1. 
   

   Sepsis is both the presence of infection and the host response to infection (systemic inflammatory response syndrome, SIRS). Sepsis is a clinical spectrum, ranging from sepsis (SIRS plus infection) to severe sepsis (organ dysfunction), to septic shock (hypotension requiring vasopressors). Outcomes in patients with sepsis are improved with an organized approach to therapy that includes rapid resuscitation, antibiotics, and source control.

   
   
2. 
   

   Source control is a key concept in the treatment of most surgically relevant infections. Infected or necrotic material must be drained or removed as part of the treatment plan in this setting. Delays in adequate source control are associated with worsened outcomes.

   
   
3. 
   

   Principles relevant to appropriate antibiotic prophylaxis for surgery: (a) select an agent with activity against organisms commonly found at the site of surgery, (b) the initial dose of the antibiotic should be given within 30 minutes prior to the creation of the incision, (c) the antibiotic should be redosed during long operations based upon the half-life of the agent to ensure adequate tissue levels, and (d) the antibiotic regimen should not be continued for more than 24 hours after surgery for routine prophylaxis.

   
   
4. 
   

   When using antimicrobial agents for therapy of serious infection, several principles should be followed: (a) identify likely sources of infection, (b) select an agent (or agents) that will have efficacy against likely organisms for these sources, (c) inadequate or delayed antibiotic therapy results in increased mortality, so it is important to begin therapy rapidly with broader coverage, (d) when possible, obtain cultures early and use results to refine therapy, (e) if no infection is identified after 3 days, strongly consider discontinuation of antibiotics, based upon the patient’s clinical course, (f) discontinue antibiotics after an appropriate course of therapy.

   
   
5. 
   

   The incidence of surgical site infections can be reduced by appropriate patient preparation, timely perioperative antibiotic administration, maintenance of perioperative normothermia and normoglycemia, and appropriate wound management.

   
   
6. 
   

   The keys to good outcomes in patients with necrotizing soft tissue infection are early recognition and appropriate debridement of infected tissue with repeated debridement until no further signs of infection are present.

   
   
7. 
   

   Transmission of HIV and other infections spread by blood and body fluid from patient to health care worker can be minimized by observation of universal precautions, which include routine use of barriers when anticipating contact with blood or body fluids, washing of hands and other skin surfaces immediately after contact with blood or body fluids, and careful handling and disposal of sharp instruments during and after use.

Although treatment of infection has been an integral part of the surgeon’s practice since the dawn of time, the body of knowledge that led to the present field of surgical infectious disease was derived from the evolution of germ theory and antisepsis. Application of the latter to clinical practice, concurrent with the development of anesthesia, was pivotal in allowing surgeons to expand their repertoire to encompass complex procedures that previously were associated with extremely high rates of morbidity and mortality due to postoperative infections. However, until recently the occurrence of infection related to the surgical wound was the rule rather than the exception. In fact, the development of modalities to effectively prevent and treat infection has occurred only within the last several decades.

A number of observations by nineteenth-century physicians and investigators were critical to our current understanding of the pathogenesis, prevention, and treatment of surgical infections. In 1846, Ignaz Semmelweis, a Magyar physician, took a post at the Allgemein Krankenhaus in Vienna. He noticed that the mortality from puerperal (“childbed”) fever was much higher in the teaching ward (1:11) than in the ward where patients were delivered by midwives (1:29). He also made the interesting observation that women who delivered prior to arrival on the teaching ward had a negligible mortality rate. The tragic death of a colleague due to overwhelming infection after a knife scratch received during an autopsy of a woman who had died of puerperal fever led Semmelweis to observe that pathologic changes in his friend were identical to those of women dying from this postpartum disease. He then hypothesized that puerperal fever was caused by putrid material transmitted from patients dying of this disease by carriage on the examining fingers of the medical students and physicians who frequently went from the autopsy room to the wards. The low mortality noted in the midwives’ ward, Semmelweis realized, was because midwives did not participate in autopsies. Fired with the zeal of his revelation, he posted a notice on the door to the ward requiring all caregivers to rinse their hands thoroughly in chlorine water prior to entering the area. This simple intervention reduced mortality from puerperal fever to 1.5%, surpassing the record of the midwives. In 1861, he published his classic work on childbed fever based on records from his practice. Unfortunately, Semmelweis’ ideas were not well accepted by the authorities of the time.¹ Increasingly frustrated by the indifference of the medical profession, he began writing open letters to well-known obstetricians in Europe, and was committed to an asylum due to concerns that he was losing his mind. He died shortly thereafter. His achievements were only recognized after Pasteur’s description of the germ theory of disease.

