Wound Infection

The ancient Egyptians were the first civilization to have trained clinicians to treat physical aliments. Medical papyri, such as the Edwin Smith papyrus (circa 1600 BCE) and the Ebers papyrus (circa 1534 BCE), provided detailed information of management of disease, including wound management with the application of various potions and grease to assist healing.[1, 2]

See 5 Body Modifications and Piercing: Dermatologic Risks and Adverse Reactions, a Critical Images slideshow, to help recognize various body modifications and the related potential complications.

Hippocrates (Greek physician and surgeon, 460-377 BCE), known as the father of medicine, used vinegar to irrigate open wounds and wrapped dressings around wounds to prevent further injury. His teachings remained unchallenged for centuries.

Galen (Greek surgeon to Roman gladiators, 130-200 CE) was the first to recognize that pus from wounds inflicted by the gladiators heralded healing (pus bonum et laudabile ["good and commendable pus"]).

Unfortunately, Galen's observation was misinterpreted, and the concept of pus preempting wound healing persevered well into the 18th century. The link between pus formation and healing was emphasized so strongly that foreign material was introduced into wounds to promote pus formation-suppuration. The concept of wound healing remained a mystery, as highlighted by the famous saying by Ambroise Paré (French military surgeon, 1510-1590), "I dressed the wound. God healed it."[3]

The scale of wound infections was most evident in times of war. During the American Civil War, erysipelas (necrotizing infection of soft tissue) and tetanus accounted for over 17,000 deaths, according to an anonymous source in 1883. Because compound fractures at the time almost invariably were associated with infection, amputation was the only option, despite a 25-90% risk of amputation stump infection.

Koch (Professor of Hygiene and Microbiology, Berlin, 1843-1910) first recognized the cause of infective foci as secondary to microbial growth in his 19th century postulates. Semmelweis (Austrian obstetrician, 1818-1865) demonstrated a fivefold reduction in puerperal sepsis by hand washing between performing postmortem examinations and entering the delivery room.

Joseph Lister (Professor of Surgery, London, 1827-1912) and Louis Pasteur (French bacteriologist, 1822-1895) revolutionized the entire concept of wound infection. Lister recognized that antisepsis could prevent infection.[4] In 1867, he placed carbolic acid into open fractures to sterilize the wound and to prevent sepsis and hence the need for amputation. In 1871, Lister began to use carbolic spray in the operating room to reduce contamination. However, the concept of wound suppuration persevered even among eminent surgeons such as John Hunter.[5]

World War I resulted in new types of wounds from high-velocity bullet and shrapnel injuries coupled with contamination by the mud from the trenches. Antoine Depage (Belgian military surgeon, 1862-1925) reintroduced wound debridement and delayed wound closure and relied on microbiological assessment of wound brushings as guidance for the timing of secondary wound closure.[6] Alexander Fleming (microbiologist, London, 1881-1955) performed many of his bacteriologic studies during World War I and is credited with the discovery of penicillin.

As late as the 19th century, aseptic surgery was not routine practice. Sterilization of instruments began in the 1880s as did the wearing of gowns, masks, and gloves. Halsted (Professor of Surgery, Johns Hopkins University, United States, 1852-1922) introduced rubber gloves to his scrub nurse (and future wife) because she was developing skin irritation from the chemicals used to disinfect instruments. The routine use of gloves was introduced by Bloodgood, a student of Halsted.

Penicillin first was used clinically in 1940 by Howard Florey. With the use of antibiotics, a new era in the management of wound infections commenced. Unfortunately, eradication of the infective plague affecting surgical wounds has not ended because of the insurgence of antibiotic-resistant bacterial strains and the nature of more adventurous surgical intervention in immunocompromised patients and in implant surgery.

Wound healing is a continuum of complex interrelated biologic processes at the molecular level. For descriptive purposes, healing may be divided into the following three phases:

• Inflammatory phase
• Proliferative phase
• Maturation phase

Inflammatory phase

The inflammatory phase commences as soon as tissue integrity is disrupted by injury; this begins the coagulation cascade to limit bleeding. Platelets are the first of the cellular components that aggregate to the wound, and, as a result of their degranulation (platelet reaction), they release several cytokines (or paracrine growth factors). These cytokines include platelet-derived growth factor (PDGF), insulinlike growth factor-1 (IGF-1), epidermal growth factor (EGF), and fibroblast growth factor (FGF).

Serotonin is also released, which, together with histamine (released by mast cells), induces a reversible opening of the junctions between the endothelial cells, allowing the passage of neutrophils and monocytes (which become macrophages) to the site of injury.

This large cellular movement to the injury site is induced by cytokines secreted by the platelets (chemotaxis) and by further chemotactic cytokines secreted by the macrophages themselves once at the site of injury. These include transforming growth factor alpha (TGF-α) and transforming growth factor beta (TGF-β).

