Impact of antimicrobial stewardship interventions on post-elective caesarean antibiotic prophylaxis and surgical site infections

Abstract

Background

Antimicrobial stewardship programs (ASP) aim to improve appropriate antimicrobial use but few studies have described its impact on unique population such as obstetrics. Post-operative antibiotics are unnecessary especially in those without surgical site infections (SSI) risk factors (e.g., obesity).

Objectives

To evaluate the impact of ASP interventions on post-elective caesarean (eLSCS) oral antibiotic prophylaxis rates and patient outcomes.

Methods

This pre-post quasi-experimental study was conducted over 18 months (2 months pre- and 16 months post-intervention) in all women admitted for eLSCS in our institution. Interventions included eLSCS surgical prophylaxis guideline dissemination and post-eLSCS oral antibiotics was actively discouraged in those without SSI risk factors. This was followed by ASP intervention notes (phase 1) for 3 months, contacting the ward team for the next 7 months (phase 2) and subsequently the primary obstetrics attending in Phase 3 (next 6 months). The primary outcome was post-operative oral antibiotics prescription rates, and secondary outcomes included 30-day post-operative SSI rates.

Results

A total of 1751 women was reviewed. Appropriateness of pre-operative antibiotic prophylaxis was 99%. There were 244 (13.9%) women pre-intervention and 1507 (86.1%) post-intervention. Post-eLSCS antibiotic prescribing rates reduced significantly post-intervention (200, 82% vs 705, 46.8%, p < 0.001). There was no significant difference in SSI rates pre-post intervention (2, 0.8% vs 28, 1.9%, p = 0.420). There was also no significant difference in SSI rates among those who received post-operative oral antibiotics compared to those without (1.9%, 17 of 905 vs 1.5%, 13 of 846, p = 0.582).

Conclusions

ASP interventions can reduce unnecessary post-eLSCS antibiotic prophylaxis use without adversely impacting patient safety.

Keywords

Antimicrobial stewardship surgical prophylaxis surgical site infections

Introduction

Surgical site infection (SSI) is a major public health concern as it can contribute to significant post-operative morbidity, mortality and healthcare costs.^1,2 Cesarean deliveries are one of the most frequently performed surgeries worldwide, accounting for 21% of births globally in 2015.³ Approximately 3 to 15% of cesarean deliveries are complicated by SSIs, with a maternal mortality rate of up to 3%.⁴ Risk factors for SSI post-cesarean deliveries include inappropriate pre-operative antimicrobial prophylaxis and obesity.^5,6 Multifaceted strategies to improve adherence to evidence-based SSIs prevention measures such as aseptic surgical practice bundles and appropriate antimicrobial prophylaxis have been explored.^7–10

Antibiotic stewardship programs (ASPs) promote the judicious use of antimicrobials^11,12.In surgical disciplines, ASPs can improve appropriate antibiotic use, especially duration, where growing concerns for antimicrobial side effects and resistance as a result of antibiotics overuse exists.^13,14 International guidelines advocate a single dose of antibiotics within 60 minutes before skin incision to reduce SSI rates.^15,16 Post-operative oral antibiotics are generally unnecessary, especially those without SSI risk factors (e.g. obesity).^5,17 Few studies have described the impact of ASP interventions on patient outcomes in unique populations e.g. obstetrics.^18–21

A prospective-review-and-feedback ASP for selected antibiotics was formally established in our hospital, KK Women’s and Children’s Hospital (KKH) since 2011. KKH is an 830-bed tertiary-care hospital and the largest referral center for pediatrics and obstetrics/gynecology (OBGYN) conditions in Singapore. Our institution provides high-risk obstetrics, gynecological cancer, and urogynecology services, with approximately 20,000 inpatient admissions yearly.

A surgical SSI prevention bundle was implemented in KKH since 2017 as appropriate pre-operative antibiotics rates was only 76% in a 2016 survey (unpublished data). Point-prevalence surveys (PPS) based on the Global-PPS methodology²² of post-operative oral antibiotic use in our elective lower section caesarean section (eLSCS) patients from 2017 to 2019 (unpublished data) showed that more than 80% received a week’s course of antibiotics.

Hence, we sought to evaluate the impact of a multifaceted, step-wise implementation of ASP interventions on post-operative oral antibiotic prophylaxis rates for eLSCS patients in KKH. We focused on elective/scheduled LSCS patients as factors predisposing to SSI risks such as inappropriate pre-operative antibiotic prophylaxis timing would be reduced. To address the safety concerns of accepting ASP recommendations, we reviewed clinical outcomes including 30-day SSI, 30-day infection-related and all-cause admission rates pre-post interventions. In addition, SSI rates in those with and without risk factors, and if they received post-operative oral antibiotics, were compared.

Materials and methods

Study design

This was a single-center pre-post quasi-experimental study. There was a 2-month pre-intervention review period (1 July to 31 August 2019), followed by a 16-month step-wise post-intervention period (1 September 2019 to 31 December 2020) (Figure 1). Our multi-disciplinary ASP OBGYN team comprised Infectious Diseases physicians, ASP pharmacists with at least 5 years of work experience and a physician champion from the OBGYN department. An ASP pharmacist reviewed patients on the daily eLSCS operative list (Monday to Friday) and discussed recommendations and to confirm if there are surgical complications based on operative notes, if any, with the ASP OBGYN physician before making the interventions within one working day.

