Surgical site infections (SSIs) are a complication in all surgical fields and they are responsible for 38% of postoperative deaths (2001) (1). The additional cost per patient affected by SSI in low- and middle-income countries (LMICs) in Europe ranges between $174 and $29,610, whereas in high-income European countries it ranges between $21 and $34,000. These variations may be attributed to differences in clinical practice and relative prices of medical care across countries; the price difference in LMIC and high-income European countries is insignificant. Furthermore, the severity of SSI is associated with greater costs (1). Therefore, identifying appropriate prophylaxis and solutions to combat SSI is of global interest (1). The Centers of Disease Control and Prevention (CDC) reported that, in 2013, 1.9% of 16 million surgeries in the United States were complicated by an SSI (2). In obstetrics, 2-4% of cesarean sections (C-sections) and 2% of hysterectomies were complicated by SSI in the United States in 2020(3). Patients with SSI are 60% more likely to spend time in the Intensive Care Unit, more than five times more likely to be readmitted and are twice as likely to die compared with patients without SSIs, according to statistics from 2016(4).

A study on SSI has raised awareness of this costly complication, both in terms of physical and mental suffering, as well as economically (5). The aim of the present review was to evaluate possible strategies to prevent SSI. A study evaluating un-planned 30-day readmissions after hysterectomies revealed that the major reason was SSI (28.8%) (4). Lynch et al (6) underlined that the cost per patient of SSI post-surgery complications is 1.73 times higher than that of non-SSI complications ($3,678 vs. $2,116) (1). The data were gathered from a trial that analyzed the impact of preoperative whole body disinfection in postoperative wound infection prophylaxis, involving 3,733 patients from a Scottish hospital in the 1990s. Higher costs were reported from a study in the UK collecting data between June 2005 and April 2009, including infectious complications after femoral neck surgery (7). Wijeratna et al (7) reported 3.2% surgical site infections in 525 patients. Furthermore, the mean financial loss per infected patient was £7,726 ($11,809), whereas an uninfected patient produced £153 ($234) of profit to the hospital. The lowest additional cost due to SSI was evaluated in a 2019 Danish study, assessing the cost-effectiveness of incisional negative-pressure wound therapy in obese women after C-section (1). The reported costs per women were €5,793.60 ($6,488.25) in patients treated with vacuum-assisted closure (VAC; n=432) compared with €5,840.898 ($6,541.22) for standard dressing (n=444). A study conducted in Spain reported an additional cost of $15,733 due to SSI per patient, including only the healthcare (hospital care, ambulatory care, medical tests and examinations, health goods and prescription drugs), besides productivity loss and informal care costs (1).

The magnitude of the cost difference between SSI and non-SSI depends on the SSI definition, severity, patient population, choice of comparator, hospital setting and cost items (1). The CDC defines SSI as an infection that occurs at or near the surgical site incision within 30 days after the surgery (3). SSI is classified as superficial when it affects the skin or subcutaneous tissue, whereas it is classified as deep incisional if fascial and muscle layers are implicated or organ/space if any tissue deeper than muscle/fascial layer is manipulated/opened during surgery (3). Clinical and paraclinical diagnostic criteria of different types of SSI is presented in Table I. In the obstetrics and gynecology (OG) field, SSIs include the superficial type (two-thirds of SSIs) such as cellulitis, deep incisional abscesses or pelvic/vaginal cuff abscesses (2,3,8).

Microbial contamination at the surgical site is the first step in developing SSI and the infection can vary from trivial wounds to life-threatening conditions (9). The epidermis is inhabited by different pathogens, including bacteria, fungi and viruses, with a density of 3 million germs per square centimeter (9). Therefore, most surgical wounds are contaminated by bacteria. However, infection will only evolve in some cases (9). In most cases, innate host defenses will successfully eliminate the pathogens (10). Bacteria virulence and adjuvant microenvironment factors favor SSI complications (10).

Despite antisepsis treatment, bacteria may enter from fomites into the wound (10). Surgeries involving the female genital tract will encounter 10⁶-10⁷ bacteria/ml (10). The more severe the bacteria's virulence, the greater the probability of infection. For instance, coagulase-positive staphylococci require a smaller inoculum than coagulase-negative species (10,11). The bacteria's virulence cannot be easily controlled by preventive measures; it is an intrinsic variable influenced by the surgery site and the bacteria which colonize the patient's skin (10).