Consequently, an inflammatory exudate that contains red blood cells, neutrophils, macrophages, and plasma proteins, including coagulation cascade proteins and fibrin strands, fills the wound in a matter of hours. Macrophages not only scavenge but they also are central to the wound healing process because of their cytokine secretion.

Proliferative phase

The proliferative phase begins as the cells that migrate to the site of injury, such as fibroblasts, epithelial cells, and vascular endothelial cells, start to proliferate and the cellularity of the wound increases. The cytokines involved in this phase include FGFs, particularly FGF-2 (previously known as basic FGF), which stimulates angiogenesis and epithelial cell and fibroblast proliferation.

The marginal basal cells at the edge of the wound migrate across the wound, and, within 48 hours, the entire wound is epithelialized. In the depth of the wound, the number of inflammatory cells decreases with the increase in stromal cells, such as fibroblasts and endothelial cells, which, in turn, continue to secrete cytokines. Cellular proliferation continues with the formation of extracellular matrix proteins, including collagen and new capillaries (angiogenesis). This process is variable in length and may last several weeks.

Maturation phase

In the maturation phase, the dominant feature is collagen. The dense bundle of fibers, characteristic of collagen, is the predominant constituent of the scar. Wound contraction occurs to some degree in primary closed wounds but is a pronounced feature in wounds left to close by secondary intention. The cells responsible for wound contraction are called myofibroblasts, which resemble fibroblasts but have cytoplasmic actin filaments responsible for contraction.

The wound continuously undergoes remodeling to try to achieve a state similar to that prior to injury. The wound has 70-80% of its original tensile strength at 3-4 months after operation.

All surgical wounds are contaminated by microbes, but in most cases, infection does not develop because innate host defenses are quite efficient in the elimination of contaminants. A complex interplay between host, microbial, and surgical factors ultimately determines the prevention or establishment of a wound infection (see the image below).

Microbiology

Microbial factors that influence the establishment of a wound infection are the bacterial inoculum, virulence, and the effect of the microenvironment. When these microbial factors are conducive, impaired host defenses set the stage for enacting the chain of events that produce wound infection.

Most surgical-site infections (SSIs) are contaminated by the patient's own endogenous flora, which are present on the skin, mucous membranes, or hollow viscera. The traditional microbial concentration quoted as being highly associated with SSIs is that of bacterial counts higher than 10,000 organisms per gram of tissue (or in the case of burned sites, organisms per cm2 of wound).[7]

The usual pathogens on skin and mucosal surfaces are gram-positive cocci (notably staphylococci); however, gram-negative aerobes and anaerobic bacteria contaminate skin in the groin/perineal areas. The contaminating pathogens in gastrointestinal surgery are the multitude of intrinsic bowel flora, which include gram-negative bacilli (eg, Escherichia coli) and gram-positive microbes, including enterococci and anaerobic organisms.[8] (See Table 1 below.)

Table 1. Pathogens Commonly Associated with Wound Infections and Frequency of Occurrence ^[8] (Open Table in a new window)

Gram-positive organisms, particularly staphylococci and streptococci, account for most exogenous flora involved in SSIs. Sources of such pathogens include surgical/hospital personnel and intraoperative circumstances, including surgical instruments, articles brought into the operative field, and the operating room air.

The group of bacteria most commonly responsible for SSIs are Staphylococcus aureus strains. The emergence of resistant strains has considerably increased the burden of morbidity and mortality associated with wound infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is proving to be the scourge of modern-day surgery. Like other strains of S aureus, MRSA can colonize the skin and body of an individual without causing sickness, and, in this way, it can be passed on to other individuals unknowingly. Problems arise in the treatment of overt infections with MRSA because antibiotic choice is very limited. MRSA infections appear to be increasing in frequency and are displaying resistance to a wider range of antibiotics.[9]

Of particular concern are the vancomycin intermediate S aureus (VISA) strains of MRSA. These strains are beginning to develop resistance to vancomycin, which is currently the most effective antibiotic against MRSA. This new resistance has arisen because another species of bacteria, called enterococci, relatively commonly express vancomycin resistance.

Risk factors (other than microbiology)

Decreased host resistance can be due to systemic factors affecting the patient's healing response, local wound characteristics, or operative characteristics, as follows:

• Systemic factors - Age, malnutrition, hypovolemia, poor tissue perfusion, obesity, diabetes, steroids, and other immunosuppressants
• Wound characteristics - Nonviable tissue in wound, hematoma, foreign material (eg, drains and sutures, dead space, poor skin preparation (eg, shaving), and preexistent sepsis (local or distant)
• Operative characteristics - Poor surgical technique; lengthy operation (>2 hours); intraoperative contamination (eg, from infected theater staff and instruments or inadequate theater ventilation), prolonged preoperative stay in the hospital, and hypothermia

The type of procedure is a risk factor. Certain procedures are associated with a higher risk of wound contamination than others. Surgical wounds have been classified as clean, clean-contaminated, contaminated, and dirty-infected (see Table 2 below).[8, 10]

