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Clinical Infection & Immunity

Original Article

Volume 4, Number 2, October 2019, pages 21-26

Chlorhexidine Vaginal Cleansing Versus Iodine Prior to Cesarean Section and the Rate of Postoperative Maternal Infection: A Randomized Controlled Trial

Cesarean delivery is one of the most common surgical procedures performed by obstetricians with rates reaching 32.3% in North and 40.5% in Latin America [1]. Women undergoing cesarean delivery have 5- to 20-fold higher risks for infectious morbidity compared with those undergoing vaginal birth [2]. These morbidities include endometritis, puerperal pyrexia, surgical site infection (SSI) and other wound complications (seroma, hematoma and skin separation). Endometritis, which is an infection of the endometrial lining, complicates postoperative course of cesarean delivery 6-27% of the time [3]. Endometritis is 10 times more frequent than after vaginal delivery and can lead to serious complications as peritonitis, intra-abdominal abscess and sepsis [4]. Additionally, cesarean deliveries are frequently complicated with wound infections with an incidence of 2-15% [5]. Clinically, significant fever was reported as 5-24% leading to prolonged hospital stay and possible hospital readmission. Preoperative antibiotics and abdominal preparation with antiseptic solution have been adopted as the standard of care to reduce the risk of developing postoperative infectious complications [5]. Nevertheless, and in spite of this intervention, the rate of post-cesarean infections remains a problem. Bacteria colonizing the vagina have been shown to be responsible for failure of antibiotic prophylaxis during cesarean deliveries [6, 7]. A systemic review and meta-analysis concluded that vaginal cleansing before cesarean delivery has been shown to decrease the incidence of post-cesarean infectious morbidities particularly endometritis [2]. The vast majority of the randomized controlled trials (RCTs) in that review used povidone-iodine as the antiseptic agent. Another recent Cochrane review found that vaginal preparation with either povidone-iodine or chlorhexidine immediately before cesarean delivery probably reduces the risk of post-cesarean endometritis [7]. This evidence, however, did not guide to the choice for the optimal antiseptic agent for vaginal preparation. For abdominal preparation, previous studies have demonstrated the superiority of chlorhexidine in reducing SSI [8]. Nevertheless, CAPICA trial could not confirm this superiority [9]. Our study is the first randomized clinical trial to compare the efficacy of concomitant vaginal and skin preparation with either chlorhexidine or povidone-iodine in the prevention of a composite of maternal infectious morbidities following cesarean delivery.

This was a single-center RCT conducted at Makassed General Hospital (MGH) from February 2018 to February 2019. The trial was registered prior to patient enrollment at clinical.gov (Clinical Trials.gov ID: NCT03431701). This study was approved by the Institutional Review Board (IRB) at MGH, and all participants gave written consent. Study included all women, over the age of 17 years, who underwent cesarean delivery. Women were excluded if they had allergy to either chlorhexidine or povidone-iodine solutions, or had any infection at admission (pneumonia, urinary tract infection, chorioamnionitis, or pyelonephritis), or received post-cesarean antibiotics. Most women underwent the consent procedure at the admission for delivery and were rescreened to confirm eligibility after the decision of cesarean delivery was made. Patients eligible for the study were divided into chlorhexidine group and povidone-iodine group. Randomization was done using the sealed envelope technique. Envelopes were opened by the resident attending the operation upon decision of cesarean delivery. After randomization of eligible participants, both abdominal and vaginal preparations with the same antiseptic solution selected was done. Vaginal cleansing with the selected intervention was done by the resident using a foam sponge soaked with either povidone-iodine or chlorhexidine, inserted into the vagina and rotated 360° in the vaginal cavity for about 20 - 30 s. All patients were catheterized with Foley catheter under aseptic conditions and received standard weight adjusted dose of antibiotic prophylaxis (cefazolin) within 30 min prior to skin incision. Patients with cephalosporin or severe penicillin allergy received clindamycin as an alternative. The cesarean delivery was then performed as usual. All participants received the routine postoperative care. Patients who received postoperative antibiotics were excluded from the study (n = 41). Maternal characteristics examined included demographics, prenatal and surgical characteristics. Patient’s age, parity, body mass index (BMI), gestational age and smoking status were recorded. Additional maternal characteristics included group B streptococcus (GBS) colonization status and diabetes status (gestational or pre-gestational). Prenatal characteristics included the duration of ruptured membranes, labor status, number of pelvic exams and operative time (time from skin incision to skin closure). Other surgical characteristics included placental removal (manual or gentle cord traction), estimated blood loss, pre- and postoperative hemoglobin levels, in addition to the type of skin closure (suture or staplers). The primary outcome was a composite of post-cesarean infectious morbidities including: endometritis, fever or SSI, occurring within 30 days after cesarean delivery. Data were collected by reviewing electronic hospital records at delivery, hospitalization, readmissions, emergency department (ED) registry and physician’s records at their clinics. Endometritis was defined as the presence of at least two of the following signs with no other recognized cause: fever greater than 38 °C, abdominal pain, uterine tenderness, or purulent drainage from the uterus. SSI was defined according to Centers for Disease Control and Prevention (CDC), as the presence of either superficial or deep SSI characterized by localized swelling, redness or hotness or purulent discharge from the incision site with or without fever and including necrotizing fasciitis or the presence of organism from an aseptically obtained culture of fluid or tissue [10]. Postpartum fever was defined as temperature ≥ 38 °C not including the first 24 postoperative hours, in absence of other clinical findings suggestive of infection (pneumonia, urinary tract infection). Secondary outcomes included other wound complications (seroma, hematoma and skin separation), adverse skin reaction or vaginal irritation. In addition, length of hospital stay, hospital readmission and number of follow-up office visits were recorded.

