Cephalosporin antibiotics
Cephalosporins are a prominent subclass of beta-lactam antibiotics, originally derived from the fungus Acremonium chrysogenum. Initially, the cephalosporin extracted was not effective enough for clinical use, leading to significant modifications that made it viable. This class of antibiotics is generally less associated with drug allergies than penicillins, making them a potential option for individuals with mild or delayed penicillin allergies, though caution is advised for those with severe allergies. Cephalosporins work by disrupting the formation of peptidoglycan, essential for bacterial cell wall stability, leading to bacterial cell death.
They are categorized into five generations, with each subsequent generation typically offering a broader spectrum of activity against various types of bacteria. First-generation cephalosporins are effective against certain penicillin-resistant bacteria, while later generations, such as third and fifth, have increased effectiveness against gram-negative bacteria and resistant strains like methicillin-resistant Staphylococcus aureus (MRSA). While generally mild, adverse effects such as nausea and diarrhea can occur, and there are rare instances of severe complications. Overall, cephalosporins play a crucial role in treating a wide range of bacterial infections, especially life-threatening ones, although most require injection for administration.
Cephalosporin antibiotics
Definition
Cephalosporins are a major subclass of beta-lactam antibiotics. The initial cephalosporin isolated from the fungus Acremonium chrysogenum (formerly known as Cephalosporium acremonium) was not active enough for clinical use, and it took substantial modifications to yield a useful antibiotic. The fermentation process required to produce cephalosporins is inefficient; when chemists developed a method of converting penicillins to cephalosporins, the class of drugs became financially viable, and substantial research was put into developing more drugs in this class.
Cephalosporins are less associated with drug allergies than penicillins, and the allergies are typically less severe. They may be given to persons with mild or delayed penicillin allergy, but caution should be used. They should not be given to persons with severe penicillin allergy.
Mechanism of Action
The beta-lactam ring is responsible for the antibacterial actions of the cephalosporins. They are believed to act like penicillins and prevent the formation of peptidoglycan, a substance crucial to the structural stability of bacteria cell walls. The weakened cell walls eventually lyse, or break apart, leading to cell death.
Drugs in this class
Cephalosporins are classified as first, second, third, fourth, and fifth generation agents. Generally, a higher generation implies a broader spectrum of activity. As gram-negative spectrum increases, however, activity against gram-positive bacteria decreases. Adverse effects are generally mild (nausea, vomiting, diarrhea), but rare cases of life-threatening pseudomembranous colitis and aplastic anemia have been recorded.
Most drugs in this class are relatively unstable in solution; injectable preparations should either be prepared just before using or be frozen until needed. Because cephalosporins are carboxylic acids, they form water-soluble sodium salts; the free acid form is relatively insoluble. If the free acid is used for an injectable formulation, it typically includes sodium bicarbonate to aid dissolution.
Unlike penicillins, cephalosporins are penicillinase resistant. They are not, however, resistant to all beta-lactamases. The first-generation cephalosporins (cefazolin and cephalexin) have a similar spectrum of penicillinase-resistant bacteria, plus activity against Enterobacteriaceae.
Second-generation agents (cefoxitin and cefaclor) are resistant to some of the beta-lactamases that inactivate the first-generation drugs. They have greater activity against Enterobacteriaceae, plus activity against some anaerobes, including Bacteroides fragilis.
Third-generation agents have a wider spectrum of activity, particularly against gram-negative bacteria. They also are highly potent and have low toxicity. This makes third-generation agents (including ceftriaxone, cefotaxime, and ceftazidime) preferred in life-threatening conditions without an isolated causative agent. Ceftazidime is the only drug in this generation to show consistent activity against Pseudomonas aeruginosa. Ceftriaxone and cefotaxime show higher activity against the major causative agents of childhood meningitis and are the drugs of choice for that indication. Most are available as injections only.
Fourth-generation cephalosporins have greater beta-lactamase resistance and improved ability to cross gram-negative bacterial membranes. Cefepime is a semisynthetic injectable agent with improved activity against staphylococci and an even broader range of activity against gram-negative bacteria than the third-generation drugs.
Fifth-generation cephalosporins, also called advanced-generation cephalosporins, have been developed to treat bacteria that are resistant to other common antibiotics. Ceftaroline and ceftobiprole are fifth-generation cephalosporins that have shown activity against methicillin-resistant Staphylococcus aureus (MRSA).
Impact
Although few cephalosporins can be given by mouth, this class has come to dominate the beta-lactam category of antibiotics. They have a broad spectrum of activity, including effectiveness against a wide range of life-threatening bacteria. Only some of the available agents have been listed, and new agents will likely continue to be introduced.
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