Figure 1.

Step-wise implementation of antimicrobial stewardship programme (ASP) interventions and phases.

Inclusion and exclusion criteria

All patients who underwent eLSCS from 1 July 2019 to 31 December 2020 were reviewed. Patients who had emergency caesarean section, concomitant infections before surgical incision, or ongoing antibiotic therapy were excluded.

ASP interventions

A seven-step SSI prevention bundle was formally implemented in our institution since February 2017. It included a pre-operative bath with chlorhexidine 4% wash, appropriate pre-operative antibiotic (right drug, dose, route and timing) within 60 minutes of skin incision and removal of wound dressing no later than post-operative day 5 unless medically indicated. Existing OBGYN procedures surgical prophylaxis guidelines recommend a single antibiotics dose of antibiotic within 60 min of skin incision. In concordance with international guidelines, IV cefazolin 2 g was prescribed if the patient was <120 kg, or 3 g if ≥ 120 kg.^15,16 If penicillin-allergic, IV clindamycin 900 mg was administered. A literature review was conducted, with at least 3 internal meetings to review pre-audit data and to finalize our approaches. Our team had at least 2 meetings with various stakeholders from the department to determine reasons for antibiotic continuation despite recommendations. A consensus guideline for caesarean procedures surgical prophylaxis guidelines was finalized, which now included recommendations to allow antibiotic continuation for 2 to 5 days only if patients were at high risk of SSI (see definitions below). This was presented at the Division meeting and disseminated to the department pre-intervention period. Post-phase updates were also presented to the Division after our internal review. An estimated of 3 months were taken for the above discussions including departmental, internal meetings and email correspondence.

The step-wise implementation of ASP interventions is described in Figure 1. The study was conducted in 3 phases. In the pre-intervention phase, the updated surgical prophylaxis guideline was shared department-wide. During phase 1, one of the 3 ASP pharmacists on duty would inform the ward team of ASP’s recommendations via documentation on the patient’s electronic medical records. Complicated cases (see “Definitions” section) would be discussed with the ASP OBGYN physician. Phase 2 consisted of an additional phone call by the ASP pharmacist to the ward team’s junior doctors. The operating surgeon was contacted by the ASP pharmacist in phase 3. At the end of each phase, the department was updated on antibiotic prescribing and SSI rates with reinforcement of surgical prophylaxis guidelines. Recommendations to stop or allow antibiotic continuation was based on patient’s SSI risk factors, and after clarification regarding operative complications with ward team or surgeons if necessary.

Definitions

Surgical site infection (SSI) was defined according to the National Healthcare Safety Network of the Centers for Disease Control and Prevention.²³ This included superficial incisional, deep incisional infections characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision and organ/space infections such as endometritis. We also included patients with antibiotic prescriptions for eLSCS-related wound infections.

In our institution, we defined high risk of SSI as: obesity [body mass index (BMI) >30, weight >80 kg], pre-existing or pregnancy-induced gestational diabetes, hypertension, immunodeficiency syndromes, rupture of membranes/ labor >18 hours and surgical complications,^5,6 where post-operative oral antibiotics may be continued at the individual physician’s discretion. Complications include situations such as dense adhesions with bowel and bladder; uterine and cervical tear during delivery as well as post-partum hemorrhage.^24,25

Outcomes

The primary outcome was post-operative oral antibiotics prescription rates. Secondary outcomes included rates of 30-day SSI, 30-day infection-related admission and all-cause admission. We reviewed the characteristics of patients who developed 30-day SSI versus those who did not.

Data collection

Patient characteristics, including age, weight and/or BMI, parity, multi-fetal gestation, smoking history, significant medical history including pre-existing or pregnancy-induced gestational diabetes, hypertension, immunodeficiency syndromes, rupture of membranes was recorded. Surgery specific data such as administration of appropriate pre-operative prophylaxis, estimated blood loss (EBL), operation time, and surgical complications (reported or as clarified with operating surgeons) were recorded. Duration of hospitalization and antibiotics prescribed were collected. Outpatient records were reviewed to determine if there were clinic or emergency department visits, or admission during the 30-day period post-eLSCS related to SSI development, as well as infection-related and all-cause admission. If wound cultures were taken, the identity and susceptibility of micro-organisms if isolated were documented. We also attempted to determine the day of SSI onset as documented in medical records.

Statistical analysis

For univariate analyses, categorical variables were compared using a chi-square test or Fisher’s exact test, where appropriate. Continuous variables were compared using a t test or Mann-Whitney U test, where appropriate. Post-hoc analysis using one-way ANOVA of different intervention phases on the primary outcome was conducted. A p value was considered statistically significant if < 0.05. All statistical analyses were performed using SPSS version 19 (IBM, Armonk, NY, USA).

This study was approved by the SingHealth Centralized Institutional Review Board (CIRB Ref: 2016/2661). A requirement for informed consent was waived, as ASP operations were part of routine clinical practice and quality improvement protocols.

