Surgical site infections (SSIs) in lower extremity vascular surgeries, post-groin incision, are not only common complications and significant contributors to patient mortality and morbidity, but also major financial burdens on healthcare systems and patients. In spite of recent advances in pre- and post-operative care, SSI rates in the vascular surgery field remain significant. However, compliant antibiotic therapy can successfully reduce the SSI incidence pre- and post-surgery. Antibiotic therapy, administered according to all peri-operative protocols described, is useful in reducing groin SSI rate in vascular surgery.
1. Introduction
Surgical site infections (SSIs) are major concerns for all surgical specialties, with the literature reporting SSI risks of 2–4% for “clean surgery” [
1]. Higher rates have been reported for post-traumatic procedures (15–50%), or in selected populations, including high-risk vascular surgery patients (15–22%), and accompanied by a considerable lengthening of hospitalization times, a high mortality rate (26–67%), and the cost-burden to community [
2,
3]. Similarly, SSI-mediated morbidity may be higher when prosthetic grafts are used in complex surgeries; thus, SSI prevention and treatment are both clinically significant. The current recommendations for clean vascular surgical procedures advocate no more than 24 h of intravenous antibiotic post-operative therapy, as no benefits are indicated past this treatment period [
4,
5,
6]. However, when overt infection signs or risks are present, in particular, when synthetic prostheses are concerned, the literature is less clear on this topic. Therefore, as these indications require clarification, interest continues to be strong in the use of new antibiotics and also in alternative methods of their delivery.
In vascular surgery, lower extremity bypass surgery for limb salvage has the highest rate of SSI incidence, with rates varying between 5% and 30% [
1,
2,
3,
4,
5,
6]. SSIs increase hospital stays, increase readmission rates, incur elevated mortality and morbidity rates, increase healthcare burdens, and increase the incidence of repeat revascularization surgeries [
4,
5]. Moreover, several health risk factors such as diabetes, smoking, being female, prosthetic grafts, obesity, and steroid use contribute to lower extremity SSIs [
7,
8,
9,
10,
11].
While some risk factors are not modifiable, identifying modifiable factors can successfully reduce SSIs. In particular, the rapid identification of causative bacteria is vital to establish and select the most appropriate antibiotic therapy. While any bacteria can theoretically infect a vascular prosthesis or contribute to an SSI, the Gram-negative
Pseudomonas aeruginosa and Gram-positive
Staphylococcus epidermidis and
Staphylococcus aureus strains are the most commonly found in SSIs of the groin, while fungal infections are found less frequently, although present in the inguinal area [
8,
12,
13,
14,
15]. A considerable challenge to SSI diagnostics and treatment are biofilms (or microfouling) [
16,
17]: these complex bacterial polymeric aggregations, consisting of bacterial glycocalyx with incorporated microcolonies, are characterized by the secretion of protective matrix adhesives that provide safe environments from external antimicrobial agents and host defenses [
16]. Biofilms become manifest as polymicrobial infections and contain dominant, highly resistant, difficult-to-eradicate bacteria, which increase patient mortality and morbidity [
18].
As in all surgical specialties, vascular SSI bacterial typology has changed over time, and is reflected by an elevated incidence of antibiotic-resistant bacteria, especially Staphylococcal family members. In particular, methicillin-resistant
S. aureus (MRSA) infections are a serious risk factor for nosocomial-morbidity and morbidity in terms of admission to intensive care, repeated surgical procedures, and major amputation infection risks [
19,
20,
21,
22]. Rarely, isolated strains of
Staphylococcus aureus are still sensitive to penicillin. More frequently, these Staphylococci are distinguished as MRSA (methicillin-resistant
Staphylococcus aureus) and MSSA (methicillin-sensitive
Staphylococcus aureus). Resistance to penicillin (MSSA) is conferred by a bacterial penicillinase. This resistance can be overcome by adding a beta-lactamase inhibitor (e.g., amoxicillin/clavulanic acid, ampicillin/sulbactam) or by using a penicillinase-resistant penicillin (e.g., oxacillin). Methicillin resistance (MRSA) is conferred by the presence of the bacterial gene mecA, which codes for a penicillin-binding protein, an enzyme that has a low affinity for beta-lactams, and therefore leads to resistance to methicillin and oxacillin. There are MRSA of hospital origin often characterized by extended resistance to antibiotics (MDR, multidrug resistance) and MRSA that is community-acquired, CA-MRSA; the latter of which can maintain sensitivity to tetracyclines (tetracycline, doxycycline, minocycline, tigecycline) [
23].
In recent years, the WHO Report on Surveillance of Antibiotic Consumption (2016–2018) described how the percentage of MRSA, in the evaluation of hospital infections, has remained stable (around 34%). Relative to Gram-positive bacteria, the highest resistance rates were observed for
S. aureus to erythromycin (38.9%), clindamycin (34.4%), methicillin (33.5%), and levofloxacin (31.5%). For many years, the treatment of choice to combat MRSA has been based on the use of glycopeptides (vancomycin and teicoplanin); however, the excessive and careless use of these antibiotics has led to the emergence of strains with decreased sensitivity to vancomycin. In recent years, new antibiotics have been introduced into clinical practice, such as linezolid, daptomycin, and more recently, ceftaroline, also in combination with vancomycin and daptomycin, for the treatment of severe MRSA infections. For the latter antibiotics too, particularly linezolid and daptomycin, the emergence of resistant strains has been observed [
24]. Thus, active SSI prevention is highly advisable for peri-operative antibiotic therapy, in addition to the usual stringent antiseptic and sterility policies. Such combinations should minimize vascular SSI onset, especially in inguinal areas.
