What is a third-generation cephalosporin (antibiotic)?

From the Guidelines

Third-generation cephalosporins, such as ceftriaxone and cefotaxime, are effective options for the treatment of mild intra-abdominal infections, but their use should be guided by local resistance patterns and the severity of the infection. According to the 2017 WSES guidelines for the management of intra-abdominal infections 1, third-generation cephalosporins may be used in combination with metronidazole for the treatment of mild intra-abdominal infections. However, in cases of healthcare-associated infections or infections with suspected multidrug-resistant organisms, broader-spectrum antibiotics such as carbapenems may be necessary.

Some key points to consider when using third-generation cephalosporins include:

• They have enhanced activity against gram-negative bacteria, but limited activity against anaerobes, enterococci, and MRSA
• They are typically used for moderate to severe infections, including pneumonia, meningitis, intra-abdominal infections, urinary tract infections, and gonorrhea
• Ceftriaxone is often dosed at 1-2g IV daily, while cefotaxime is typically given as 1-2g IV every 4-8 hours
• Ceftazidime, which has enhanced activity against Pseudomonas, is usually dosed at 1-2g IV every 8 hours
• Side effects include diarrhea, allergic reactions, and potential for Clostridioides difficile infection

It's also important to note that the use of third-generation cephalosporins should be guided by local resistance patterns and the severity of the infection. In areas with high prevalence of multidrug-resistant organisms, alternative antibiotics such as carbapenems may be necessary 1. Additionally, the use of third-generation cephalosporins should be balanced with the risk of promoting antibiotic resistance, and antibiotic stewardship principles should be followed to minimize this risk.

From the FDA Drug Label

Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibacterial drug for parenteral administration. The FDA drug label describes ceftazidime as a third-generation cephalosporin is not explicitly stated, however, based on the information provided about its broad-spectrum activity and its classification as a beta-lactam antibacterial drug, it can be inferred that ceftazidime belongs to the third generation of cephalosporins due to its effectiveness against Gram-negative bacteria, including Pseudomonas aeruginosa.

• Key characteristics of ceftazidime include its ability to inhibit bacterial cell wall synthesis and its resistance to some beta-lactamases.
• Mechanism of action: Ceftazidime acts by inhibiting bacterial cell wall synthesis, making it a bactericidal agent.
• The drug label does not explicitly state that ceftazidime is a third-generation cephalosporin, but its properties and uses are consistent with this classification 2, 2.

From the Research

Characteristics of Third Generation Cephalosporins

• Third generation cephalosporins are broad-spectrum antimicrobial agents useful in a variety of clinical situations 3
• They have a similar mechanism of action to that of other beta-lactam antibiotics 4
• None of the agents is particularly active against certain gram-positive bacteria, including methicillin-resistant Staphylococcus aureus 4
• The drugs are effective against gonococci, Haemophilus influenzae, and Neisseria meningitidis 4

Spectrum of Activity

• Third generation cephalosporins have good activity against Streptococcus pneumoniae, methicillin-susceptible staphylococci, Haemophilus influenzae, Moraxella catarrhalis and Neisseria spp. 5
• Although active against Enterobacteriaceae, the recent spread of derepressed mutants which hyperproduce chromosomal beta-lactamases and extended-spectrum beta-lactamases has diminished the activity of all third-generation cephalosporins against these pathogens 5
• About 50% of Pseudomonas aeruginosa isolates are susceptible to third generation cephalosporins 4

Clinical Use

• Ceftriaxone is effective in treating infections due to other 'difficult' organisms such as multidrug-resistant Enterobacteriaceae 6
• Third generation cephalosporins are indicated for the treatment of bacterial meningitis 3, 4
• Ceftriaxone has been effective in complicated and uncomplicated urinary tract infections, lower respiratory tract infections, skin, soft tissue, bone and joint infections, bacteraemia/septicaemia, and paediatric meningitis due to susceptible organisms 6
• Ceftriaxone is also useful for the treatment of Lyme disease and sexually transmitted diseases 3

Pharmacokinetics and Administration

• Ceftriaxone has a long half-life which permits once-daily administration 6, 5
• The half-life of ceftriaxone allows once-daily dosing in many patients 4
• Ceftriaxone is administered intravenously or intramuscularly 6

Adverse Effects

• Adverse effects associated with use of the third-generation cephalosporins are generally similar to those that occur with other beta-lactam antibiotics 4
• Ceftriaxone has a good tolerability profile, the most common events being diarrhoea, nausea, vomiting, candidiasis and rash 5
• Ceftriaxone may cause reversible biliary pseudolithiasis, notably at higher dosages of the drug 5