Table 2: Surgical Wound Classification and Subsequent Risk of Infection (If No Antibiotics Used) ^{[8, 10]} (Open Table in a new window)

United States statistics

SSIs are not an extinct entity; they account for 14-16% of the estimated 2 million nosocomial infections affecting hospitalized patients in the United States.[11]

International statistics

Internationally, the frequency of SSI is difficult to monitor because criteria for diagnosis might not be standardized. A survey sponsored by the World Health Organization (WHO) demonstrated a prevalence of nosocomial infections in the range of 3-21%, with wound infections accounting for 5-34% of the total.[12]

The 2002 survey report by the Nosocomial Infection National Surveillance Service (NINSS; now the Surgical Site Infection Surveillance Service [SSISS]),[13] which covered the period between October 1997 and September 2001, indicated that the incidence of hospital-acquired infection related to surgical wounds in the United Kingdom was as high as 10% and cost the country's National Health Service (NHS) approximately 1 billion pounds annually.

Collated data on the incidence of wound infections probably underestimate the true incidence because most wound infections occur when the patient is discharged, and these infections may be treated in the community without hospital notification.

SSIs are associated not only with increased morbidity but also with substantial mortality. In one study, 77% of the deaths of surgical patients were related to surgical wound infection.[14] Kirkland et al calculated a relative risk of death of 2.2 attributable to SSIs, in comparison with matched surgical patients without infection.[15]

Surgical-site infection (SSI) is a difficult term to define accurately because it has a wide spectrum of possible clinical features.

The Centers for Disease Control and Prevention (CDC) has defined SSI to standardize data collection for the National Nosocomial Infections Surveillance (NNIS) program.[8, 16] SSIs are classified into incisional SSIs, which can be superficial or deep, and organ/space SSIs, which affect the rest of the body other than the body wall layers (see the image below). These classifications are defined as follows:

• Superficial incisional SSI - Infection involves only skin and subcutaneous tissue of incision
• Deep incisional SSI - Infection involves deep tissues, such as fascial and muscle layers; this also includes infection involving both superficial and deep incision sites and organ/space SSI draining through incision
• Organ/space SSI - Infection involves any part of the anatomy in organs and spaces other than the incision, which was opened or manipulated during operation

Superficial incisional SSI is more common than deep incisional SSI and organ/space SSI. Superficial incisional SSI accounts for more than half of all SSIs for all categories of surgery. The postoperative length of stay is longer for patients with SSI, even when adjusted for other factors influencing length of stay.

A report by the NNIS program[17] cited particular clinical findings as characteristic of the different types of SSI.

Superficial incisional SSI is characterized by the following:

• Occurs within 30 days after the operation
• Involves only the skin or subcutaneous tissue
• Includes at least one of the following: (a) purulent drainage is present (culture documentation not required); (b) organisms are isolated from fluid/tissue of the superficial incision; (c) at least one sign of inflammation (eg, pain or tenderness, induration, erythema, local warmth of the wound) is present; (d) the wound is deliberately opened by the surgeon; (e) the surgeon or clinician declares the wound infected
• Note: A wound is not considered a superficial incisional SSI if a stitch abscess is present; if the infection is at an episiotomy, a circumcision site, or a burn wound; or if the SSI extends into fascia or muscle

Deep incisional SSI is characterized by the following:

• Occurs within 30 days of the operation or within 1 year if an implant is present
• Involves deep soft tissues (eg, fascia and/or muscle) of the incision
• Includes at least one of the following: (a) purulent drainage is present from the deep incision but without organ/space involvement; (b) fascial dehiscence or fascia is deliberately separated by the surgeon because of signs of inflammation; (c) a deep abscess is identified by direct examination or during reoperation, by histopathology, or by radiologic examination; (d) the surgeon or clinician declares that a deep incisional infection is present

Organ/space SSI is characterized by the following:

• Occurs within 30 days of the operation or within 1 year if an implant is present
• Involves anatomic structures not opened or manipulated during the operation
• Includes at least one of the following: (a) purulent drainage is present from a drain placed by a stab wound into the organ/space; (b) organisms are isolated from the organ/space by aseptic culturing technique; (c) an abscess in the organ/space is identified by direct examination, during reoperation, or by histopathologic or radiologic examination; (d) a diagnosis of organ/space SSI is made by the surgeon or clinician

Examples of wound infections are shown in the images below.

The simplest, and usually the quickest, staining method involves obtaining a Gram stain for infective organisms. Staining for fungal elements can be obtained at the same time.

Most laboratories routinely will culture for both aerobic and anaerobic organisms. Fungal cultures can be requested. Isolation of single colonies allows further growth and identification of the specific organism. Sensitivity testing then follows mainly for aerobic organisms.

