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Meta-Analysis
. 2014 Dec 19;2014(12):CD010976.
doi: 10.1002/14651858.CD010976.pub2.

Antibiotic regimens for management of intra-amniotic infection

Evelina Chapman  1 , Ludovic Reveiz, Eduardo Illanes, Xavier Bonfill Cosp
Affiliations
Meta-Analysis

Antibiotic regimens for management of intra-amniotic infection

Evelina Chapman et al. Cochrane Database Syst Rev. .

Abstract

Background: Chorioamnionitis is a common infection that affects both mother and infant. Infant complications associated with chorioamnionitis include early neonatal sepsis, pneumonia, and meningitis. Chorioamnionitis can also result in maternal morbidity such as pelvic infection and septic shock.Clinical chorioamnionitis is estimated to occur in 1% to 2% of term births and in 5% to 10% of preterm births; histologic chorioamnionitis is found in nearly 20% of term births and in 50% of preterm births. Women with chorioamnionitis have a two to three times higher risk for cesarean delivery and a three to four times greater risk for endomyometritis, wound infection, pelvic abscess, bacteremia, and postpartum hemorrhage.

Objectives: To assess the effects of administering antibiotic regimens for intra-amniotic infection on maternal and perinatal morbidity and mortality and on infection-related complications.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2014), CENTRAL, MEDLINE, Embase, LILACS, and the WHO ICTRP (September 2014). We also searched reference lists of retrieved studies and contacted experts in the field.

Selection criteria: Randomized controlled trials (RCTs) that included women who experienced intra-amniotic infection. Trials were included if they compared antibiotic treatment with placebo or no treatment (if applicable), treatment with different antibiotic regimens, or timing of antibiotic therapy (intrapartum and/or postpartum). Therefore, this review assesses trials evaluating intrapartum antibiotics, intrapartum and postpartum antibiotic regimens, and postpartum antibiotics. Diagnosis of intra-amniotic infection was based on standard criteria (clinical/test), and no limit was placed on gestational age.

Data collection and analysis: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data and checked them for accuracy. We assessed the quality of the evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and included a 'Summary of findings' table.

Main results: Our prespecified primary outcomes were maternal and neonatal mortality, maternal and neonatal severe infection, and duration of maternal and neonatal hospital stay.We included 11 studies (involving 1296 women) and assessed them as having low to moderate risk of bias - mainly because allocation concealment methods were not adequately reported, most studies were open, and outcome reporting was incomplete. The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. The following antibiotics were assessed in the included trials: ampicillin, ampicillin/sulbactam, gentamicin, clindamycin, and cefotetan. During labor: meta-analysis of two studies found no clear differences in rates of neonatal sepsis (163 neonates; risk ratio (RR) 1.07, 95% confidence interval (CI) 0.40 to 2.86; I² = 9%; low quality of evidence), treatment failure (endometritis) (163 participants; RR 0.86, 95% CI 0.27 to 2.70; I² = 0%; low quality of evidence), and postpartum hemorrhage (RR 1.39, 95% CI 0.76 to 2.56; I² = 0%; low quality of evidence) when two different dosages/regimens of gentamicin were assessed. No clear differences between groups were found for any reported maternal or neonatal outcomes. The review did not identify data for a comparison of antibiotics versus no treatment/placebo. Postpartum: meta-analysis of two studies that evaluated use of antibiotics versus placebo after vaginal delivery showed no significant differences between groups in rates of treatment failure or postpartum endometritis. No significant differences were found in rates of neonatal death and postpartum endometritis when use of antibiotics was compared with no treatment. Four trials assessing two different dosages/regimens of gentamicin or dual-agent therapy versus triple-agent therapy, or comparing antibiotics, found no significant differences in most reported neonatal or maternal outcomes; the duration of hospital stay showed a difference in favor of the group of women who received short-duration antibiotics (one study, 292 women; mean difference (MD) -0.90 days, 95% CI -1.64 to -0.16; moderate quality of evidence). Intrapartum versus postpartum: one small study (45 women) evaluating use of ampicillin/gentamicin during intrapartum versus immediate postpartum treatment found significant differences favoring the intrapartum group in the mean number of days of maternal postpartum hospital stay (one trial, 45 women; MD -1.00 days, 95% CI -1.94 to - 0.06; very low quality of evidence) and the mean number of neonatal hospital stay days (one trial, 45 neonates; MD -1.90 days, 95% CI -3.91 to -0.49; very low quality of evidence). Although no significant differences were found in the rate of maternal bacteremia or early neonatal sepsis, for the outcome of neonatal pneumonia or sepsis we observed a significant difference favoring intrapartum treatment (one trial, 45 neonates; RR 0.06, 95% CI 0.00 to 0.95; very low quality of evidence).

