(644) Impact of Azithromycin Dose on Amniotic Fluid Cytokines in Preterm Premature Rupture of Membranes

Azithromycin is an antibiotic with both bacteriostatic and immunomodulatory effect. It is used in various obstetric settings including preterm premature rupture of membranes (PPROM). The impact of azithromycin dosing regimen on amniotic fluid inflammation in the setting of PPROM is unclear. We aimed to compare inflammatory cytokines in amniotic fluid in patients with PPROM who received 1g once vs 500mg dailyx7 days azithromycin for PPROM.

Study Design:

This is a planned secondary analysis of a prospective study of singletons with PPROM at two sites who received either 1g once or 500mg dailyx7d of azithromycin per site protocol. Amniotic fluid (AF) was collected opportunistically over a seven-day period from admission, non-invasively by extracting amniotic fluid from sanitary pads. ELISA assay was used to quantify pro-inflammatory cytokines IL-1a, IL-1b, IL-6, IL-8, and TNFa, and anti-inflammatory IL-10. Log-corrected values used for analysis; generalized estimated equations linear model was developed examining each cytokine, time from first dose, and dosing group. Two-sided alpha=0.05 used for all analyses.

Results:

16 (N=7with 1g once and N=9 with 500mg daily) participants with 109 amniotic fluid samples were included. Gestational age at enrollment was similar (28.2±3.1 vs 29.9±2.1 wks, p=0.22). There were significantly higher levels of IL-1a and TNFa (Figure) in those who had received 1g once azithromycin compared to 500mg daily, with similar trend observed for IL-1b and IL-6 (Table).

Conclusion:

In patients admitted with PPROM, treatment with 1g azithromycin once was associated with higher inflammatory cytokines in amniotic fluid compared to those who received 500mg daily. Prospective randomized trial is warranted to evaluate the impact of azithromycin dosing regimen on infectious/inflammatory outcomes in the setting of PPROM.