Other techniques include the following:

• Tests for antigens from the organism through enzyme-linked immunoassay (ELISA) or radioimmunoassay
• Detection of antibody response to the organism in the host sera
• Detection of RNA or DNA sequences or protein from the infective organism by Northern, Southern, or Western blotting, respectively
• Polymerase chain reaction (PCR) to detect small amounts of microbial DNA

Ultrasonography (US) can be applied to the infected wound area to assess whether there is a collection for which drainage is required.

Most patients with wound infections are managed in the community. Management usually takes the form of dressing changes to optimize healing, which usually is by secondary intention.

Resultant increased hospital stay due to surgical-site infection (SSI) has been estimated at 7-10 days, increasing hospitalization costs by 20%.[18, 19, 20] Occasionally, further intervention in the form of wound debridement and subsequent packing and frequent dressing is necessary to allow healing by secondary intention.

Guidelines for the management of SSI were published in 2014 by the Infectious Diseases Society of America[21] (IDSA), in 2017 by the Centers for Disease Control and Prevention[22] (CDC), in 2018 by the World Health Organization[23]  (WHO), and in 2019 by the Asia Pacific Society of Infection Control[24] (APSIC). (See Guidelines.)

The use of antibiotics was a milestone in the effort to prevent wound infection. The concept of prophylactic antibiotics was established in the 1960s when experimental data established that antibiotics had to be in the circulatory system at a high enough dose at the time of incision to be effective.[25, 26]

It is generally agreed that prophylactic antibiotics are indicated for clean-contaminated and contaminated wounds (see Table 2 in Overview). Antibiotics for dirty wounds are part of the treatment because infection is established already. Clean procedures might be an issue of debate. No doubt exists regarding the use of prophylactic antibiotics in clean procedures in which prosthetic devices are inserted; infection in these cases would be disastrous for the patient. However, other clean procedures (eg, breast surgery) may be a matter of contention.[27, 28]

Criteria for the use of systemic preventive antibiotics in surgical procedures are as follows:

• Systemic preventive antibiotics should be used in the following cases: A high risk of infection is associated with the procedure (eg, colon resection); consequences of infection are unusually severe (eg, total joint replacement); the patient has a high NNIS risk index
• The antibiotic should be administered preoperatively but as close to the time of the incision as is clinically practical; antibiotics should be administered before induction of anesthesia in most situations
• The antibiotic selected should have activity against the pathogens likely to be encountered in the procedure
• Postoperative administration of preventive systemic antibiotics beyond 24 hours has not been demonstrated to reduce the risk of SSIs

Qualities of prophylactic antibiotics include efficacy against predicted bacterial microorganisms most likely to cause infection (see Table 3 below), good tissue penetration to reach wound involved, cost effectiveness, and minimal disturbance to intrinsic body flora (eg, gut).[29]

Table 3. Recommendations for Prophylactic Antibiotics as Indicated by Probable Infective Microorganism Involved ^{[8, 30]} (Open Table in a new window)

The timing of administration is critically important because the concentration of the antibiotic should be at therapeutic levels at the time of incision, during the surgical procedure, and, ideally, for a few hours postoperatively.[8] Antibiotics are administered intravenously, generally 30 minutes prior to incision[30] ; they should not be administered more than 2 hours prior to surgery.

Colorectal surgical prophylaxis additionally requires bowel clearance with enemas and oral nonabsorbable antimicrobial agents 1 hour before surgery.[18] High-risk cesarean surgical cases require antibiotic administration as soon as the clamping of the umbilical cord is completed.[8]

The current risk index used to predict the risk of developing a wound infection is the NNIS system of the CDC.[8] The risk index category is established by the added total of the risk factors present at the time of surgery. For each risk factor present, a point is allocated; risk index values range from 0-3. This risk index is a better predictor for SSIs (see Table 4 below) than the surgical wound classification is (see Table 2 in Overview).[31]

Table 4. Predictive Percentage of SSI Occurrence by Wound Type and Risk Index* ^[31] (Open Table in a new window)

The NNIS risk index integrates the three main determinants of infection—namely, bacteria, local environment, and systemic host defenses (patient health status). The risk index does not include other risk variables, like smoking, tissue oxygen tension, glucose control, shock, and maintenance of normothermia. All these factors are relevant for clinicians but difficult to monitor and fit into a manageable risk assessment.

The elements constituting this index are as follows:

• Preoperative patient physical status assessed by the anesthesiologist and classified by the American Society of Anesthesiologists (see Table 5 below) as greater than 3
• Operation status as either contaminated or dirty-infected (see Table 2 in Overview)
• Operation lasting longer than T hours, where T is the 75th percentile of the specific operation performed

Table 5. American Society of Anesthesiologists (ASA) Classification of Physical Status ^[32] (Open Table in a new window)

Perioperative recommendations have been made for minimizing wound infection and SSI, supported by varying degrees of evidence (see Table 6 below).

