Adjunctive Azithromycin Prophylaxis for Cesarean Delivery

Garrett Brown, Mercer University College of Pharmacy

 

In 2011, it was reported that one in three women who gave birth in the United States did so by cesarean delivery.  Pregnancy-associated infection is reported to be the fourth most common cause of maternal death in the United States. [1]  Cesarean delivery has been shown to have a rate of surgical-site infection that is 5-10 times the rate for vaginal delivery.  As many as 60-70% of all cesarean deliveries are non-elective; postoperative infections occur in up to 12% of women undergoing non-elective cesarean delivery with standard pre-incision prophylaxis.  [2]

 

According to the Guideline for Use of Prophylactic Antibiotics in Labor and Delivery, antimicrobial prophylaxis is recommended for all cesarean deliveries, unless the patient is already receiving appropriate antibiotics.  The administration of antibiotics is recommended to begin within 60 minutes before the start of the cesarean delivery.  It is stated that a first-generation cephalosporin is the first-line antibiotic of choice.  A single-dose combination of clindamycin with an aminoglycoside is suggested to be an alternative choice for cesarean delivery prophylaxis for women with a history of significant penicillin or cephalosporin allergy.  [3]

Adjunctive Azithromycin Prophylaxis for Cesarean Delivery [4]

Design Multicenter, double blinded, pragmatic, randomized; N= 2,013
Objective To assess whether the addition of azithromycin to standard antibiotic prophylaxis before cesarean section would decrease the risk of infection and adverse maternal outcomes
Study Groups Azithromycin (n= 1,019); placebo (n= 994)
Methods Patients were randomly assigned to receive either azithromycin (at a dose of 500 mg in 250 ml of saline) or an identically-appearing saline placebo.  Treatment was given after the decision was made to proceed with cesarean section at one hour before the incision.  All patients received standard prophylaxis with cefazolin.  Patients who were allergic to cephalosporins or penicillins received clindamycin alone or in combination with gentamicin.
Duration April 2011 – November 2014
Primary Outcome Measure Composite of endometritis, wound infection, or other infections (abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis) occurring up to 6 weeks after surgery
Baseline Characteristics
Azithromycin Placebo
Average age (yrs) 28.2 28.4
Race
Black, n (%) 351 (34.4) 341 (34.3)
White, n (%) 356 (34.9) 342 (34.4)
Average gestational age at randomization, weeks 38.9 39.0
Results
Azithromycin Placebo Relative Risk

95% CI

p-value
Primary composite outcome, n (%) 62 (6.1) 119 (12.0) 0.51 (0.38-0.68) p< 0.001
Endometritis, n (%) 39 (3.8) 61 (6.1) 0.62 (0.42-0.92) p= 0.02
Wound infection, n (%) 24 (2.4) 66 (6.6) 0.35 (0.22-0.56) p< 0.001
Other Infection, n (%) 3 (0.3) 6 (0.6) 0.49 (0.12-1.94) p= 0.34
Adverse Events Common Adverse Events:  N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Extended-spectrum prophylaxis with adjunctive azithromycin for cesarean delivery in women at increased risk for infection safely reduces the rates of infection and maternal use of health care resources without increasing the risk of neonatal adverse outcomes.

 

One of the limitations of this study was the exclusion of women who had planned cesarean deliveries, limiting the generalizability of this study.  One strength of the study was that the standard of care therapy was used as an active placebo, making a significant difference between treatment and placebo more difficult to achieve.  The incidence of infections was clinically significant and meaningful to patients.  The results of this study will likely precipitate further clinical trials and possibly be reflected in the next guidelines governing cesarean antibiotic prophylaxis.

 

References

  1. Berg CJ, Chang J, Callaghan WM, Whitehead SJ. Pregnancy-related mortality in the United States, 1991-1997. Obstet Gynecol 2003;101:289-296
  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). Use of prophylactic antibiotics in labor and delivery. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2011 Jun. 12 p. (ACOG practice bulletin; no. 120).
  4. Tita, Alan T.N., Szychowski, Jeff M. (2016) Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. New England Journal of Medicine 375:1231-1241

 

 

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