What antibiotics are safe to use in pregnant women?

Antibiotic Choice in Pregnancy

First-Line Safe Antibiotics

Penicillins, particularly amoxicillin, and cephalosporins, particularly cephalexin, are the safest first-line antibiotics for pregnant women, with decades of clinical experience demonstrating no teratogenic effects and compatibility throughout all trimesters. 1, 2, 3

Penicillins (Preferred First-Line)

• Amoxicillin is the preferred first-line agent, classified as Category A/B with extensive human data showing no harm to the fetus at therapeutic doses and compatibility throughout all trimesters and during breastfeeding 1, 2, 4
• Ampicillin is an acceptable alternative to penicillin, particularly for Group B Streptococcus prophylaxis, with proven efficacy and safety when administered intravenously 1, 2
• Penicillin G is recommended for Group B Streptococcus prophylaxis at a dose of 5 million units IV initially, then 2.5-3.0 million units IV every 4 hours until delivery 1, 2, 3
• Reproduction studies in mice and rats at doses up to 2000 mg/kg showed no evidence of harm to the fetus due to amoxicillin 4

Cephalosporins (Preferred First-Line)

• Cephalexin is the preferred first-generation cephalosporin, with moderate-quality evidence supporting safety throughout pregnancy and no demonstrated fetal harm 1, 2, 3
• Cefazolin is the preferred agent for penicillin-allergic women without history of anaphylaxis, angioedema, respiratory distress, or urticaria 1, 2
• Cefuroxime and ceftazidime are safe throughout pregnancy with no demonstrated fetal harm 1, 2
• Ceftriaxone is safe throughout pregnancy 1

Alternative Safe Options

For Penicillin-Allergic Patients

• Erythromycin base (NOT erythromycin estolate, which is contraindicated due to hepatotoxicity) is safe for penicillin-allergic patients at 500 mg orally four times daily for 7 days 1
• Azithromycin is considered a safe alternative for penicillin-allergic patients, though preliminary data remain insufficient for routine recommendation 1
• Clindamycin has moderate evidence supporting its safety in pregnancy with no significant risks of congenital anomalies or preterm delivery 1, 5

Other Safe Agents

• Metronidazole is considered safe during pregnancy and breastfeeding, though if a single 2g dose is used during breastfeeding, feeding should be stopped for 12-24 hours 1, 3, 5
• Nitrofurantoin is generally considered safe and effective in pregnancy 5
• Fosfomycin is generally considered safe and effective in pregnancy 5
• Vancomycin is generally considered safe and effective in pregnancy 5

Antibiotics to STRICTLY AVOID

Tetracyclines (CONTRAINDICATED)

• Doxycycline and all tetracyclines must be avoided after the fifth week of pregnancy due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy 1, 2, 3, 6
• Tetracyclines are strictly contraindicated after week 5 of pregnancy 1

Trimethoprim-Sulfamethoxazole (AVOID)

• TMP-SMX should be avoided, especially during the first trimester, due to increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, and fetal hemolytic anemia 1, 2, 6

Fluoroquinolones (AVOID)

• Fluoroquinolones (such as ciprofloxacin) should be avoided due to potential fetal cartilage damage in animal studies 1, 2
• Ciprofloxacin should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother 7
• While some observational studies showed no increased risk of major malformations, these data are insufficient to evaluate the risk for less common defects 7

Aminoglycosides (AVOID IF POSSIBLE)

• Aminoglycosides (gentamicin, tobramycin) should be avoided if possible due to eighth cranial nerve toxicity and nephrotoxicity risk 1, 2, 6
• If life-threatening infections with gram-negative pathogens occur or recommended antibiotics fail, aminoglycosides may be used with careful serum level monitoring 8, 6

Critical Clinical Pitfalls to Avoid

Screening Requirements

• All pregnant women must be screened for asymptomatic bacteriuria and Group B Streptococcus at 35-37 weeks gestation 1, 2, 3

Penicillin Allergy Management

• Patients with history of anaphylaxis, angioedema, respiratory distress, or urticaria to penicillin should NOT receive penicillin, ampicillin, or cefazolin 1, 2
• Pregnant women with penicillin allergy requiring treatment for syphilis should be referred for skin testing and desensitization, as no alternatives to penicillin have been proven effective and safe for prevention of fetal infection 9, 1

Specific Drug Warnings

• Amoxicillin-clavulanic acid is not recommended in women at risk of pre-term delivery due to a very low risk of necrotizing enterocolitis in the fetus 2
• Erythromycin estolate is contraindicated due to hepatotoxicity 1

Infection-Specific Recommendations

Group B Streptococcus Prophylaxis

• First-line: Penicillin G - 5 million units IV initially, then 2.5-3.0 million units IV every 4 hours until delivery 1, 2, 3
• Alternative: Ampicillin - proven efficacy for intrapartum prophylaxis 1, 2
• For penicillin allergy without high-risk features: Cefazolin 1, 2

Chlamydia Treatment

• Erythromycin base 500 mg orally four times daily for 7 days OR amoxicillin 500 mg orally three times daily for 7-10 days 1, 3

Syphilis Treatment

• Treatment must consist of penicillin regimen appropriate for disease stage, with consideration of a second injection 1 week after the first for HIV-infected pregnant women 9, 1
• There are no proven alternatives to penicillin for treatment of syphilis during pregnancy 9
• Tetracycline and doxycycline usually are not used during pregnancy; erythromycin should not be used because it does not reliably cure an infected fetus 9

Toxoplasmosis Treatment

• Spiramycin should be administered until delivery in women with negative AF PCR test results and negative follow-up fetal ultrasonographic results or low suspicion of fetal infection 9
• Spiramycin is not teratogenic and is available in the United States only through the Investigational New Drug process at the FDA 9
• For fetal infections, maternal treatment with pyrimethamine/sulfadiazine/folinic acid should be instituted 9

Salmonella Gastroenteritis

• Pregnant women with Salmonella gastroenteritis should receive treatment due to risk of extraintestinal spread leading to placental and amniotic fluid infection 1

Breastfeeding Considerations

• Penicillins and cephalosporins are compatible with breastfeeding and considered low risk 3, 5
• Monitor all breastfed infants for gastrointestinal effects when mother receives antibiotics 2, 3
• Antibiotics in breast milk may cause falsely negative cultures if febrile infant requires evaluation 2, 3
• Macrolides have very low risk of hypertrophic pyloric stenosis if used during first 13 days (safe after 2 weeks) 3