A few microorganisms are encountered more frequently in SSI following gynecological surgeries (3,12). In abdominal approaches, Staphylococcus aureus and Staphylococcus epidermis infection are the most prevalent (12), whereas in vulvar/perinea incisions anaerobic bacteria, gram-negative aerobes or polymicrobial pathogens (vaginal incision) are more frequent (3,12). For C-sections, ureaplasma species, coagulase-negative staphylococci, anaerobes, gram-negative species, Staphylococcus aureus and B group Streptococcus seem to prevail (3).

The microenvironment and the integrity of host defenses dictate a certain minimum amount of inoculum that results in an SSI, and consequently, its outcome (10,13).

In summary, the patients' skin is not sterile and the host defense mechanisms may be faulty. Therefore, known risk factors for the development of SSIs and mitigating strategies represent an important target in the pursuit of decreasing SSI prevalence.

The risk factors for SSI are divided into patient- and procedure-related risk factors, modifiable or non-modifiable. Details are presented in Table II. SSIs are often the result of multiple non-modifiable risk factors. Procedure-related risk factors should be considered to be modifiable (8).

SSI and diabetes have been linked in numerous studies (4,8,10). A recent literature review indicated perioperative hyperglycemia (in diabetic and non-diabetic patients) as a more significant risk factor for the development of SSI than hemoglobin A1c (14-17). Furthermore, perioperative hyperglycemia of 110-150 mg/dl increases the risk of SSI (14-17).

Diabetes has also been identified as a risk factor for SSI in gynecological surgery (18). In 2015, Al-Niaimi et al (19) recommended intensive glycemic control for the first 24 h for diabetics undergoing oncological gynecological surgeries. They retrospectively compared three groups: Patients with diabetes whose blood glucose was controlled via intermittent, subcutaneous insulin injections; patients with diabetes and postoperative hyperglycemia whose blood glucose was controlled through insulin infusion; and patients with neither diabetes nor postoperative hyperglycemia. The results of the study emphasized that patients in the second group had an SSI rate of 19%, which was similar to that of the third group (21%), whereas in the first group, the rate of SSI was higher (29%). The results of the study indicated that intensive glycemic control for patients with diabetes undergoing onco-gynecological surgeries reduces the rate of SSI by 35% (19).

Tobacco users develop vasoconstriction that leads to hypoxia and ischemia and ultimately translates into poor tissue perfusion (2). Smokers and former smokers have a risk of SSI that is higher than that in nonsmokers (14). Furthermore, smoking is associated with a range of morbidities (16).

Abnormal serum albumin levels (normal range, 3.4-5.4 g/dl), which is an index for the nutritional status, can be found in the elderly, obese and diabetic population (2).

Obesity and diabetes are two major risk factors for SSI (17). Obesity and diabetes increase the risk of SSI in C-sections by 2 and 1.4 times, respectively (17). The coexistence of both is associated with a 9-fold increased risk compared with the risk of women with neither of these (20). Obesity-related pathophysiological factors that are associated with the increased risk of SSI are considered to be the poor tissue perfusion, the decreased antibiotic penetration, the altered innate host defenses and a suboptimal metabolic function (2,21,22). These altered factors are also found in diabetes (16,21,22).

Immunosuppression due to HIV infection or long-term steroid use poses a high risk for SSI due to downregulation of the immune system, which serves a critical role in infection susceptibility (2). Cell proliferation and normal inflammatory responses are impaired by both long-term steroid use and smoking (2).

Comorbidities, including chronic renal insufficiency, chronic obstructive pulmonary disease, an American Society of Anesthesiologists (ASA) score >3 (the ASA score evaluates the basal status of individuals, including comorbidities), advanced age and male sex, are likewise risk factors for SSI (12,17,23).

An increased duration of the surgical procedure (>180 min) has been demonstrated to be a risk factor for SSI in both abdominal and laparoscopic approaches (2,8,9,12). Furthermore, an incision length ≥20 cm has been demonstrated to serve a role in SSI development (5).

