Is IV (intravenous) ceftriaxone effective against gram-negative bacilli?

From the Guidelines

IV ceftriaxone is effective against many gram-negative bacilli, including Enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli, as demonstrated in a multicenter, randomized study where ceftriaxone 1 g once daily was equivalent to ertapenem 1 g once daily for community-acquired pneumonia (CAP) due to Enterobacteriaceae 1. This third-generation cephalosporin antibiotic works by inhibiting bacterial cell wall synthesis, making it particularly potent against gram-negative organisms. The typical adult dosage ranges from 1-2 grams once daily, with the higher dose often used for more severe infections. Ceftriaxone has a long half-life (approximately 8 hours) allowing for convenient once-daily dosing. However, it's essential to note that ceftriaxone is not effective against Pseudomonas aeruginosa or extended-spectrum beta-lactamase (ESBL) producing organisms, which have developed resistance mechanisms, as highlighted in a study on clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection 1. Additionally, it has limited activity against anaerobes. When administering IV ceftriaxone, it should be infused over 30 minutes to minimize vein irritation. Common side effects include pain at the injection site, diarrhea, and potential for allergic reactions in patients with penicillin allergies due to cross-reactivity. Before initiating therapy, appropriate cultures should be obtained to confirm susceptibility of the infecting organism. Some key points to consider when using ceftriaxone include:

• Ceftriaxone is a reasonable alternative to penicillin for the treatment of infective endocarditis caused by viridans group streptococci, as stated in guidelines for the management of infective endocarditis in adults 1.
• The addition of gentamicin to ceftriaxone may be considered for the treatment of infective endocarditis caused by certain streptococcal species, as recommended in guidelines for the management of infective endocarditis in adults 1.
• Ceftriaxone may be used as an alternative to cefotaxime for the treatment of pneumococcal infective endocarditis, as suggested in guidelines for the management of infective endocarditis in adults 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-negative bacteria Acinetobacter calcoaceticus Enterobacter aerogenes Enterobacter cloacae Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella oxytoca Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Neisseria meningitidis Proteus mirabilis Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens

IV ceftriaxone is effective against gram-negative bacilli, including:

• Enterobacteriaceae such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae
• Other gram-negative bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae However, it is essential to note that resistance patterns may vary, and susceptibility testing should be performed to determine the effectiveness of ceftriaxone against specific gram-negative bacilli 2.

From the Research

Effectiveness of IV Ceftriaxone Against Gram-Negative Bacilli

• IV ceftriaxone has been shown to be effective against many gram-negative aerobic bacilli, including Escherichia coli, Proteus, Klebsiella, Morganella, Providencia, Citrobacter, and Enterobacter agglomerans 3.
• The drug has a broad spectrum of activity against Gram-positive and Gram-negative aerobic, and some anaerobic, bacteria 4.
• Ceftriaxone has been effective in treating infections due to "difficult" organisms such as multidrug-resistant Enterobacteriaceae 4.
• The clinical efficacy of ceftriaxone has been evaluated in several studies, with response rates consistently exceeding 90% 3, 5, 6.

Specific Gram-Negative Bacilli Covered by IV Ceftriaxone

• Escherichia coli: ceftriaxone has excellent activity against this organism 3, 6.
• Klebsiella pneumoniae: ceftriaxone is the preferred treatment for bacteraemia caused by non-MDR Klebsiella pneumoniae 7.
• Proteus mirabilis: ceftriaxone has high in vitro activity against this organism 6.
• Pseudomonas aeruginosa: ceftriaxone has only minimal activity against this organism, and is not recommended as sole antibiotic therapy in pseudomonal infections 4, 6.

Clinical Efficacy and Safety

• Ceftriaxone has been shown to be safe and effective in the treatment of serious bacterial infections, with few adverse reactions reported 3, 5, 6.
• The drug has a long serum half-life, allowing for less frequent dosing than other antimicrobials 3, 4.
• Ceftriaxone may be a ceftriaxone-sparing alternative treatment for antibiotic-susceptible Klebsiella pneumoniae bacteraemia 7.