Louis Pasteur performed a body of work during the latter part of the nineteenth century that provided the underpinnings of modern microbiology, at the time known as “germ theory.” His work in humans followed experiments identifying infectious agents in silkworms. He was able to elucidate the principle that contagious diseases are caused by specific microbes and that these microbes are foreign to the infected organism. Using this principle he developed techniques of sterilization critical to oenology, and identified several bacteria responsible for human illnesses, including Staphylococcus and Streptococcus pneumoniae (pneumococcus).

Joseph Lister, the son of a wine merchant, was appointed professor of surgery at the Glasgow Royal Infirmary in 1859. In his early practice, he noted that over 50% of his patients undergoing amputation died because of postoperative infection. After hearing of Pasteur’s theory, Lister experimented with the use of a solution of carbolic acid, which he knew was being used to treat sewage. He first reported his findings to the British Medical Association in 1867 using dressings saturated with carbolic acid on 12 patients with compound fractures; 10 recovered without amputation, one survived with amputation, and one died of causes unrelated to the wound. In spite of initial resistance, his methods were quickly adopted throughout Europe.

From 1878 until 1880, Robert Koch was the District Medical Officer for Wollstein, which was an area in which anthrax was endemic. Performing experiments in his home, without the benefit of scientific equipment and academic contact, Koch developed techniques for culture of Bacillus anthracis and proved the ability of this organism to cause anthrax in healthy animals. He developed the following four postulates to identify the association of organisms with specific diseases: (a) the suspected pathogenic organism should be present in all cases of the disease and absent from healthy animals, (b) the suspected pathogen should be isolated from a diseased host and grown in a pure culture in vitro, (c) cells from a pure culture of the suspected organism should cause disease in a healthy animal, and (d) the organism should be reisolated from the newly diseased animal and shown to be the same as the original. He used these same techniques to identify the organisms responsible for cholera and tuberculosis. During the next century, Koch’s postulates, as they came to be called, became critical to our understanding of surgical infections and remain so today.²

The first intra-abdominal operation to treat infection via “source control” (i.e., surgical intervention to eliminate the source of infection) was appendectomy. This operation was pioneered by Charles McBurney at the New York College of Physicians and Surgeons, among others.³ McBurney’s classic report on early operative intervention for appendicitis was presented before the New York Surgical Society in 1889. Appendectomy for the treatment of appendicitis, previously an often fatal disease, was popularized after the 1902 coronation of King Edward VII of England was delayed due to his need for an appendectomy, which was performed by Sir Frederick Treves. The king desperately needed an appendectomy but strongly opposed going into the hospital, protesting, “I have a coronation on hand.” However, Treves was adamant, stating, “It will be a funeral, if you don’t have the operation.” Treves carried the debate, and the king lived.

During the twentieth century the discovery of effective antimicrobials added another tool to the armamentarium of modern surgeons. Sir Alexander Fleming, after serving in the British Army Medical Corps during World War I, continued work on the natural antibacterial action of the blood and antiseptics. In 1928, while studying influenza virus, he noted a zone of inhibition around a mold colony (Penicillium notatum) that serendipitously grew on a plate of Staphylococcus, and he named the active substance penicillin. This first effective antibacterial agent subsequently led to the development of hundreds of potent antimicrobials, set the stage for their use as prophylaxis against postoperative infection, and became a critical component of the armamentarium to treat aggressive, lethal surgical infections.