With respect to surgical approaches, in the gynaecological field, the rates of SSI appear to be low in vaginal and laparoscopic hysterectomy techniques (50% reduction in SSI incidence) compared with laparotomy (3.9% rate of SSI for open hysterectomies and 1.4% for minimally invasive procedures) (4,8). Some reviews suggest that robotic interventions are associated with a higher risk due to the increased duration of the surgical procedure (2,8). Despite developments in minimally invasive procedures, the approach for most hysterectomies is laparotomy (54.2%), followed by vaginal (16.7%) and laparoscopic (8.6%) approaches, while robotic intervention is employed less (8.2%) (4).

A randomized controlled trial of 595 laparoscopic procedures reviewing the risk of SSI has highlighted the difference among different types of entry (Veress needle, direct trocar insertion or open entry) (2,24). The results of the trial revealed fewer complications in direct trocar insertion and even fewer complications in open entries (2,24).

Another important element to be considered regarding SSI risk is the difference between scheduled and emergency surgeries. Emergency surgery does not allow for standard preoperative preparation; therefore, the incidence of SSI is higher in emergency surgical cases than in scheduled cases (8.4% vs. 2.5%) (23).

Obstetric surgeries have a lower SSI incidence compared with gynecological surgeries (1.2% vs. 10.3%) (15). A study performed in India evaluated risk factors for SSI in an OG department with the following results (18): i) Women >40 years old have a higher risk for SSI and young maternal age represents a risk factor for SSI following C-section; ii) grand-multipara women (>5 deliveries) have a 3 times higher risk than primiparous women; iii) a number of vaginal examinations >10 up to 48 h prior to surgery increases the risk of SSI and each vaginal examination increased the risk by 31%; iv) presence of abnormal vaginal discharge (OG possesses a unique challenge as pathogens can ascend from vagina/endocervix to the surgical site) is associated with an increased risk of SSI; v) chorioamnionitis represents a major risk for SSI post C-section; vi) comorbidities, such as diabetes, anemia, arterial hypertension (gestational hypertension implies a 2.9 times higher risk for developing SSI) and systemic diseases, increased the risk nearly 6-fold; and vii) general risk factors: ASA score >3 imposes a 1.52-2.7 times higher SSI risk, each additional intraoperative hour doubled the risk after the first hour of surgery, antibiotic prophylaxis not within 1 h of surgery increased the risk by nearly five times and each hospitalization day after surgery increased the risk by 5%.

The complete and correct diagnosis of SSI is based on medical history, physical examination, wound cultures and blood tests (3). Imaging techniques are not mandatory; they are required when physical examination fails to localize the SSI (3). Patients can harbor indolent infections (dental, urinary, skin and soft tissues) at the time of surgery (9). Thus, pre-existing infections can be the source for hematogenous spread or a contiguous site for bacterial transfer (9). These remote infections increase the risk of SSI 3 to 5-fold (9). For instance, bacterial vaginosis as well as other pathogen colonization should be treated before hysterectomy (9).

In 2016, the WHO issued guidelines with evidence-based recommendations to reduce SSI (42). Several hospitals have designed preoperative ‘bundles’ (based on prevention techniques described in previous studies) to prevent bacterial colonization, adapted to each surgical field, type of surgery and risk factor status (1,6,14,25,26). The American College of Surgeons and Surgical Infection Society has also offered recommendations for preventing SSI, which are particularly required in the era of drug-resistant bacterial pathogens (12,44).

The ‘bundle’ contributes to decreasing SSI incidence, and thus, is becoming a routine practice (14). In a previous study, SSI was reduced from 4.9 to 1.6% after using a colorectal ‘bundle’ (14).

Several physicians have investigated the potential aid of creating and incorporating a SSI bundle in daily practice (25,26). For instance, in a previous study, surgeons set up six perioperative measures that were linked to independent risk factors of SSI and evaluated >4000 surgery cases (colostomies) (8). A strong inverse association was found between the rates of SSI and the number of measures followed. The measures implemented in the study were: Appropriate prophylactic antibiotics, mechanical bowel preparation with oral antibiotics, postoperative normothermia, minimally invasive approach, surgery time <100 min and glucose ≤140 mg/dl in postoperative day 1.