According to a recent meta-analysis, the prevalence of post-cesarean infectious complications ranges between 2% and 27%. Most specifically, endometritis (6-27%), clinically significant fever (5-24%) and wound infection (2-9%) have been reported [2]. Assuming that the frequency of the expected outcome (composite infectious morbidity) is 24%, a 50% reduction to observe 12% would need 160 patients in each arm, with alpha 0.05 and beta of 80% [11]. The statistical package for social sciences (IBM-SPSS, version 24) program was used for statistical analysis. Categorical variables were presented as numbers and percentages, whereas continuous variables were presented as means and standard deviations. Chi-square was used for comparing categorical variables, whereas the continuous ones were compared using the analysis of variance test. A P-value of less than 0.05 indicated statistical significance. Multivariate analysis was done to control for confounding variables.

From February 2018 through February 2019, a total of 435 pregnant women were available for cesarean delivery. Fifty-six patients declined participation, while 379 patients were assessed for eligibility. Five women were excluded for the following reasons: three cases of chorioamnionitis and two cases of fetal distress. A total of 374 patients were randomly assigned to receive preparation with either chlorhexidine or povidone-iodine. Then 41 patients were excluded due to postoperative antibiotic use. In the final analysis, 333 patients were distributed as follows: 159 in chlorhexidine group and 174 in the povidone-iodine group. The allocation of women was described in Figure 1. Most of the participants were multiparous and in labor (57.9-66.1%) and 15.5-19.5% presented with rupture of membranes. Suturing was more used among patients in the povidone-iodine group (78.6%) while staplers use was more in the chlorhexidine group (32.1%) (P = 0.03). Another significant difference among both groups was noted in longer operative time in povidone-iodine group (64.6 min) compared to that in chlorhexidine group (61.0 min) with P-value of 0.03. Otherwise, patients in both groups had similar mean age, mean parity, frequency of smoking, GBS screen status, diabetes mellitus and other surgical variables (Table 1). The rate of composite infectious morbidity was 4.4% in the chlorhexidine group versus 8.0% in the povidone-iodine group; this difference however, did not reach statistical significance (P = 0.17). The same was seen among individual components of the composite outcome (Table 2). There were no significant difference between chlorhexidine and povidone-iodine with respect to the rates of wound complications (seroma, hematoma and skin separation), length of hospital stay and hospital readmission for infection-related complications. Likewise, there was no significant difference between the two groups with respect to adverse skin reaction or vaginal irritation. Patients assigned to povidone-iodine group were found to have significantly more clinic visits than those assigned to chlorhexidine group (0.59 ± 0.51 vs. 0.44 ± 0.49; P = 0.005) (Table 2). No difference was elicited also between the two antiseptic agents in patients with labor or premature rupture of membranes (Table 3)

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Figure 1. Randomization and follow-up of study participants.

