Human Reproduction Archives
Human Reproduction Archives
Review Article Fetal Medicine

Antibiotic prophylaxis in preterm rupture of membranes

Daniela Cristina Schroff Machado, Joice de Moura Dias, Luiza Emylce Pelá Rosado

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 Preterm premature rupture of membranes (PPROM) occurs before 37 weeks of gestation, accounting for approximately one-third of cases of preterm birth and increased maternal and neonatal morbidity and mortality. Several protocols recommend expectant management between 24 and 36 weeks of gestation, in order to allow acomplishment of fetal maturation and to avoid the dramatic consequences of prematurity. Despite benefits related to gestational prolongation, the most feared risk from this protocol is the increase of maternal-fetal infection. For this reason, the use of prophylactic antibiotics is recommended, although there is no consensus regarding the best choice. The objective of the present review was to analyze the impact of antibiotic prophylaxis on maternal and neonatal outcomes in cases of PPROM. It was observed that further studies are needed with the aim of standardizing the best antibiotic regimen in PPROM, as well as defining the actual maternal and neonatal outcomes, at long term, from its use.


premature rupture of fetal membranes; antibiotic prophylaxis; review.


1. Morris JM, Roberts CL, Bowen JR, Patterson JA, Bond DM, Algert CS,  et  al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet. 2016;387(10017):444-52. PMid:26564381.

2. Brasil. Ministério da Saúde. Amniorrexe prematura e corioamnionite. 5th ed. Brasília: Editora MS; 2010. Gestação de alto risco: manual técnico; p. 79-84.

3. Gracia PV, Savransky R, Wuff JAP, Gutierréz JD, Morais EN. Premature rupture of membranes. Panamà: FLASOG; 2011. (Guía Clínica; 1).

4. Wojcieszek AM, Stock OM, Flenady V. Antibiotics for prelabour rupture of membranes at or near term. Cochrane Database Syst Rev. 2014;(10):CD001807. PMid:25352443.

5. Lajos GJ, Passini Jr R, Nomura ML, Amaral E, Pereira BG, Milanez H, et al. Colonização bacteriana do canal cervical em gestantes com trabalho de parto prematuro ou ruptura prematura de membranas. Rev Bras Ginecol Obstet. 2008;30(8):393-9. PMid:19142522.

6. American College of Obstetricians and Gynecologists. Practice bulletins No. 139: premature rupture of membranes. Obstet Gynecol. 2013;122(4):918-30. PMid:24084566.

7. Federação Brasileira das Associações de Ginecologia e Obstetrícia. Rotura prematura das membranas: projeto diretrizes. São Paulo: FEBRASGO; 2008.

8. Yudin MH, van Schalkwyk J, Eyk NV. Antibiotic therapy in preterm premature rupture of the membranes. J Obstet Gynaecol Can. 2009;31(9):863-7. PMid:19941711.

9. Sociedad Española de Ginecología y Obstetricia. Rotura prematura de membranas. Prog Obstet Ginecol. 2012;55:520-40.

10. Royal College of Obstetricians and Gynaecologists. Preterm prelabour rupture of membranes. London: RCOG; 2006. p. 2-12. (Green-Top Guideline; 44).

11. National Institute for Health and Care Excellence. Preterm labour and birth. NICE guideline. London: NICE; 2015.

12. World Health Organization. WHO recommendations on interventions to improve preterm birth outcome. Geneva: WHO; 2015.

13. Eleje GU, Adinma JI, Ghasi S, Ikechebelu JI, Igwegbe AO, Okonkwo JE,  et  al. Antibiotic susceptibility pattern of genital tract bacteria in pregnant women with preterm premature rupture of membranes in a resource-limited setting. Int J Gynaecol Obstet. 2014;127(1):10-4. PMid:24994495.

14. Sáez-López E, Guiral E, Fernández-Orth D, Villanueva S, Goncé A, López M, et al. Vaginal versus obstetric infection Escherichia coli isolates among pregnant women: antimicrobial resistance and genetic virulence profile. PLoS One. 2016;11(1):e0146531. PMid:26784330.

15. Lee MY, Kim MH, Lee WI, Kang SY, Jeon YL. Prevalence and antibiotic susceptibility of mycoplasma hominis and ureaplasma urealyticum in pregnant women. Yonsei Med J. 2016;57(5):1271-5. PMid:27401661.

16. Melo SCCS, Santos NCS, Oliveira M, Scodro RBL, Cardoso RF, Padua RAF,  et  al. Antimicrobial susceptibility of streptococcus agalactiae isolated from pregnant women. Rev Inst Med Trop Sao Paulo. 2016;58:83. PMid:27828624.

17. Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes: a randomized controlled trial. JAMA. 1997;278(12):989-95. PMid:9307346.

18. Ovalle A, Gómez R, Martínez MA, Rubio R, Fuentes A, Valderrama O, et al. Antibiotic therapy in patients with preterm premature rupture of membranes: A prospective, randomized, placebo-controlled study with microbiological assessment of the amniotic cavity and lower genital tract. Prenat Neonatal Med. 1997;2(3):213-22.