Results

Study population

A total of 1751 women was reviewed. Baseline patient and procedure characteristics in the pre- and post-intervention periods are displayed in Table 1. The mean age of patients reviewed was 33.6 (SD 4.5) years. SSI risk factors were present in 699 patients (39.9%). Overall appropriate pre-operative antibiotics rates were 99.0%.

Table 1.

Patients’ characteristics and outcomes.

Number	Overall		Pre-intervention		Post-intervention								p value**
	Overall		Pre-intervention		Phase 1		Phase 2		Phase 3		Phase 1 to 3
	1751		244		274		658		575		1507
Baseline characteristics
Maternal age (years)^a	33.6	(4.5)	33.4	(4.5)	33.1	(4.6)	33.7	(4.4)	33.8	(4.6)	33.6	(4.5)	0.396
Weight (kg)^a	72.9	(4.0)	70.5	(14.2)	72.2	(13.4)	73.5	(14.0)	73.5	(14.2)	73.3	(14.0)	1.000
Body mass index^a	29.4	(5.3)	28.4	(5.3)	29.0	(4.9)	29.7	(5.2)	29.7	(5.5)	29.6	(5.3)	1.000
Parity^a	1.03	(0.2)	1.03	(0.3)	1.2	(0.9)	1.3	(1.1)	1.2	(0.9)	1.03	(0.2)	0.980
Multifetal gestation	71	(4.1)	16	(6.6)	12	(4.4)	27	(4.2)	16	(2.8)	55	(3.6)	0.980
Medical history	186	(10.6)	32	(13.1)	31	(13.1)	82	(12.5)	41	(7.1)	154	(10.2)	0.173
Smoking	13	(0.7)	2	(0.8)	2	(0.7)	6	(0.9)	3	(0.5)	11	(0.7)	0.701
Obesity	414	(23.6)	50	(20.5)	57	(20.8)	164	(24.9)	143	(24.9)	364	(24.2)	0.212
Diabetes	355	(20.2)	47	(19.3)	45	(16.4)	136	(20.7)	127	(22.1)	308	(20.5)	0.672
Diet control	239	(13.6)	36	(14.8)	27	(9.9)	91	(13.8)	85	(14.8)	203	(13.5)	0.332
On medications	116	(6.6)	11	(4.5)	18	(6.6)	45	(6.8)	42	(7.3)	105	(7.0)	0.152
Hypertension	49	(2.8)	9	(3.7)	5	(1.8)	18	(2.7)	17	(3.0)	40	(2.7)	0.363
Immuno-compromised	6	(0.3)	2	(0.8)	2	(0.7)	0	(0.0)	2	(0.3)	4	(0.3)	0.199
Rupture of membranes/labour >18 hours	2	(0.1)	0	(0.0)	1	(0.4)	1	(0.2)	0	(0.0)	2	(0.1)	0.569
Procedural characteristics
Appropriate pre-operative antibiotics	1735	(99.0)	244	(100)	267	(97.4)	652	(99.1)	572	(99.5)	1491	(98.9)	1.000
Duration of surgery (min)^a	46.3	(21.0)	47.4	(21.0)	46.1	(23.5)	45.3	(19.0)	47.0	(21.7)	46.1	(21.0)	0.377
Estimated blood loss (mL)^a	396.0	(244.0)	425.4	(296.2)	396.0	(283.2)	390.9	(210.0)	389.1	(234.1)	391.2	(234.1)	0.137
Surgical complications	66	(3.8)	1	(0.4)	8	(2.9)	16	(2.4)	41	(7.1)	65	(4.3)	0.003
Overall risk factors present	699	(39.9)	86	(35.2)	99	(36.1)	260	(39.5)	254	(44.2)	613	(40.7)	0.108
Duration of hospitalization (days)^a	3.0	(1.6)	3.1	(1.4)	3.1	(1.3)	2.9	(1.1)	3.0	(2.1)	3.0	(1.6)	0.516
Outcomes
Single dose IV antibiotic	603	(34.4)	24	(9.8)	91	(33.2)	213	(32.4)	274	(47.8)	578	(38.4)	<0.001
Post-operative oral antibiotics^b	905	(51.7)	200	(82.0)	148	(54.0)	331	(50.3)	226	(39.3)	705	(46.8)	<0.001
Duration of antibiotics (days)^a,c	5.0	(2.3)	5.8	(1.7)	5.1	(2.1)	4.9	(2.4)	4.9	(2.6)	4.9	(2.4)	<0.001
Duration of oral antibiotics (days)^a	3.4	(2.9)	5.2	(2.3)	3.5	(2.8)	3.4	(2.9)	2.7	(3.0)	3.1	(2.9)	<0.001
Pharmacists’ interventions^d	-	-	-	-	67	(24.5)	145	(22.0)	103	(17.8)	315	(20.9)	-
Intervention acceptance	-	-	-	-	7	(10.4)	14	(9.7)	14	(13.6)	35	(11.1)	0.528
Appropriate antibiotic duration	971	(55.5)	98	(40.2)	159	(58.0)	401	(60.9)	349	(60.7)	909	(60.3)	<0.001
30-day surgical site infection	30	(1.7)	2	(0.8)	5	(1.8)	17	(2.6)	6	(1.0)	28	(1.9)	0.420
30-day infection related admission	7	(0.4)	0	(0.0)	2	(0.7)	4	(0.6)	1	(0.2)	7	(0.5)	1.000
30-day all-cause admission	10	(0.6)	1	(0.4)	3	(1.1)	4	(0.6)	2	(0.3)	9	(0.6)	1.000

All no. (%).

