TAILORED Therapeutic Regime in Patients With Preterm Premature Rupture Of Membranes to Prolong Pregnancy, Improve Maternal and Neonatal Outcomes, and Reduce Antibiotic Burden

In Arm A, Amniocentesis will be performed once a week until delivery, with a maximum of seven procedures per patient. If the pregnancy continues beyond this period, follow-up will proceed without further amniocentesis. * If IL-6 ≥ 2600: * steroids and initial broad spectrum ABX will be administered, * rotation of ABX according to cultures and PCR. * If steroids already administered, a second course can be administered prior to 34+0 if at least 7 days have passed after the previous course.

1. Clinical and/or laboratory signs of chorioamnionitis will result in an intervention consisting of the course of antenatal steroids (if not already administered, or as a single course prior 34+0 if at least 7 days have passed after the previous course), initial broad spectrum antibiotics, or delivery, depending on the week of pregnancy and clinical status. 2. Uterine activity with progression of vaginal finding will result in course of antenatal steroids (if not already administered, or as a single course prior 34+0 if at least 7 days have passed after the previous course) and tocolysis

In patients with imminent preterm birth prior 32+0 week of pregnancy, foetal neuroprotection will be administered consisting of MgSO4 in an intravenous loading dose of 4 g (administered slowly over 20-30 min), followed by a 1 g per hour maintenance dose. This regimen should continue until birth but should be stopped after 24 h if undelivered.

Antibiotics - Group B Streptococcus (GBS) prophylaxis + macrolides, always at admission.

1. GBS prophylaxis + macrolides: Penicillin G (benzylpenicillin) 5mil IU IV initially and then 2-3 IU (dose adjusted to body weight) IV every 4h twice, then every 6h + Clarithromycin 500mg po every 12h for 7-10 days or till delivery. 2. Initial broad spectrum ABX: Ampicillin/sulbactam 3g IV every 6 hours + Gentamicin 5 mg/kg IV (\<60 kg 240 mg, 61-80 kg 320 mg, \>80 kg 400 mg) every 24h for 5-7 days according to the clinical state. Comments: Alternative ABX in patients with allergy to PCN/AMP: Vancomycin 1g IV every 12 h or Clindamycin 600-900g IV every 8h taking antibiotic sensitivity into account. Before administering the third dose of gentamicin, its serum level should be determined (at a level \>4 umol/l, the dose must be reduced).