What is the difference between first-generation cephalosporins and second- or third-generation cephalosporins?

From the Guidelines

The main difference between first-generation cephalosporins and second- or third-generation cephalosporins is their spectrum of activity, with first-generation cephalosporins having a narrower spectrum primarily effective against gram-positive bacteria, while second- and third-generation cephalosporins have expanded gram-negative coverage. The generations of cephalosporins are categorized based on their spectrum of activity and when they were developed:

• First-generation: Narrow spectrum, primarily effective against gram-positive bacteria (e.g., cefazolin, cephalexin) 1
• Second-generation: Expanded gram-negative coverage (e.g., cefuroxime, cefaclor) 1
• Third-generation: Further improved gram-negative coverage, including some Pseudomonas species (e.g., ceftriaxone, cefotaxime) 1 Second- and third-generation cephalosporins are more advanced versions with broader antimicrobial coverage compared to first-generation drugs, and are often used for more serious infections or when broader coverage is needed 1. When prescribing, it's essential to choose the appropriate generation based on the suspected pathogens and local resistance patterns, and to consider the narrowest effective spectrum to reduce the risk of antibiotic resistance 1. Key points to consider when selecting a cephalosporin include:
• The type of infection being treated
• The suspected pathogens involved
• Local resistance patterns
• The need for broader coverage in more serious infections By considering these factors and choosing the most appropriate generation of cephalosporin, healthcare providers can optimize treatment outcomes and minimize the risk of antibiotic resistance 1.

From the Research

Difference between First-Generation and Second- or Third-Generation Cephalosporins

• The first-generation cephalosporins are most active against sensitive staphylococci and streptococci 2, whereas second- and third-generation cephalosporins have a broader spectrum of activity against gram-negative bacteria.
• Second-generation cephalosporins, except cefoxitin, and third-generation cephalosporins show substantial activity against Haemophilus influenzae 2.
• Third-generation cephalosporins have pronounced activity against Enterobacteriaceae, which is not seen in first-generation cephalosporins 2, 3.
• The generation classification of cephalosporins does not correlate with activity against gram-positive bacteria or anaerobes 3.
• First-generation cephalosporins have a narrow gram-negative spectrum but are most active against gram-positive bacteria, particularly Staphylococcus aureus 3.
• Third-generation compounds have excellent activity against gram-negative bacteria 3, 4.
• The cephamycins, a second-generation subgroup, have the best activity against anaerobes 3.
• Second- and third-generation cephalosporins are more effective against gram-negative bacteria and anaerobes than first-generation agents 5.

Spectrum of Activity

• First-generation cephalosporins: active against streptococci and staphylococci 4, 6.
• Second-generation cephalosporins: active against Haemophilus influenzae and some anaerobes 2, 3.
• Third-generation cephalosporins: active against Enterobacteriaceae, Pseudomonas, and some anaerobes 2, 4, 6.

Clinical Use

• First-generation cephalosporins are often used for prophylaxis due to their lower cost 5.
• Second- and third-generation cephalosporins are reserved for the treatment of more severe infections, such as meningitis and resistant nosocomial infections 5.