Changes in vaginal Ureaplasma and Lactobacillus due to antibiotic regimen for premature rupture of membranes:

Abstract Preterm premature rupture of membranes (PPROM) is associated with preterm delivery and neonatal complications. PPROM is often complicated by intra-amniotic inflammation and/or microbial invasion of the amniotic cavity with Ureaplasma or Mycoplasma. Various prophylactic antibiotic therapies have been proposed to prolong latency between PPROM and delivery, reduce the risk of clinical chorioamnionitis, and improve neonatal complications. However, information on the potential of azithromycin administration to reduce the microbial load of vaginal Ureaplasma and Mycoplasma remains lacking. This prospective cohort study included singleton pregnancies managed with prophylactic antibiotics for PPROM at less than 36 weeks of gestation. All patients received the standard antibiotic regimen for PPROM, which consisted of a single oral azithromycin and intravenous ampicillin every for 2 days followed by 5 days of oral amoxicillin. Vaginal swabs samples were collected when PPROM was confirmed and after the antibiotic regimen administration. The main outcome measures were to investigate the changes in vaginal Ureaplasma, Mycoplasma, and Lactobacillus spp. due to the antibiotic regimen. In addition, the association between the presence and changes in vaginal Ureaplasma and Mycoplasma, pregnancy outcomes, and neonatal complications were examined. Out of 82 eligible PPROM, 51 had positive vaginalUreaplasma. Thirty-six patients (52.2%) completed the antibiotic regimen. Among those with positive vaginal Ureaplasma who completed the antibiotic regimen, 75% experienced an increase in vaginal Ureaplasma levels. For those who delivered before completing all antibiotic doses, 40% had increased vaginal Ureaplasma levels. Furthermore, the antibiotic regimen resulted in decreased Lactobacillusspp. in almost all cases. However, vaginal Ureaplasma changes were not found to be associated with neonatal sepsis or bronchopulmonary dysplasia. This suggests that Ureaplasma became resistant to azithromycin. Future studies are needed to revalidate current antibiotic therapy for PPROM. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the ethical review board of Osaka Women’s and Children’s Hospital I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable All relevant data are within the manuscript and its Supporting Information files.