June 2009 SUPPORT Summary of a systematic review

Who is this summary for?

Which antibiotic regimens should be used for endometritis after delivery?

Postpartum endometritis, also known as puerperal fever, is caused by infection of the womb (uterus) during childbirth. It occurs in about 1% to 3% of births, and is up to ten times more common after caesarean section. The diagnosis of endometritis should be considered when a postpartum woman has febrile morbidity (oral temperature 38.0C on two occasions between day 1-10 after birth) abdominal pain or foul smelling lochia.

People making decisions concerning maternal health.

This summary is based on the following systematic review:

LM French, FM Smaill. Antibiotic regimens for endometritis after delivery. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD001067. DOI: 10.1002/14651858.CD001067.pub2.

What is a systematic review?

A summary of studies addressing a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise the relevant research, and to collect and analyse data from the included studies.

Key messages
The combination of gentamicin and clindamycin is effective for the treatment

of endometritis but is very expensive.

There is a need for more studies in low-income countries to evaluate optimal

antibiotic regimens and the cost-effectiveness of different antibiotic regimens.

Key findings from research based on a systematic review Considerations about the relevance of this research for low and middle income countries

This summary includes:

Recommendations Additional evidence not included in the systematic review Detailed descriptions of interventions or their implementation SUPPORT an international collaboration funded by the EU 6th Framework Programme to support the use of policy relevant reviews and trials to inform decisions about maternal and child health in low and middle-income countries. www.support-collaboration.org Glossary of terms used in this report: www.supportcollaboration.org/summaries/explanations.ht m Background references on this topic: See back page

Not included:

Background
Endometritis is a major cause of maternal death, particularly in developing countries. The predisposing factors or conditions leading to the development of endometritis are quite varied and include: prolonged rupture of membranes, prolonged labour, multiple vaginal examinations, obstetrical manoeuvres, etc. The incidence of endometritis is higher after caesarean section compared to vaginal delivery. Between 1% to 17% of women could have endometritis following caesarean section. Once endometritis is diagnosed, appropriate antibiotic treatment should be started.

How this summary was prepared

After searching widely for systematic reviews that can help inform decisions about health systems, we have selected ones that provide information that is relevant to low and middle-income countries. The methods used to assess the quality of the review and to make judgements about its relevance are described here: http://www.supportcollaboration.org/summaries/methods.htm

Knowing whats not known is important

A good quality review might not find any studies from low and middle-income countries or might not find any well-designed studies. Although that is disappointing, it is important to know what is not known as well as what is known.

Review objective: To study the effect of different antibiotic regimens for the treatment of postpartum endometritis on failure of therapy and complications. What the review authors searched for Interventions Trials if a comparison was made between different antibiotic regimens (including but not limited to different drug/drugs, different route of administration, and different duration of therapy). What the review authors found Thirty-nine trials (4221 women). Clindamycin and an aminoglycoside with another regimen (19 studies); aminoglycoside and penicillin or ampicillin with other regimens either clindamycin/gentamicin or piperacillin/tazobactam (2 studies), a beta-lactam/beta-lactamase inhibitor combination with any other regimen (12 studies); any second or third generation cephalosporin (excluding the cephamycins) with another regimen (usually clindamycin and gentamicin) (7 studies); aztreonam plus clindamycin with other regimens (4 studies); agents with a longer half-life to a drug in the same class with a shorter half-life (2 studies). Women with postpartum endometritis after caesarean section or vaginal delivery USA (32 studies), France (1 study), Mexico (2 studies), Italy (1 study), Peru (1 study), and Colombia (1 study). One study was a multicentre study. Therapeutic failure (37 studies); severe complications (18 studies); allergic reactions (16 studies); diarrhoea (17 studies); length of stay (12 studies), wound infection(12 studies); treatment failure post caesarean with prophylaxis (2 studies); nephrotoxicity (3 studies); recurrent endometritis (3 studies); urinary tract infection (1 study).