**p-values refer to comparison pre- versus post-intervention (phase 1 to 3), except intervention acceptance (between phases).

^aMean (SD).

^bOral antibiotics prescribed included either oral amoxicillin-clavulanate or cephalexin or clindamycin if beta-lactam allergy.

^cIncludes patients who received >1 dose of IV antibiotic.

^dNumbers excluded those with inappropriate antibiotic duration but were discharged/ additional antibiotics given before interventions could be made.

There were 244 (13.9%) patients in the pre-intervention phase, and a total of 1507 in the post-intervention phase. In the post-intervention phase, there were 274 (15.6%) patients in phase 1, 658 (37.6%) in phase 2 and 575 (32.8%) in phase 3. There were no major differences in characteristics in those in the pre- versus post-intervention phase, except for surgical complications (1, 0.4% vs 65, 4.3%, p = 0.003) (Table 1). There were no significant differences in the mean age, proportion with significant medical history, appropriate pre-operative antibiotic prophylaxis, duration of surgery, estimated blood loss and length of hospital stay in all of the phases. There were a total of 66 cases with surgical complications, which were discussed with the OBGYN ASP physician.

Study outcomes

Post-operative antibiotics

Pre-intervention post-eLSCS oral antibiotic prescribing rates was 82% (200 of 244 patients), which reduced significantly post-intervention to 46.7% (705 of 1507 patients) (p < 0.001) (Table 1). Antibiotic prescribing rates were 54% (148 of 274 patients) in phase 1, 50% (331 of 658) in phase 2 and 39% (226 of 575) in phase 3 (p < 0.001) (Table 1). Post-hoc analysis within the different phases showed a significant reduction in antibiotic prescribing rates between the pre-intervention phase versus phase 1 and 3 (82% vs 54% and 39% respectively), as well as between phase 2 and 3 (50% vs 39%, p < 0.001), but there was no significant difference between phase 1 and 2 (54% vs 50%, p = 1.000) (Figure 2). This is similar after excluding the 66 patients with surgical complications, with pre-intervention phase versus phase 1 and 3 (82% vs 53% and 36% respectively), as well as between phase 2 and 3 (49% vs 36%, p < 0.001), but there was no significant difference between phase 1 and 2 (53% vs 49%, p = 1.000).

Figure 2.

Comparison of post-operative oral antibiotic prescribing rates between intervention phases. Percentages and dashed lines and represent the mean (%) post-operative antibiotic use during each phase. There was a significant difference in antibiotic prescribing rates between phase 1 and pre-intervention periods (54% vs 82%, p < 0.001) and between phase 2 and 3 (50% vs 39%, p < 0.001). There was no significant difference between phase 1 and 2 (54% vs 50%, p = 1.000).

The mean duration of oral antibiotics prescribed was 5.2 (SD 2.3) days in the pre-intervention phase and decreased significantly to 3.1 (SD 2.9) days post-intervention (p < 0.001). Post-hoc analysis within the different intervention phases showed a similar trend to antibiotics prescribing rates (Table 1). In the pre-intervention phase, only 9.8% received a single dose of antibiotics compared to a significant increase in 38.4% post-intervention (p < 0.001). After excluding patients who received only a single dose of IV antibiotic in all groups, the mean duration of antibiotics also decreased from 5.8 (SD 1.7) days in the pre-intervention phase compared to 4.9 (SD 2.4) days post-intervention phase (p < 0.001) (Table 1).

Post-operative 30-day SSI rates and characteristics

The 30-day SSI rate in our institution was low (30 of 1751, 1.7%). It was 0.8% (2 of 244) pre-intervention, compared to 1.9% (28 of 1507) in the post-intervention phase (p = 0.420) (Table 1). In the post-intervention phase, SSI rates were 1.8% (5 of 274) in phase 1, 2.6% (17 of 658) in phase 2 and 1.0% (6 of 575) in phase 3 respectively (Table 1). Post-hoc analysis showed no significant difference among the different phases (all p > 0.05).

In addition, SSI rates were similar among those who received post-operative oral antibiotics versus none (1.9%, 17 of 905 vs 1.5%, 13 of 846, p = 0.582). In sub-groups of those with and without SSI risk factors, there was no significant difference in SSI rates between those who received oral antibiotics or none (Figure 3).

Figure 3.

Comparison of post-operative 30–day surgical site infection (SSI) rates. SSI: surgical site infection.

A comparison of baseline patient and procedure characteristics in the patients who developed SSI or are displayed in Table 2. There were no major differences except for those with rupture of membranes or prolonged labor >18 hours (1 of 30, 3.3% vs 1 of 1721, 0.1%, p = 0.034).

Table 2.

Comparison of characteristics of patients with and without 30-day SSI.

