Cephalosporin antibiotics

Cephalosporin antibiotics are a class of beta-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium. These antibiotics are widely used to treat a variety of bacterial infections, particularly those caused by bacteria that are resistant to other antibiotics. Cephalosporins work by disrupting the synthesis of the bacterial cell wall, leading to cell death. They are broadly categorized into generations, each with a different spectrum of bacterial activity.

Generations of Cephalosporins

Cephalosporins are divided into five generations, each with varying effectiveness against gram-positive and gram-negative bacteria.

First Generation

The first-generation cephalosporins, such as Cephalexin and Cefazolin, are effective against gram-positive bacteria and some gram-negative bacteria. They are often used to treat skin and soft tissue infections, as well as surgical prophylaxis.

Second Generation

Second-generation cephalosporins, including Cefuroxime and Cefaclor, have enhanced activity against gram-negative bacteria while still retaining some effectiveness against gram-positive bacteria. They are used for respiratory tract infections and otitis media, among other infections.

Third Generation

The third-generation cephalosporins, such as Ceftriaxone and Ceftazidime, have a broad spectrum of activity, including significant effectiveness against gram-negative bacteria and some ability to overcome bacterial resistance mechanisms. They are commonly used for more severe infections like meningitis, gonorrhea, and infections in immunocompromised patients.

Fourth Generation

Fourth-generation cephalosporins, like Cefepime, have a wider spectrum of activity against both gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. They are used in the treatment of serious hospital-acquired infections.

Fifth Generation

The fifth-generation cephalosporins, such as Ceftaroline, are effective against a broad range of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). They represent the latest development in cephalosporin therapy, targeting even more resistant strains of bacteria.

Mechanism of Action

Cephalosporins act by inhibiting the synthesis of the bacterial cell wall. They bind to specific penicillin-binding proteins (PBPs) inside the bacterial cell wall, preventing the cross-linking of peptidoglycan chains necessary for cell wall strength and rigidity. This action leads to the rupture of the bacterial cell wall and ultimately causes cell death.

Resistance

Bacterial resistance to cephalosporins can occur through several mechanisms, including the production of beta-lactamase enzymes that break down the antibiotic, alterations in PBPs that reduce drug binding, and changes in membrane permeability that decrease drug uptake. The development of later generations of cephalosporins has been partly in response to the emergence of resistant bacterial strains.

Clinical Use

Cephalosporins are used to treat a wide range of infections, including respiratory tract infections, skin and soft tissue infections, urinary tract infections, bone and joint infections, and certain sexually transmitted infections. Their use must be guided by the susceptibility of the bacteria involved and the specific pharmacokinetic properties of the cephalosporin being considered.

Side Effects

Common side effects of cephalosporins include gastrointestinal disturbances, allergic reactions, and changes in blood clotting. As with all antibiotics, the use of cephalosporins can lead to the development of antibiotic-resistant bacteria and should be used judiciously.