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Table 1. Characteristics of Study Participants

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Table 2. Post-Cesarean Infectious Morbidities

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Table 3. Composite Infectious Morbidities for Specific Subgroups

Multivariate analysis demonstrated no significant difference for the primary outcome with respect to the type of antiseptic used and other risk factors for infection such as operative time, staplers use and whether the patient was in labor or with prelabor rupture of membranes (PROM) (Table 4).

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Table 4. Multivariate Analysis of Variables in Relation to Primary Composite Outcome

In this RCT, we found that the risk of composite infectious morbidities following cesarean delivery was not statistically different upon using either chlorhexidine or povidone-iodine for combined abdominal and vaginal preparation. Nevertheless, we could observe a trend towards clinical reduction in the composite outcome as well as in all individual components of this composite. The only statistically significant benefit was seen in the secondary outcome with chlorhexidine showing an association with less follow-up visits probably for wound care. It was interesting to find that the rate of post-cesarean infectious morbidity in the entire cohort was rare compared to those reported in the literature. Similar finding was reported by Lakhi et al who attributed this low rate to a probable effect of adding vaginal cleansing to the standard preoperative care [12]. The intervention of vaginal cleansing is not recent, as it was previously used prior to abdominal hysterectomy where it showed reduction in the bacterial vaginal count and lower postoperative infectious morbidity [13]. Prior studies have evaluated whether vaginal cleansing before cesarean delivery with various antiseptic solutions could reduce the incidence of endometritis or other infectious morbidities [11, 14, 15]. Hass et al in their Cochrane review (10 trials and 3,283 women) concluded that vaginal preparation with povidone-iodine or chlorhexidine solution immediately before cesarean delivery reduced the risk of endometritis from 8.7% in control group to 3.8% in vaginal preparation group (risk ratio (RR) 0.36; 95% confidence interval (CI) 0.02 - 0.63), but this reduction was limited to women who were in labor or with ruptured membranes [7]. This meta-analysis showed that the risk of experiencing wound infection or postoperative fever was slightly lowered by vaginal preparation [7]. Two trials reported a lower risk of composite outcome of wound complications or endometritis in women receiving preoperative vaginal preparation [11, 16]. One pitfall was that the abdominal preparation technique and solutions were not described. Another meta-analysis by Caissutti et al (15 studies, 4,726 participants) showed that vaginal cleansing with 10% povidone-iodine significantly decreased the rate of endometritis (4.5% compared with 8.8%; RR 0.52; 95% CI 0.37 - 0.72) and of postoperative fever (9.4% compared with 14.9%; RR 0.65; 95% CI 0.50 - 0.86) compared with the control group. Again, the reduction in incidence of endometritis was limited to women in labor and with ruptured membranes. Regarding wound infection and other wound complications (seroma, hematoma and skin separation), there were no significant difference between the two groups [2]. In most trials, vaginal cleansing was done using povidone-iodine. As for chlorhexidine, fewer trials were conducted using this agent for vaginal cleansing. Ahmed et al evaluated the efficacy of preoperative vaginal cleansing using chlorhexidine wipes on rates of post-cesarean infectious morbidities. He concluded that post-cesarean infectious morbidities as overall were significantly reduced from 24.4% in the control group to 8.8% in the chlorhexidine group (P < 0.05). Marked reduction was noticed in the incidence of endometritis (13.2% in the control group versus 2.9% in the chlorhexidine group; P < 0.05). However, no significant difference was found between the two groups in the rates of fever and wound infection [11]. Also, Rouse et al studied 1,024 women randomized to chlorhexidine or placebo and found that the rate of endometritis did not differ between the two groups [16]. None of these two trials used povidone-iodine as a comparator. Chlorhexidine has a number of properties that may lead to greater effectiveness than iodine as an antiseptic. It acts by destruction of bacterial cell wall leading to leakage of cellular components and to a decrease in bacterial count. Furthermore, it has greater residual activity, and unlike iodine, it is not inactivated by organic matters or other body fluids [17]. Some studies showed greater reduction in skin flora after application of chlorhexidine compared with povidone-iodine [17]. For preoperative abdominal preparation, prior RCTs have demonstrated superiority of chlorhexidine compared with povidone-iodine in reducing SSI post-cesarean delivery [8]. The CAPICA trial, on the other hand, did not confirm this superiority [9]. For vaginal cleansing, Tewfik et al conducted the first RCT that compared vaginal cleansing with chlorhexidine to povidone-iodine prior to elective cesarean delivery. The study had shown that chlorhexidine was significantly associated with reduced risk of postoperative fever (RR 3.07; 95% CI 1.07 - 8.81). However, the rates of endometritis and SSI did not show statistically significant reduction. He recruited smaller sample size (n = 93) and only women who were planned for elective cesarean that were considered as low risk population [18]. A more recent trial comparing chlorhexidine to povidone-iodine vaginal cleansing has shown that the rate of wound infection was significantly reduced in the chlorhexidine group compared with povidone-iodine (0.6% vs. 2.0%; P = 0.039), yet, rates of endometritis and postoperative fever were similar in both groups. Similar to our study, Lakhi et al found that the constant usage of vaginal preparation with either chlorhexidine or povidone-iodine reflects a much lower percentage of infection [12]. This may explain the statistically insignificant results in our study.

