A new anti-microbial combination prolongs the latency period, reduces acute histologic chorioamnionitis as well as funisitis, and improves neonatal outcomes in preterm PROM

Abstract

Objective Antibiotic administration is a standard practice in preterm premature rupture of membranes (PROM). Specific antimicrobial agents often include ampicillin and/or erythromycin. Anaerobes and genital mycoplasmas are frequently involved in preterm PROM, but are not adequately covered by antibiotics routinely used in clinical practice. Our objective was to compare the outcomes of PROM treated with standard antibiotic administration versus a new combination more effective against these bacteria. Study Design A retrospective study compared perinatal outcomes in 314 patients with PROM <34 weeks receiving antimicrobial regimen 1 (ampicillin and/or cephalosporins; n=195, 1993–2003) versus regimen 2 (ceftriaxone, clarithromycin, and metronidazole; n=119, 2003–2012). Intra-amniotic infection/inflammation was assessed by positive amniotic fluid culture and/or an elevated amniotic fluid MMP-8 concentration (>23ng/mL). Results 1) Patients treated with regimen 2 had a longer median antibiotic-to-delivery interval than those with regimen 1 [median (interquartile range) 23 days (10–51 days) versus 12 days (5–52 days), p<0.01]; 2) patients who received regimen 2 had lower rates of acute histologic chorioamnionitis (50.5% vs. 66.7%, p<0.05) and funisitis (13.9% versus 42.9%, p<0.001) than those who had received regimen 1; 3) the rates of intra-ventricular hemorrhage (IVH) and cerebral palsy (CP) were significantly lower in patients allocated to regimen 2 than regimen 1 (IVH: 2.1% versus 19.0%, p<0.001 and CP: 0% vs. 5.7%, p<0.05); and 4) subgroup analysis showed that regimen 2 improved perinatal outcomes in pregnancies with intra-amniotic infection/inflammation, but not in those without intra-amniotic infection/inflammation (after adjusting for gestational age and antenatal corticosteroid administration). Conclusion A new antibiotic combination consisting of ceftriaxone, clarithromycin, and metronidazole prolonged the latency period, reduced acute histologic chorioamnionitis/funisitis, and improved neonatal outcomes in patients with preterm PROM. These findings suggest that the combination of antimicrobial agents (ceftriaxone, clarithromycin, and metronidazole) may improve perinatal outcome in preterm PROM.

The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis

“…66,67 A recent study, however, examined treatment with an antibiotic regimen of ceftriaxone, clarithromycin, and metro-nidazole, which the authors found reduced histologic chorioamnionitis and funisitis. 68 Therefore, further investigation is necessary to understand how antibiotics may or may not alter the placental membrane microbiome.…”

Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome

“…This antibiotic combination was also associated with a more successful eradication of intra-amniotic inflammation/infection and prevented secondary intraamniotic inflammation/infection more frequently than an antibiotic regimen which included ampicillin and/or cephalosporins in patients with PPROM [108].…”

“…Lee et al found that the combination of ceftriaxone, clarithromycin and metronidazole prolonged the latency period, reduced acute histologic chorioamnionitis/funisitis, and improved neonatal outcomes in patients with PPROM, especially with a intra-amniotic infection/ inflammation assessing by positive amniotic fluid culture and/or an elevated amniotic fluid MMP-8 concentration (>23 ng/mL) [107,108]. This antibiotic combination was also associated with a more successful eradication of intra-amniotic inflammation/infection and prevented secondary intraamniotic inflammation/infection more frequently than an antibiotic regimen which included ampicillin and/or cephalosporins in patients with PPROM [108].…”

Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance

“…Biofilms are also more common in infections associated with a device (e.g., intra-uterine contraceptive device, prosthetic valves, catheters). Notably, the eradication of intra-amniotic infection diagnosed by amniocentesis in patients with preterm prelabor rupture of membranes (PROM) 184, 185 and those with an asymptomatic short cervix 137 is possible with the administration of intravenous antibiotics to the mother. Success has been documented by demonstrating the absence of microorganisms at the time of a second amniocentesis 137, 184 .…”