Concurrent with the development of numerous antimicrobial agents were advances in the field of clinical microbiology. Many new microbes were identified, including numerous anaerobes; the autochthonous microflora of the skin, gastrointestinal tract, and other parts of the body that the surgeon encountered in the process of an operation were characterized in great detail. However, it remained unclear whether these organisms, anaerobes in particular, were commensals or pathogens. Subsequently, the initial clinical observations of surgeons such as Frank Meleney, William Altemeier, and others provided the key, when they observed that aerobes and anaerobes could synergize to cause serious soft tissue and severe intra-abdominal infection.^4,5 Thus, the concepts that resident microbes were nonpathogenic until they entered a sterile body cavity at the time of surgery, and that many, if not most, surgical infections were polymicrobial in nature, became critical ideas, and were promulgated by a number of clinician-scientists over the last several decades.^6,7 These tenets became firmly established after microbiology laboratories demonstrated the invariable presence of aerobes and anaerobes in peritoneal cultures obtained at the time of surgery for intra-abdominal infection due to a perforated viscus or gangrenous appendicitis. Clinical trials provided ample evidence that optimal therapy for these infections required effective source control, plus the administration of antimicrobial agents directed against both types of pathogens.

William Osler, a prolific writer and one of the fathers of American medicine, made an observation in 1904 in his treatise The Evolution of Modern Medicine that was to have profound implications for the future of treatment of infection: “Except on few occasions, the patient appears to die from the body’s response to infection rather than from it.”⁸ The discovery of the first cytokines began to allow insight into the human organism’s response to infection, and led to an explosion in our understanding of the host inflammatory response. Expanding knowledge of the multiple pathways activated during the response to invasion by infectious organisms has permitted the design of new therapies targeted at modifying the inflammatory response to infection, which seems to cause much of the organ dysfunction and failure. Preventing and treating this process of multiple organ failure during infection is one of the major challenges of modern critical care and surgical infectious disease.

Host Defenses

The mammalian host possesses several layers of endogenous defense mechanisms that serve to prevent microbial invasion, limit proliferation of microbes within the host, and contain or eradicate invading microbes. These defenses are integrated and redundant so that the various components function as a complex, highly regulated system that is extremely effective in coping with microbial invaders. They include site-specific defenses that function at the tissue level, as well as components that freely circulate throughout the body in both blood and lymph. Systemic host defenses invariably are recruited to a site of infection, a process that begins immediately upon introduction of microbes into a sterile area of the body. Perturbation of one or more components of these defenses (e.g., via immunosuppressants, foreign body, chronic illness, and burns) may have substantial negative impact on resistance to infection.

Entry of microbes into the mammalian host is precluded by the presence of a number of barriers that possess either an epithelial (integument) or mucosal (respiratory, gut, and urogenital) surface. Barrier function, however, is not solely limited to physical characteristics. Host barrier cells may secrete substances that limit microbial proliferation or prevent invasion. Also, resident or commensal microbes (endogenous or autochthonous host microflora) adherent to the physical surface and to each other may preclude invasion, particularly of virulent organisms (colonization resistance).⁹

The most extensive physical barrier is the integument or skin. In addition to the physical barrier posed by the epithelial surface, the skin harbors its own resident microflora that may block the attachment and invasion of noncommensal microbes. Microbes are also held in check by chemicals that sebaceous glands secrete and by the constant shedding of epithelial cells. The endogenous microflora of the integument primarily comprises gram-positive aerobic microbes belonging to the genera Staphylococcus and Streptococcus, as well as Corynebacterium and Propionibacterium species. These organisms plus Enterococcus faecalis and faecium, Escherichia coli and other Enterobacteriaceae, and yeast such as Candida albicans can be isolated from the infraumbilical regions of the body. Diseases of the skin (e.g., eczema and dermatitis) are associated with overgrowth of skin commensal organisms, and barrier breaches invariably lead to the introduction of these microbes.

The respiratory tract possesses several host defense mechanisms that facilitate the maintenance of sterility in the distal bronchi and alveoli under normal circumstances. In the upper respiratory tract, respiratory mucus traps larger particles, including microbes. This mucus is then passed into the upper airways and oropharynx by ciliated epithelial cells, where the mucus is cleared via coughing. Smaller particles arriving in the lower respiratory tract are cleared via phagocytosis by pulmonary alveolar macrophages. Any process that diminishes these host defenses can lead to development of bronchitis or pneumonia.

