What antibiotics are safe to use in pregnancy for treating a streptococcal infection, including first‑line penicillins and alternatives for a penicillin‑allergic pregnant woman?

Pregnancy-Safe Antibiotics for Streptococcal Infections

Penicillin G or ampicillin are the first-line antibiotics for treating streptococcal infections during pregnancy, with proven safety and efficacy across all trimesters. 1, 2

First-Line Treatment for Non-Allergic Patients

Penicillin remains the gold standard because all Group B Streptococcus (GBS) isolates worldwide maintain 100% susceptibility, and decades of clinical experience confirm its safety profile for both mother and fetus. 2, 3, 4

Recommended Regimens:

• Penicillin G: 5 million units IV initially, then 2.5–3.0 million units IV every 4 hours until delivery 2, 3
• Ampicillin: 2 g IV initially, then 1 g IV every 4 hours until delivery (acceptable alternative when penicillin G unavailable) 2, 3

Both penicillins and cephalosporins achieve adequate fetal circulation and amniotic fluid levels while avoiding neurotoxic concentrations, making them ideal for pregnancy. 1 The narrow spectrum of penicillin reduces selection pressure for resistant organisms compared to broader agents. 1

Treatment for Penicillin-Allergic Pregnant Women

The severity of penicillin allergy determines the alternative regimen. You must stratify allergy risk before selecting an antibiotic. 2, 3

Low-Risk Allergy (no anaphylaxis, angioedema, respiratory distress, or urticaria):

• Cefazolin: 2 g IV initially, then 1 g IV every 8 hours until delivery 1, 2, 3

Cefazolin is preferred because it achieves high intra-amniotic concentrations with pharmacokinetics similar to penicillin. 1 However, approximately 10% of penicillin-allergic patients exhibit cross-reactivity to cephalosporins, so this option requires careful allergy history verification. 1

High-Risk Allergy (history of anaphylaxis, angioedema, respiratory distress, or urticaria):

Susceptibility testing for clindamycin and erythromycin is mandatory before selecting treatment. 2, 3, 5

• If susceptible to both clindamycin and erythromycin: Clindamycin 900 mg IV every 8 hours until delivery 2, 3, 5
• If resistant to either agent or susceptibility unknown: Vancomycin 1 g IV every 12 hours until delivery 2, 3, 5

Critical pitfall: Clindamycin resistance ranges from 3–15% among GBS isolates, and erythromycin resistance is 7–21%. 2, 3, 5 When an isolate is erythromycin-resistant but clindamycin-susceptible, D-zone testing must be performed to detect inducible clindamycin resistance. 2, 3, 5 If D-zone testing is positive, clindamycin will fail despite appearing susceptible on standard testing.

Erythromycin is no longer recommended for intrapartum prophylaxis due to increasing resistance and unreliable fetal tissue penetration. 1, 5

Critical Safety Considerations

Penicillins, cephalosporins, and erythromycins have decades of documented safety in pregnancy, with well-established pharmacokinetics and minimal fetal risk. 4, 6 Anaphylaxis from penicillin occurs in only 4 per 10,000 to 4 per 100,000 recipients, and maternal anaphylaxis is sufficiently rare that benefits far outweigh risks. 1

The fetus cannot experience anaphylaxis from maternal antibiotic administration because specific maternal IgE antibodies do not cross the placenta, and the fetus has no prior antibiotic exposure. 1

Common Pitfalls to Avoid

Never treat asymptomatic GBS vaginal colonization with oral antibiotics before labor—this approach is completely ineffective at eliminating carriage, does not prevent neonatal disease, and promotes antibiotic resistance. 2, 7 Treatment is only indicated during active labor (intrapartum prophylaxis) or for symptomatic urinary tract infections. 2

For GBS bacteriuria during pregnancy (any concentration ≥10,000 CFU/mL), immediate treatment of the UTI is required, plus mandatory intrapartum IV prophylaxis during labor regardless of whether the UTI was treated earlier. 2, 3 Treating the UTI does not eliminate genital tract colonization. 2

Aminoglycosides should be avoided during pregnancy due to nephrotoxicity and ototoxicity unless life-threatening gram-negative infections occur with treatment failure of recommended agents. 8

Tetracyclines are contraindicated after the fifth week of pregnancy. 8 Fluoroquinolones are contraindicated throughout pregnancy as a precautionary measure. 8, 9