La Rosa et al in a secondary analysis of the Cesarean Section Optimal Antibiotic Prophylaxis Trial [19] compared the rate of post-cesarean SSI in 523 women delivered in institutions with vaginal antisepsis policies before cesarean delivery and 1,490 delivered in institutions without such policies. They concluded that there was no difference in SSI rates between the two groups (5.5% vs. 4.1%; OR 1.38; 95% CI 0.87 - 2.17). They did not find significant difference between the groups in the rates of postpartum fever and endometritis [20]. The main weakness of their study was that women were not randomized to vaginal preparation. Also, the technique of vaginal preparation varied based on the institutional policy. A possible alternative explanation to their findings was the adding of azithromycin to the standard regimens for antibiotic prophylaxis before cesarean delivery that might have further reduced the rate of postoperative infections. To our best knowledge, this is the only RCT to address the effect of combined vaginal and skin preparation with one antiseptic agent compared to another antiseptic in reducing post-cesarean infectious morbidities. Unlike different studies that targeted only elective cesarean delivery, the mixed-risk nature of our cohort is more representative of actual life scenario. We could notice that using any of these two antiseptic solutions was complicated with only 6.2% of composite infectious morbidity, 5.3% of skin infection, 1.1% of endometritis and 2.1% of fever which are far below other reported figures from other trials. Our study was not without limitations. First, this was a single-center trial, which raises a question about the potential generalizability of our findings. Second, the unexpected low frequency of the infectious morbidities rendered the sample size inadequate to have enough power to show any real difference between the study and the control groups. In fact, we feel that the sample size calculation depending on old infectious morbidity rates (before vaginal cleansing) was inaccurate. Future studies should consider lower morbidity rates and accordingly should have larger sample size to have enough power to elicit a superiority of either solution, if existent. In summary, chlorhexidine or povidone-iodine for skin and vaginal preparation were not different in reducing post-cesarean infectious morbidities, despite a clinically evident reduction with the preoperative use of the former agent. This simple, low cost intervention (vaginal cleansing), in adjunct to prophylactic antibiotics and abdominal preparation, may further decrease post-cesarean infectious morbidities.

Acknowledgments

We would like to acknowledge our colleagues, residents, nurses at the department of obstetrics and gynecology, and Ms. Loubna Sinno (Research Coordinator) at Makassed General Hospital for their effort and cooperation while conducting this study.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Informed Consent

Informed consent was obtained from patients.

Author Contributions

Mohamad K. Ramadan helped in designing the study, analyzing the data and manuscript writing. Zeinab Maita helped in conducting the study and in manuscript writing. Rana El-Tal helped in conducting the study. Manal Hubeish helped in conducting the study and in manuscript writing.