Table 6. Data Support Recommendations (Open Table in a new window)

Preoperative patient preparation

Category IA recommendations for preoperative patient preparation include the following:

• Identify and treat all infections remote from the surgical site; delay operation in elective cases until infection is treated
• Do not remove hair unless it infringes on the surgical field; if hair removal is required, it should be removed immediately before operation and preferably with electric clippers

Category IB recommendations include the following:

• Patients should cease tobacco consumption in any form for at least 1 month preoperatively
• Optimize blood glucose level and avoid hyperglycemia
• Patients are to shower/bathe with antiseptic on at least the night before surgery
• Necessary blood products may be administered

The category II recommendation is as follows: Provided that preoperative patient preparation is adequate, minimize preoperative hospital stay.

No recommendations are made regarding the following:

• Gradual reduction/discontinuance of steroid use before elective surgery
• Enhanced nutritional intake solely to prevent SSI
• Preoperative topical antibiotic use in nares to prevent SSI
• Measures to enhance wound space oxygenation

Preoperative considerations for surgical team members

Category IB recommendations regarding preoperative considerations for surgical team members are as follows:

• Keep fingernails short; do not wear artificial nails
• Scrub hands and forearms as high as the elbows for at least 2-5 minutes with appropriate antiseptic
• After scrub, keep hands up with elbows flexed and away from the body; use a sterile towel to dry the hands and put on a sterile gown and gloves
• Masks should be worn in the operating suite if sterile instruments are exposed and throughout the surgical procedure; masks should cover the mouth and nose
• The hair on the head and face is to be covered with a hood or cap
• Liquid-resistant sterile surgical gowns and sterile gloves are to be worn by scrubbed surgical team members
• Visibly soiled gowns are to be changed
• Shoe covers are not necessary
• Routine exclusion of personnel colonized by organisms, such as S aureus or group A streptococci, is not necessary unless they are specifically linked to dissemination of such organisms
• Personnel with skin lesions that are draining are to be excluded from duty until treated and the infection has resolved
• Educate and encourage surgical personnel regarding reporting illness of transmissible nature to supervisory and occupational health personnel
• Policies should be established concerning patient care responsibilities for personnel with potentially transmissible infective illnesses, to include aspects of work restrictions, personnel responsibility in utilizing health services, and declaring illness; policies also should direct the responsible person to remove personnel from duty, and policy should be established for clearance to resume work

Category II recommendations are as follows:

• Clean under the fingernails prior to the first scrub of the day
• Do not wear arm/hand jewelry

No recommendations are made regarding the following:

• Nail polish
• Restriction of scrub suits to the operating theater
• Covering the scrub suits when outside the theater
• How or where to launder theater suites

Preoperative and postoperative wound care

A category IA recommendation for preoperative and postoperative wound care is that asepsis is necessary in the insertion of indwelling catheters, such as intravascular, spinal, or epidural catheters, and subsequent infusion of drugs. (See the image below.)

Category IB recommendations include the following:

• Handle tissues gently with good hemostasis, minimize foreign bodies, and minimize devitalized tissue and dead space
• For class III and IV wounds, use delayed closure or leave the wound incision open to heal by secondary intention
• If draining of a wound is necessary, the drain exit should be via separate incision distant from the wound; remove the drain as soon as possible
• Primary closed incisions should be protected with a sterile dressing for 24-48 hours
• Hands are to be washed before and after wound dressing changes/or contact

Category II recommendations include the following:

• Use sterile technique for wound dressing change
• Educate the patient and relatives regarding wound care symptoms of SSIs and the need to report such problems

Theater environment and care of instrumentation

Category IB recommendations for the theater environment and the care of instrumentation include the following:

• Maintain positive-pressure ventilation of the operating suite relative to corridors and surrounding areas
• Maintain a minimum of 15 air changes per hour, with at least three being fresh air
• Appropriate filters (as recommended by the American Institute of Architects) should be used for filtration of all air, whether recirculated or fresh
• Air should enter through the ceiling and exit near the floor
• Keep operating room doors closed except for necessary entry
• The use of ultraviolet lamps in the theater is not necessary as a deterrent of SSI
• Prior to subsequent procedures, visibly soiled surfaces should be cleaned with Environmental Protection Agency (EPA)–approved disinfectants
• After a contaminated or dirty procedure, special cleaning or closure of the operating suite is not necessary
• Use of tacky mats prior to entry in the operating suite is not necessary
• Sterile surgical instruments and solutes should be assembled just prior to use
• All surgical instruments should be sterilized according to guidelines; flush sterilization should only be used for instruments that are required for immediate patient use

Category II recommendations include the following:

• Limit the number of personnel entering the operating suite.
• Orthopedic implant surgery should be performed in an ultraclean-air environment.
• Wet-vacuum the floor of the operating theater at the end of day/night using an EPA-approved disinfectant

Special situations

Elective colon surgery

Bowel surgery results in the breakdown of the protective intestinal mucous membrane, with release of the facultative and anaerobic bacteria that heavily colonize the distal small bowel and colon. Eradication of aerobes and anaerobes is necessary to reduce infective complications following intestinal procedures. Mechanical cleansing and antibiotics could achieve this.

