Expert Commentary

Is azithromycin a good alternative to erythromycin for PPROM prophylaxis?

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Yes. There were no significant differences in time from preterm premature rupture of membranes (PPROM) to labor onset, adverse drug effects, and adverse fetal effects in 168 women taking ampicillin plus either azithromycin or erythromycin in this retrospective study.

Pierson RC, Gordon SS, Haas DM. A retrospective comparison of antibiotic regimens for preterm premature rupture of membranes. Obstet Gynecol. 2014;124(3):515-519.


 

References

The objective of this investigation by Pierson and colleagues was to determine if there was any significant difference between erythyromycin and azithromycin, used in combination with ampicillin, for prophylaxis in women with PPROM.

Details of the study
The authors conducted a retrospective study of 168 women at 24 to 34 weeks’ gestation. At the discretion of the attending physician, patients received either ampicillin plus erythromycin or ampicillin plus azithromycin as their prophylactic antibiotic regimen. Patients were excluded from the study if they had a cerclage, a multiple gestation, a history of amniocentesis or fetal surgery, a history of abdominal trauma, or if they had a fetus with a lethal anomaly.

The primary study end point was the duration of the latency period between rupture of membranes and onset of labor. The secondary outcomes were gestational age at delivery, adverse drug effects, neonatal birth weight, Apgar scores, and rates of neonatal death, respiratory distress syndrome, and sepsis.

The mean (SD) duration of the latent period was 9.4 (10.4) days in the azithromycin group and 9.6 (13.2) days in the erythromycin group (P = .4). There also were no significant differences in any of the secondary outcome measures. Accordingly, the authors concluded that azithromycin was an acceptable alternative to erythromycin in the prophylactic antibiotic regimen for patients with PPROM.

Several factors make azithromycin the favored PPROM prophylactic option
In the original Maternal-Fetal Medicine Network trial of prophylactic antibiotics for PPROM, Mercer and colleagues1 used the combination regimen of ampicillin plus erythromycin. In this regimen, ampicillin primarily targets group B streptococci and Escherichia coli. Erythromycin specifically targets mycoplasma organisms, which can be part of the polymicrobial flora that causes chorioamnionitis. The drug also is effective against chlamydia.

However, erythromycin may cause troublesome gastrointestinal adverse effects, notably diarrhea, in some patients. Therefore, in recent years, several investigators have advocated use of azithromycin in lieu of erythromycin. Azithromycin has a similar spectrum of activity as erythromycin, but it has a more favorable pharmacokinetic profile. When given in a single oral dose of 1,000 mg, it has a half-life of 68 hours, compared with erythromycin’s half-life of 1.6 hours. Thus, it is much easier to administer. Moreover, it is usually much better tolerated than erythromycin and, now that generic versions of the drug are available, it is relatively inexpensive.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although this study is retrospective (Level II evidence), it is the first to demonstrate that, from the perspective of clinical effectiveness, azithromycin is comparable to erythromycin when used in combination with ampicillin for prophylaxis in patients with PPROM. For the reasons outlined above, I strongly favor azithromycin in lieu of erythromycin.
At our center we administer the drug in a single 1,000-mg oral dose. If the patient cannot tolerate oral medication at the time of admission, the drug can be administered intravenously.

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