19. Lovett SM, Weiss JD, Diogo MJ, Williams PT, Garite TJ. A prospective, double-blind, randomized, controlled clinical trial of ampicillin-sulbactam for preterm premature rupture of membranes in women receiving antenatal corticosteroid therapy. Am J Obstet Gynecol. 1997;176(5):1030-8. PMid:9166164.

20. Kenyon SL, Taylor DJ, Tarnow-Mordi W. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet. 2001;357(9261):979-88. PMid:11293640.

21. Ryo E, Ikeya M, Sugimoto M. Clinical study of the effectiveness of imipenem/cilastatin sodium as the antibiotics of first choice in the expectant management of patients with preterm premature rupture of membranes. J Infect Chemother. 2005;11(1):32-6. PMid:15729485.

22. Fuhr NA, Becker C, van Baalen A, Bauer K, Hopp H. Antibiotic therapy for preterm premature rupture of membranes: results of a multicenter study. J Perinat Med. 2006;34(3):203-6. PMid:16602839.

23. Ehsanipoor RM, Chung JH, Clock CA, McNulty JA, Wing DA. A retrospective review of ampicillin-sulbactam and amoxicillin + clavulanate vs. cefazolin/cephalexin and erythromycin in the setting of preterm premature rupture of membranes: maternal and neonatal outcomes. Am J Obstet Gynecol. 2008;198(5):e54-6.

24. Hernández y Ballinas A, López Farán JA, Gámez Guevara C. Comparación de resultados maternos y perinatales en el tratamiento conservador de la rotura prematura de membranas pretérmino entre el uso de eritromicina y clindamicina. Ginecol Obstet Mex. 2011;79(7):403-10. PMid:21966834.

25. Kwak HM, Shin MY, Cha HH, Choi SJ, Lee JH, Kim JS, et al. The efficacy of cefazolin plus macrolide (erythromycin or clarithromycin) versus cefazolin alone in neonatal morbidity and placental inflammation for women with preterm premature rupture of membranes. Placenta. 2013;34(4):346-52. PMid:23465535.

26. Nabhan AF, Elhelaly A, Elkadi M. Antibiotic prophylaxis in prelabor spontaneous rupture of fetal membranes at or beyond 36 weeks of pregnancy. Int J Gynaecol Obstet. 2014;124(1):59-62. PMid:24140220.

27. Pierson RC, Gordon SS, Haas DM. A Retrospective comparison of antibiotic regimens for preterm premature rupture of membranes. Obstet Gynecol. 2014;124(3):515-9. PMid:25162251.

28. Finneran MM, Appiagyei A, Templin M, Mertz H. Comparison of azithromycin vs. erythromycin for prolongation of latency interval in pregnancies complicated by preterm premature rupture of membranes. Am J Obstet Gynecol. 2017;216(1):S230-1.

29. Navathe RS, Heidari P, Ward A, Hoffman M, Berghella V, Roman A. Azithromycin vs. erythromycin for the management of preterm premature rupture of membranes. Am J Obstet Gynecol. 2017;216(1):S239-40.

30. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt A,  et  al. Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial. Lancet. 2008;372(9646):1310-8. PMid:18804274.

31. Marlow N, Bower H, Jones D, Brocklehurst P, Kenyon S, Pike K, et al. The ORACLE Children Study: educational outcomes at 11 years of age following antenatal prescription of erythromycin or co-amoxiclav. Arch Dis Child Fetal Neonatal Ed. 2017;102(2):F131-5. PMid:27515985.

32. Bendon RW, Faye-Petersen O, Pavlova Z, Qureshi F, Mercer B, Miodovnik M, et al. Fetal membrane histology in preterm premature rupture of membranes: comparison to controls, and between antibiotic and placebo treatment. The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network, Bethesda, MD, USA. Pediatr Dev Pathol. 1999;2(6):552-8. PMid:10508879.

33. Ovalle A, Martínez MA, Kakarieka E, Gómez R, Rubio R, Valderrama O, et al. Antibiotic administration in patients with preterm premature rupture of membranes reduces the rate of histological chorioamnionitis: a prospective, randomized, controlled study. J Matern Fetal Neonatal Med. 2002;12(1):35-41. PMid:12422907.

34. Mercer BM, Goldenberg RL, Das AF, Thurnau GR, Bendon RW, Miodovnik M, et al. What we have learned regarding antibiotic therapy for the reduction of infant morbidity after preterm premature rupture of the membranes. Semin Perinatol. 2003;27(3):217-30. PMid:12889589.

35. Gomez R, Romero R, Nien JK, Medina L, Carstens M, Kim YM, et al. Antibiotic administration to patients with preterm premature rupture of membranes does not eradicate intra-amniotic infection. J Matern Fetal Neonatal Med. 2007;20(2):167-73. PMid:17437216.

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