Two-drug Antibiotic Prophylaxis in Scheduled Cesarean Deliveries

Study Overview
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Brief Summary
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Cesarean deliveries are the most common surgical procedure performed in the United States. A significant decrease in cesarean delivery associated maternal morbidity has been achieved with preoperative prophylactic single-dose cephalosporin, widely used before skin incision. Also, on laboring patients and/or with rupture of membranes, several studies suggest that adding azithromycin to standard cephalosporin prophylaxis is cost-effective and reduces overall rates of endometritis, wound infection, readmission, use of antibiotics and serious maternal events. Azithromycin has effective coverage against Ureaplasma, associated with increased rates of endometritis. Although two-drug regimen has been suggested for laboring and/or patients that undergo cesarean delivery, no studies have investigated the potential benefits of two-drug regimen in non-laboring patients.

Detailed Description
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Cesarean deliveries are the most common surgical procedure performed in the United States, and scheduled cesarean deliveries account for at least 40% of all cesarean deliveries every year. A significant decrease in cesarean delivery associated maternal morbidity has been achieved with preoperative prophylactic single-dose cephalosporin given within 60 minutes of skin incision. Also, on laboring patients and/or with rupture of membranes, several studies suggest that adding azithromycin to standard cephalosporin prophylaxis is not only cost-effective but reduces overall rates of endometritis and wound infection. Azithromycin provides effective coverage against Ureaplasma, commonly associated with increased rates of endometritis. Although two-drug regimen has been suggested for laboring and/or patients that undergo cesarean delivery, no studies have investigated the potential benefits of two-drug regimen in non-laboring patients. No increase in neonatal morbidity was noted with adjunctive azithromycin prophylaxis, including adverse events.

Official Title
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Azithromycin-based Extended-spectrum Prophylaxis in Scheduled Cesarean Deliveries

Conditions
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Endometritis, Cesarean Section; Infection, Wound Infection

Intervention / Treatment
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* Drug: Azithromycin 500 mg
* Drug: Mefoxin 2g


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women 18 years or older Women undergoing primary or repeat cesarean delivery Singleton gestation Gestational age greater than 34 weeks Pregnant patients undergoing scheduled cesarean delivery Intact membranes Non-laboring Signed informed consent Exclusion Criteria: Maternal age < 18 years Multi-fetal gestation Known allergy to cephalosporin or azithromycin Patient unwilling or unable to provide consent Diagnosis of rupture of membranes Intraamniotic infection, or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization. Immunocompromising medical conditions: HIV positive with CD4 count below 200, chronic steroid use, current diagnosis of cancer and/or chemotherapy age use Emergent cesarean precluding consent or availability of study medication Need for hysterectomy at time of delivery Use of antibiotic in the 72 hours prior to admission, with exception to patient receiving antibiotics for GBS Inability to contact patient on postpartum period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pregnant patients admitted to Labor and Delivery unit between June 2019 and July 2020 will be randomized to received either standard prophylaxis or azithromycin and cephalosporin for preoperative prophylaxis after inclusion and exclusion criteria are met and informed consent for participation is signed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: One-drug Prophylaxis<br>Mefoxin 2g IV, Piggyback, once | Drug: Mefoxin 2g<br>* Standard Prophylaxis<br>* Other names: Cefoxitin;|
| Experimental: Two-drug Prophylaxis<br>Mefoxin 2g IV, Piggyback, once and Azithromycin 500mg IV, Piggyback, once | Drug: Azithromycin 500 mg<br>* Additional IV Azithromycin 500 mg to Standard Prophylaxis<br>Drug: Mefoxin 2g<br>* Standard Prophylaxis<br>* Other names: Cefoxitin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Endometritis | Presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38°C [100.4°F]), abdominal pain, uterine tenderness, or purulent drainage from the uterus. | Up to 6 weeks after delivery | 
| Rates of Wound Infection | Presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis. Wound hematoma, seroma, abscess or breakdown alone in the absence of the preceding signs did not constitute infection. | Up to 6 weeks after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Maternal Fever | Temperature equal or greater than 100.4F | Up to 6 weeks after delivery | 
| Rates of Maternal Postpartum Readmission or Unscheduled Visit | Admission to hospital or unscheduled appointment in additional to regular 1-week and 6-week postpartum visit | Up to 6 weeks after delivery | 
| Rates of Postpartum Antibiotic Use | Antibiotic use for any reason including other infections such as UTI and sepsis. | Up to 6 weeks after delivery | 
| Rates of Serious Adverse Events | MICU admission, thromboembolic events, sepsis, maternal death | Up to 6 weeks after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cesarean Delivery, Endometritis, Wound Infection, Azithromycin, Antibiotic Prophylaxis