	Overall (n = 1751)		Without SSI (n = 1721)		With SSI (n = 30)		p value
Intervention group	-	-	1479	(85.9)	28	(93.3)	0.420
Baseline characteristics
Maternal age (years)^a	33.6	(4.5)	33.6	(4.5)	34.3	(3.9)	0.353
Weight (kg)^a	72.9	(4.0)	72.8	(13.9)	77.3	(17.9)	0.180
Body mass index^a	29.4	(5.3)	29.4	(5.3)	31.3	(6.4)	0.123
Parity^a	1.0	(0.2)	1.2	(1.0)	1.3	(0.6)	0.619
Multifetal gestation	71	(4.1)	70	(4.1)	1	(3.3)	0.995
Medical history	186	(10.6)	182	(10.6)	4	(13.3)	0.552
Smoking	13	(0.7)	13	(0.8)	0	(0.0)	1.000
Risk factors present	699	(39.9)	686	(39.9)	13	(43.3)	0.700
Obesity	414	(23.6)	406	(23.6)	8	(26.7)	0.694
Diabetes	355	(20.2)	349	(20.3)	6	(20.0)	0.970
Diet control	239	(13.6)	234	(13.6)	5	(16.7	0.717
On medications	116	(6.6)	115	(6.7)	1	(3.3)	0.717
Hypertension	49	(2.8)	48	(2.8)	1	(3.3)	0.576
Immunocompromised	6	(0.3)	6	(0.3)	0	(0.0)	1.000
Procedural characteristics
Rupture of membranes/ labour >18 hours	2	(0.1)	1	(0.1)	1	(3.3)	0.034
Appropriate pre-operative antibiotics	1735	(99.0)	1463	(98.9)	30	(100.0)	1.000
Duration of surgery (min)^a	46.3	(21.0)	46.2	(21.0)	51.9	(21.1)	0.151
Estimated blood loss (mL)^a	396.0	(244.0)	395.4	(242.1)	433.3	(338.2)	0.545
Surgical complications	66	(3.8)	64	(3.7)	2	(6.7)	0.313
Duration of hospitalization (days)^a	3.0	(1.6)	3.0	(1.6)	3.3	(1.8)	0.401
Post-operative oral antibiotics	905	(51.7)	888	(51.6)	17	(56.7)	0.582
Duration of antibiotics (days)^a	3.4	(2.9)	3.4	(2.9)	3.9	(2.9)	0.392

All no. (%).

^aMean (SD).

All 30 patients who developed SSI received appropriate pre-operative antibiotics, of which 13 of them (43%) had SSI risk factors. Nine of these 13 patients (69.2%) with SSI risk factors received a mean of 6.1 (SD 0.5) days duration of post-operative oral antibiotics. The mean time to reported SSI development was 15.8 (SD 7.2) days post-eLSCS. Wound swab cultures were done in 17 (56.7%) patients, of which 14 returned positive for micro-organisms. The most common pathogens identified were methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (four patients each).

Other outcomes

There were no significant differences in 30-day infection-related and all-cause admission rates pre- and post-intervention (0, 0% vs 7, 0.5% and 1, 0.4% vs 9, 0.6%, all p = 1.000). Seven of 30 patients with post-op SSI (23.3%) were admitted for infection-related complications. One was admitted on post-operative day 26 for Clostridiodes difficile gastroenteritis. She had high BMI and was prescribed a week of oral amoxicillin-clavulanate. There were four patients admitted for endometritis, one for concomitant urinary tract infection and MRSA wound abscess, and another with mastitis and superficial wound redness. There were three patients admitted for non-infection-related causes (dizziness, peripartum vasculopathy, and bilateral lower limb swelling).

Comment

Principal findings

In our study, multifaceted ASP interventions effectively reduced unnecessary post-eLSCS oral antibiotic prophylaxis rates without adversely impacting pertinent patient safety outcomes such as 30-day SSI or admission rates.

Results in the context of what is known

Optimizing surgical antibiotic prescribing is complex as measures across the surgical pathway are key aspects in prevention of surgical related complications including SSIs.^26,27 As appropriate pre-operative antibiotic prophylaxis remains one of the most effective intervention to prevent SSIs, interventions in antibiotic use have been primarily focused on this.^26–28

Our approach built upon the implementation of a successful perioperative surgical bundle, where adherence rates were excellent where overall compliance was 99%. This was higher than other centers, where appropriateness rates ranged widely from 14 to 92%.^18–21,29 Post-operative SSI rates were lower in our institution at 1.7%, compared to 5% in a US center to 43% in a resource limited setting, though differences in classification criteria exist.^30–32

International guidelines recommend no further antibiotics after incision closure for most procedures, but rates of prolonged prophylaxis remain high.^15,30 Duration was the most common reason for inappropriateness (54%) in an Australian review.³⁰ This is similar to our institution, where post-operative antibiotics rates were high at 82%. As many studies have demonstrated effectiveness of collaborative strategies, ASP measures to reduce unnecessary antibiotics use were introduced in our institution.^18–21,33

