Wound Infection 

History

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 BC) and the Ebers papyrus (circa 1534 BC), provided detailed information of management of disease, including wound management with the application of various potions and grease to assist healing.^{[1, 2]} (See images below.)

Hippocrates (Greek physician and surgeon, 460-377 BC), 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 (Roman gladiatorial surgeon, 130-200 AD) was first to recognize that pus from wounds inflicted by the gladiators heralded healing (pus bonum et laudabile ["good and commendable pus"]). Unfortunately, this 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 5-fold 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, Lister 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, 1728-1793.^[5]

World War I (WWI) 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 bacteriological studies during WWI 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 introduces by Halsted's student J. Bloodgood.

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 biological processes at the molecular level. Healing is divided into the following phases for descriptive purposes: inflammatory phase, proliferative phase, and maturation 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-alpha) and transforming growth factor beta (TGF-beta). 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.

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.

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 postoperative.

Frequency

United States

Surgical site infections (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.^[7]

International

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 demonstrated a prevalence of nosocomial infections varying from 3-21%, with wound infections accounting for 5-34% of the total.^[8] The 2002 survey report by the Nosocomial Infection National Surveillance Service (NINSS), which covers the period between October 1997 and September 2001, indicates that the incidence of hospital acquired infection related to surgical wounds in the United Kingdom is as high as 10% and costs the National Health Service in the United Kingdom approximately 1 billion pounds (1.8 billion dollars) annually.

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

Mortality/Morbidity

SSIs are associated not only with increased morbidity but also with mortality. Seventy-seven percent of the deaths of surgical patients were related to surgical wound infection.^[9] Kirkland et al calculated a relative risk of death of 2.2 attributable to SSIs, compared to matched surgical patients without infection.^[10]