years and older it is approved to treat:

Pneumonia that is acquired in the community (not in hospital)
Skin and skin structure infections.

What are the differences between next 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.

Generic name	Brand name examples
ceftaroline	Teflaro

Are next generation cephalosporins safe?

Next generation cephalosporins are generally safe, with low toxicity and good efficacy against susceptible bacteria.

Allergic reactions have been reported with all cephalosporins including ceftaroline 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.

A positive Coombs test (a test that checks your blood for antibodies that attack red blood cells) has been reported in up to 18% of children and 11% of adults taking ceftaroline. This may be associated with red blood cell hemolysis and drug-induced hemolytic anemia should be suspected if anemia develops during or after treatment.

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.

Rarely, seizures have been reported with ceftaroline; the risk may be greatest in those with kidney disease.

Recent advances in genomics have transformed drug discovery and clinical research towards precision medicine. This has created the opportunity to target the genetic drivers of rare and chronic disease to alter the course of disease and enable long-lasting treatment.

Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics, particularly in Russia and Georgia.

What are the side effects of next generation cephalosporins?

Ceftaroline generally causes few side effects. The most common side effects reported include:

Abdominal pain
Constipation
Diarrhea
Dyspepsia
A headache
Insomnia
Itchy skin
Gastritis
Nausea
Rash
Vomiting.

Transient increases in liver enzymes have also been reported

Cefiderocol is a novel injectable siderophore cephalosporin that hijacks the bacterial iron transport machinery to facilitate cell entry and achieve high periplasmic concentrations.

There are two fourth-generation cephalosporins that are currently widely available: cefpirome and cefepime 20.

The new oral cephalosporins can be divided into those absorbed as the parent compound (cefdinir, ceftibuten, cefixime and cefprozil) and those absorbed in the form of ester prodrugs (cefuroxime axetil, cefpodoxime proxetil and cefetamet pivoxil).

Ceftaroline was developed by modifying the structure of the fourth-generation cephalosporin cefozopran. The prodrug, ceftaroline fosamil, which contains a phosphono group to increase water solubility, is rapidly converted in plasma into the bioactive agent, ceftaroline

The following list includes eight of the most common classes of antibiotics, what they are generally used for and some of the potential side effects.