Clinical implications

Understanding the contextual and cultural determinants of infection management and antibiotic prescribing is critical to the development of context-specific interventions.^30,34,35 Clinical autonomy of individual prescribers and existing hierarchies within teams require consideration, together with a certain flexibility in implementation of measures.^30,34,35 Potential resistance of prescribers to change practice were cited, such as lack of knowledge and confidence, innate reluctance for change, fear of “rocking the boat” and failure to communicate.³⁶

In phase 1, there was a significant decrease in antibiotic prophylaxis prescription rates from 82% to 54%. It was possibly due to a high level of engagement with the OBGYN department, as pertinent stakeholders were involved in crafting of surgical prophylaxis guidelines. Some flexibility in continuation of antibiotic prophylaxis for those perceived at being at higher risk to ease acceptability of this new guideline. Phase 3 involved a department physician champion, who reviewed cases with the ASP pharmacists in a timely review-and-feedback method may be better received.

Although ASP pharmacist intervention acceptance rates did not differ significantly throughout the 3 intervention phases, there were the least interventions required in phase 3 and intervention rates were the highest in phase 3. This was similar to reviews of ASP strategies, where prospective audit-and-feedback strategies has been reported to be highly effective.^33,37 Physician involvement in “handshake stewardship” were also described to have positive impact on interventions acceptance,^38,39 which could be explored in future intervention strategies.

There was a rising trend of antibiotic prescribing rates towards the end of phase 2, where it was previously trending down towards the end of phase 1. There was an initial drop after verbal communication with the junior doctors, but this seemed to have waned as fatigue from repeated calls might have set in especially as phase 2 was lengthier, along with unfamiliarity of this initiative due to rotating physicians on service. Hence, we decided to implement phase 3 where the operating surgeon was contacted. Antibiotic prescribing rates decreased significantly subsequently. One reason may be that periodic updates such as consistent excellent pre-operative antimicrobial appropriateness and low SSI rates despite a reduction in post-eLSCS antibiotic use would help bolster confidence in those initially reluctant to accept ASP. We also sought to highlight these positive results at the division meeting, which may have assisted in reinforcing good practices.

In addition, verbal communication proved crucial, similarly reported in Morton et al. and Stevens et al., where telephonic and verbal communication with providers improved acceptance of interventions up to 20%.^39,40 This would be viable, as face-to-face communication may not always be practical or feasible. Interestingly, although Stevens et al. reported higher intervention acceptance rates in telephonic methods versus electronic medical record notes, we only saw a significant difference when we communicated directly with the operating surgeons versus junior doctors.³⁹ This is likely due to the hierarchical nature within teams, as the operating surgeon would often make the final decision. Also, discussion with surgeons themselves would facilitate better understanding of their beliefs, the nature of surgery and potentially a more collegial, effective and sustainable approach to antimicrobial stewardship.^41,42

Most of the SSIs that developed in our cohort were of late onset as most occurred after 2 weeks, similar to Couto et al.⁴³ During our review, two patients reported scratching of the wound. This would suggest that focusing on post-surgical factors such as proper wound care education, instead of prescribing antibiotics, was key in SSI prevention.^7–10 In our SSI prevention bundle, standardized patient education on wound care pre-discharge was done, coupled with a follow-up phone call at 2-3 days post-discharge by the nurses to instruct patients to remove their dressings.

Research implications

Our study focused first on low-risk patients followed by periodic evaluation and communication of pertinent outcomes. This would aid in future ASP collaborations once physicians are cognizant of the benefits of ASP measures and the assurance that patient safety outcomes are not compromised. Building a culture of appropriate antibiotic prescribing will require more effort and time as compared to approaches such as formulary restriction or guidelines. However, the impact could be far-reaching and sustainable, and should be further explored.

Strengths and limitations

Our study has several limitations. One, we excluded women undergoing emergency caesarean as they would inherently be at a higher risk of infection or non-compliance to pre-operative prophylaxis due to the urgent nature of the operation, hence limiting the generalizability of our findings. However, our findings fortify existing literature that post-operative surgical prophylaxis may be unnecessary in low-risk patient groups, and could potentially be extended to other elective surgeries. Second, although there was no randomization, the cohort was select and homogenous. The increase in surgical complications rates in phase 3 was partly attributed by the team’s direct communication with operating surgeons to ascertain reasons for post-operative antibiotics which may not be explicitly described in operative records. We analyzed rates of antibiotic prescription after excluding patients with surgical complications and there was no significant change in results. In addition, as only one patient with surgical complication each in phase 1 and 3 developed SSI, and both received a course of oral antibiotics, it was unlikely to have a significant impact on outcomes.

Another limitation was the low rates of pharmacists’ interventions. Interventions were made within one working day due to other operational duties or when further clarification was required, and up to 3 days for Friday cases (over the weekend till the following Monday). Hence, no interventions were reported in those without risk factors who had received more than a single dose of antibiotics, or discharged before intervention could be made. Some prescribers accepted interventions partially e.g. only agreeable for a reduced antibiotic duration, and we deemed it as not accepted. There were some patients where there were no antibiotics planned in the post-operative notes, but oral antibiotics were ordered at discharge and hence timely intervention was not able to be made. However, our overall approach was multipronged, i.e. besides pharmacists’ interventions, physician buy-in and reviewing of SSI data at the different time points may have made a larger impact as compared to individual interventions. Involvement of ward-level pharmacists to intervene at the point of medication order and at discharge as well may have been more effective and explored in future. For sustainability, further consistent engagement of prescribers may be more effective versus active intervention which may be deemed as too restrictive.