Mechanical cleansing can take the form of dietary restrictions; whole gut lavage with one of several preparations, such as 10% mannitol solution, Fleet's phospho-soda, or polyethylene glycol, usually is performed on the day of surgical intervention. Enteral antibiotic regimes to eradicate intrinsic bowel flora vary, with oral neomycin and erythromycin being the most popular combination in the United States. Other combinations with neomycin include the use of metronidazole and tetracycline. Prophylactic parenteral antibiotics also are used with the above.

Intravascular device-related infections

Intravascular devices are of vital use in daily hospital practice. They are used for the parenteral administration of fluids, blood products, nutritional fluids, and medication and for access in hemodialysis; equally important is their use in the monitoring of critically ill patients.

Unfortunately, because the use of these devices constitutes an invasive procedure, they are associated with infectious complications that could be of a local or systemic nature. Recommendations for prevention[33] and treatment[34] are available to limit their associated morbidity and mortality (which could be as high as 20% in patients with catheter-related bloodstream infections).

In a double-blind, randomized, controlled study of 400 patients with nontunnelled central venous catheters, Dettenkofer et al investigated the effectiveness of the antiseptic octenidine dihydrochloride, used in combination with alcohol-based antiseptic, against infection at central venous catheter insertion sites.[35] One group of patients received skin disinfection with 0.1% octenidine with 30% 1-propanol and 45% 2-propanol, while a control group was disinfected with 74% ethanol with 10% 2-propanol.

In this study, microbial skin colonization at the catheter insertion site and positive microbial cultures at the catheter tip were significantly reduced in the octenidine group.[35] No significant differences in catheter-associated bloodstream infections were found between the groups.

Although the goal of every surgeon is to prevent wound infections, they will arise. Treatment is individualized to the patient, the wound, and the nature of the infection. The operating surgeon should be made aware of the possibility of infection in the wound and determine the treatment for the wound.

Ideally, surgical care should start with meticulous detail to strategies that prevent the development of SSIs in the first place. Preoperatively, attention should be paid to factors like optimization of patient status, proper asepsis, and surgical site preparation. Intraoperatively, adherence to good basic surgical principles of minimal and fine tissue dissection, proper selection of suture materials, and proper wound closure is important.

If a SSI sets in, the treatment often involves opening the wound, evacuating pus, and cleansing the wound. The deeper tissues are inspected for integrity and for a deep space infection or source. Dressing changes allow the tissues to granulate, and the wound heals by secondary intention over several weeks. Early/delayed closure of infected wounds is often associated with relapse of infection and wound dehiscence.

Additional preventive strategies

Evidence shows that the close regulation of blood sugar may be a major determinant of wound morbidity.[36] Although investigators have vigorously pursued for decades the identification of a specific innate or acquired immune deficiency among patients with diabetes, it may be the blood sugar that is the determinant of infection for these patients.

A second issue of considerable interest is body temperature. A prospective randomized study demonstrated that failure to maintain intraoperative core body temperature within 1-1.5°C of normal increases the SSI rate by a factor of 2.[37] It raises the scientific question of whether increasing core temperature during operations over normal temperature might in fact protect against infection.

A third issue is oxygenation.[38] The fresh, hemostatic surgical incision is a hypoxic, ischemic environment. Maintaining or increasing oxygen delivery to the wound by increasing the inspired oxygen concentration administered to the patient perioperatively has also been shown to reduce the incidence of SSIs. It is presumed that increased oxygen availability is a positive host factor, perhaps via enhanced production of oxidant products that facilitate phagocytic eradication of microbes.

A strategy that could bear fruit for preventing SSIs in the future is the establishment of dedicated infection surveillance units in hospitals with the aim of accomplishing the following:

• Identify epidemics by common or uncommon organisms
• Establish the correct use of prophylaxis (ie, timing, dose, duration, choice)
• Document costs, risk factors, and readmission rates
• Monitor postdischarge infections and secondary consequences
• Ensure patient safety

A major concern is how to prevent or minimize the emergence of resistance. Although resistance is not a new phenomenon, the incidence has increased dramatically over the past two decades. The development of new drugs has slowed considerably and may be unable to keep pace with the continuing growth of pathogen resistance.

Accordingly, effective strategies are needed to prevent the continuing emergence of antimicrobial resistance. These strategies include avoiding unnecessary antibiotic administration and increasing the effectiveness of prescribed antibiotics, as well as implementing improvements in infection control and optimizing medical practice.

Although an SSI rate of zero may not be achievable, continued progress in understanding the biology of infection at the surgical site and consistent applications of proven methods of prevention will further reduce the frequency, cost, and morbidity associated with SSIs.

