Cephalosporins are a class of antibiotics that are widely used both to treat existing infections and prevent infections from occurring. They can be given both orally and through an intravenous line. They were initially discovered in 1948 from the fungus Cephalosporium acrimonium. Filtrates from this fungus were found to inhibit the growth of Stapholococcus aureus and cure staph infections and typhoid fever in humans. Eventually, the chemical compounds excreted by the fungus responsible for the antibacterial activity were isolated and synthesized in much more powerful forms. Synthetic addition of side chains to the antibacterial compounds alters their antibacterial activity and has resulted in the creation of a wide range of cephalosporin antibiotics.
Mechanism of action
Cephalosporins work in a manner similar to penicillins. All bacterial cells contain cell walls, the main difference being that gram-positive bacteria have much thicker cell walls than gram-negative bacteria. Cell walls are formed in three stages. First, the precursors of the cell wall are formed. Second, the precursors are combined to form a long polymer. Third, a reaction called a transpeptidation reaction crosslinks the polymers to form a wall. It is during this third step that the cephalosporins interfere, severely limiting the bacteria's ability to form and maintain their cell walls. The bacteria cannot survive without their cell walls, and they are destroyed. Human cells are not affected, because they lack cell walls, surrounded instead by a thin lipid bilayer membrane.
Therapeutic uses
The cephalosporins are by convention classified into four generations. The first generation cephalosporins are widely used for skin and soft tissue infections from Staph. aureus and Strep. pyogenes. Oftentimes, a single dose of the first generation cephalosporin cefazolin is given before surgery to protect against infection from bacteria residing on the skin. According to "Goodman and Gilman's Pharmacology," the second-generation cephalosporins are rarely used nowadays because of the greater efficacy of third generation cephalosporins or penicillins. The third generation cephalosporins are used for such varied infections as gonorrhea, meningitis and pneumonia. The fourth generation cephalosporins are typically reserved for hospital-acquired infections caused by antibiotic-resistant bacteria.
Adverse reactions
The most common side effects caused by cephalosporins are hypersensitivity reactions, according to "Current Medical Diagnosis and Treatment." These are characterized by itching, rashes, anaphylaxis and bronchospasm. It should be noted that due to the similar structures of penicillins and cephalosporins, a patient with a penicillin allergy may be at risk of developing a cephalosporin allergy as well. High doses of cephalosporins may cause bone marrow depression, kidney toxicity or a breakdown of red blood cells known as hemolysis. Fortunately, the serious adverse reactions are rare. Much more common are simple reactions such as gastrointestinal upset or diarrhea.
References
- "Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e"; Laurence L. Brunton, Ed.; 2006
- "Current Medical Diagnosis & Treatment 2010, Forty-Ninth Edition"; Stephen J. McPhee, Maxine A. Papadakis, Eds.; 2010