Authors' conclusions: This review included 11 studies (having low to moderate risk of bias). The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. Only one outcome (duration of hospital stay) was considered to provide moderate quality of evidence when antibiotics (short duration) were compared with antibiotics (long duration) during postpartum management of intra-amniotic infection. Our main reasons for downgrading the quality of evidence were limitations in study design or execution (risk of bias), imprecision, and inconsistency of results.Currently, limited evidence is available to reveal the most appropriate antimicrobial regimen for the treatment of patients with intra-amniotic infection; whether antibiotics should be continued during the postpartum period; and which antibiotic regimen or what treatment duration should be used. Also, no evidence was found on adverse effects of the intervention (not reported in any of the included studies). One small RCT showed that use of antibiotics during the intrapartum period is superior to their use during the postpartum period in reducing the number of days of maternal and neonatal hospital stay.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
3.1
3.1. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 1 Treatment failure (endometritis).
3.2
3.2. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 2 Initial successful response to antibiotics.
3.3
3.3. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 3 Maximum maternal temperature.
3.4
3.4. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 4 Postpartum hemorrhage.
3.5
3.5. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 5 Blood transfusion.
3.6
3.6. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 6 Maternal postpartum hospital stay (days).
3.7
3.7. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 7 Histologic chorioamnionitis.
3.8
3.8. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 8 Neonatal sepsis.
3.9
3.9. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 9 Respiratory distress syndrome.
3.10
3.10. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 10 Neonatal antibiotic (days).
3.11
3.11. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 11 Treatment failure.
3.12
3.12. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 12 Maternal death.
3.13
3.13. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 13 Postpartum endometritis (double vs triple therapy).
3.14
3.14. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 14 Postpartum endometritis vaginal delivery (double vs triple therapy).
3.15
3.15. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 15 Postpartum endometritis cesarean section (double vs triple therapy).
3.16
3.16. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 16 Neonatal sepsis (blood culture).
3.17
3.17. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 17 Neonatal deaths.
3.18
3.18. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 18 Intraventricular hemorrhage.
3.19
3.19. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 19 Respiratory distress syndrome.
3.20
3.20. Analysis
Comparison 3 Antibiotics versus antibiotics during labor, Outcome 20 Neonatal seizures.
4.1
4.1. Analysis
Comparison 4 Antibiotics versus no treatment during postpartum period, Outcome 1 Postpartum endometritis.
4.2
4.2. Analysis
Comparison 4 Antibiotics versus no treatment during postpartum period, Outcome 2 Wound infection.
4.3
4.3. Analysis
Comparison 4 Antibiotics versus no treatment during postpartum period, Outcome 3 Neonatal sepsis.
4.4
4.4. Analysis
Comparison 4 Antibiotics versus no treatment during postpartum period, Outcome 4 Neonatal death.
4.5
4.5. Analysis
Comparison 4 Antibiotics versus no treatment during postpartum period, Outcome 5 Trasient tachypnea.
5.1
5.1. Analysis
Comparison 5 Antibiotics versus placebo during postpartum period, Outcome 1 Treatment failure.
5.2
5.2. Analysis
Comparison 5 Antibiotics versus placebo during postpartum period, Outcome 2 Endomyometritis.
5.3
5.3. Analysis
Comparison 5 Antibiotics versus placebo during postpartum period, Outcome 3 Wound infection.
5.4
5.4. Analysis
Comparison 5 Antibiotics versus placebo during postpartum period, Outcome 4 Maternal sepsis.
5.5
5.5. Analysis
Comparison 5 Antibiotics versus placebo during postpartum period, Outcome 5 Readmission to hospital.
6.1
6.1. Analysis
Comparison 6 Antibiotic versus antibiotics during postpartum period, Outcome 1 Treatment failure.
6.2
6.2. Analysis
Comparison 6 Antibiotic versus antibiotics during postpartum period, Outcome 2 Nephrotoxicity.
6.3
6.3. Analysis
Comparison 6 Antibiotic versus antibiotics during postpartum period, Outcome 3 Length of treatment (days).
7.1
7.1. Analysis
Comparison 7 Antibiotics (short duration) versus antibiotics (long duration) in postpartum, Outcome 1 Duration of hospital stay (days).
7.2
7.2. Analysis
Comparison 7 Antibiotics (short duration) versus antibiotics (long duration) in postpartum, Outcome 2 Treatment failure (vaginal and cesarean delivery).
7.3
7.3. Analysis
Comparison 7 Antibiotics (short duration) versus antibiotics (long duration) in postpartum, Outcome 3 Treatment failure (cesarean delivery).
7.4
7.4. Analysis
Comparison 7 Antibiotics (short duration) versus antibiotics (long duration) in postpartum, Outcome 4 Treatment failure (vaginal delivery).
7.5
7.5. Analysis
Comparison 7 Antibiotics (short duration) versus antibiotics (long duration) in postpartum, Outcome 5 Wound infection.
7.6
7.6. Analysis
Comparison 7 Antibiotics (short duration) versus antibiotics (long duration) in postpartum, Outcome 6 Pelvic abscess.
8.1
8.1. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 1 Maximum maternal temperature postpartum.
8.2
8.2. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 2 Maternal postpartum hospital stay (days).
8.3
8.3. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 3 Maternal febrile days.
8.4
8.4. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 4 Maternal bacteremia.
8.5
8.5. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 5 Early neonatal sepsis.
8.6
8.6. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 6 Neonatal pneumonia or sepsis.
8.7
8.7. Analysis
Comparison 8 Intrapartum versus postpartum treatment, Outcome 7 Neonatal hospital stay.
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Update of

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