About the systematic review underlying this summary

Participants

Women who were diagnosed with endometritis during the first six weeks of the postpartum period. Not stated

Settings

Outcomes

Duration of fever; therapeutic failure; complications (including pelvic abscess and septic pelvic vein thrombophlebitis); death. Other outcome measures: any change made to the initial antibiotic regimen; allergic reactions; diarrhea; superinfection or colonization with resistant organisms; quantity of resources (e.g. length of stay, etc.) utilized; financial costs.

Date of most recent search: January 2007 Limitations: This is a good quality systematic review
LM French, FM Smaill. Antibiotic regimens for endometritis after delivery. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD001067. DOI: 10.1002/14651858.CD001067.pub2. Background 2

Summary of findings
Thirty-nine trials (4221 participants) were included. Allocation concealment was adequate in only 5 studies. The main outcome measures in the trials were treatment failure, complications and side-effects. Fifteen studies comparing clindamycin and an aminoglycoside with another regimen showed more treatment failures with the other regimen. Twelve studies showed less severe complications with clindamycin and an aminoglycoside (not significant). There was no consistent approach to the definition of serious morbidity. Regimens of antibiotics not active against penicillin-resistant anaerobic bacteria had more treatment failures. In three studies that compared continued oral antibiotic therapy after intravenous therapy with no oral therapy, no differences were found in recurrent endometritis or other outcomes. In four studies comparing once daily with thrice daily dosing of gentamicin there were fewer failures with once daily dosing (not significant). There was no evidence of difference in incidence of allergic reactions. Cephalosporins were associated with less diarrhea (not significant). Maternal mortality was not reported.

About quality of evidence (GRADE)

High: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low: We are very uncertain about the estimate. For more information, see last page.

Any other regimen versus clindamycin and aminoglycoside

There is low quality of evidence that combination of clindamycin and gentamicin reduce the treatment failures by

44% compared with other antibiotics.

There is moderate quality of evidence that combination of clindamycin and gentamicin could reduce severe com-

plications by 30 % compared with other antibiotics but this result was not statistically significant.

Treatment failure and severe complications Patient or population: Patients with endometritis Settings: USA, Peru, Colombia Intervention: Any other regimen Comparison: Clindamycin and aminoglycoside Outcomes Illustrative comparative risks* (95% CI) Assumed risk Clindamycin and aminoglycoside Treatment failure Severe complication 114 per 1000 11 per 1000 Relative effect N of Participants Quality of the evidence (95% CI) (studies) (GRADE) Corresponding risk

Any other regimen 164 per 1000 (131 to 205) 14 per 1000 (6 to 34) RR 1.44 (1.15 to 1.80) RR 1.29 (0.54 to 3.09) 1902 (19 studies) 1120 (12 studies) low1,2 moderate1

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio 1 Allocation Concealment unclear in the studies.2 Point estimates are compatible with benefit and harm. Summary of findings 3

Relevance of the review for low and middle-income countries

Findings
APPLICABILITY The combination of clindamycin and an aminoglycoside (such as gentamicin) is appropriate for the treatment of endometritis. A regimen with activity against the Bacteroides Fragilis group and other penicillin resistant anaerobic bacteria is better than one without. There is no evidence that any regimen is associated with fewer side-effects, with the exception of cephalosporins that is associated with less diarrhea. EQUITY The included studies did not provide data regarding differential effects of the interventions on disadvantaged populations. Very few studies have been conducted outside of the United States with only four studies performed in the developing world. ECONOMIC CONSIDERATIONS There is no data on costs for either the health providers or the consumers. Z Although no information regarding cost-effectiveness or other economic consideration was provided, widespread implementation of an expensive antibiotic regimen is likely to increase health care costs Z Postpartum endometritis is an important cause of maternal morbidity and mortality in low-income countries. The lack of studies conducted in such environments is a important gap in the knowledge. A multicentre randomized controlled trial with sufficient power is needed to compare the efficacy of regimens that are currently used in developing countries with the regimen clindamycin plus gentamicin. Z We cannot anticipate differences in effectiveness among different settings within the countries. Z Only four trials were conducted in developing countries. Nevertheless, the results of this review are probably applicable to most developing countries because the etiology of endometritis following delivery is polymicrobial and the pathogens are likely to be the same in all parts of the world. The main barrier is the cost of clindamycin and thus the recommended combined regimen of gentamicin and clindamycin may not be feasible in other developing countries.