In 2019, the Asia Pacific Society of Infection Control (APSIC) issued the following guidelines for the prevention of surgical-site infection (SSI)[24] :

• Perform surveillance of SSIs using accepted international methodology.
• It is necessary for patients who will undergo surgery to have at least one preoperative bath with soap (antimicrobial or nonantimicrobial).
• A combination of mechanical bowel preparation and oral antibiotic preparation is recommended for all elective colorectal surgery in adults.
• Hair removal should be avoided unless hair interferes with the operative procedure. If hair removal is necessary, a razor should be avoided, and an electric clipper should be used. No recommendation is made regarding the timing of hair removal by clipper.
• Hospitals should evaluate their SSI rate, Staphylococcus aureus and methicillin-resistant S aureus (MRSA) rates, and mupirocin resistance rate, if available, to determine whether implementation of a screening program is appropriate.
• Patients undergoing cardiothoracic and orthopedic surgery with known nasal carriage of S aureus should receive perioperative intranasal application of mupirocin 2% ointment, with or without a combination of chlorhexidine body wash.
• Surgical hand preparation is to be performed either by scrubbing with a suitable antiseptic soap and water or by using a suitable alcohol-based hand rub (ABHR) before sterile gown and gloves are donned. ABHRs used in surgical hand preparation should comply with EN 12791 or ASTM E-1115 standards.
• Where the quality of water used is not assured, use of an ABHR is recommended.
• Alcohol-based skin antiseptic preparations should be used, unless contraindicated.
• Administration of prophylactic antimicrobials should be performed only when indicated. It should take place within 1 hour before incision for all antimicrobials except vancomycin and fluoroquinolones, for which it should take place within 2 hours before incision. Redosing should be considered to maintain adequate tissue levels on the basis of on agent half-life. A single dose of a prophylactic antimicrobial is adequate for most surgical procedures.
• Underweight patients undergoing major surgical procedures, especially oncologic and cardiovascular operations, may benefit from the administration of oral or enteral multiple nutrient-enhanced nutritional formulas for the purpose of preventing SSI.
• Preoperative hemoglobin A1c levels should be below 8%.
• Maintain perioperative normothermia by using active warming devices.
• Hemodynamic goal-directed therapy is recommended to reduce SSI.
• There is insufficient evidence to recommend for or against saline irrigation of incisional wounds before closure for the purpose of preventing SSI. Avoid using antimicrobial agents to irrigate incisional wounds before closure to reduce the risk of SSI.
• Where there are high SSI rates in clean surgical procedures in spite of basic preventive measures, individual centers may consider the use of antimicrobial-impregnated sutures.
• When using adhesive incise drapes for surgery, do not use non-iodophor-impregnated drapes; they may increase the risk of SSI. In orthopedic and cardiac surgical procedures where adhesive incise drapes are used, consider using an iodophor-impregnated incise drape, unless the patient has an iodine allergy or other contraindication.
• Careful evaluation of wound protectors must be done before the use of wound protectors is introduced as a routine measure to reduce SSI.
• Do not apply vancomycin powder into the surgical site for prevention of SSI.
• Installation of laminar airflow is not required in new or renovated operating rooms (ORs) to prevent SSI.
• Primary vacuum dressings or negative-pressure wound therapy (NPWT; ie, for clean-contaminated and contaminated surgical procedures) and silver-based dressings have mixed results; individualized decisions on their use are suggested. Routine use for prevention of SSI is not recommended.

In 2018, the World Health Organization (WHO) published the second edition of its guidelines regarding SSI,[23] which included the following strong recommendations:

• Patients with known nasal carriage of S aureus should receive intranasal applications of mupirocin 2% ointment, with or without a combination of chlorhexadine gluconate (CHG) body wash.
• Mechanical bowel preparation alone (without oral antibiotics) should not be used in adult patients undergoing elective colorectal surgery.
• In patients undergoing any surgical procedure, hair either should not be removed or, if removal is absolutely necessary, should be removed only with a clipper. Shaving is strongly discouraged at all times, whether preoperatively or in the OR.
• Surgical antibiotic prophylaxis (SAP), when indicated, should be administered within 120 minutes before incision, with consideration given to the half-life of the antibiotic.
• Surgical hand preparation should be performed either by scrubbing with a suitable antimicrobial soap and water or by using a suitable alcohol-based hand rub before donning sterile gloves.
• Alcohol-based antiseptic solutions based on CHG should be used for surgical-site skin preparation in patients undergoing surgical procedures.
• Adult patients undergoing general anesthesia with endotracheal intubation for surgical procedures should receive 80% fraction of inspired oxygen intraoperatively and, if feasible, immediately after the procedure for 2-6 hours.
• SAP should not be prolonged after completion of the operation.

