What are cephalosporins used for? What are the differences between cephalosporins? Are cephalosporins safe?

Cephalosporins: An Overview

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

Generations of Cephalosporins

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. This resulted in the development of five generations of cephalosporins, each differing slightly in their antibacterial spectrum and other properties.

First Generation Cephalosporins

First-generation cephalosporins have optimum activity against gram-positive bacteria such as staphylococci and streptococci, with little activity against gram-negative bacteria. Examples include cephalexin and cefadroxil, which can be given orally, and cefazolin, which can only be administered by injection (IV/IM).

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 single third-generation cephalosporin treats all infectious disease scenarios. Cefotaxime and ceftizoxime (discontinued) offer the best gram-positive coverage, while ceftazidime and cefoperazone (discontinued) provide antipseudomonal coverage. Ceftriaxone has a long half-life, allowing 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.

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. Cefepime is the only fourth-generation cephalosporin available in the United States, while 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, while also retaining the activity of the later-generation cephalosporins and being effective against susceptible gram-negative bacteria.

Uses of Cephalosporins

Cephalosporins may be used to treat infections caused by susceptible bacteria, such as bone infections, ear infections (e.g., otitis media), skin infections, upper respiratory tract infections, and urinary tract infections.

Safety of Cephalosporins

Cephalosporins are generally safe, with low toxicity and good efficacy against susceptible bacteria. However, allergic reactions have been reported, with symptoms that 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, and 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, particularly in those with kidney or liver disease, those who are nutritionally deprived, or those taking cephalosporins long-term or concurrently.

Conclusion

Cephalosporins are a large group of antibiotics with five generations, each with its own characteristics and uses. They are generally safe, with low toxicity, but can cause allergic reactions and other side effects, particularly in certain patient populations. Understanding the differences between the generations of cephalosporins and their appropriate uses is essential for healthcare providers when prescribing these medications.