From the Guidelines
Third generation cephalosporins, such as ceftriaxone and cefotaxime, are recommended as empirical treatment for community-acquired spontaneous bacterial peritonitis (SBP) in patients with low risk of multidrug-resistant organisms (MDROs) 1.
Key Characteristics
- Third generation cephalosporins have enhanced activity against gram-negative bacteria and some effectiveness against gram-positive organisms.
- They work by inhibiting bacterial cell wall synthesis, specifically by binding to penicillin-binding proteins and disrupting peptidoglycan cross-linking.
- These antibiotics are valuable for treating serious infections like meningitis, pneumonia, intra-abdominal infections, and complicated urinary tract infections.
Usage and Dosage
- Typical dosing for ceftriaxone is 1-2g IV/IM daily or divided twice daily, while cefotaxime is usually given 1-2g IV every 4-8 hours.
- The standard treatment duration is 5 to 10 days, but may vary according to symptoms and/or results of antimicrobial susceptibility testing.
Limitations and Concerns
- Third generation cephalosporins have limited activity against anaerobes and methicillin-resistant Staphylococcus aureus (MRSA).
- Increasing bacterial resistance through extended-spectrum beta-lactamases (ESBLs) has become a significant concern with these antibiotics.
- In settings with high prevalence of MDROs, carbapenem-based empirical therapy may be more effective than third-generation cephalosporin-based regimen 1.
Important Considerations
- The choice of empirical antibiotic treatment for SBP should consider the severity of infection, local resistance profile, and the environment of the infection (community-acquired vs healthcare-associated vs nosocomial) 1.
- Active agents against ESBL-producing pathogens, such as carbapenems, should be considered for the empirical treatment of healthcare-associated SBP 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Definition and Characteristics of Third-Generation Cephalosporins
- Third-generation cephalosporins are a class of antibiotics with a broad spectrum of activity against gram-negative bacteria, including Enterobacteriaceae, Haemophilus, Neisseria, and some anaerobic species 2, 3.
- They have a similar mechanism of action to other beta-lactam antibiotics, but with increased stability to beta-lactamases compared to first- and second-generation cephalosporins 2, 4.
- Examples of third-generation cephalosporins include cefotaxime, moxalactam, cefoperazone, ceftizoxime, ceftriaxone, and cefmenoxime 2.
Spectrum of Activity
- Third-generation cephalosporins are effective against a wide range of gram-negative bacteria, including Escherichia coli, Klebsiella, Citrobacter diversus, Proteus, and Morganella 2.
- They are also active against Haemophilus influenzae, Neisseria meningitidis, and some anaerobic species, such as Bacteroides fragilis 2, 3.
- However, they have limited activity against certain gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and enterococci 2, 3.
Pharmacokinetics and Clinical Use
- The pharmacokinetic profiles of third-generation cephalosporins vary, with some agents having longer half-lives and allowing for less frequent dosing 2, 3.
- Ceftriaxone, for example, has a long half-life and can be administered once daily in some cases 2, 4.
- Third-generation cephalosporins are commonly used to treat serious infections, including gram-negative bacillary meningitis, intra-abdominal infections, and nosocomial gram-negative infections 2, 3, 4.
Adverse Effects and Resistance
- Third-generation cephalosporins are generally well-tolerated, with adverse effects similar to those of other beta-lactam antibiotics 2, 4.
- However, there are growing concerns about resistance to these agents, particularly among Enterobacteriaceae and Pseudomonas aeruginosa 3, 4.
- The use of third-generation cephalosporins should be guided by susceptibility testing and clinical judgment to minimize the risk of resistance and ensure effective treatment 4.