Antibiotic prophylaxis in pregnant with premature rupture of ovular membranes: systematic review and meta-analysis

Pereira, Ana Maria Gomes; Pannain, Gabriel Duque; Esteves, Bruna Helena Gonçalez; Bacci, Maria Luiza de Lima; Rocha, Maria Luiza Toledo Leite Ferreira da; Lopes, Reginaldo Guedes Coelho

doi:10.31744/einstein_journal/2022RW0015

Brasil

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Review • Einstein (São Paulo) 20 • 2022 • https://doi.org/10.31744/einstein_journal/2022RW0015 linkcopy

Antibiotic prophylaxis in pregnant with premature rupture of ovular membranes: systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective To perform a systematic review and meta-analysis of randomized clinical trials that compared the use of antibiotics versus placebo in premature rupture of membranes preterm and evaluated maternal, fetal and neonatal outcomes in pregnant women with premature rupture of ovular membranes at a gestational age between 24 and 37 weeks.

Methods A search was conducted using keywords in PubMed, Cochrane, Biblioteca Virtual em Saúde and Biblioteca Digital de Teses e Dissertações da USP between August 2018 and December 2021. A total of 926 articles were found. Those included were randomized clinical trials that compared the use of antibiotics versus placebo in the premature rupture of preterm membranes. Articles referring to antibiotics only for streptococcus agalactiae prophylaxis were excluded. The retrieved articles were independently and blindly analyzed by two reviewers. A total of 24 manuscripts met the inclusion criteria and 21 articles were included for quantitative analysis.

Results Among the maternal outcomes analyzed, there was a prolongation of the latency period that was ≥7 days. In addition, we observed a reduction in chorioamnionitis in the group of pregnant women who used antibiotics. As for endometritis and other maternal outcomes, there was no statistically significant difference between the groups. Regarding fetal outcomes, antibiotic prophylaxis worked as a protective factor for neonatal sepsis. Necrotizing enterocolitis and respiratory distress syndrome showed no statistically significant differences.

Conclusion The study showed positive results in relation to antibiotic prophylaxis to prolong the latency period, new randomized clinical trials are needed to ensure its beneficial effect.

Prospero database registration (www.crd.york.ac.uk/prospero) under number CRD42020155315.

Keywords Fetal membranes; premature rupture; Gestational age; Pregnant women; Antibiotic prophylaxis; Anti-bacterial agents; Infant; premature

Author	Gestational age	Number of participants	Gestational age rupture Intervention average/median	Gestational age rupture Control mean/median
Almeida et al.,(⁹)	37	106	32 (±2.1)	31.7 (±4.0)
Amon et al.,(¹⁰)	34	82	NR	NR
Camli et al.,(¹¹)	34	31	NR	NR
Christmas et al.,(¹²)	34	94	30.4	29.9
Cox et al.,(¹³)	34	62	26.9 (±1.9)	26.7 (±2.2)
August Fuhr et al.,(¹⁴)	34	105	NR	NR
Garcia-Burguillo et al.,(¹⁵)	37	60	NR	NR
Grable et al.,(¹⁶)	37	60	NR	NR
Johnston et al.,(¹⁷)	34	85	29.5 (±0.70)	30.3 (±0.5)
Kenyon et al.,(¹⁸)	37	4,809	E 27.5 (±6.1) AXC 28.0 (±6.0) AXCE 27.8 (±6.1)	27.9 (±6.1)
Kurki et al.,(¹⁹)	37	101	32.4 (±2.3)	32.3 (±2.4)
Lockwood et al.,(²⁰)	37	75	NR	NR
Lovett et al.,(²¹)	37	102	ASAXC 30.17 (±0.57) AAXC 29.73 (±0.42)	29.58 (±0.54)
Magwali et al.,(²²)	37	170	32.8 (±2.7)	32.8 (±2.5)
McCaul et al.,(²³)	34	37	NR	NR
McGregor et al.,(²⁴)	37	55	30.5 (±3.5)	31.5 (±2.8)
Mercer et al.,(²⁵)	37	220	30.3 (±3.4)	29.8 (±3.6)
Mercer,(²⁶)	34	614	28.6 (±2.2)	28.5 (±2.4)
Morales et al.,(²⁷)	34	78	29.4 (±2.3)	29.3 (± 2.7)
Ovalle et al.,(²⁸)	34	88	29.9 (±2.5)	29.3 (± 2.9)
Svare et al.,(²⁹)	34	67	NR	NR

