In this episode, I’ll discuss the recommended ceftriaxone dose for 5 different scenarios:
1. Variceal hemorrhage
2. Spontaneous bacterial peritonitis (SBP)
3. Community-acquired pneumonia (CAP)
4. Community acquired bacterial meningitis
5. Obesity
Variceal hemorrhage
Patients with gastrointestinal bleeding due to esophageal varices and cirrhosis frequently experience bacterial infection. Antibiotic prophylaxis with ceftriaxone decreases the incidence of bacterial infections. Up to half of patients with cirrhosis who are hospitalized with gastrointestinal bleeding develop an infection while hospitalized.
Ceftriaxone is an appropriate choice for antibiotic prophylaxis in these patients. A dose of 1 gram ceftriaxone daily has been found effective in previous studies in cirrhotic patients with gastrointestinal hemorrhage.
Spontaneous bacterial peritonitis (SBP) treatment
While a dose of 1 gram ceftriaxone daily may be commonly used to treat SBP, I have only been able to locate trials that use a 2 gram daily dose. A retrospective study compared 1 gram vs 2 gram ceftriaxone for SBP treatment. Unfortunately, after correction for multiple variables, no significant differences in outcomes were found between doses. However, the trends indicated patients receiving 2 grams of ceftriaxone may require fewer intensive care days and improved survival compared to those receiving 1 gram daily. Even though these results are not statistically significant, the fact that previous studies of ceftriaxone in SBP only used the 2 gram dose is enough to warrant routinely using 2 grams ceftriaxone for these patients, in my opinion.
Community acquired pneumonia (CAP) treatment
IDSA guidelines from 2007 do not give specific dose recommendations for ceftriaxone for the treatment of CAP. These guidelines are being updated and will be availalbe Spring 2018. Original studies of ceftriaxone in the 1980s and 1990s demonstrated 1 gram doses were as good as 2 gram doses for the treatment of moderate to severe CAP. But resistance profiles of streptococcus and patient demographics such as average weight may have changed significantly since the 20+ years those studies were published.
Unpublished data quoted by some antibiotic resource guides suggest that younger patients (those below 60 years) may have suboptimal plasma levels with the 1 gram dose and should be given 2 grams instead. I would like to see additional studies in this area before deciding whether to routinely use 1 gram or 2 gram ceftriaxone doses in these patients. For now, it is up to a patient-specific risk-benefit assessment on which dose to give.
Community acquired bacterial meningitis
Ceftriaxone achieves excellent central nervous system (CNS) levels with inflamed meninges and is a mainstay of treatment for community acquired bacteria meningitis. For CNS infections, the dose of ceftriaxone is 2 grams every 12 hours. Because ceftriaxone is highly protein bound, a 2 gram dose will provide better CNS levels due to an increased amount of free drug with the higher dose. There is no reason that I can think of to ever give a 1 gram dose to these patients.
Obesity
Very little data exist to guide the dosing of ceftriaxone in obese critically ill patients. Because ceftriaxone is hydrophilic, obesity may not have a large effect on the volume of distribution. Additionally, critically ill patients have a higher unbound fraction of ceftriaxone compared to healthy controls. This increased unbound fraction may result in higher tissue levels but it can also result in increased clearance. Given the general lack of dose-related severe side effects, most references recommend giving doses at the higher end of the normal dose range for obese patients. Most of the time, this will mean obese patients will get a 2 gram dose of ceftriaxone.
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