The Efficacy of Antiseptic Treatment of Surgical Drains on Bacterial Colonisation and Surgical Site Infection Post Breast Surgery: A Systematic Review and Meta-Analysis

Surgical site infection (SSI) is a common complication in women with post-operative drains following breast surgery, with the risk being as high as 19%. The authors aimed to conduct the first meta-analysis to determine the efficacy of antiseptic treatment of drains to reduce the incidence of infections by comparing it to drains with no antiseptic coating. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed with an extensive search of the electronic databases retrieving 114 articles. Four articles met the inclusion criteria. The primary outcome measure was the incidence of SSIs and secondary outcome measures included the incidence of bacterial colonisation in the bulb fluid and drain tube. The incidence of SSIs was significantly lower in the antiseptic group compared to the control (CI 95% 0.09 - 0.82, p = 0.02). In addition, there was a lower incidence of colonisation from both the bulb fluid and drain tube with P values of < 0.00001 and P < 0.0001 respectively. The authors report the first meta-analysis within the literature showing the efficacy of antiseptic treatment of surgical drains on colonisation and SSIs following breast surgery. More high-quality trials are recommended to further the current evidence base.


Introduction And Background
Breast cancer is the most common cancer amongst women and surgery contributes to being one of the mainstay modalities of treatment [1]. Common complications include surgical site infections (SSIs) and seroma formation. Studies have shown that the risk of SSIs following breast surgery can be as high as 19% [1]. Underlying risk factors that can exacerbate the clinical course include obesity, smoking, radiotherapy to the site, chemotherapy, and skin necrosis [2,3].
Breast reconstructive surgery can involve large tissue dissections and some surgeons to use post-operative drains. This can prevent the accumulation of fluid but increases the risk of infection [2]. The use of postoperative antibiotics until drain removal is a common practice amongst many surgeons. Antimicrobial therapy has the potential to cause adverse reactions as well as propagate antimicrobial resistance [2,4]. A meta-analysis conducted by Xue et al. looking into the risk factors contributing to SSIs, concluded that postoperative drains increase the risk [5]. Antiseptic treatment of surgical drains following mastectomies with or without prosthetic reconstruction reduces the risk of bacterial colonisation [4,6]. Studies by Stevens et al. and Hayhurst et al. demonstrated that using cranial shunt drains and ventricular drains impregnated with antibiotics or antibiotics close to the drain site reduces the rate of bacterial colonisation and SSIs [7,8].
Several studies have reported the use of antiseptic treatment of surgical drains on bacterial colonisation and surgical site infection post breast surgery [1,2,4,6]. This includes both mastectomies and reconstructive surgery. Currently, the literature is devoid of a meta-analysis to quantitatively amalgamate the results of reports comparing the use of drain antisepsis versus untreated surgical drains on the incidence of bacterial colonisation and SSIs. The authors aim to perform the first systematic meta-analysis to enhance the current evidence base on the role of drain antisepsis in mitigating the incidence of SSIs.

Review Methods
This systematic review and meta-analysis study was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [9]. The authors did not register the review on the Prospero database, the international prospective register of systematic reviews.
The eligibility criteria included all observational and randomised controlled trials of patients that underwent breast surgery with drain placement comparing drain insertion with an antiseptic coating against a comparative group with no antiseptic coating. There was no restriction on sex, age or co-morbidities. There was no exclusion on the type of antiseptic applied to the drain. Case reports, case series as well as abstracts were not included in this review. Studies not reported in English were also excluded. There was no restriction on studies that involved pre-operative antibiotic administration on induction. However, studies involving the use of post-operative antibiotics were excluded to minimise bias when assessing the efficacy of antiseptic drain coating on minimising SSIs.

Primary and Secondary Outcomes
The primary outcome measure was the incidence of SSIs and secondary outcome measures included the incidence of bacterial colonisation in the bulb fluid and drain tube.

Literature Search Strategy
The literature search was conducted independently by both NT and SR. The search included the following electronic databases: Pubmed, MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) as well as ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home). The last search was done on 14th May 2023. The search was conducted using the terms: "breast surgery", "mastectomy", "drain", "antiseptic drain", " breast reconstruction", "bacterial colonisation", "non-antiseptic coating", "surgical site infection" and "SSI". These were combined with adjuncts of "and as well as "or". A review of the bibliographic lists of relevant articles was also conducted.

Selection of Studies
The abstracts of the articles generated from the literature search were reviewed by authors NT and SR independently. Those which met the selection criteria were subsequently assessed for their full texts. A third author AK was consulted in cases of any discrepancy.

Data Extraction and Management
A data extraction spreadsheet was created that aligned with Cochrane's data collection form for intervention reviews. This was pilot tested in random articles and adjusted accordingly. Two authors NT and SR independently extracted and entered the data. Consultation with a third author AK was done to resolve any disagreements in the process. The data extraction spreadsheet included the study-related date, first author, year of publication, study design, the antiseptic agent used and drain care, patient's age and BMI, and primary and secondary outcome data of the studies.

Data Synthesis
Review Manager 5.4 (RevMan; The Cochrane Collaboration, 2020, Copenhagen) was used to conduct the data synthesis, and the data was entered using the random effects model. The results were reported using forest plots with 95% confidence intervals (CIs). The odds ratio (OR) was used to evaluate outcomes for dichotomous variables.

Heterogeneity Assessment
To assess the heterogeneity of studies, Cochran's Q test (χ2) was used. In addition, the I2 assessment score was calculated to quantify any discrepancy and interpreted as follows: 0% to 25% low, 25% to 75% moderate, and 75% to 100% high heterogeneity.