Z Interpretation*

MONITORING & EVALUATION Any further studies that compare clindamycin and an aminoglycoside with an alternative regimen, with efficacy as the primary outcome, should include regimens that are routinely used outside of North America and consider alternatives suitable for use in low-income countries. Novel ways of managing endometritis should be explored and more creative study designs should evaluate early switching to the oral route. It is important that any new regimen compared with clindamycin and an animoglycoside include ototoxicity and nephrotoxicity as outcomes. Studies should be designed comparing different strategies for selecting an antibiotic regimen.

*Judgements made by the authors of this summary, not necessarily those of the review authors, based on the findings of the review and consultation with researchers and policymakers in low and middle-income countries. For additional details about how these judgements were made see: http://www.supportcollaboration.org/summaries/methods.htm

Relevance of the review for low and middle-income countries

Additional information
Related literature
- Chongsomchai C. Antibiotic regimens for endometritis after delivery: RHL practical aspects (last revised: 27 October 2004). The WHO Reproductive Health Library; Geneva: World Health Organization.

About quality of evidence (GRADE)

The quality of the evidence is a judgement about the extent to which we can be confident that the estimates of effect are correct. These judgements are made using the GRADE system, and are provided for each outcome. The judgements are based on the type of study design (randomised trials versus observational studies), the risk of bias, the consistency of the results across studies, and the precision of the overall estimate across studies. For each outcome, the quality of the evidence is rated as high, moderate, low or very low using the definitions on page 3. For more information about GRADE: http://www.supportcollaboration.org/summaries/grade.pdf

This summary was prepared by

Evelina Chapman, Centro Rosarino de Estudios Perinatales, Rosario, Argentina.

Conflict of interest
None declared. For details, see: www.support-collaboration/summaries/coi.htm

Acknowledgements
This summary has been peer reviewed by: Eugene J. Kongnyuy, MD, MPH. Lecturer in sexual and reproductive health. Liverpool School of Tropical Medicine. Liverpool. United Kingdon.

This summary should be cited as:

Chapman E, Mignini L, Abalos E. Which antibiotic regimens should be used for endometritis after delivery A SUPPORT Summary of a systematic review. June 2009. www.supportcollaboration.org/summaries

SUPPORT collaborators:
The WHO Reproductive Health Library (RHL) is an electronic review journal covering the field of sexual and reproductive health. It has been published annually since 1997 by the Department of Reproductive Health and Research at the World Health Organization. RHL takes the best available evidence on sexual and reproductive health from Cochrane systematic reviews and presents it as practical actions for clinicians to take to improve health outcomes, especially in developing countries. www.who.int/rhl The Cochrane Effective Practice and Organisation of Care Group (EPOC) is a Collaborative Review Group of the Cochrane Collaboration: an international organisation that aims to help people make well informed decisions about health care by preparing, maintaining and ensuring the accessibility of systematic reviews of the effects of health care interventions. www.epoc.cochrane.org For more information, see: www.support-collaboration.org To receive e-mail notices of new SUPPORT summaries, go to: www.supportcollaboration.org/summaries/newsletter.ht m To provide feedback on this summary, go to: http://www.supportcollaboration.org/summaries/feedback.htm

This summary was prepared with additional support from:

Centro Rosarino de Estudios Perinatales.

www.crep.org.ar

Additional information