Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section
The administration of prophylactic antibiotics reduces the incidence of especially endometritis following both elective and non-elective cesarean section. However, the evidence in this review is based on studies that did not assess potential adverse effects of antibiotics on the baby.
RHL Commentary by Bastu E and Gulmezoglu AM
Caesarean delivery is the single most important factor associated with postpartum infection and carries a 5-fold to 20-fold increased risk of infection compared with vaginal delivery (1). Following caesarean delivery, maternal mortality and infectious morbidity may result from a number of postpartum infections including endometritis, urinary tract infection and surgical site infection (2), all of which increase hospital stay and cost for each case (3). Endometritis is the most common infection-related complication following caesarean delivery, which can be reduced by 50% with the use of prophylactic antibiotics as indicated in this review. These antibiotics have usually been administered intraoperatively after umbilical cord clamping for two theoretic concerns related to the fetus: antibiotics in neonatal serum may mask newborn positive bacterial culture results; and fetal antibiotic exposure could lead to an increase in newborn colonization or infection with antibiotic-resistant organisms. This Cochrane review (4) aimed to evaluate the effects of prophylactic antibiotics compared with no prophylactic antibiotics on infection-related complications in women undergoing cesarean section.
The review authors used appropriate standard Cochrane methodology, including a comprehensive search for trials, inclusion of trials according to predefined quality criteria, transparent data extraction, and pre-specified analyses. Owing to insufficiency of information provided in the included trials, the authors were unable to judge adequately the risk of bias in the trials, which was a major limitation of this review.
3. RESULTS OF THE REVIEW
The review included 86 studies (mostly from the 1970s and 1980s) involving over 13 000 women. Based on these data, the review authors were able to perform 14 meta-analyses.
3.1. Antibiotic prophylaxis versus no prophylaxis
There were reductions in all the maternal primary outcomes: febrile morbidity [average risk ratio (RR) 0.45, 95% confidence interval (CI) 0.39–0.51, 50 studies, 8141 women]; wound infection (average RR 0.39, 95% CI 0.32–0.48, 77 studies, 11 961 women); endometritis (RR 0.38, 95% CI 0.34–0.42, 79 studies, 12 142 women) and serious infectious morbidity (RR 0.31; 95% CI 0.19–0.48, 31 studies, 5047 women).
3.2. Antibiotic prophylaxis versus no prophylaxis, subgroups by type of cesarean section
There was no difference between groups with respect to maternal febrile morbidity, wound infection or endometritis. The results suggest that there are benefits for the mother, irrespective of whether the cesarean section is elective or performed as an emergency operation.
3.3. Antibiotic prophylaxis versus no prophylaxis, subgroups by timing of administration
There was no difference in maternal febrile morbidity, wound infection or endometritis.
This review concludes that the prophylactic antibiotics reduce the incidence of endometritis following both elective and non-elective cesarean section by two thirds to three quarters and the incidence of wound infection by up to three quarters. Postpartum febrile morbidity and the incidence of urinary tract infections are also decreased. The administration of prophylactic antibiotics before or after clamping of the cord for women undergoing cesarean section seems equally effective as well. Furthermore, the need for better data on the safety of the intervention for the mother and infant, particularly longer-term effects, is highlighted.
4.1. Applicability of the results
The 86 studies that met the inclusion criteria were mostly conducted in developed countries (e.g. Western European countries and the USA). However, there was a small number of studies from developing countries including, China, Kenya, Malaysia, Mexico, Nigeria, Sudan, South Africa, Tunisia, Turkey and Zimbabwe. Since most of the studies included in the review were done in the 1970s and 1980s (i.e. before the sources of bias in randomized controlled trials were brought under the spotlight) the quality of the included studies remains unverified. Another limitation in terms of applicability of the findings is the lack of details provided in the included studies on the incidence of bacterial vaginosis; such detail is likely to have implications for current prophylactic recommendations. In addition, the included studies did not compare the use of narrow-range antibiotic with broad-spectrum regimens.
4.2. Implementation of the intervention
The administration of prophylactic antibiotics reduces the incidence of especially endometritis following both elective and non-elective cesarean section. However, the evidence in this review is based on studies that did not assess potential adverse effects of antibiotics on the baby. Hence, administration of prophylactic antibiotics before cord clamping should be avoided until the safety of doing so for the baby is established.