Another potential limitation was the incomplete SSIs surveillance for our patients. However, they would be scheduled for a follow-up visit either at the hospital’s outpatient clinic or an affiliated primary care center within a month which would be captured in their medical records. We also reviewed re-attendance records at our urgent OBGYN center (similar to an emergency department). Despite having a more stringent criteria for SSI definitions as antibiotic prescriptions for eLSCS related wound infections were recorded regardless of whether it was explicitly reported as per criteria,²³ it was reassuring that SSI rates were low. We further evaluated pertinent risk factors for SSI development in this cohort, but neither receipt of antibiotics nor surgical complications were identified to be influencing variables. Rupture of membranes or labor >18a0hours was a potential risk factor similar to Valent et al.,⁵ but our study was not powered to detect a significant difference given the extremely low occurrence rate.

Conclusions

ASP measures can reduce unnecessary post-eLSCS antibiotic prophylaxis rates without deleterious effects to patients. Most ASPs are focused on medical specialties, with few in surgical and specialized populations such as obstetrics. Our study advocated a multifaceted, collaborative ASP to improve antibiotic prescribing practices in our OBGYN department.

Footnotes

Author’s note

This study was presented in part at IDWeek 2020, Oct 21–25, 2020, and was published in its proceedings, Open Forum Infectious Diseases.

Author contributions

SXFV, RYLO, CWMP researched literature, developed the protocol and collected data. SXFV analysed, interpreted the data and wrote the first draft of the manuscript. TKC, KKQ, SHMS were involved in protocol development and interpretation of the data. TKC conceptualised the study. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article. This study was conducted as part of our routine work.

Ethical statement

ORCID iD

Valerie Xue Fen Seah

References

Awad

. Adherence to surgical care improvement project measures and post-operative surgical site infections. Surg Infect 2012; 13: 234–237.

Zimlichman

Henderson

Tamir

, et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med 2013; 173: 2039–2046.

Betrán

Moller

, et al. The increasing trend in caesarean section rates: global, regional and national estimates: 1990-2014. PLoS One 2016; 11: e0148343.

Zuarez-Easton

Zafran

Garmi

, et al. Postcesarean wound infection: prevalence, impact, prevention, and management challenges. Int J Womens Health 2017; 9: 81–88.

Valent

DeArmond

Houston

, et al. Effect of post-cesarean delivery oral cephalexin and metronidazole on surgical site infection among obese women: a randomized clinical trial. JAMA 2017; 318: 1026–1034.

Olsen

Butler

Willers

, et al. Risk factors for surgical site infection after low transverse cesarean section. Infect Control Hosp Epidemiol 2008; 29: 477–484.

Ariyo

Zayed

Riese

, et al. Implementation strategies to reduce surgical site infections: a systematic review. Infect Control Hosp Epidemiol 2019; 40: 287–300.

Villers

. Reducing cesarean delivery surgical site complications. Obstet Gynecol Clin N Am 2020; 47: 429–437.

McKibben

Pitts

Suarez-Cuervo

, et al. Practices to reduce surgical site infections among women undergoing cesarean section: a review. Infect Control Hosp Epidemiol 2015; 36: 915–921.

10.

Carter

Temming

Fowler

, et al. Evidence-based bundles and cesarean delivery surgical site infections: a systematic review and meta-analysis. Obstet Gynecol 2017; 130: 735–746.

11.

Society for Healthcare Epidemiology of AmericaInfectious Diseases Society of AmericaPediatric Infectious Diseases Society . Policy statement on antimicrobial stewardship by the society for healthcare epidemiology of America (SHEA), the infectious diseases society of America (IDSA), and the pediatric infectious diseases society (PIDS). Infect Control Hosp Epidemiol 2012; 33: 322–327.

12.

Barlam

Cosgrove

Abbo

, et al. Implementing an antibiotic stewardship program: guidelines by the infectious diseases society of America and the society for healthcare epidemiology of America. Clin Infect Dis 2016; 62: e51–e77.

13.

Tarchini

Liau

Solomkin

. Antimicrobial stewardship in surgery: challenges and opportunities. Clin Infect Dis 2017; 64: S112–S114.

14.

Branch-Elliman

O'Brien

Strymish

, et al. Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg 2019; 154: 590–598.

15.

Bratzler

Dellinger

Olsen

, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70: 195–283.

16.

Committee on Practice Bulletins-Obstetrics . ACOG practice bulletin. No. 120: use of prophylactic antibiotics in labor and delivery. Obstet Gynecol 2018; 132(3): e103–e119.

17.

Nabhan

Allam

Hamed Abdel-Aziz Salama

. Routes of administration of antibiotic prophylaxis for preventing infection after caesarean section. Cochrane Database Syst Rev 2016; 17: CD011876.

18.