Author	Intervention	Corticosteroid	Tocolysis	Intervention duration
Almeida et al.,(⁹)	AX 750mg 8/8 hours VO	NR	NR	NR
Amon et al.,(¹⁰)	A 1g 6/6 hours IV for 24 hours + A 500mg 6/6 hours VO until delivery	SN	Yes	Until birth
Camli et al.,(¹¹)	A 1g 6/6 hours IV	NR	No	NR
Christmas et al.,(¹²)	AGC (A 2g 6/6 hours IV + G 60-90mg 8/8 hours IV + C 900mg 8/8 hours IV) 1 day, AXC 500 + 125mg 8/8 hours 7 days VO	No	No	7 days
Cox et al.,(¹³)	AS 1+2g 6/6 hours 4 doses IV, AXC 500 + 125mg 6/6 hours VO for 5 days	NR	NR	5 days
August Fuhr et al.,(¹⁴)	MZ 2g 8/8 hours IV 7 days	Yes	Yes	7 days
Garcia-Burguillo et al.,(¹⁵)	E 500mg 6/6 hours VO until birth	No	No	Until birth
Grable et al.,(¹⁶)	A 2g 6/6 hours IV (1 day) + A 500mg 6/6 hours VO until birth	NR	NR	Until birth
Johnston et al.,(¹⁷)	MZ por 2 days + A VO	No	No	Until birth
Kenyon et al.,(¹⁸)	AXC 250 + 125mg 8/8 hours VO + E 250mg VO AXC 250 + 125mg 8/8 hours VO E 250mg	SN	SN	Until birth
Kurki et al.,(¹⁹)	P 5000mUI 2 doses IV	NR	Yes	1 day
Lockwood et al.,(²⁰)	PP 3g 6/6 hours IV 72 hours	SN	SN	3 days
Lovett et al.,(²¹)	AS 1.5g 6/6 hours IV 72 hours + AXC 500+125mg 8/8 hours A 2g IV 72 hours + AXC 500+125mg 8/8 hours	SN	Yes	Until birth
Magwali et al.,(²²)	AXC VO 5 days	SN	NR	5 days
McCaul et al.,(²³)	A 2g IV + A 500mg 6/6 hours 7 days	No	No	7 days
McGregor et al.,(²⁴)	E 333mg 8/8 hours	No	No	NR
Mercer et al.,(²⁵)	E 333mg 8/8 hours	SN	SN	NR
Mercer,(²⁶)	A 2g 6/6 hours + E 250mg 6/6 hours IV AX 250mg 8/8 hours VO + E 333mg 8/8 hours VO 5 days	No	No	5 days
Morales et al.,(²⁷)	A 2g 6/6 hours	No	No	NR
Ovalle et al.,(²⁸)	CG (C 600mg 6/6 hours IV + G 4mg/kg/day 48 hours) and CG (C 300mg 6/6 hours + G 2mg/kg/day 12/12 hours) IM	NR	NR	5 days
Svare et al.,(²⁹)	A 2g 6/6 hours IV (1 day) and M 500mg 8/8 hours IV (1 day) + PVM (PV 500mg 8/8 hours 7 days + M 400mg 8/8 hours) VO	NR	NR	7 days

