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.
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 antimicrobials11,12.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 methodology 22 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. 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
Patients’ characteristics and outcomes.
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). 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). Comparison of post-operative 30–day surgical site infection (SSI) rates. SSI: surgical site infection.
Comparison of characteristics of patients with and without 30-day SSI.
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.
