Safest Antibiotics During Pregnancy
Penicillins (particularly amoxicillin) and cephalosporins (particularly cephalexin) are the safest first-line antibiotics during pregnancy, with decades of clinical experience demonstrating their safety and effectiveness for both mother and fetus. 1, 2
First-Line Safe Antibiotics
Beta-Lactams: The Gold Standard
- Penicillins are the preferred agents for most infections during pregnancy, with amoxicillin being the most commonly used due to its broad spectrum and excellent safety profile 1, 3
- Penicillin G remains the agent of choice for Group B Streptococcal prophylaxis, with ampicillin as an acceptable alternative 4
- Cephalosporins, especially cephalexin, are equally safe alternatives and are recommended for penicillin-allergic patients without anaphylaxis history 1, 5
- Animal reproduction studies at doses up to 3-6 times the human dose showed no evidence of fetal harm with amoxicillin 2
- These agents have moderate-quality evidence supporting their safety with no demonstrated fetal harm 5, 6
Other Safe Options
- Azithromycin is safe throughout pregnancy with no adverse effects reported in studies of pregnant patients 1
- Azithromycin 1g orally as a single dose is effective for chlamydial infections 1, 7
- Metronidazole is considered safe despite earlier concerns about teratogenicity that have not been confirmed in humans 8, 7
- Metronidazole 500mg twice daily for 7 days is recommended for Trichomonas vaginalis and bacterial vaginosis in high-risk women 7
Conditional Use Antibiotics
- Clindamycin has moderate evidence for safety but should be used with awareness of potential gastrointestinal effects in infants if breastfeeding 1, 9
- Clindamycin is reserved for penicillin-allergic patients at high risk for anaphylaxis when susceptibility testing confirms sensitivity 4
- Nitrofurantoin is preferred for urinary tract infections and is generally safe, though 7-day courses are more effective than single doses for preventing low birth weight 4, 8
Antibiotics to Strictly Avoid
Absolute Contraindications
- Tetracyclines (including doxycycline) are contraindicated after the fifth week of pregnancy due to dental staining and potential bone growth inhibition in the fetus 10, 6
- Fluoroquinolones are contraindicated as a precautionary measure despite limited human data, due to concerns about cartilage damage from animal studies 10, 6
- Trimethoprim-sulfamethoxazole should be avoided, particularly in the first trimester, due to potential birth defects and near term due to neonatal hyperbilirubinemia risk 1, 10
Use Only When Absolutely Necessary
- Aminoglycosides should be avoided when possible due to eighth cranial nerve damage and nephrotoxicity risks, reserved only for life-threatening gram-negative infections 10, 6
- If aminoglycosides must be used, careful serum level monitoring in the mother is essential 3
- Vancomycin has limited first-trimester experience and should only be used for life-threatening infections 10
Infection-Specific Recommendations
Group B Streptococcal Prophylaxis
- Penicillin G: 5 million units IV initially, then 2.5 million units IV every 4 hours until delivery 1
- For penicillin allergy without anaphylaxis: Cefazolin 2g IV initially, then 1g IV every 8 hours 1
- For high anaphylaxis risk: Clindamycin or vancomycin only if susceptibility confirmed 1
Urinary Tract Infections and Asymptomatic Bacteriuria
- Pregnant women should be screened and treated for asymptomatic bacteriuria as it reduces pyelonephritis and may reduce preterm labor 4
- Nitrofurantoin or beta-lactams (ampicillin, cephalexin) for 4-7 days are preferred 4
- Single-dose therapy is less effective and associated with lower birth weight 4
Sexually Transmitted Infections
- Chlamydia: Azithromycin 1g orally single dose OR amoxicillin 500mg three times daily for 7-10 days 1, 7
- Gonorrhea: Ceftriaxone 125-250mg IM OR cefixime 400mg orally 7
- Syphilis: Benzathine penicillin 2.4 million units IM (once or twice 7 days apart) 7
Critical Clinical Considerations
Physiologic Changes Affecting Dosing
- Pregnancy increases glomerular filtration rate, total body volume, and cardiac output, which may require dose adjustments for renally cleared antibiotics 8
- Penicillins and cephalosporins may require increased or more frequent dosing due to enhanced renal clearance, though standard dosing is typically adequate 3, 11
Common Pitfalls to Avoid
- Do not withhold necessary antibiotics due to pregnancy concerns—untreated infections pose greater risks than appropriate antibiotic therapy 6, 8
- Untreated urinary or sexually transmitted infections are associated with low birth weight, preterm birth, and spontaneous abortion 8
- Always screen for concomitant infections when one STD is diagnosed, as co-infections are common 7
- Consider test of cure and re-testing after several weeks, as partner notification may be less efficient during pregnancy 7