Author	Intervention latency (≥7 days)	Control latency (≥7 days)	Chorioamnionitis Intervention	Chorioamnionitis Control	Endometritis Intervention	Endometritis Control	Maternal sepsis Intervention	Maternal sepsis Control	Maternal death Intervention	Maternal death Control
Almeida et al.,(⁹)	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR
Amon et al.,(¹⁰)	20/43	10/39	7/43	4/39	5/43	3/39	NR	NR	NR	NR
Camli et al.,(¹¹)	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR
Christmas et al.,(¹²)	20/48	7/46	5/48	8/46	3/48	1/46	NR	NR	NR	NR
Cox et al.,(¹³)	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR
August Fuhr et al.,(¹⁴)	30/47	26/58	NR	NR	NR	NR	NR	NR	NR	NR
Garcia Burguillo et al.,(¹⁵)	NR	NR	3/30	1/30	NR	NR	NR	NR	NR	NR
Grable et al.,(¹⁶)	NR	NR	4/31	8/29	NR	NR	NR	NR	NR	NR
Johnston et al.,(¹⁷)	18/40	8/45	3/40	16/45	5/40	15/45	NR	NR	0/40	0/45
Kenyon et al.,(¹⁸)	1767/3,584	775/1,225	NR	NR	NR	NR	896/3,584	330/1,225	NR	NR
Kurki et al.,(¹⁹)	NR	NR	1/50	7/51	0/50	1/51	0/50	0/51	NR	NR
Lockwood et al.,(²⁰)	16/38	4/37	10/35	10/37	NR	NR	NR	NR	NR	NR
Lovett et al.,(²¹)	NR	NR	11/75	12/37	NR	NR	NR	NR	NR	NR
Magwali et al.,(²²)	15/82	6/86	14/82	20/86	NR	NR	10/82	17/86	NR	NR
McCaul et al.,(²³)	NR	NR	10/41	9/43	NR	NR	10/41	9/43	NR	NR
McGregor et al.,(²⁴)	NR	NR	7/28	6/27	NR	NR	NR	NR	NR	NR
Mercer et al.,(²⁵)	29/106	20/114	NR	NR	NR	NR	NR	NR	NR	NR
Mercer,(²⁶)	NR	NR	69/299	101/312	NR	NR	0/299	0/312	0/299	0/312
Morales et al.,(²⁷)	NR	NR	0/37	16/41	NR	NR	NR	NR	NR	NR
Ovalle et al.,(²⁸)	NR	NR	2/42	11/45	NR	NR	NR	NR	NR	NR
Svare et al.,(²⁹)	NR	NR	6/30	5/37	NR	NR	NR	NR	0/30	0/37

Author	Gestational age at delivery Mean intervention (SD)	Gestational age at delivery Mean control (SD)	Weight newborn± Average Intervention (SD)	Weight newborn Control (SD)	Apgar5 <7 Intervention	Apgar5 <7 Control	Neonatal death Intervention	Neonatal death Control
Almeida et al.,(⁹)	NR	NR	2,094 (±459)	2,045 (±462)	NR	NR	NR	NR
Amon et al.,(¹⁰)	31.5 (±3.3)	30.7 (±3.2)	1,670 (±580)	1,742 (±846)	5/42	6/36	1/42	3/36
Camli et al.,(¹¹)	NR	NR	NR	NR	NR	NR	NR	NR
Christmas et al.,(¹²)	31.4	30.7	1,639	1,839	NR	NR	NR	NR
Cox et al.,(¹³)	26.8 (±5.4)	27.9 (±2.1)	1,282 (±409)	1,305 (±413)	NR	NR	1/31	5/31
August Fuhr et al.,(¹⁴)	NR	NR	NR		NR	NR	NR	NR
Garcia-Burguillo et al.,(¹⁵)	NR	NR	2,022 (±607)	2,170 (±799.7)	NR	NR	NR	NR
Grable et al.,(¹⁶)	NR	NR	NR	NR	NR	NR	NR	NR
Johnston et al.,(¹⁷)	NR	NR	1,897 (±600)	1,587 (±592)	NR	NR	3/40	3/45
Kenyon et al.,(¹⁸)	NR	NR	2,103 (±764)	2,072 (±769)	NR	NR	226/3,584	82/1,225
Kurki et al.,(¹⁹)	33.2 (±2.1)	33.1 (±1.8)	2,124 (±390)	2,090 (±516)	5/57	8/58	1/57	1/58
Lockwood et al.,(²⁰)	31.7 (±3.5)	31.2 (±3.3)	1,837 (±759)	1,697 (±581)	3/37	3/35	2/37	2/35
Lovett et al.,(²¹)	NR	NR	ASAXC 1,870 (±101) AAXC 1,674 (±71)	1,543 (±95)	NR	NR	0/76	3/37
Magwali et al.,(²²)	NR	NR	1,985	2,150	NR	NR	8/82	11/86
McCaul et al.,(²³)	30.1 (±2.7)	31.2 (±3.9)	1,724 (±587.3)	1,925.3 (±842.5)	NR	NR	NR	NR
McGregor et al.,(²⁴)	31.4 (±3.4)	32.3 (±2.3)	1,638,5 (±530,8)	1,741,4 (±444)	NR	NR	6/28	0/27
Mercer et al.,(²⁵)	NR	NR	1,771 (±653)	1,817 (±637)	15/107	20/109	1/106	3/114
Mercer,(²⁶)	NR	NR	1,549 (±497)	1,457 (±508)	NR	NR	19/299	18/312
Morales et al.,(²⁷)	NR	NR	NR	NR	NR	NR	NR	NR
Ovalle et al.,(²⁸)	NR	NR	1,849 (±458.4)	1,645 (±521.4)	NR	NR	4/11	3/13
Svare et al.,(²⁹)	NR	NR	1,962 (±712)	1,838 (±785)	NR	NR	NR	NR

