Ayodeji Sanusi1, Yuanfan Ye, Kim Boggess, George Saade, Sherri Longo, Erin Clark, Sean Esplin, Kirsten Cleary, Ron Wapner, Michelle Owens, Sean Blackwell, Jeff M Szychowski, Alan T N Tita, Akila Subramaniam. 1. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, the Center for Women's Reproductive Health, and the Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, and Mission Hospital, Asheville, North Carolina; and the Departments of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas, Ochsner Health System, New Orleans, Louisiana, University of Utah and Intermountain Health Care, Salt Lake City, Utah, Columbia University, New York, New York, University of Mississippi, Jackson, Mississippi, University of Texas Health Sciences Center, Houston, Texas.
Abstract
OBJECTIVE: To estimate the association between timing of administration of adjunctive azithromycin for prophylaxis at unscheduled cesarean delivery and maternal infection and neonatal morbidity. METHODS: We conducted a secondary analysis of a randomized trial of adjunctive azithromycin prophylaxis in patients with singleton gestations who were undergoing unscheduled cesarean delivery. The primary exposure was the timing of initiation of the study drug (after skin incision or 0-30 minutes, more than 30-60 minutes, or more than 60 minutes before skin incision). The primary outcome was a composite of endometritis, wound infection, and other maternal infections occurring up to 6 weeks after cesarean delivery. Secondary outcomes included composite neonatal morbidity, neonatal intensive care unit admission for longer than 72 hours, and neonatal sepsis. The association of azithromycin with outcomes was compared within each antibiotic timing group and presented as risk ratios (RRs) with 95% CIs. A Breslow-Day homogeneity test was applied to assess differences in association by antibiotic timing. RESULTS: Of 2,013 participants, antibiotics were initiated after skin incision (median 3 minutes, range 0-229 minutes) in 269 (13.4%), 0-30 minutes before skin incision in 1,378 (68.5%), more than 30-60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61-218 minutes) in 96 (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin compared with placebo were significantly lower for groups that initiated azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13-0.76; 0-30 minutes before: RR 0.62, 95% CI 0.44-0.89; more than 30-60 minutes before: 0.31, 95% CI 0.13-0.66). Risks were not significantly different in patients who received azithromycin more than 60 minutes before skin incision (RR 0.59, 95% CI 0.10-3.36). Results were similar when endometritis and wound infections were analyzed separately. Neonatal outcomes were not significantly different for azithromycin compared with placebo across all timing groups. CONCLUSION: Adjunctive azithromycin administration up to 60 minutes before or at a median of 3 minutes after skin incision was associated with reduced risks of maternal composite postoperative infection in unscheduled cesarean deliveries. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01235546.
OBJECTIVE: To estimate the association between timing of administration of adjunctive azithromycin for prophylaxis at unscheduled cesarean delivery and maternal infection and neonatal morbidity. METHODS: We conducted a secondary analysis of a randomized trial of adjunctive azithromycin prophylaxis in patients with singleton gestations who were undergoing unscheduled cesarean delivery. The primary exposure was the timing of initiation of the study drug (after skin incision or 0-30 minutes, more than 30-60 minutes, or more than 60 minutes before skin incision). The primary outcome was a composite of endometritis, wound infection, and other maternal infections occurring up to 6 weeks after cesarean delivery. Secondary outcomes included composite neonatal morbidity, neonatal intensive care unit admission for longer than 72 hours, and neonatal sepsis. The association of azithromycin with outcomes was compared within each antibiotic timing group and presented as risk ratios (RRs) with 95% CIs. A Breslow-Day homogeneity test was applied to assess differences in association by antibiotic timing. RESULTS: Of 2,013 participants, antibiotics were initiated after skin incision (median 3 minutes, range 0-229 minutes) in 269 (13.4%), 0-30 minutes before skin incision in 1,378 (68.5%), more than 30-60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61-218 minutes) in 96 (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin compared with placebo were significantly lower for groups that initiated azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13-0.76; 0-30 minutes before: RR 0.62, 95% CI 0.44-0.89; more than 30-60 minutes before: 0.31, 95% CI 0.13-0.66). Risks were not significantly different in patients who received azithromycin more than 60 minutes before skin incision (RR 0.59, 95% CI 0.10-3.36). Results were similar when endometritis and wound infections were analyzed separately. Neonatal outcomes were not significantly different for azithromycin compared with placebo across all timing groups. CONCLUSION: Adjunctive azithromycin administration up to 60 minutes before or at a median of 3 minutes after skin incision was associated with reduced risks of maternal composite postoperative infection in unscheduled cesarean deliveries. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01235546.
Authors: Leo Pevzner; Morgan Swank; Candace Krepel; Deborah A Wing; Kenneth Chan; Charles E Edmiston Journal: Obstet Gynecol Date: 2011-04 Impact factor: 7.661
Authors: Akila Subramaniam; Ken B Waites; Victoria C Jauk; Joseph R Biggio; Amelia L M Sutton; Jeff M Szychowski; William W Andrews; Alan T N Tita Journal: Am J Perinatol Date: 2018-11-30 Impact factor: 1.862
Authors: Maged M Costantine; Mahbubur Rahman; Labib Ghulmiyah; Benjamin D Byers; Monica Longo; Tony Wen; Gary D V Hankins; George R Saade Journal: Am J Obstet Gynecol Date: 2008-09 Impact factor: 8.661
Authors: Manuel C Vallejo; Ahmed F Attaallah; Robert E Shapiro; Osama M Elzamzamy; Michael G Mueller; Warren S Eller Journal: J Anesth Date: 2016-10-12 Impact factor: 2.078
Authors: Amelia L Sutton; Edward P Acosta; Kajal B Larson; Corenna D Kerstner-Wood; Alan T Tita; Joseph R Biggio Journal: Am J Obstet Gynecol Date: 2015-01-13 Impact factor: 8.661
Authors: José Villar; Guillermo Carroli; Nelly Zavaleta; Allan Donner; Daniel Wojdyla; Anibal Faundes; Alejandro Velazco; Vicente Bataglia; Ana Langer; Alberto Narváez; Eliette Valladares; Archana Shah; Liana Campodónico; Mariana Romero; Sofia Reynoso; Karla Simônia de Pádua; Daniel Giordano; Marius Kublickas; Arnaldo Acosta Journal: BMJ Date: 2007-10-30
Authors: Karel Allegaert; Tim van Mieghem; Rene Verbesselt; Jan de Hoon; Maissa Rayyan; Roland Devlieger; Jan Deprest; Brian J Anderson Journal: Am J Obstet Gynecol Date: 2008-11-11 Impact factor: 8.661