Antibiotic prophylaxis for caesarean section at a Ugandan hospital: a randomised clinical trial evaluating the effect of administration time on the incidence of postoperative infections

A 2006 WHO systematic review of the causes of maternal death worldwide estimated that 9.7% of maternal deaths in Africa were due to puerperal sepsis [1]. One of the most important risk factors of postpartum infection in both developed and developing countries is caesarean section [2]. The second most common cause of maternal mortality is infection, and it contributes to 15% of the causes of maternal mortality in Uganda [3]. In low-income settings, improving the safety and care provided when performing a caesarean section can improve maternal and neonatal outcomes, which is in line with Millennium Development Goals number 4 and 5 [4].

Caesarean section is one of the most common surgical procedures performed in medical practice worldwide, and it is the most common surgical procedure performed in obstetrics and gynaecology practice at Mulago hospital. On average Caesarean section account for about 24% of 35 000 births per annum managed by Mulago hospital. Women giving birth by caesarean section present a 5- to 20-fold greater risk of infection than women giving birth by vaginal delivery [5]. Rates of severe wound infection can be as high as 25% [6]. One of the measures applied to prevent infectious complications following caesarean section is the use of prophylactic antibiotics [7,8]. The purpose of antibiotic prophylaxis in surgical procedures is not to sterilise tissues but to reduce colonisation pressure of microorganisms introduced at the time of the operation to a level that can be overcome by the patient’s immune system [9,10].

Whether antibiotic prophylaxis for caesarean section should be administered prior to the skin incision or at the time of the umbilical cord clamping remains controversial [11]. Traditionally, prophylaxis has been delayed in an effort to avoid masking a neonatal infection and to prevent an unnecessary septic workup. However, recent evidence shows no increase in neonatal sepsis, sepsis investigations, or length of stay [12-14]. A meta-analysis by Constantine et al. published in 2008 supports the use of antibiotic prophylaxis prior to caesarean incision to reduce total infectious morbidity without negative effects on neonatal outcomes [14]. Though more recent studies suggest there may be long-term effects of antibiotic prophylaxis on neonates, these still need to be validated by long-term follow-up studies of neonates exposed to antibiotics [15,16]. Thus, the American Congress of Obstetricians and Gynaecologists announced, in 2010, a new recommendation for antibiotic prophylaxis during caesarean delivery [17]. The new recommendation states that women giving birth by caesarean section should receive antibiotics routinely within 1 hour before the start of surgery. In the case of an emergency caesarean delivery, prophylaxis should be started as soon as possible. Further, a survey conducted in 2011 in the United States showed that 85% percent of patients received antibiotics preoperatively [18], indicating a change in the current practices in the country owing to the new recommendation. Very little is known about this practice in low-income countries in Africa, and in Uganda in particular.

At Mulago Hospital, there is evidence of increased postoperative infection in post-caesarean section patients as per an unpublished dissertation by Ssebuko. Currently there is no clear indication as to when antibiotic prophylaxis was administered and whether it contributed to the results of postoperative infection. Therefore, we sought to compare the relationship of timing of the administration of prophylactic antibiotics, within 1 hour before skin incision or after skin incision, and determine if either practice would affect the incidence of infection post-caesarean section.

In this study, we assessed 493 patients who were scheduled for caesarean section between January 2014 and March 2014. Twenty-nine patients were excluded from the study: 21 did not meet the inclusion criteria and eight refused participation in the study. The remaining 464 patients were then randomised and received intervention as per allocated groups A (Pre-incision) or B (Post-incision). Of these, only 432 were analysed as the other 32 were lost to follow-up (Figure 1). This difference did not affect the power of the study because the sample size calculation indicated that 421 patients were needed for a power of 80% and level of significance of 0.05.

The distribution and characteristics of patients are shown in Table 1. The general characteristics were generally evenly distributed, except for type of incision and type of anaesthesia given, which were significantly different (P values < 0.05, respectively). These variables were considered later in a multivariate model to determine their effects on study outcomes (Table 2).

On average, patients in group A received prophylaxis [mean (standard deviation)] 26.09 (9.67) minutes before the skin incision was performed. This timing falls within the 15 to 60 minutes that was specified in the protocol for this group. On average, patients in group B received prophylaxis 13.00 (12.93) minutes after the skin incision (Table 3).

The primary outcomes are presented in Table 4. Overall, infection was observed in 65.9% (139/211) of patients in group A and in 85.1% (188/221) of patients in group B, and the difference between groups was statistically significant (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.62–0.97; P value = 0.022). Wound infection was observed in 51.2% (108/211) in group A and 61.5% (136/221) in group B. Endometritis was seen in 14.7% (31/211) in group A and 23.5% (52/221) in group B, and the difference in the risk of endometritis was statistically significant (RR 0.62;95% CI 0.39–0.99; P = 0.036). Neonatal outcomes were seen in 1.4% (3/211) in group A and 0.4% (1/221) in group B, but the difference between groups was not statistically significant. These were neonates admitted into the neonatal intensive care unit during the observation period and were treated for infection.

A multivariate model was used to assess the general characteristics of patients that were not evenly distributed between the groups, but that were significantly different. These included type of incision (P = 0.018) and type of anaesthesia (P = 0.001). As presented in Table 2, the risk of overall infection remained significantly lower in group A compared with group B, even after controlling for effects of Pfannenstiel incision and general anaesthesia.

We conducted a single-blind randomised clinical trial to compare the effect of the time of administration of prophylactic antibiotics on the risk of postoperative infection.

Administration of prophylactic antibiotics within 1 hour before skin incision significantly reduced the overall incidence of postoperative infections. Regarding the different types of infection, endometritis was significantly reduced. There were no significant adverse neonatal outcomes associated with the timing of antibiotic prophylaxis.

Based on the results of this study, we can recommend that prophylactic antibiotics be administered within 1 hour before skin incision in patients scheduled to undergo caesarean section in order to reduce the overall incidence of postoperative infection at Mulago Hospital. Additionally, we recommend the conduct of further investigations to determine other means of prevention of postoperative infections in an effort to reduce the incidence rate.