Can first generation and third generation cephalosporins (antibiotics) be administered?

From the Guidelines

First-generation and third-generation cephalosporins should not be administered simultaneously in most clinical situations, as they have overlapping spectrums of activity and using both simultaneously typically represents unnecessary duplication of therapy without additional clinical benefit. The most recent and highest quality study, published in 2022 by the European Society of Clinical Microbiology and Infectious Diseases 1, emphasizes the importance of antibiotic stewardship and recommends against using multiple cephalosporins simultaneously.

Key Considerations

• Third-generation cephalosporins, such as ceftriaxone and cefotaxime, provide broader coverage than first-generation agents, such as cefazolin or cephalexin 1.
• Using both simultaneously may increase the risk of adverse effects and contribute to antibiotic overuse, without providing additional clinical benefit 1.
• Different antibiotic classes are usually preferred for combination therapy to achieve broader spectrum coverage with complementary mechanisms of action 1.

Exceptions and Alternatives

• In certain complex polymicrobial infections, combination therapy with different antibiotic classes may be considered to achieve broader spectrum coverage 1.
• If broad-spectrum coverage is needed, it's generally more appropriate to select a single agent with the necessary coverage profile or combine antibiotics from different classes rather than using multiple cephalosporins 1.

Clinical Implications

• The approach of minimizing antibiotic overuse and reducing the risk of adverse effects supports antimicrobial stewardship principles and is in line with the recommendations of the European Society of Clinical Microbiology and Infectious Diseases 1.
• Clinicians should carefully consider the potential benefits and risks of combination therapy and choose the most appropriate treatment regimen based on the individual patient's needs and the latest available evidence 1.

From the FDA Drug Label

Patients should be counseled that antibacterial drugs including ceftriaxone should only be used to treat bacterial infections. The FDA drug label does not answer the question about the administration of first generation and third generation cephalosporins.

From the Research

Administration of First and Third Generation Cephalosporins

• First generation cephalosporins can be administered, but their use is limited by their narrow spectrum of activity compared to third generation cephalosporins 2.
• Third generation cephalosporins, such as ceftriaxone, can be administered once daily due to their long half-life, making them a convenient option for outpatient treatment 3.
• The administration of third generation cephalosporins, including cefotaxime, moxalactam, and cefoperazone, is effective against a wide range of gram-negative bacteria, but may not be as effective against certain gram-positive bacteria 4.

Clinical Indications

• First and third generation cephalosporins can be used to treat various infections, including upper and lower respiratory, genitourinary, and soft-tissue infections 5, 2.
• Third generation cephalosporins, such as ceftriaxone, are effective in treating complicated and uncomplicated urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections 3.
• Ceftriaxone is also effective in treating bacterial meningitis, particularly in adults, and has been shown to be effective in treating gonorrhoea due to non-penicillinase-producing and penicillinase-producing strains of Neisseria gonorrhoeae 3.

Pharmacokinetics and Safety

• Third generation cephalosporins, such as ceftriaxone, have a favorable pharmacokinetic profile, with a long half-life that allows for once-daily dosing 3.
• The third generation cephalosporins are generally well tolerated, but may cause adverse effects such as diarrhea, coagulopathies, and disulfiram reactions 5, 4.
• Ceftriaxone has been shown to be safe and effective, with few significant differences in response rates compared to other antibacterials, but larger studies are needed to confirm its safety and efficacy 3.