Ampicillin and gentamicin prophylaxis is superior to ampicillin alone in patients with prelabor rupture of membranes at term: the results of a randomized clinical trial.

Summary

In a single-center randomized controlled trial of term prelabor rupture of membranes with unknown GBS status (n=204), ampicillin plus gentamicin significantly reduced clinical chorioamnionitis (1.0% vs 7.8%), intrapartum fever, overall peripartum infections, and neonatal adverse outcomes compared with ampicillin alone. Enterobacteriaceae recovery from chorioamniotic swabs was also lower in the combination group, supporting broader Gram-negative coverage.

Key Findings

• Clinical chorioamnionitis was reduced with ampicillin+gentamicin vs ampicillin alone (1.0% vs 7.8%, P=.035; NNT=14.7).
• Lower intrapartum fever (8.0% vs 18.0%, P=.036) and overall peripartum infections (1.0% vs 9.8%, P=.005) in the combination group.
• Neonatal composite adverse outcome decreased (10.8% vs 21.6%, P=.036), with fewer sepsis workups (7.8% vs 17.6%, P=.036) and shorter NICU stay (median 3.0 vs 3.5 days, P=.047).
• Enterobacteriaceae isolation from chorioamniotic swabs was lower with combination therapy (20% vs 51%, P<.001).

Clinical Implications

Consider adding gentamicin to ampicillin for term prelabor rupture of membranes with unknown GBS status at ≥18 hours, while monitoring aminoglycoside toxicity and stewardship.

Limitations

• Single-center design with modest sample size (n=204)
• Open-label to clinicians at the time of antibiotic initiation; aminoglycoside safety and ecological resistance impact not fully assessed

Future Directions

Multicenter RCTs assessing safety (ototoxicity/nephrotoxicity), resistance ecology, and cost-effectiveness; stratification by colonization risk and rapid diagnostics integration.