2. Pre-Operative Antibiotic Therapy
Although SSIs are relatively rare in vascular surgery, they have serious effects. Thus, pre-operative infection prophylaxes are advised to minimize infection risks, especially for patients with synthetic grafts. To address this, we analyzed the evidence on pre-operative antibiotics prior to vascular surgery. Firstly, for most vascular interventions, Gram-positive bacteria, in particular
S. aureus, represent approximately 80% of all SSIs [
2,
3]. In contrast, Gram-negative bacteria are implicated in 20% to 25% of infections [
1,
2,
3,
4]; however, for effective antibiotic prophylaxis, both bacterial types should be targeted and controlled.
Synthetic vascular prosthesis implantation generates particular microenvironments and conditions that can promote bacterial wound invasion and biofilm formation; this latter functionality defends enclosed bacteria from antibiotic therapy and host defense [
38]. To reduce or eliminate the bacterial colonization of damaged tissues, an antibiotic prophylaxis should be administered for effective drug concentrations in tissue at the surgical site before surgery commences. Therefore, the administration of pre-operative antibiotic therapy is advisable 60 min before surgery, and also in additional intraoperative doses if the operation lasts more than 4 h and/or more than 1500 cc blood is lost [
25,
38].
To combat SSIs in vascular surgery, the prophylaxes of choice are primarily first or second-generation cephalosporins, as they are low-cost options (the most common prophylaxis is cefazolin). Vancomycin or clindamycin appear to be preferentially used for patients with β-lactam allergy [
38].
It is useful to remember that allergies related to common antibiotics such as cephalosporins are among the most frequently reported allergies, but only 10% of these patients are truly allergic to these drugs. This situation leads to potential unintended damage for patients and creates difficulties for doctors’ treatment decisions. The detection of actual allergies with skin tests is therefore important for decision-making strategies in these patients [
25].
Gram-negative bacterial coverage is also an important factor as groin and abdominal surgeries are often infected with gastrointestinal tract flora [
41]. While other studies [
25,
26] compared single- and multiple-dose antimicrobials, no significant differences were identified.
Due to the higher prevalence of MRSA, infection trends are changing [
15]. In hospitals with high MRSA prevalence rates, or patients at high infection risk (e.g., geriatric, oncological, and dialysis patients), vancomycin may be used for prophylaxis. When this antibiotic is administered with cefazolin, it is more effective in stopping SSI and targeting Gram-negative bacteria [
41].
Stone et al. compared cefazolin with the association of cefazolin plus daptomycin administration to prevent pre-operative vascular SSIs and identified lower SSI rates in the combined antibiotics cohort (3.9% versus 12.9%) [
28]. In a similar study, these authors compared combined cefazolin/daptomycin with cefazolin/vancomycin in patients undergoing vascular surgery. The combined vancomycin group showed decreased Gram-positive SSI rates during the post-operative course [
27].
3. Intraoperative Use of Local Antibiotics
Optimized aseptic surgery techniques and correct antibiotic prophylaxis are ideal preventative measures against SSIs. Prolonged antibiotic administration may increase resistance risks, allergy, and/or toxicity rates. In addition, tissue trauma during surgery and healing processes may partially reduce tissue perfusion and cause decreased tissue penetration of systemically administered antibiotics [
47,
48]. Collagen implants containing gentamicin can be used to reduce groin wound SSIs and the requirement for repeated surgery by providing high, local concentrations of antibiotics (gentamicin), but at low levels in serum [
32,
33,
34]. Gentamicin-containing collagen implants limit wound complications and repeated surgeries and are completely absorbable, unlike polymethylmethacrylate (PMMA) spheres, which need to be removed [
48]. Furthermore, when gentamicin is used intraoperatively (local), its concentration levels rapidly decrease, thereby avoiding antibiotic resistance [
47,
48]. Similarly, collagen is advantageous as it simultaneously functions as an adjuvant for hemostasis and for the healing processes [
34].
Investigations on collagen implants containing antibiotics (gentamicin) for local intraoperative use have shown they reduce SSIs in patients having undergone general surgery, orthopedic, gynecological, and other general surgeries [
35,
49]. A single, prospective randomized investigation by Costa Almeida et al. evaluated gentamicin collagen implants for vascular surgery [
36]. The study included 60 non-diabetic and non-obese patients treated with gentamicin collagen implants at the groin wound site at the end of vascular prosthetic surgery, compared to a control group. No (0%) SSI was identified in the study group compared with 6 (10%) SSI cases in controls. Moreover, significantly decreased hospital stays were observed between groups. Other smaller studies have produced similar results [
37,
50], but larger multi-center RCTs are required to validate these observations.
This entry is adapted from the peer-reviewed paper 10.3390/antibiotics11020134