Prophylactic Use of Azithromycin brings down Postcesarean Infections.

Clinical pearls:

• Among women undergoing non-elective cesarean section, addition of azithromycin to the standard protocol of prophylactic antibiotic reduces the risk of postoperative infection significantly. (P<0.001).
• A single dose of 500 mg used Intravenously before the skin incision.

According to data by CDC, out of nearly 4 million children born in USA, 1,284,551 are delivered by cesarean sections. The Cesarean section rate in US is 32.2%.[1] Women who undergo cesarean delivery are 5-10 times more at risk for puerperal infection as compared to women undergoing a natural birth. [2]Puerperal infection is responsible for 10% of pregnancy-related mortality. 

Postoperative infectious morbidity also encompasses other causes like mastitis, septic pelvic thrombophlebitis, drug fever, urinary tract infection/pyelonephritis and pneumonia but two major contributors to maternal morbidity and mortality are endometritis (incidence without prophylaxis, 4 to 18%) and of surgical-site infections (incidence without prophylaxis, 7 to 10%.).

To prevent surgical site infections ACOG recommends the use of a single dose of a narrow spectrum first-generation cephalosporin (cefazolin), or a single-dose combination of clindamycin with an aminoglycoside for those with a significant penicillin allergy, as prophylaxis for cesarean delivery.[3]

A large randomized trial published in the September 29 issue of the New England Journal of Medicine presents the result of adding Azithromycin (a macrolide antibiotic) to standard prophylaxis for cesarean deliveries at 14 U.S. hospitals.[4]

The study was also presented in part at the 36th annual meeting of the Society for Maternal–Fetal Medicine, Atlanta, February 1–6, 2016.

The study included 2013 women who were at least 24+ weeks into pregnancy, with singleton fetus, undergoing an emergency section in labor with or without rupture of membranes. Women with elective or planned cesarean sections were excluded from the study. The study cohort was divided into 2 groups. The study group received single 500-mg dose of azithromycin intravenously before the cesarean incision, in addition to the intravenous dose of cefazolin that is standardized protocol followed at each center.

The control group received cefazolin plus placebo.

Data Analysis showed that the occurrence of primary composite outcome like surgical site infection, endometritis (measured 6 weeks postpartum) and other infection were significantly lower in the group receiving Azithromycin (6.1% vs. 12.0%, P<0.001).

Secondary outcome like readmissions, emergency visit to hospital and need for antibiotics postpartum were also less in the study group. 

Neonatal outcomes were similar in both the groups. "Pharmacologic data indicating that azithromycin only minimally crosses the placenta into the fetal circulation suggest limited exposure for the infant," write Dr Weinstein and Dr Boyer in an accompanying editorial.

The study results also showed that 17 women need to be treated to prevent the occurrence of primary study outcome, while the number for preventing one case of endometritis and wound infections is 43 and 24 respectively.

The number of eligible women who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections. 

The editorial authors hypothesized that Azithromycin is effective against some of vaginal microbiota. Earlier studies have shown that genital or placental colonization with Ureaplasma urealyticum increases the risks of endometritis/ wound site infection.

Azithromycin is also concentrated and retained for many days in myometrium and adipose tissue, hence a single dose preoperatively works well for this surgery.

So, does the study implicate the routine use of Azithromycin as a preoperative prophylaxis in cesarean section?  The editorial authors opine that it is too early to make any recommendation. "Time will tell whether such findings result in changes in routine antibiotic prophylaxis before cesarean deliveries," write Dr Weinstein and Dr Boyer. 

However, on the basis of the results, the addition of azithromycin "would reduce a number of infectious complications for some women without established infections who are undergoing nonelective cesarean section."

The emergence of antibiotic resistant organism after long use also has to be kept in mind, but a single I/V dose is unlikely to do so.

The study findings show that by adding prophylactic azithromycin to the routine protocol for cesarean delivery extends   the spectrum of coverage and decreases the chances of puerperal infection without compromising maternal or neonatal safety.    

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[1] http://www.cdc.gov/nchs/fastats/delivery.htm

[2] Gibbs RS. Clinical risk factors for puerperal infection. Obstet Gynecol 1980;55:5 Suppl:178S-184S

[3] American College of Obstetricians and Gynecologists (ACOG), authors Use of prophylactic antibiotics in labor and delivery. [Accessed May 13, 2012]. Practice Bulletin No. 120, June 2011. US Department of Health & Human Services Web site.

[4] http://www.nejm.org/doi/full/10.1056/NEJMoa1602044