Another survey evaluated 16 studies on the efficiency of ‘surgical bundles’ with clinically important impact (45). The SSI rate in the bundle group was 7.0%, whereas that in the standard care group was 15.1%, so the rate of SSI was reduced by more than half. In 2013, a 51% SSI reduction was observed in the vascular surgery field by applying a four-component ‘bundle’: Hair removal, prophylactic antibiotics, normothermia and operating room discipline (26).

‘Bundle’ prevention has been applied and showed efficiency in colorectal surgery, C-section delivery and oncological gynecological surgeries (8).

Oncological gynecological surgery has been demonstrated to be a field suitable for SSI reduction by ‘bundle’ programs (26). Rates of SSI reduction among surgeries for ovarian cancer, with or without bowel resection (by 77.6 and 79.3% respectively) and uterine cancer (by 100%) validated this program's efficiency (26). Recently, a multidisciplinary team convened by the Council on Patient Safety in Women's Health Care published a thorough SSI prevention ‘bundle’ in benign gynecology (9).

Regarding C-sections, an SSI reduction ‘bundle’ was implemented in a previous study (25). This included hair removal by electric clipper, skin preparation with chlorhexidine, antibiotic prophylaxis before incision (cefazolin 1 g IV bolus and azithromycin 500 mg bolus IV), placenta removal by traction of the umbilical cord, closure of deep subcutaneous layer >2 cm and subcuticular suture for skin closure. Other measures included jewelry wearing restriction, prohibition of long sleeves for neonatal attire in the operation room and hand hygiene compliance. Their conclusion stated that C-section ‘bundles’ reduced the rate of SSI (98.4% positive outcome) (25).

‘Bundle’ measures may vary among studies, but they all include important prevention methods such as antibiotic administration, appropriate hair removal, normothermia, glycemic control (9), and hand and forearm scrub (46). A Consensus Statement for SSI prevention in major gynecologic surgery recommends ‘bundle’ programs and provides a mnemonic (WASHING) of risk factors (4): i) Weight; ii) antibiotic resistant skin flora (MRSA); iii) smoking cessation; iv) hygiene (skin preparation); v) immune deficiency status; vi) nutritional status; and vii) glycaemic control.

In addition, Gillispie-Bell (46) considers the operating room environment to be a crucial factor in the development of SSI. Hypothermic (34.5˚C) patients display a decreased blood perfusion that reduces antibiotic penetration into the subcutaneous and adipose tissue (46). Hypothermia also enhances intraoperative blood loss, deteriorates wound healing and augments cardiac morbidity (46). Gillispie-Bell (46) defines normothermia as a core temperature of at least 36˚C measured immediately on the post-anesthesia care unit. A gynaecology-specific ‘bundle’ has been assessed in other studies that found a reduction in the SSI rate from 1.3 to 0.5% in patients undergoing hysterectomies (43,46-48). Implementing surgical ‘bundles’ is a multidisciplinary effort involving physicians (both gynaecologists and anaesthesiologists), nurses and patients (43). The gynaecology-specific ‘bundle’ is extrapolated from general surgery ‘bundles’ on the basis of existing evidence and best practice guidelines and includes: Wipes with chlorhexidine gluconate; hair removal; preoperative warming (forced-air warming devices); skin preparation (abdominal and, specifically, vaginal preparation); change gloves before closing fascia; sterile dressing; intraoperative normothermia; antimicrobial prophylaxis; and monthly meetings to assess feedback (43,47,48). Moving forward in the SSI prevention with evidence-based ‘surgical bundles’ that are rapidly covering all surgical fields (4), OG departments should take into consideration the main prevention methods to build ‘bundles’ in reducing SSI. Given the success of these strategies in other surgical fields and also recently in the OG field (16), it is recommended that these are adapted in each hospital. Reducing SSI and contributing to lowering multi-drug resistant pathogens is a collective struggle. A way to obtain good health outcomes in an efficient manner is to cover an entire cycle of care for a surgical procedure as a ‘bundle’.

The risk of SSI is determined by patient factors and preoperative, intraoperative and postoperative care. Consequently, it is difficult to predict when or which wound will become infected. On this account, healthcare personnel should focus on the early identification of risk factors, especially the modifiable ones, including obesity, alcohol use and smoking, and glycemic control, to minimize the risk of SSI. All evidence-based methods of preventing and treating SSI should be considered as integral components of the best care.