1. Betran AP, Ye J, Moller AB, Zhang J, Gulmezoglu AM, Torloni MR. The increasing trend in caesarean section rates: global, regional and national estimates: 1990-2014. PLoS One. 2016;11(2):e0148343.
   doi pubmed
2. Caissutti C, Saccone G, Zullo F, Quist-Nelson J, Felder L, Ciardulli A, Berghella V. Vaginal cleansing before cesarean delivery: a systematic review and meta-analysis. Obstet Gynecol. 2017;130(3):527-538.
   doi pubmed
3. Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2014;10:CD007482.
   doi pubmed
4. Mackeen AD, Packard RE, Ota E, Speer L. Antibiotic regimens for postpartum endometritis. Cochrane Database Syst Rev. 2015;2:CD001067.
   doi pubmed
5. Berrios-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, Reinke CE, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017;152(8):784-791.
   doi pubmed
6. Watts DH, Hillier SL, Eschenbach DA. Upper genital tract isolates at delivery as predictors of post-cesarean infections among women receiving antibiotic prophylaxis. Obstet Gynecol. 1991;77(2):287-292.
   doi pubmed
7. Haas DM, Morgan S, Contreras K, Enders S. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Syst Rev. 2018;7:CD007892.
   doi
8. Tuuli MG, Liu J, Stout MJ, Martin S, Cahill AG, Odibo AO, Colditz GA, et al. A Randomized trial comparing skin antiseptic agents at cesarean delivery. N Engl J Med. 2016;374(7):647-655.
   doi pubmed
9. Springel EH, Wang XY, Sarfoh VM, Stetzer BP, Weight SA, Mercer BM. A randomized open-label controlled trial of chlorhexidine-alcohol vs povidone-iodine for cesarean antisepsis: the CAPICA trial. Am J Obstet Gynecol. 2017;217(4):463 e461-463 e468.
   doi pubmed
10. Keely Boyle K, Rachala S, Nodzo SR. Centers for disease control and prevention 2017 guidelines for prevention of surgical site infections: review and relevant recommendations. Curr Rev Musculoskelet Med. 2018;11(3):357-369.
    doi pubmed
11. Ahmed MR, Aref NK, Sayed Ahmed WA, Arain FR. Chlorhexidine vaginal wipes prior to elective cesarean section: does it reduce infectious morbidity? A randomized trial. J Matern Fetal Neonatal Med. 2017;30(12):1484-1487.
    doi pubmed
12. Lakhi N, Tricorico G, Osipova Y, Moretti M. Vaginal cleansing with chlorhexidine gluconate or povidone-iodine prior to cesarean delivery: a randomized comparator-controlled trial. Am J Obstet Gynecol MFM. 2019;1:2-9.
    doi
13. Haeri AD, Kloppers LL, Forder AA, Baillie P. Effect of different pre-operative vaginal preparations on morbidity of patients undergoing abdominal hysterectomy. S Afr Med J. 1976;50(49):1984-1986.
14. Haas DM, Pazouki F, Smith RR, Fry AM, Podzielinski I, Al-Darei SM, Golichowski AM. Vaginal cleansing before cesarean delivery to reduce postoperative infectious morbidity: a randomized, controlled trial. Am J Obstet Gynecol. 2010;202(3):310 e311-316.
    doi pubmed
15. Asghania M, Mirblouk F, Shakiba M, Faraji R. Preoperative vaginal preparation with povidone-iodine on post-caesarean infectious morbidity. J Obstet Gynaecol. 2011;31(5):400-403.
    doi pubmed
16. Rouse DJ, Hauth JC, Andrews WW, Mills BB, Maher JE. Chlorhexidine vaginal irrigation for the prevention of peripartal infection: a placebo-controlled randomized clinical trial. Am J Obstet Gynecol. 1997;176(3):617-622.
    doi
17. American College of O, Gynecologists Women's Health Care P, Committee on Gynecologic P. Committee Opinion No. 571: Solutions for surgical preparation of the vagina. Obstet Gynecol. 2013;122(3):718-720.
    doi pubmed
18. Tewfik H, Ibrahim A, Hanafi S, Fahmy A, Khaled MA, Abdelazim IA. Preoperative vaginal preparation using povidone iodine versus chlorhexidine solutions in prevention of endometritis in elective cesarean section. Int J Curr Microbiol App Sci. 2015;4:486-492.
19. La Rosa M, Jauk V, Saade G, Boggess K, Longo S, Clark EAS, Esplin S, et al. Institutional protocols for vaginal preparation with antiseptic solution and surgical site infection rate in women undergoing cesarean delivery during labor. Obstet Gynecol. 2018;132(2):371-376.
    doi pubmed
20. Tita AT, Szychowski JM, Boggess K, Saade G, Longo S, Clark E, Esplin S, et al. Adjunctive azithromycin prophylaxis for cesarean delivery. N Engl J Med. 2016;375(13):1231-1241.
    doi pubmed

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