In 2017, the Centers for Disease Control and Prevention (CDC) published an updated guideline for the prevention of SSIs,[22]  which included the following recommendations:

• Administer preoperative antimicrobial agents only when indicated by published clinical practice guidelines, and time administration so that a bactericidal concentration is established in serum and tissues when the incision is made (strong recommendation; accepted practice).
• Administer appropriate parenteral prophylactic antimicrobial agents before skin incision in all cesarean section procedures (strong recommendation; high-quality evidence).
• In clean and clean-contaminated procedures, do not administer additional prophylactic antimicrobial agent doses after the surgical incision is closed in the OR, even in the presence of a drain (strong recommendation; high-quality evidence).
• Do not apply antimicrobial agents (ie, ointments, solutions, or powders) to the surgical incision with the aim of preventing SSI (strong recommendation; low-quality evidence).
• Application of autologous platelet-rich plasma is not necessary for the prevention of SSI (weak recommendation; moderate-quality evidence suggesting a trade-off between clinical benefits and harms).
• Consider the use of triclosan-coated sutures for the prevention of SSI (weak recommendation; moderate-quality evidence).
• Implement perioperative glycemic control, and use blood glucose target levels lower than 200 mg/dL in patients with and without diabetes (strong recommendation; high- to moderate-quality evidence).
• Maintain perioperative normothermia (strong recommendation; high- to moderate-quality evidence).
• For patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation, employ an increased fraction of inspired oxygen (FiO ₂) during the surgical procedure and after extubation in the immediate postoperative period; to optimize tissue oxygen delivery, maintain perioperative normothermia and adequate volume replacement (strong recommendation; moderate-quality evidence).
• Advise patients to shower or bathe the full body with either antimicrobial or nonantimicrobial soap or an antiseptic agent on at least the night before the day of the procedure (strong recommendation; accepted practice).
• Perform intraoperative skin preparation with an alcohol-based antiseptic agent unless this is contraindicated (strong recommendation; high-quality evidence).
• Application of a microbial sealant immediately after intraoperative skin preparation is not necessary for the prevention of SSI (weak recommendation; low-quality evidence).
• The use of plastic adhesive drapes with or without antimicrobial properties is not necessary for the prevention of SSI. (weak recommendation; high- to moderate-quality evidence).
• Consider intraoperative irrigation of deep or subcutaneous tissues with aqueous iodophor solution for the prevention of SSI; intraperitoneal lavage with aqueous iodophor solution is not necessary in contaminated or dirty abdominal procedures (weak recommendation; moderate-quality evidence).
• Do not withhold transfusion of necessary blood products from surgical patients undergoing prosthetic joint arthroplasty as a means of preventing SSI (strong recommendation; accepted practice).
• In clean or clean-contaminted prosthetic joint arthroplasties, do not administer additional antimicrobial prophylaxis doses after the surgical incision is closed in the OR, even in the presence of a drain (strong recommendation; high-quality evidence).

In 2014, the Infectious Diseases Society of America (IDSA) issued the following practice guidelines for the management of SSIs[21] :

• Suture removal plus incision and drainage should be performed for SSIs (strong recommendation, low-quality evidence)
• Adjunctive systemic antimicrobial therapy is not routinely indicated but, in conjunction with incision and drainage, may be beneficial for SSIs associated with a significant systemic response, such as erythema and induration extending more than 5 cm from the wound edge, temperature exceeding 38.5°C, heart rate higher than 110 beats/min, or white blood cell (WBC) count higher than 12,000/µL (weak recommendation, low-quality evidence)
• A brief course of systemic antimicrobial therapy is indicated in patients with SSIs after clean operations on the trunk, head and neck, or extremities that also have systemic signs of infection (strong recommendation, low-quality evidence)
• A first-generation cephalosporin or an antistaphylococcal penicillin for methicillin-sensitive  S aureus (MSSA)—or vancomycin, linezolid, daptomycin, telavancin, or ceftaroline where risk factors for methicillin-resistant  S aureus (MRSA) are high (nasal colonization, prior MRSA infection, recent hospitalization, or recent antibiotics)—is recommended (strong recommendation, low-quality evidence)
• Agents active against gram-negative bacteria and anaerobes, such as a cephalosporin or fluoroquinolone in combination with metronidazole, are recommended for infections after operations on the axilla, gastrointestinal tract, perineum, or female genital tract (strong recommendation, low-quality evidence)

The choice of antibiotic depends on 2 factors—the patient and the known or probable infecting microorganism. Patient factors include allergies, hepatic and renal function, severity of disease process, interaction with other medication(s), and age. In women, pregnancy and breastfeeding must be considered.

Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Cefazolin (Ancef, Kefzol, Zolicef)

First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus. Typically used alone for skin and skin-structure coverage. IV and IM dosing regimens are similar.

Erythromycin (EES, E-Mycin, Eryc)

Inhibits bacterial growth possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.

In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Cefoxitin (Mefoxin)

Second-generation cephalosporin indicated for gram-positive cocci and gram-negative rod infections. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

Cefotetan (Cefotan)

Second-generation cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods.

Dose and route of administration depend on condition of patient, severity of infection, and susceptibility of causative organism.