Antibiotic regimens for postpartum endometritis

Intravenous clindamycin plus gentamicin is more effective than other antibiotics or combinations of antibiotics for treatment of womb infection after childbirth.

Inflammation of the lining of the womb (endometritis) can be caused by vaginal bacteria entering the womb (uterus) during childbirth and causing infection within six weeks of the birth (postpartum endometritis). Postpartum endometritis occurs after about 1% to 3% of vaginal births, and up to 27% of cesarean births. Prolonged rupture of the membranes (breaking the bag of water that surrounds the baby) and multiple vaginal examinations during birth also appear to increase the risk.

Endometritis causes fever, tenderness in the pelvic region and unpleasant-smelling vaginal discharge after the birth. It can have serious complications such as the formation of pelvic abscesses, blood clots, infection of the thin layer of tissue that covers the inside of the abdomen and abdominal organs (peritonitis), and whole body inflammation (sepsis). It is also an important cause of maternal deaths worldwide, although with the use of antibiotics, this is very rare in high-income countries.

There are many antibiotic treatments currently in use. This review compared different antibiotics, routes of administration and dosages for endometritis. The review identified 42 relevant randomised controlled studies, which are the most reliable type of medical trial for this type of investigation; 40 of these (involving 4240 women) contributed data for analysis.

The results showed that the combination of intravenous gentamicin and clindamycin, and drugs with a broad range of activity against the relevant penicillin-resistant bacterial strains, are the most effective for treating endometritis after childbirth. Women treated with clindamycin plus an aminoglycoside (gentamicin) showed fewer treatment failures than those treated with penicillin, but this difference was not evident when women treated with clindamycin plus an aminoglycoside were compared to women who received other antibiotic treatments.

There were more treatment failures in women treated with an penicillin plus gentamicin (one study) compared with those treated with clindamycin plus gentamicin. Seven trials showed that an antibiotic treatment that had poor activity against bacteria resistant to penicillin had a higher failure rate and more wound infections than an antibiotic treatment that had good activity against these bacteria.

There was no evidence that any of the antibiotic combinations had fewer adverse effects - including allergic reaction - than other antibiotic combinations. If the endometritis was uncomplicated and improved with intravenous antibiotics, there did not appear to be a need to follow the intravenous antibiotics with a course of oral antibiotics.

Overall the reliability of the studies' results was unclear, the numbers of women studied were often small and data on other outcomes were limited; furthermore, a number of the studies had been funded by drug companies that conceivably would have had a vested interest in the results.

Authors' conclusions: 

The combination of clindamycin and gentamicin is appropriate for the treatment of endometritis. Regimens with good activity against penicillin-resistant anaerobic bacteria are better than those with poor activity against penicillin-resistant anaerobic bacteria. There is no evidence that any one regimen is associated with fewer side-effects. Following clinical improvement of uncomplicated endometritis which has been treated with intravenous therapy, the use of additional oral therapy has not been proven to be beneficial.

Read the full abstract...
Background: 

Postpartum endometritis occurs when vaginal organisms invade the endometrial cavity during the labor process and cause infection. This is more common following cesarean birth. The condition warrants antibiotic treatment.

Objectives: 

Systematically, to review treatment failure and other complications of different antibiotic regimens for postpartum endometritis.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014) and reference lists of retrieved studies.

Selection criteria: 

We included randomized trials of different antibiotic regimens after cesarean birth or vaginal birth; no quasi-randomized trials were included.

Data collection and analysis: 

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.

Main results: 

The review includes a total of 42 trials, and 40 of these trials contributed data on 4240 participants.

Twenty studies, involving 1918 women, compared clindamycin plus an aminoglycoside (gentamicin for all studies except for one that used tobramycin) with another regimen.

When assessing the individual subgroups of other antibiotic regimens (i.e. cephalosporins, monobactams, penicillins, and quinolones), there were fewer treatment failures in those treated with clindamycin plus an aminoglycoside as compared to those treated with cephalosporins (RR 0.69, 95% CI 0.49 to 0.99; participants = 872; studies = 8; low quality evidence) or penicillins (RR 0.65, 95% CI 0.46 to 0.90; participants = 689; studies = 7, low quality evidence). For the remaining subgroups for the primary analysis, the differences were not significant. There were significantly fewer wound infections in those treated with clindamycin plus aminoglycoside versus cephalosporins (RR 0.53, 95% CI 0.30 to 0.93; participants = 500; studies = 4; low quality evidence). Similarly, there were more treatment failures in those treated with an gentamicin/penicillin when compared to those treated with gentamIcin/clindamycin (RR 2.57, 95% CI 1.48 to 4.46; participants = 200; studies = 1).

There were fewer treatment failures when an agent with a longer half-life that is administered less frequently was used (RR 0.61, 95% CI 0.40 to 0.92; participants = 484; studies = 2) as compared to using cefoxitin. There were more treatment failures (RR 1.94, 95% CI 1.38 to 2.72; participants = 774; studies = 7) and wound infections (RR 1.88, 95% CI 1.17 to 3.02; participants = 740; studies = 6) in those treated with a regimen with poor activity against penicillin-resistant anaerobic bacteria as compared to those treated with a regimen with good activity against penicillin-resistant anaerobic bacteria. Once-daily dosing was associated with a shorter length of hospital stay (MD -0.73, 95% CI -1.27 to -0.20; participants = 322; studies = 3).

There were no differences between groups with respect to severe complications and no trials reported any maternal deaths.

Regarding the secondary outcomes, three studies that compared continued oral antibiotic therapy after intravenous therapy with no oral therapy, found no differences in recurrent endometritis or other outcomes. There were no differences between groups for the outcomes of allergic reactions.

The overall risk of bias was unclear in the most of the studies. The quality of the evidence using GRADE comparing clindamycin and an aminoglycoside with another regimen (compared with cephalosporins or penicillins) was low to very low for therapeutic failure, severe complications, wound infection and allergic reaction.

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