Literature Search Results
A literature search was conducted by two authors (NT and SR) independently which retrieved a total of 114 articles. Four studies were chosen based on the eligibility criteria which included three randomised control trials and one retrospective study. The search process is demonstrated in the flow chart in Figure 1.

Description of Studies
The baseline characteristics of the included studies are summarised in Table 1. With 462 drains overall, the intervention of using chlorhexidine as drain antiseptic was used in three studies and a quaternary ammonium salt (QAS-3PAC) was used in one.

Degnim et al. (2014) Study
Degnim et al. (2014) conducted a two-sited randomised control trial that included 97 patients undergoing a bilateral mastectomy and reconstruction including 194 drains. Participants were randomised to which side (left or right) would receive the chlorhexidine-soaked drain and the contralateral side would receive standard drain care [6].

Strong et al. (2018) Study
Strong et al conducted a retrospective study including 20 patients undergoing either tissue expander placement or deep inferior epigastric perforator flap reconstruction with 31 surgical drains. Participants were randomised to the drains soaked in a quaternary ammonium salt, 3-trimethoxysilyl propyldimethyloctadecyl ammonium chloride (QAS-3PAC; Bio-spear) in the treatment group or nonimpregnated gauze in the control group [2].

Rivera-Buendía et al. (2019) Study
Rivera-Buendía et al performed a randomised control trial including 104 patients undergoing breast cancer surgery with 167 surgical drains. Participants were randomised to the antiseptic dressing group with chlorhexidine or standard drain care in the control [1].

Risk of Bias Assessment
Two authors (NT and SR) independently assessed the methodological quality and risk of bias for all included articles. The Newcastle-Ottawa Quality Assessment Scale 18 was used to assess risk bias for the one observational study, demonstrated in Table 2. It involves a star scoring system where the study is judged on three domains: selection, comparability, and ascertainment of the exposure or outcome. There is a maximum of nine stars for each study. The aim is to provide a tool for the assessment of bias of the single observation study included in this review [10]. The study conducted by Strong et al. was assessed and scored well for domains of selection and outcome, but comparability was low [2]. The results included a validated measurement tool to record the incidence of bacterial colonisation with a satisfactory response rate.

Discussion
The authors present the first meta-analysis within the literature assessing the efficacy of antiseptic treatment of surgical drains post breast surgery and demonstrate that local anti-septic measures result in a significant reduction in the incidence of bacterial colonisation and SSIs. On assessment, the Cochrane Q test showed no significant difference in the heterogeneity of studies, giving further consistency to the outcome variables. The Cochrane Collaboration Tool for Risk of Bias generated good overall scores, particularly in selection and performance biases in the three randomised controlled trials. The retrospective study by Strong et al. scored well on the Newcastle Ottawa scale for domains on selection and outcome, but comparability was low [2].
SSI prevention is essential in reducing healthcare costs and morbidity. The infection rates following breast reconstruction can be as high as 19% in what is considered a 'clean surgery' [6]. A surgical drain provides a conduit for bacterial contamination into the wound [11]. SSIs can result in implant or flap loss and patients will often require intravenous antibiotics and implant exchange or flap debridement to salvage the breast [6]. In a retrospective analysis by Reish et al. looking at the salvage rates of breast implants in patients developing an SSI following implant-based reconstructive surgery, it was found that patients admitted with a higher white cell count were at increased risk to fail implant salvage [3]. There are modifiable and nonmodifiable risk factors that contribute to the risk of developing an SSI. Modifiable risk factors include diabetes and BMI, which can be optimised pre-operatively. Non-modifiable factors include the administrated of radiation and chemotherapy which are difficult to mitigate [3]. Local antiseptic coating of drains in breast surgery is simple to instigate and can assist in minimising the infection rate.
The intervention of using chlorhexidine as a drain antiseptic was used in three studies and a quaternary ammonium salt (QAS-3PAC) was used in one. Rivera-Buendía et al found that the drains were more secure with the chlorhexidine dressing applied and resulted in fewer kinks than in the standard gauze dressing [1]. Not only does the antiseptic coating to the drain reduce infection rates in the breast, but it has also been shown to reduce the risk when applied to drains in other anatomical locations [12,13]. In a randomised control trial by Timsit et al., the use of chlorhexidine-impregnated sponges on intravascular catheter dressings has been shown to reduce catheter-related infections from 1.1% to 0.5% [12]. Another randomised control trial by Levy et al. used chlorhexidine-impregnated sponges to reduce the rate of central venous catheter colonisation in infants and children after cardiac surgery, showing to reduce colonisation rates from 29% in the control group to 14.8% in the study group and reduce blood-stream infections from 5.4% to 4.2% [13].
There is widespread use of post-operative antibiotics to reduce the infection risk associated with drains following breast surgery. However, the efficacy of this is not proven and increases the burden of antibiotic resistance and side effects [4,14]. By using local drain antisepsis, the risk is avoided and is a simple intervention where side effects are uncommon and self-limiting.
This study has some limitations including a low number of randomised control trials. The use of chlorhexidine has been linked to antimicrobial resistance, but the studies involved in this study do not evaluate this. Although there is variation in the antiseptic agent used, three of the studies have used the same solution and the authors have done a sensitivity analysis on the studies using chlorhexidine drain coating alone and it has shown a significant reduction in SSIs. The authors recommend more high-quality trials assessing the efficacy of drain antisepsis in breast surgery to further evaluate its effectiveness.

Conclusions
This meta-analysis demonstrates that the treatment of surgical drains with an antiseptic coating following breast surgery significantly reduces the incidence of bacterial colonisation and SSIs. The authors recommend further high-quality trials to improve the current evidence base.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.