Apart from the cost of the interventions, which will vary from one country to another, antimicrobial prophylaxis interventions is feasible for all cesarean deliveries unless the patient is already receiving appropriate antibiotics (i.e. for chorioamnionitis) and that prophylaxis should be administered within 60 minutes of the start of the cesarean delivery. When this is not possible (i.e. need for emergent delivery), prophylaxis should be administered as soon as possible.
4.3. Implications for research
With the rise in caesarean delivery rates worldwide, post-caesarean delivery infections are likely to become a significant health and economic burden for countries. The available data are limited to administration of narrow-range antibiotics, instead of broad-spectrum antibiotics that are used in patients undergoing other major surgery in routine clinical practice. Recent evidence suggests that broad-spectrum antibiotics are more effective in preventing post-caesarean delivery infections than narrow-range antibiotics (5–8). As a result, a broad-spectrum antibiotics strategy has been adopted by the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatricians (9), although national guidelines have yet to reflect these changes.
The currently available data suggest that pre-operative antimicrobial prophylaxis for cesarean delivery is not associated with an increase in neonatal infectious morbidity or the selection of antimicrobial resistant bacteria causing neonatal sepsis (10). On the other hand, because the studies are not powered to analyse these outcomes, additional prospective evaluation is clearly warranted. Moreover, the combination of broad-spectrum antibiotic prophylaxis for caesarean delivery versus narrow-range antibiotics has not been tested and there is an urgent need for this definitive study to be performed. Such studies must address both maternal and neonatal infectious morbidity as well as long-term follow-up for neonatal safety, including variables like surgical technique (i.e. suture material, etc.) (11) and type of caesarean delivery (i.e. emergency, repeat, etc.).
- Chaim W, Bashiri A, Bar-David J, Shoham-Vardi I, Mazor M. Prevalence and clinical significance of postpartum endometritis and wound infection. Infectious Diseases in Obstetrics and Gynecology 2000;8:77-82.
- Berg CJ, Chang J, Callaghan WM, Whitehead SJ. Pregnancy-related mortality in the United States, 1991–1997. Obstetrics and Gynecology 2003;101:289-296.
- Anderson DJ, Kaye KS, Classen D, Arias KM, Podgorny K, Burstin H, et al. Strategies to prevent surgical site infections in acute care hospitals. Infection Control and Hospital Epidemiology 2008;29 (Suppl 1): S51-S61.
- Smaill FM, Gyte GML. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database of Systematic Reviews 2010;Issue 1. Art. No.: CD007482. DOI: 10.1002/14651858; CD007482.pub2.
- Andrews WW, Hauth JC, Cliver SP, Savage K, Goldenberg RL. Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis. Obstetrics and Gynecology 2003;101:1183-1189.
- Meyer NL, Hosier KV, Scott K, Lipscomb GH. Cefazolin versus cefazolin plus metronidazole for antibiotic prophylaxis at cesarean section. Southern Medical Journal 2003;96:992-995.
- O’Leary JA, Mullins JH Jr, Andrinopoulos GC. Ampicillin vs. ampicillin-gentamicin prophylaxis in high-risk primary cesarean section. The Journal of Reproductive Medicine 1986;31:27-30.
- Pitt C, Sanchez-Ramos L, Kaunitz AM. Adjunctive intravaginal metronidazole for the prevention of postcesarean endometritis: a randomized controlled trial. Obstetrics and Gynecology 2001;98:745-750.
- American Academy of Pediatrics and American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care, 6th ed. Washington DC: American College of Obstetricians and Gynecologists, 2007.
- Antimicrobial prophylaxis for cesarean delivery: timing of administration. Committee Opinion No. 465. American College of Obstetricians and Gynecologists. Obstetrics and Gynecology 2010;116:791-792.
- Ramsey PS, White AM, Guinn DA, Lu GC, Ramin SM, Davies JK, et al. Subcutaneous tissue reapproximation, alone or in combination with drain, in obese women undergoing cesarean delivery. Obstetrics and Gynecology 2005;105:967-973.
This document should be cited as: Bastu E, Gulmezoglu AM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section: RHL commentary (last revised: 1 December 2012). The WHO Reproductive Health Library; Geneva: World Health Organization.