Gentilotti

De Nardo

Nguhuni

, et al. Implementing a combined infection prevention and control with antimicrobial stewardship joint program to prevent caesarean section surgical site infections and antimicrobial resistance: a Tanzanian tertiary hospital experience. Antimicrob Resist Infect Control 2020; 9: 69.

19.

Sarang

Tiwary

Gadgil

, et al. Implementing antimicrobial stewardship to reduce surgical site infections: experience and challenges from two tertiary-care hospitals in Mumbai, India. J Glob Antimicrob Resist 2020; 20: 105–109.

20.

Abubakar

Syed Sulaiman

Adesiyun

. Impact of pharmacist-led antibiotic stewardship interventions on compliance with surgical antibiotic prophylaxis in obstetric and gynecologic surgeries in Nigeria. PLoS One 2019; 14: e0213395.

21.

Wang

Dong

, et al. Impact of pharmacist interventions on rational prophylactic antibiotic use and cost saving in elective cesarean section. Int J Clin Pharmacol Ther 2015; 53: 605–615.

22.

Global point prevalence survey of antimicrobial consumption and resistance (Global-PPS). https://www.global-pps.com/documents/. Accessed 24 October 2024.

23.

Centers for Disease Control and Prevention . Surgical site infection event. https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. Accessed 14 June 2021.

24.

Sikirica

Broder

Chang

, et al. Clinical and economic impact of adhesiolysis during repeat cesarean delivery. Acta Obstet Gynecol Scand 2012; 91(6): 719–725.

25.

Bergholt

Stenderup

Vedsted-Jakobsen

, et al. Intraoperative surgical complication during cesarean section: an observational study of the incidence and risk factors. Acta Obstet Gynecol Scand 2003; 82(3): 251–256.

26.

Charani

Ahmad

Tarrant

, et al. Opportunities for system level improvement in antibiotic use across the surgical pathway. Int J Infect Dis 2017; 60: 29–34.

27.

Tiri

Bruzzone

Priante

, et al. Impact of antimicrobial stewardship interventions on appropriateness of surgical antibiotic prophylaxis: how to improve. Antibiotics 2020; 9: 168.

28.

Murri

de Belvis

Fantoni

, et al. Impact of antibiotic stewardship on perioperative antimicrobial prophylaxis. Int J Qual Health Care 2016; 28: 502–507.

29.

Fujibayashi

Niwa

Tsuchiya

, et al. Antimicrobial stewardship intervention for the clinical pathways improves antimicrobial prophylaxis in surgical or non-surgical invasive therapies. Int J Clin Pract 2018; 10: e13293.

30.

Ierano

Thursky

Marshall

, et al. Appropriateness of surgical antimicrobial prophylaxis practices in Australia. JAMA Netw Open 2019; 2: e1915003.

31.

Moulton

Munoz

Lachiewicz

, et al. Surgical site infection after cesarean delivery: incidence and risk factors at a US academic institution. J Matern Fetal Neonatal Med 2018; 31: 1873–1880.

32.

Ketcheson

Woolcott

Allen

, et al. Risk factors for surgical site infection following cesarean delivery: a retrospective cohort study. CMAJ Open 2017; 5: E546–E556.

33.

Hurst

Child

Pearce

, et al. Handshake stewardship: a highly effective rounding-based antimicrobial optimization service. Pediatr Infect Dis J 2016; 35: 1104–1110.

34.

Ierano

Thursky

Peel

, et al. Influences on surgical antimicrobial prophylaxis decision making by surgical craft groups, anaesthetists, pharmacists and nurses in public and private hospitals. PLoS One 2019; 14: e0225011.

35.

Charani

Tarrant

Moorthy

, et al. Understanding antibiotic decision making in surgery-a qualitative analysis. Clin Microbiol Infect 2017; 23: 752–760.

36.

Goldstein

Goff

Reeve

, et al. Approaches to modifying the behavior of clinicians who are noncompliant with antimicrobial stewardship program guidelines. Clin Infect Dis 2016; 63: 532–538.

37.

Davey

Marwick

Scott

, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2017; 2: CD003543.

38.

Molloy

McGrath

Thomas

, et al. Acceptance of pharmacist-driven antimicrobial stewardship recommendations with differing levels of physician involvement in a children's hospital. Clin Pediatr 2017; 56: 744–751.

39.

Stevens

Fjeld

Cutchins

, et al. Method to the madness: impact of method of contact on intervention acceptance rates for antimicrobial stewardship interventions. Infect Control Hosp Epidemiol 2020; 41: 959–961.

40.

Morton

Curzake

Parente

, et al. Antimicrobial stewardship intervention acceptance: impact of verbal and nonverbal communication. Open Forum Infect Dis 2015; 2: 1402.

41.

Langford

Nisenbaum

Brown

, et al. Antibiotics: easier to start than to stop? Predictors of antimicrobial stewardship recommendation acceptance. Clin Microbiol Infect 2020; 26: 1638–1643.

42.

MacBrayne

Williams

Levek

, et al. Sustainability of handshake stewardship: extending a hand is effective years later. Clin Infect Dis 2020; 70: 2325–2332.

43.

Couto

Pedrosa

Nogueira

, et al. Post-discharge surveillance and infection rates in obstetric patients. Int J Gynaecol Obstet 1998; 61: 227–231.