Do we need to reconsider our antibiotic regimen for preterm premature rupture of membranes? Pathogens and perinatal outcome in PPROM

BACKGROUND: The antibiotic regimen currently recommended in most guidelines in case of preterm premature rupture of membranes (PPROM) with an aminopenicillin and a macrolide is mainly based on studies performed more than 25 years ago. In view of the changing pathogens in neonatal and perinatal infectious morbidity and their increasing aminopenicillin-resistance in recent decades, the question arises as to whether these data are still applicable to our current situation and whether an adjustment of our antibiotic standard regimen with amoxicillin and azithromycin is necessary. METHODS: We retrospectively analyzed the pathogens and the perinatal outcome, particularly the perinatal and neonatal infectious morbidity, in 293 pregnancies with PPROM < 37 + 0 weeks and delivery in our department from 01/2020 to 12/2023. RESULTS: In PPROM < 34+0 weeks, we found neonatal infection (defined by clinical infection criteria) in 14.5%, neonatal early-onset sepsis (defined by clinical infection criteria plus invasive pathogen detection) in 3.6% and one case of maternal sepsis. The causative pathogens of the 6 neonatal early-onset sepsis cases were in 3 cases (50%) E.coli (2/3 amoxicillin-resistant) and in one case each Enterococcus faecalis, Streptococcus mitis and Haemophilus influenzae. The most common pathogens in the vaginal swabs were Ureaplasma species (25%). The most common pathogens in the placental swabs were, in general, coagulase-negative Staphylococci (21.2%), followed by E.coli (10.2%) and Ureaplasma species (8.8%) and, in case of histological confirmed chorioamnionitis, Ureaplasma species (21.4%), followed by E. coli (17.9%) and coagulase-negative Staphylococci (14.3%). In PPROM ≥ 34+0 weeks, we found neonatal infection in 2.6% and there was no case of neonatal or maternal sepsis. CONCLUSIONS: E.coli and coagulase-negative Staphylococci, both predominantly resistant to aminopenicillins, as well as Ureaplasma species seem to be the currently most relevant pathogens in PPROM. Therefore, azithromycin should be administered, but amoxicillin no longer appears to be the optimal regimen. Further research comparing different antibiotic regimens with better coverage of the currently relevant pathogens such as co-amoxiclav (amoxicillin + clavulanic acid) or cephalosporins is needed.