In the management of preterm premature rupture of membranes (PPROM), a combination therapy of fosfomycin, clindamycin, and metronidazole has shown superiority over erythromycin plus metronidazole, while azithromycin has emerged as a promising alternative to erythromycin, with both regimens associated with favourable outcomes, as shown in two studies presented at RCOG 2024.

Novel antibiotic combination regimen

The first study included 78 patients with PPROM aged 22?38 years and between 29 and 34 weeks of gestation who presented to a tertiary referral hospital for expectant management.

Of the patients, 41 received oral fosfomycin (6 gm daily) plus IV clindamycin (600 mg every 8 hours) and IV metronidazole (500 mg twice daily) (protocol A), and 37 were initiated on oral erythromycin (250 mg four times daily) plus IV metronidazole (500 mg twice daily) (protocol B). Treatment was given for 7 days. In addition to the antibiotic regimen, all patients received 12 mg of dexamethasone, two doses administered 12 hours apart, and 4 gm of magnesium sulfate.

Maternal and neonatal outcomes examined were significantly better in patients who received the antibiotic protocol A. Compared with erythromycin plus metronidazole, fosfomycin plus clindamycin and metronidazole was associated with longer latency period (p=0.031), later gestational age at delivery (p<0.05), and fewer cases of clinical chorioamnionitis (p=0.042) and respiratory distress syndrome among newborns (31.1 percent vs 49.2 percent; p<0.05). [RCOG 2024, abstract OS-03]

Postpartum endometritis also occurred with significantly less frequency in the protocol A than in the protocol B arm (p<0.05). There were no cases of neonatal sepsis and drug-related complications documented in either arm.

“PPROM is defined as the spontaneous rupture of the foetal membranes before 37 weeks of gestation, complicating approximately 3 percent of pregnancies and is one of the leading causes of prematurity. It is frequently associated with intra-amniotic infection,” said presenting author Dr Aisha Elbareg from Misrata University in Misrata, Libya.

“Antibiotic treatment is recommended to prolong the latency period and reduce foetal morbidity, decrease risk of clinical chorioamnionitis, and improve neonatal outcomes… The combination of fosfomycin with clindamycin and metronidazole … should be used as a first-line management of PPROM,” Elbareg said.

Azithromycin use

In the second study, which was conducted in India, a single dose of IV azithromycin (1 g) outperformed the standard 7-day course of oral erythromycin in terms of increasing latency period and reducing the incidence of chorioamnionitis.

The mean latency period was 5.05 days with azithromycin vs 4.33 days with erythromycin, with the difference reaching statistical significance (p=0.02). The incidence of chorioamnionitis was also significantly lower with azithromycin (p=0.03). [RCOG 2024, abstract OS-05]

There were no significant between-group differences noted for postpartum endometritis (p=0.22), MSAF (p=0.43), caesarean deliveries (p=0.66), and neonatal sepsis (p=0.36).

The analysis included 200 patients with PPROM between 24 and 33 weeks of gestation. These patients were randomly assigned to receive a single dose of 1-g intravenous azithromycin (n=100) or a 7-day course of 250-mg oral erythromycin given every 6 hours (n=100). Both treatment regimens included a 2-day course of IV ampicillin, followed by a 5-day course of oral amoxicillin. The patients were followed until 42 days after delivery.

“This interventional study is first of its kind in India,” and shows that azithromycin is efficacious in expectant management of PPROM, according to presenting author Dr Sifat Tanveer from Jawaharlal Nehru Medical College, Department of Obstetrics and Gynaecology in Aligarh, India.