The objective of the study is to compare a new antibiotic protocol with the current prophylactic treatment in routine use and to evaluate obstetric and neonatal outcome: preterm labor, chorioamnionitis and early onset sepsis

Preterm premature rupture of membranes (PPROM) occurs in approximately 3% of all pregnancies and is associated with approximately one-third of preterm births. The incidence of chorioamnionitis in women with premature rupture of membranes (PROM) at < 27, 28 to 36, and > 37weeks' gestation is 41, 15, and 2%, respectively. Intra-amniotic infection is usually polymicrobial, comprised vaginal or enteric flora including aerobic and anaerobic bacteria and atypical agents, such as Mycoplasma. Group B streptococcus (GBS) has been a frequent pathogen. The American College of Obstetricians and Gynecologists approach to PPROM consists of recommending induction of labor in all women > 34 weeks' gestation. In the absence of intrauterine infection, placental abruption or non-reassuring fetal heart rate, management of women with PPROM < 34 weeks consists of hospitalization from the time of diagnosis until delivery, administration of antenatal corticosteroids, and a 7-day course of antibiotic prophylactic therapy to prolong the latency period. Antibiotic therapy has been associated with significant reductions in chorioamnionitis, deliveries within 48 hours, and early-onset (within 3 days of delivery) neonatal sepsis (EOS). The antibiotic regimen in PPROM usually consists of ampicillin intravenously for 48 hours, followed by oral amoxicillin for 5 days (specifically targeting GBS), and a macrolide targeting atypical agents.

An increase in EOS due to gram negative Enterobacteriaceae have been reported lately with a relative decrease in GBS related EOS . These data may have an impact on the antibiotic regimen used for PPROM. The Local pathogens distribution in cases of EOS and their antibiotic sensitivity profiles in Northern Israel have been explored in a multicenter study There were 27 neonates diagnosed with EOS with positive blood cultures. Aerobic Enterobacteriaceae accounted for 14 cases (52%) and group B streptococcus for 7 cases (26%). Of the Escherichia coli and Klebsiella sp.,only 38% were sensitive to ampicillin. As a result the most effective antibiotic protocol to cover those pathogens is required. The purpose of the current study is to compare a new antibiotic protocol with the current prophylactic treatment in use and to evaluate pregnancy and neonatal outcome.

The diagnosis of preterm premature rupture of membranes (PPROM) is clinical, and is based on visualization of amniotic fluid in the vagina of a woman who presents with a history of leaking fluid. Laboratory tests as "Amniosure" can be used to confirm the clinical diagnosis when it is uncertain.

Women who meet the study criteria and have signed inform consent will be randomly divided in two groups to receive prophylactic antibiotic treatment as follow:

1. I.V ampicillin 2 gram x4/d for 2 days followed by P.O moxypen 500 mgx3/d for additional 5 days+ P.O roxithromycin 150 mg*2/d for 7 days
2. I.V cefuroxime 750 mg*3/d for 2days followed by P.O cefuroxime 500 mgx2/d + P.O roxithromycin 150 mg*2/d for 7 days

A course of corticosteroids will be given to all women participating in the study

Expectant management:

1. Vital signs *3/day
2. Uterine tenderness evaluation
3. Complete Blood Count + C-reactive protein every second day
4. Urine culture and GBS recto-vaginal swab
5. Fetal heart monitoring*6 /d
6. Sonography evaluation every 2-3 days
7. Vaginal swab once a week
8. Fetal movements follow up

Labor induction will be conducted at 34 weeks of gestation If chorioamnionitis is suspected amniocentesis should be considered or expeditious delivery

Inclusion Criteria:

• Women with PPROM between 24+0 and 34+0 weeks of gestation who are suitable for conservative management

Exclusion Criteria:

• P-PROM>34 weeks of gestation
• Suspected fetal distress or chorioamnionitis
• Active labor
• Drug allergy to one of the study regiments
• Immune deficiency
• Multiple pregnancy