Is ceftriaxone (a third-generation cephalosporin antibiotic) safe during pregnancy?

From the Guidelines

Ceftriaxone is generally considered safe for use during pregnancy, and its use is supported by the most recent evidence. According to the European Respiratory Journal study from 2020 1, most cephalosporin antibiotics, including ceftriaxone, are considered safe to use in pregnancy. The study notes that there is no evidence of fetal damage in animals and no increase in risk in humans.

Key Points to Consider

• Ceftriaxone can be used throughout all trimesters of pregnancy when clinically indicated for infections such as urinary tract infections, pyelonephritis, gonorrhea, and other susceptible bacterial infections.
• The typical adult dose is 1-2 grams intravenously or intramuscularly once or twice daily, depending on the severity and type of infection being treated.
• For most infections, a 7-10 day course is sufficient, though this may vary based on clinical response.
• When treating gonorrhea in pregnancy, a single 250 mg intramuscular dose is typically recommended.
• Ceftriaxone works by inhibiting bacterial cell wall synthesis and is effective against many gram-positive and gram-negative bacteria.
• It crosses the placenta but has not been associated with teratogenic effects.
• While using ceftriaxone, patients should be monitored for allergic reactions, particularly if they have a history of penicillin allergy due to potential cross-reactivity.
• Adequate hydration should be maintained during treatment to prevent crystalluria.

Evidence Summary

The evidence from the European Respiratory Journal study from 2020 1 and other studies 1 suggests that ceftriaxone is safe to use during pregnancy. However, it is essential to weigh the benefits and risks of each medication and consider the maternal risk of therapy versus no therapy and the fetal risk of uncontrolled maternal disease with the risk of therapy on the newborn.

Recommendation

Ceftriaxone should be used during pregnancy when clinically indicated, with careful monitoring for potential side effects and allergic reactions. The decision to use ceftriaxone during pregnancy should be made on a case-by-case basis, considering the severity of the infection and the potential risks and benefits of treatment.

From the FDA Drug Label

Reproductive studies have been performed in mice and rats at doses up to 20 times the usual human dose and have no evidence of embryotoxicity, fetotoxicity or teratogenicity. In primates, no embryotoxicity or teratogenicity was demonstrated at a dose approximately 3 times the human dose. There are, however, no adequate and well-controlled studies in pregnant women Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed

• Pregnancy category: The FDA drug label does not provide a clear pregnancy category for ceftriaxone.
• Use in pregnancy: Ceftriaxone should be used during pregnancy only if clearly needed, as there are no adequate and well-controlled studies in pregnant women 2.
• Key considerations:
  • No evidence of embryotoxicity, fetotoxicity, or teratogenicity in animal studies.
  • Animal reproductive studies may not always be predictive of human response.

From the Research

Ceftriaxone in Pregnancy

• Ceftriaxone is a cephalosporin antibiotic that has been studied in the context of pregnancy, particularly in terms of its pharmacokinetics and safety 3.
• A study from 1993 found that the pharmacokinetic parameters of ceftriaxone in pregnant women were similar to those in healthy subjects, and that the drug did not accumulate during treatment 3.
• The study also found that the residual concentrations of ceftriaxone in serum were greater than the minimum inhibitory concentrations (MICs) for susceptible organisms, both on the first day of treatment and at steady state 3.
• Another study from 2021 found that ceftriaxone exposure during pregnancy altered the maternal gut microbiota and affected the immunity of the mothers and their offspring in mice 4.
• However, it is worth noting that the evidence on ceftriaxone in pregnancy is limited, and more studies are needed to fully understand its effects on the mother and the fetus.

Comparison with Other Antibiotics

• Ceftriaxone has been compared to other antibiotics, such as clindamycin and gentamicin, in terms of its safety and efficacy in pregnancy 5, 6, 7.
• A study from 2020 found that clindamycin was associated with an increased risk of Clostridium difficile infection, while gentamicin was associated with an increased risk of acute kidney injury 5.
• Another study from 2020 found that cefazolin and clindamycin, which are commonly used for surgical prophylaxis during pregnancy, had limited penetration into the amniotic fluid compartment 6.
• A study from 2021 found that penicillin allergy evaluation in pregnant patients was safe and associated with reduced broad-spectrum antibiotic use and increased first-line beta-lactam antibiotic use 7.

Safety and Efficacy

• The safety and efficacy of ceftriaxone in pregnancy have been evaluated in several studies, with most finding that the drug is well-tolerated and effective in treating bacterial infections 3, 4.
• However, as with any antibiotic, there is a risk of adverse effects, such as allergic reactions and gastrointestinal disturbances.
• The use of ceftriaxone in pregnancy should be carefully considered, taking into account the potential benefits and risks, as well as the availability of alternative antibiotics.