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(HealthNewsDigest.com) – About one-third of the 4 million babies born in the United States each year are delivered by cesarean section, which puts women at higher risk of infection than vaginal deliveries. Such infections are five to 10 times more common after C-sections.
In an editorial in the Sept. 29 issue of the New England Journal of Medicine,two physicians at Rush assess a research paper published in the same issue that presents a study of an enhanced drug regimen for preventing these infections. The study (in which Rush was not involved) gave women undergoing a C-section the antibiotic azithromycin in addition to another antibiotic, cefazolin (a first-generation of the class of antibiotics called cephalosporin), that routinely is recommended for these women to examine whether the extra antibiotic would reduce infection rates.
“On the basis of this well-designed, pragmatic, multicenter trial, it seems likely that a single adjunctive 500-mg dose of intravenous azithromycin would reduce a number of infectious complications for some women without established infections who are undergoing nonelective cesarean section,” conclude the editorial’s authors, Robert A. Weinstein, MD, a professor of medicine at Rush University, and Kenneth Boyer, MD, a professor and former chairperson of Rush’s Department of Pediatrics.
Here, Weinstein and Boyer — both infectious disease specialists and researchers themselves — discuss the problem of infection after cesarean section, the study they evaluated, and its implications for the future care of mothers who deliver their babies via C-section.
What were the methodology and the main findings in the study you assessed?
Boyer: This was a pragmatic, double-blind study involving 2,013 women who had non-elective cesareans at 14 hospitals in the United States. All the hospitals gave the study subjects their standard protocol of antibiotic, most often cefazolin, a widely used intravenous antibiotic.
Half the women, the control group, got only that antibiotic and a placebo. The other half got, in addition to the standard protocol, a single dose of azithromycin, administered just before the incision.
The group that got the azithromycin had 62 infections compared with 119 for the control group — about half. In terms of percentages, 6.1 percent of the azithromycin group got infections, compared with 12 percent of the control group. So the study shows pretty convincingly that when you add azithromycin to the standard prophylaxis, you get a significantly lower incidence of post-partum wound infection and endometritis, that is, infection of the lining of the uterus.
Why did the New England Journal of Medicine ask you to evaluate the study?
Weinstein: This is a really well done study, but there are always questions. The halving of infection risk — 12 percent to 6.1 percent — in this study was striking. When results are so dramatic, journals often commission editorials to put the study findings into perspective — how to explain such success, are there any wrinkles in the data, should this preventive regimen become standard of care?
Boyer: Our job was to put the paper itself into context. For example, almost three-fourths of the women in the study had body mass indexes (BMIs) above 25, and one-quarter of those were above 40. It wasn’t possible for us ferret out from the paper when those BMIs were assessed — if they were adjusted for added weight gain in pregnancy — or if all 14 hospitals gave higher-than-standard doses of antibiotic based on those higher weights. It was something we noticed, so we commented on it.
Obesity makes a difference; so do staples rather than sutures to close up a wound — staples are associated with a higher incidence of infection. But this was a pragmatic study; it was designed to evaluate the effects of a dose of azithrimycin in the context of these hospitals’ routine practice conditions. Still, we mentioned those things.
Are women who undergo unplanned cesareans more susceptible to infection than other women giving birth?
Boyer: Yes. The typical unscheduled cesarean comes after a prolonged labor without progress. The cervix may be open, the water may have broken, and you’ve tried a bunch of things that may have additionally exposed the uterine cavity to vaginal and skin flora (microorganisms).
Ordinarily, while the baby is in the uterus, that’s a sterile environment. With a scheduled cesarean, the cervix is typically not dilated, the membranes are intact, and the uterus is not as stressed.
What kinds of infections do these women get?
Boyer: Infection is a pretty inclusive term. Wound infections could range from a small inflamed area at the site of one or more of the stitches, all the way to extensive, deep, spreading cellulitis of the abdominal wall — from relatively trivial to life-threatening. Most are relatively minor. Endometritis can also vary in severity, ranging from a fever the first day or two after delivery to sepsis and systemic illness.
Weinstein: Ninety-five percent of them get better with a short course of antibiotics. Five percent might require more aggressive treatment. The outcome is usually good.
What is azithromycin, and how does it help in this case?
Weinstein: Azithromycin is the most commonly used oral antibiotic in the United States. In this case, it may have been active against bacteria coming up from the vagina into the C-section incision that are not reached by cefazolin.
Boyer: Azithromycin hangs around for about 48 hours in the skin and the uterine wall. It’s possible that it is extending the species of microorganisms that can be knocked out with antibiotics.
The major hypothesis on which the study is based is the inhibitory effect of azithromycin on ureaplasma, a bacterium whose presence is associated with increased post-partum issues, which cefazolin does not affect. We acknowledged that the results could be explained by that broader coverage, but we wished the study’s authors had asked whether the benefit come because azithromycin was active against a different spectrum of organisms, or just because women got twice as much antibiotic.
We wondered if the increased protection was simply additive. We’d like to see a study where women who received this treatment, cefazolin plus azithromycin, were compared with another group that received a double dose of cefazolin alone.
Weinstein: We thought it was possible that some of the obese women were not receiving enough cefazolin. Body weight should factor into the dose a woman is prescribed.
Are there risks involved in this treatment?
Boyer: Any antibiotic carries risks, usually allergies, which can be severe and even life-threatening, but any complications would be extremely unlikely with either azithromycin or cefazolin.
Are the findings of this study applicable to women having scheduled cesareans?
Boyer: No. You have to compare apples to apples and oranges to oranges. These researchers wanted to look at women with a higher probability of developing an infection.
What happens now?
Weinstein: When the study gets out and gets read, along with the editorial, there may be letters coming in full of different opinions. It’s a process, and it’s important to look at the study from a number of angles before we get to the point where an official body like the American College of Obstetricians and Gynecologists might recommend this practice as standard care.
Four million women have babies every year, and one-third of those are delivered by cesarean section — about 1.2 million. Many of those C-sections are not planned. This could affect hundreds of thousands of women every year.
Boyer: My experience is that it sometimes takes a while for a study like this to make it to being recommended as a standard of care.
Weinstein: That’s the only thing we’re somewhat split on. I think this will be coming to the delivery room soon.
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