Is ceftriaxone (a third-generation cephalosporin antibiotic) effective?

From the Guidelines

Ceftriaxone is an effective antibiotic for treating various bacterial infections, including those caused by gram-negative and some gram-positive organisms, as evidenced by its use in guidelines for community-acquired pneumonia and Lyme disease 1.

Key Points

• Ceftriaxone works by inhibiting bacterial cell wall synthesis, leading to cell death.
• It is commonly used for serious infections such as meningitis, pneumonia, intra-abdominal infections, complicated urinary tract infections, gonorrhea, and bacteremia.
• The typical adult dose ranges from 1-2 grams once or twice daily, usually administered intravenously or intramuscularly, with treatment duration varying from a single dose (for gonorrhea) to several weeks depending on the infection type and severity.
• Ceftriaxone has good penetration into most body tissues, including cerebrospinal fluid, making it valuable for treating central nervous system infections.
• However, resistance is increasing in some bacterial populations, particularly through extended-spectrum beta-lactamase (ESBL) production, so susceptibility testing is important before initiating therapy when possible 1.

Use in Specific Infections

• For community-acquired pneumonia, ceftriaxone is recommended for treatment of pneumococcal pneumonia without meningitis for strains with reduced susceptibility to penicillin but with MICs of ceftriaxone of ≤2 mg/mL 1.
• In the treatment of Lyme disease, ceftriaxone is a preferred parenteral regimen, with a dosage of 2 g intravenously once per day for adults and 50–75 mg/kg intravenously per day in a single dose (maximum, 2 g) for children 1.

Important Considerations

• The increasing resistance of bacterial populations to ceftriaxone and other antibiotics highlights the need for susceptibility testing and responsible antibiotic use.
• Ceftriaxone is not recommended for treatment of patients with early Lyme disease in the absence of neurologic involvement or advanced atrioventricular heart block, due to the potential for serious adverse effects 1.

From the FDA Drug Label

Ceftriaxone for Injection is indicated for the treatment of the following infections when caused by susceptible organisms: LOWER RESPIRATORY TRACT INFECTIONS Caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis or Serratia marcescens ACUTE BACTERIAL OTITIS MEDIA Caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase producing strains) or Moraxella catarrhalis (including beta-lactamase producing strains). SKIN AND SKIN STRUCTURE INFECTIONS Caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Viridans group streptococci, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis or Peptostreptococcus species
URINARY TRACT INFECTIONS (complicated and uncomplicated) Caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae UNCOMPLICATED GONORRHEA (cervical/urethral and rectal) Caused by Neisseria gonorrhoeae, including both penicillinase- and nonpenicillinase-producing strains, and pharyngeal gonorrhea caused by nonpenicillinase-producing strains of Neisseria gonorrhoeae. PELVIC INFLAMMATORY DISEASE Caused by Neisseria gonorrhoeae Ceftriaxone sodium, like other cephalosporins, has no activity against Chlamydia trachomatis. BACTERIAL SEPTICEMIA Caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae or Klebsiella pneumoniae. BONE AND JOINT INFECTIONS Caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae or Enterobacter species INTRA-ABDOMINAL INFECTIONS Caused by Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis, Clostridium species (Note: most strains of Clostridium difficile are resistant) or Peptostreptococcus species. MENINGITIS Caused by Haemophilus influenzae, Neisseria meningitidis or Streptococcus pneumoniae

Ceftriaxone is effective against a variety of bacterial infections, including:

• Lower respiratory tract infections
• Acute bacterial otitis media
• Skin and skin structure infections
• Urinary tract infections
• Uncomplicated gonorrhea
• Pelvic inflammatory disease
• Bacterial septicemia
• Bone and joint infections
• Intra-abdominal infections
• Meningitis when caused by susceptible organisms 2.

From the Research

Effectiveness of Ceftriaxone

• Ceftriaxone is a third-generation cephalosporin antibiotic with broad-spectrum activity against Gram-positive and Gram-negative bacteria, including some anaerobic bacteria 3, 4.
• Studies have shown that ceftriaxone is effective in treating various infections, including skin and soft tissue infections, urinary tract infections, pneumonia, and biliary tract infections 3, 4.
• The response rate to ceftriaxone treatment has been reported to be around 91%, with improvement or cure occurring in 32 out of 35 episodes of infection 3.
• Ceftriaxone has also been shown to be effective against multidrug-resistant Gram-negative bacteria, making it a valuable option for the treatment of serious infections 4, 5.

Pharmacokinetics and Pharmacodynamics

• Ceftriaxone has a long half-life, which allows for once-daily administration, and excellent tissue penetration 4, 6.
• The pharmacodynamic parameter AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) is used to evaluate the efficacy of ceftriaxone, with a free AUC/MIC of at least 125 required to achieve efficacy 6.
• Ceftriaxone is highly protein-bound, which can affect its pharmacodynamics, and the free fraction of the drug is important for its antibacterial activity 6.

Clinical Use and Cost-Effectiveness

• Ceftriaxone is used for a variety of infections, including meningitis, gonorrhoea, and community-acquired pneumonia 4, 6.
• The use of ceftriaxone has been shown to be cost-effective, particularly in the treatment of serious infections, due to its long half-life and once-daily administration schedule 5.
• Ceftriaxone has been compared to other antibiotics, including levofloxacin, and has been shown to be effective and well-tolerated 7.