Is ceftriaxone (Ceftriaxone) effective for treating Gram-positive bacteremia?

From the Guidelines

Ceftriaxone is not the most effective option for gram-positive bacteremia, particularly against resistant organisms like MRSA, as evidenced by studies comparing its efficacy to newer generation cephalosporins like ceftaroline 1.

Key Points to Consider

• Ceftriaxone has bactericidal activity against certain gram-positive pathogens, including streptococci and methicillin-sensitive Staphylococcus aureus (MSSA) 1.
• However, its effectiveness is limited against resistant gram-positive organisms such as MRSA, Enterococcus species, and certain strains of S. pneumoniae that are resistant to ceftriaxone 1.
• Newer generation cephalosporins like ceftaroline have shown superior efficacy against a broader range of gram-positive pathogens, including MRSA and DRSP, making them a preferable choice for empiric treatment of suspected gram-positive bacteremia 1.
• The choice of antibiotic should always be guided by blood cultures with susceptibility testing to ensure appropriate coverage and to minimize the risk of resistance development.

Treatment Considerations

• For empiric treatment of suspected gram-positive bacteremia, consideration should be given to using antibiotics with a broader spectrum of activity against resistant gram-positive organisms, such as ceftaroline or vancomycin, especially in cases where MRSA or other resistant pathogens are suspected 1.
• Ceftriaxone may still be considered for treatment of gram-positive bacteremia caused by susceptible organisms, but its use should be guided by local resistance patterns and susceptibility testing results 1.
• Treatment duration and dosing should be adjusted based on the specific organism, source of infection, and clinical response, with typical durations ranging from 7-14 days 1.

From the FDA Drug Label

Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. The following in vitro data are available, but their clinical significance is unknown At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftriaxone. Gram-positive bacteria Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus pyogenes Viridans group streptococci BACTERIAL SEPTICEMIA Caused by Staphylococcus aureus, Streptococcus pneumoniae

• Ceftriaxone is expected to be effective against certain gram-positive bacteria, including:

• Staphylococcus aureus
• Streptococcus pneumoniae
• Streptococcus pyogenes
• Viridans group streptococci

• Ceftriaxone is indicated for the treatment of bacterial septicemia caused by susceptible gram-positive organisms, including Staphylococcus aureus and Streptococcus pneumoniae 2 2

From the Research

Effectiveness of Ceftriaxone for Gram-Positive Bacteremia

• Ceftriaxone is a third-generation cephalosporin commonly used for treating bacteremia caused by gram-positive organisms such as Streptococcus spp. and gram-negative organisms such as Enterobacterales 3.
• A study published in 2002 found that ceftriaxone has retained its potent activity against the most commonly encountered Gram-positive and Gram-negative human pathogens despite widespread and ongoing clinical use for more than 15 years 4.
• However, the effectiveness of ceftriaxone for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections is still a topic of debate, with some studies suggesting that it could be an alternative to standard therapies 5.
• A systematic review and meta-analysis published in 2022 found that ceftriaxone was not statistically different from standard of care therapy in terms of clinical cure, microbiological cure, 30- and 90-day mortality, 90-day hospital readmission, and adverse drug reactions for MSSA bloodstream infections 5.
• Another study published in 2023 found that definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days compared to cefazolin or antistaphylococcal penicillins for MSSA bacteremia 6.

Ceftriaxone Resistance

• A study published in 2002 found that ceftriaxone resistance among methicillin-susceptible Staphylococcus aureus (MSSA) was low and consistent from 1996 to 2000, ranging from 0.1-0.3% per year 4.
• However, another study published in 2023 found that ceftriaxone was associated with a higher risk of treatment failure within 90 days compared to cefazolin or antistaphylococcal penicillins for MSSA bacteremia, suggesting that ceftriaxone may not be as effective against certain gram-positive organisms 6.

Clinical Use of Ceftriaxone

• Ceftriaxone is commonly used for treating bacteremia caused by gram-positive organisms such as Streptococcus spp. and gram-negative organisms such as Enterobacterales 3.
• The typical doses for treating bacteremia are either 1 gram or 2 grams daily 3.
• A study published in 2022 found that ceftriaxone could provide an alternative for the treatment of MSSA bloodstream infections in acute care and outpatient parenteral antimicrobial therapy (OPAT) settings, except in patients whose bloodstream infections were due to infective endocarditis 5.