Author	RDS Intervention	RDS Control	NEC Intervention	NEC Control	Neonatal sepsis Intervention	Neonatal sepsis Control
Almeida et al.,(⁹)	NR	NR	NR	NR	NR	NR
Amon et al.,(¹⁰)	18/42	15/36	5/42	4/36	1/42	6/36
Camli et al.,(¹¹)	NR	NR	NR	NR	NR	NR
Christmas et al.,(¹²)	20/48	21/46	4/48	2/46	0/46	2/48
Cox et al.,(¹³)	27/31	21/31	5/31	0/31	0/31	1/31
August Fuhr et al.,(¹⁴)	7/47	11/58	1/47	3/58	1/47	7/58
Garcia-Burguillo et al.,(¹⁵)	7/30	6/30	NR	NR	4/30	5/30
Grable et al.,(¹⁶)	6/31	9/29	1/31	1/29	NR	NR
Johnston et al.,(¹⁷)	6/40	11/45	2/40	3/45	3/40	11/45
Kenyon et al.,(¹⁸)	719/3,584	266/1,225	117/3,584	33/1,225	233/3,584	100/1,225
Kurki et al.,(¹⁹)	NR	NR	NR	NR	0/57	1/58
Lockwood et al.,(²⁰)	23/37	20/35	2/37	0/35	2/37	3/35
Lovett et al.,(²¹)	18/75	14/37	NR	NR	6/75	6/37
Magwali et al.,(²²)	NR	NR	NR	NR	13/82	21/86
McCaul et al.,(²³)	8/41	6/43	NR	NR	2/41	3/43
McGregor et al.,(²⁴)	15/26	15/25	2/26	4/27	1/24	1/27
Mercer et al.,(²⁵)	27/107	24/109	8/107	12/109	14/107	15/109
Mercer,(²⁶)	121/299	152/312	24/299	27/312	16/299	20/312
Morales et al.,(²⁷)	21/37	20/41	1/37	3/37	1/37	5/41
Ovalle et al.,(²⁸)	5/11	3/13	0/42	1/43	7/42	7/43
Svare et al.,(²⁹)	3/30	3/37	0/30	1/37	7/30	16/37

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[TFN1] NR: not reported; E: Erythromycin; AXC: Amoxicillin + Clavulanate; AXCE: Amoxicillin + Clavulanate + Erythromycin; ASAXC: Ampicillin + Sulbactam + Amoxicillin + Clavulanate; AAXC: Ampicillin + Amoxicillin + Clavulanate.