Agent, Dose and Duration: The Unanswered Questions Behind Latency Antibiotic Therapy for Preterm Prelabour Rupture of...

Latency antibiotic therapy is an established component of expectant management after preterm prelabour rupture of membranes (PPROMs). Pooled randomised evidence from 22 trials involving 6872 women and infants shows that antibiotics prolong pregnancy, reduce chorioamnionitis (risk ratio 0.66) and reduce neonatal infection (risk ratio 0.67), without a significant reduction in perinatal mortality. The evidence supporting the therapeutic principle is stronger than the evidence defining how the therapy should be configured. This narrative review examines the three decisions an obstetrician makes at the bedside, namely, which agent, at which dose and route, and for how long, and the comparative evidence behind each. Contemporary practice descends from two protocols: the ampicillin-erythromycin regimen of the NICHD Maternal-Fetal Medicine Units Network trial and the erythromycin arm of ORACLE I. Neither was designed to identify an optimal regimen. Substitution of azithromycin for erythromycin rests predominantly on observational cohorts together with one small open-label randomised comparison that pre-specified no non-inferiority margin and is therefore pragmatic and guideline-permitted rather than confirmed by an adequately powered randomised trial. No randomised dose comparison using clinical endpoints has been performed in PPROM, although randomised pharmacokinetic data exist for azithromycin. The seven-day course derives from a trial protocol rather than from a duration-ranging study, and the two randomised duration comparisons published since 2023 point in opposite directions. Guideline agreement reflects shared historical ancestry rather than independent confirmation of optimality. Adequately powered pragmatic trials, stratified by gestational age, remain the principal unmet need.