Department of Obstetrics and Gynecology, National Hospital Organization, Saga National Hospital, Saga, Japan.
Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, Saga, Japan.
J Matern Fetal Neonatal Med. 2023 Dec;36(2):2286189. doi: 10.1080/14767058.2023.2286189. Epub 2023 Nov 28.
Intra-amniotic infections increase the risk of preterm delivery and short- and long-term fetal morbidity; however, no consensus exists on the choice of antimicrobial agents as treatment for these infections. We aimed to examine the efficacy of intravenous administration of sulbactam/ampicillin (SBT/ABPC) and azithromycin (AZM) for intra-amniotic infection in patients with preterm premature rupture of membranes (PPROM).
This study followed a single-centered retrospective cohort design. We compared changes in interleukin 6 (IL-6) levels and the load of species DNA in the amniotic fluid between singleton pregnancy patients with intra-amniotic infection (Group A) and without either intra-amniotic inflammation (IAI) or microbial invasion of the amniotic cavity (MIAC) (Group B) who developed PPROM between week 22, day 0 and week 33, day 6 of gestation and maintained pregnancy for ≥7 d after diagnosis (August 2014 to April 2020). Patients in Group A were treated with SBT/ABPC and AZM, whereas those in Group B were treated with ABPC and AZM or clarithromycin.
Thirty-one patients with IAI and 48 patients without either IAI or MIAC at diagnosis of PPROM underwent pregnancy/delivery management at our hospital. Following the study population selection, we evaluated six patients in Group A and 13 patients in Group B. Amniotic fluid IL-6 concentrations at the initial amniocentesis were high, ranging from 11.7 ng/mL to 139.2 ng/mL, indicating a state of severe IAI in all six patients in Group A. In five of the six patients in Group A, the amniotic fluid cultures during the first amniocentesis included species only. In both groups, the amniotic fluid IL-6 concentration at the follow-up amniocentesis was lower than that at the initial amniocentesis (Group A: follow-up median 3.06 ng/mL [quartiles, 1.75-6.74], initial median 30.53 ng/mL [quartiles, 15.60-67.07], ＝.03; Group B: follow-up median 0.40 ng/mL [quartiles, 0.18-0.69], initial median 0.96 ng/mL [quartiles, 0.65-1.42], ＝.005); Group A showed a greater decrease than Group B ( < .001). No difference was found between the microbial loads of species DNA in the initial and follow-up amniocentesis ( = .13).
In patients with PPROM and intra-amniotic infection, IL-6 levels in the amniotic fluid decreased significantly from before antimicrobial administration to day 7. This decrease is thought to be mainly due to the effects of intravenous AZM. The efficacy of AZM in patients with PPROM needs to be further confirmed randomized controlled studies in the future.
羊膜内感染会增加早产及胎儿短期和长期发病率的风险；然而，对于这些感染的治疗药物选择，目前尚未达成共识。本研究旨在探讨对于胎膜早破（PPROM）孕妇，羊膜内感染时使用氨苄西林/舒巴坦（SBT/ABPC）联合阿奇霉素（AZM）静脉给药治疗的疗效。
本研究采用单中心回顾性队列设计。我们比较了妊娠 22+0 周至 33+6 周期间发生 PPROM 且羊膜内存在感染（A 组）或无羊膜内炎症（IAI）或微生物经羊膜腔侵袭（MIAC）（B 组）的单胎妊娠患者羊水中白细胞介素 6（IL-6）水平和 种 DNA 负荷的变化。这些患者在确诊后维持妊娠≥7d。A 组患者接受 SBT/ABPC 和 AZM 治疗，B 组患者接受 ABPC 和 AZM 或克拉霉素治疗。
31 例 IAI 患者和 48 例无 IAI 或 MIAC 患者在我院接受妊娠/分娩管理。经过研究人群选择，我们评估了 A 组的 6 例患者和 B 组的 13 例患者。A 组所有 6 例患者初始羊膜穿刺时的羊水中 IL-6 浓度较高，范围为 11.7ng/mL 至 139.2ng/mL，表明所有患者均存在严重的 IAI。A 组 6 例患者中，有 5 例在第一次羊膜穿刺时的培养中仅包括 种。在两组中，随访羊膜穿刺术时的羊水中 IL-6 浓度均低于初始羊膜穿刺术（A 组：随访中位数 3.06ng/mL [四分位距，1.75-6.74]，初始中位数 30.53ng/mL [四分位距，15.60-67.07]，＝.03；B 组：随访中位数 0.40ng/mL [四分位距，0.18-0.69]，初始中位数 0.96ng/mL [四分位距，0.65-1.42]，＝.005）；A 组的下降幅度大于 B 组（ < .001）。两组初始和随访羊膜穿刺术时 种 DNA 的微生物负荷无差异（ = .13）。
对于胎膜早破合并羊膜内感染的患者，在开始使用抗生素治疗前至第 7 天，羊水中的 IL-6 水平显著下降。这种下降可能主要是由于 AZM 的静脉给药作用。未来需要进一步开展随机对照研究来确认 AZM 在胎膜早破患者中的疗效。
