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.
[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
