Comparison of Azithromycin versus Erythromycin for Prolongation of Latency in Pregnancies Complicated by Preterm Premature Rupture of Membranes

Abstract

Objective To assess the impact on the duration of latency to delivery when a single oral dose of azithromycin is substituted for erythromycin in the standard antibiotic regimen used in pregnancies complicated by preterm premature rupture of membranes (PPROM).

Study Design A retrospective cohort study of singleton pregnancies complicated by PPROM between 23 and 33 6/7 weeks of gestation from January 2012 to June 2016. Patients prior to June 2014 received a standard antibiotic regimen of 7 days of erythromycin and ampicillin/amoxicillin. After this period, patients received a single oral dose of azithromycin 1 g substituted for erythromycin in this regimen. Primary outcome was latency from PPROM to delivery.

Results One hundred sixty-two women met the inclusion criteria, 84 in the erythromycin group and 78 in the azithromycin group. There was no difference in the median latency from PPROM to delivery between the groups (erythromycin: 6.37 days, interquartile range [IQR]: 3.59–10.93 vs. azithromycin: 5.86 days, IQR: 3.12–12.05, p = 0.75). There was a higher rate of cesarean delivery (48.8 vs. 29.5%, p = 0.01) and positive neonatal blood cultures (13.6 vs. 4.1%, p = 0.05) in the erythromycin group.

Conclusion There is no difference in latency to delivery when a single oral dose of azithromycin 1 g is substituted for erythromycin in the standard antibiotic regimen used in singleton pregnancies complicated by PPROM.

Keywords

azithromycin - erythromycin - latency - preterm premature rupture of membranes - antibiotics - preterm prelabor rupture of membranes

Condensation

Substitution of a single oral dose of azithromycin for erythromycin in pregnancies complicated by preterm premature rupture of membranes does not affect latency to delivery.

Note

This research was previously presented as a poster presentation at The Society for Maternal Fetal Medicine (abstract no. 383) on January 26, 2017 in Las Vegas, NV.

• References

• 1 Yudin MH, van Schalkwyk J, Van Eyk N. , et al; Society of Obstetricians and Gynaecologists of Canada. Antibiotic therapy in preterm premature rupture of the membranes. [Article in English, French] J Obstet Gynaecol Can 2009; 31 (09) 863-867 ; 868–874
• 2 Dudley J, Malcolm G, Ellwood D. Amniocentesis in the management of preterm premature rupture of the membranes. Aust N Z J Obstet Gynaecol 1991; 31 (04) 331-336
• 3 Porreco RP, Heyborne KD, Shapiro H. Amniocentesis in the management of preterm premature rupture of the membranes: a retrospective cohort analysis. J Matern Fetal Neonatal Med 2008; 21 (08) 573-579
• 4 Shim SS, Romero R, Hong JS. , et al. Clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 2004; 191 (04) 1339-1345
• 5 Witt A, Berger A, Gruber CJ. , et al. Increased intrauterine frequency of Ureaplasma urealyticum in women with preterm labor and preterm premature rupture of the membranes and subsequent cesarean delivery. Am J Obstet Gynecol 2005; 193 (05) 1663-1669
• 6 Rodríguez-Trujillo A, Cobo T, Vives I. , et al. Gestational age is more important for short-term neonatal outcome than microbial invasion of the amniotic cavity or intra-amniotic inflammation in preterm prelabor rupture of membranes. Acta Obstet Gynecol Scand 2016; 95 (08) 926-933
• 7 Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev 2010; (08) CD001058 . Doi: 10.1002/14651858.CD001058.pub2
• 8 Mercer BM, Miodovnik M, Thurnau GR. , et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. JAMA 1997; 278 (12) 989-995
• 9 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 172: Premature Rupture of Membranes. Obstet Gynecol 2016; 128 (04) e165-e177
• 10 Amsden GW. Erythromycin, clarithromycin, and azithromycin: are the differences real?. Clin Ther 1996; 18 (01) 56-7 ; discussion 55
• 11 Edwards MS, Newman RB, Carter SG, Leboeuf FW, Menard MK, Rainwater KP. Randomized clinical trial of azithromycin vs. erythromycin for the treatment of Chlamydia cervicitis in pregnancy. Infect Dis Obstet Gynecol 1996; 4 (06) 333-337
• 12 Hopkins S. Clinical toleration and safety of azithromycin. Am J Med 1991; 91 (3A): 40S-45S
• 13 Pierson RC, Gordon SS, Haas DM. A retrospective comparison of antibiotic regimens for preterm premature rupture of membranes. Obstet Gynecol 2014; 124 (03) 515-519
• 14 Drassinower D, Friedman AM, Običan SG, Levin H, Gyamfi-Bannerman C. Prolonged latency of preterm premature rupture of membranes and risk of neonatal sepsis. Am J Obstet Gynecol 2016; 214 (06) 743.e1-743.e6
• 15 Peaceman AM, Lai Y, Rouse DJ. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Length of latency with preterm premature rupture of membranes before 32 weeks' gestation. Am J Perinatol 2015; 32 (01) 57-62
• 16 American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric care consensus no. 1: safe prevention of the primary cesarean delivery. Obstet Gynecol 2014; 123 (03) 693-711
• 17 Isaacs D. ; Australasian Study Group For Neonatal Infections. A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units. Arch Dis Child Fetal Neonatal Ed 2003; 88 (02) F89-F93
• 18 Nelson MU, Gallagher PG. Methicillin-resistant Staphylococcus aureus in the neonatal intensive care unit. Semin Perinatol 2012; 36 (06) 424-430
• 19 Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988; 319 (15) 972-978
• 20 Yoon BH, Romero R, Park JS. , et al. Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments. Am J Obstet Gynecol 1998; 179 (05) 1254-1260
• 21 Acosta EP, Grigsby PL, Larson KB. , et al. Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model. J Infect Dis 2014; 209 (06) 898-904
• 22 Ramsey PS, Vaules MB, Vasdev GM, Andrews WW, Ramin KD. Maternal and transplacental pharmacokinetics of azithromycin. Am J Obstet Gynecol 2003; 188 (03) 714-718
• 23 Azithromycin: pharmacokinetics (2017). In Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Available at: http://www.micromedexsolutions.com Accessed April 15, 2017
• 24 Mercer BM. Is there a role for tocolytic therapy during conservative management of preterm premature rupture of the membranes?. Clin Obstet Gynecol 2007; 50 (02) 487-496
• 25 Nijman TA, van Vliet EO, Naaktgeboren CA. , et al. Nifedipine versus placebo in the treatment of preterm prelabor rupture of membranes: a randomized controlled trial: assessment of perinatal outcome by use of tocolysis in early labor-APOSTEL IV trial. Eur J Obstet Gynecol Reprod Biol 2016; 205: 79-84
• 26 Ehsanipoor RM, Shrivastava VK, Lee RM. , et al. A randomized, double-masked trial of prophylactic indomethacin tocolysis versus placebo in women with premature rupture of membranes. Am J Perinatol 2011; 28 (06) 473-478