Is ceftriaxone (Ceftriaxone) and metronidazole safe during pregnancy?

From the Guidelines

Ceftriaxone and metronidazole can be used during pregnancy when medically necessary, though with some considerations. Ceftriaxone (a third-generation cephalosporin antibiotic) is generally considered safe during all trimesters of pregnancy, with no consistent evidence of harm to the developing fetus, as most reports in humans have found no association with increased risk of structural defects to the fetus 1. Metronidazole is also considered acceptable for use during pregnancy, though some clinicians prefer to avoid it during the first trimester if possible, as it can be used during pregnancy and lactation if there are no other safer alternatives, and it has been associated with fetal damage in animals, but no reports confirmed in humans 1. When treating serious infections like intra-abdominal infections, pelvic inflammatory disease, or certain mixed bacterial infections, the benefits of this combination therapy typically outweigh potential risks. The standard adult dosing for ceftriaxone is typically 1-2 grams IV/IM daily, while metronidazole is usually given as 500 mg orally or IV every 8-12 hours, as seen in guidelines for treating various infections 1. Treatment duration depends on the specific infection being treated. These medications work together effectively because ceftriaxone targets aerobic bacteria while metronidazole covers anaerobic organisms, providing broad-spectrum coverage. Any antibiotic use during pregnancy should be monitored by healthcare providers, with dosing potentially adjusted based on the stage of pregnancy and severity of infection, and long-term therapy of the mother could result in risk of neonatal bleeding by inhibition of vitamin K synthesis: treat mother and neonate with phytomenadione (vitamin K) 1. It's also worth noting that metronidazole can be used to treat bacterial vaginosis in pregnant women, with a recommended regimen of 250 mg orally three times a day for 7 days, or alternative regimens such as 2 g orally in a single dose, or metronidazole gel, 0.75%, one full applicator (5 g) intravaginally, twice a day for 5 days 1. Overall, the use of ceftriaxone and metronidazole during pregnancy should be guided by the principles of using the lowest effective dose for the shortest duration necessary to achieve the desired clinical effect, while minimizing the risk of adverse effects on the mother and the fetus.

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 Teratogenic Effects Pregnancy category B Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to metronidazole

The combination of ceftriaxone and metronidazole should be used during pregnancy only if clearly needed.

• Ceftriaxone: There are no adequate and well-controlled studies in pregnant women, but animal studies have shown no evidence of embryotoxicity, fetotoxicity, or teratogenicity 2.
• Metronidazole: Although animal reproduction studies have revealed no evidence of impaired fertility or harm to the fetus, the drug is a carcinogen in rodents, and its use during pregnancy should be carefully evaluated 3.

From the Research

Safety of Ceftriaxone and Metronidazole During Pregnancy

• The safety of ceftriaxone and metronidazole during pregnancy has been evaluated in several studies 4, 5, 6, 7, 8.
• Ceftriaxone has been shown to have good transplacental passage and transfer into amniotic fluid, making it potentially useful for treating perinatal infections 6.
• Metronidazole has been found to be effective in preventing preterm births when used in conjunction with other antibiotics, and its use does not predict birth defects or congenital abnormalities 5, 7.
• However, metronidazole has been associated with a 70% increased risk of spontaneous abortion, although this risk should be interpreted cautiously due to the severity of genitourinary infection 5.

Use of Ceftriaxone and Metronidazole in Pregnancy

• A study found that antibiotic administration, including ceftriaxone, clarithromycin, and metronidazole, was effective in treating a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency 8.
• The study reported that 75% of patients had resolution of intra-amniotic inflammation or intra-amniotic infection, and treatment success occurred in 59% of cases 8.
• Another study recommended metronidazole as a preferred treatment for bacterial vaginosis in pregnant women, with a dosage of 250 mg orally three times a day for 7 days 4.

Potential Risks and Benefits

• The use of ceftriaxone and metronidazole during pregnancy should be carefully considered, weighing the potential benefits against the potential risks 5, 7.
• The benefits of using these antibiotics in pregnancy include the prevention of preterm births and the treatment of intra-amniotic infection/inflammation 5, 7, 8.
• However, the potential risks, such as spontaneous abortion, should be carefully monitored and managed 5.