The urogenital, biliary, pancreatic ductal, and distal respiratory tracts do not possess resident microflora in healthy individuals, although microbes may be present if these barriers are affected by disease (e.g., malignancy, inflammation, calculi, or foreign body), or if microorganisms are introduced from an external source (e.g., urinary catheter or pulmonary aspiration). In contrast, significant numbers of microbes are encountered in many portions of the gastrointestinal tract, with vast numbers being found within the oropharynx and distal colon or rectum, although the specific organisms differ.

One would suppose that the entire gastrointestinal tract would be populated via those microbes found in the oropharynx, but this is not the case.⁹ This is because after ingestion these organisms routinely are killed in the highly acidic, low-motility environment of the stomach during the initial phases of digestion. Thus, small numbers of microbes populate the gastric mucosa ~10² to 10³ colony-forming units (CFU)/mL. This population expands in the presence of drugs or disease states that diminish gastric acidity. Microbes that are not destroyed within the stomach enter the small intestine, in which a certain amount of microbial proliferation takes place, such that approximately 10⁵ to 10⁸ CFU/mL are present in the terminal ileum.

The relatively low-oxygen, static environment of the colon is accompanied by the exponential growth of microbes that comprise the most extensive host endogenous microflora. Anaerobic microbes outnumber aerobic species approximately 100:1 in the distal colon, and approximately 10¹¹ to 10¹² CFU/g are present in feces. Large numbers of facultative and strict anaerobes (Bacteroides fragilis,distasonis, and thetaiotaomicron, Bifidobacterium, Clostridium, Eubacterium, Fusobacterium, Lactobacillus, and Peptostreptococcus species) as well as several orders of magnitude fewer aerobic microbes (Escherichia coli and other Enterobacteriaceae, Enterococcus faecalis and faecium, Candida albicans and other Candida spp.) are present. Intriguingly, although colonization resistance on the part of this extensive, well-characterized host microflora effectively prevents invasion of enteric pathogens such as Salmonella, Shigella, Vibrio, and other enteropathogenic bacterial species, these same organisms provide the initial inoculum for infection should perforation of the gastrointestinal tract occur. It is of great interest that only some of these microbial species predominate in established intra-abdominal infections.

Once microbes enter a sterile body compartment (e.g., pleural or peritoneal cavity) or tissue, additional host defenses act to limit and/or eliminate these pathogens. Initially, several primitive and relatively nonspecific host defenses act to contain the nidus of infection, which may include microbes as well as debris, devitalized tissue, and foreign bodies, depending on the nature of the injury. These defenses include the physical barrier of the tissue itself, as well as the capacity of proteins, such as lactoferrin and transferrin to sequester the critical microbial growth factor iron, thereby limiting microbial growth. In addition, fibrinogen within the inflammatory fluid has the ability to trap large numbers of microbes during the process in which it polymerizes into fibrin. Within the peritoneal cavity, unique host defenses exist, including a diaphragmatic pumping mechanism whereby particles, including microbes within peritoneal fluid are expunged from the abdominal cavity via specialized structures (stomata) on the undersurface of the diaphragm that lead to thoracic lymphatic channels. Concurrently, containment by the omentum, the so-called “gatekeeper” of the abdomen and intestinal ileus, serves to wall off infections. However, the latter processes and fibrin trapping have a high likelihood of contributing to the formation of an intra-abdominal abscess.

Microbes also immediately encounter a series of host defense mechanisms that reside within the vast majority of tissues of the body. These include resident macrophages and low levels of complement (C) proteins and immunoglobulins (e.g., antibodies).¹⁰ The response in macrophages is initiated by genome-encoded pattern recognition receptors which respond to invading microbes. With exposure to a foreign organism, these receptors recognize microbial pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). Toll-like receptors (TLRs) are one well-defined example of a PAMP that plays an important role in pathogen signaling.¹¹ Resident macrophages secrete a wide array of substances in response to the above-mentioned processes, some of which appear to regulate the cellular components of the host defense response. This results in recruitment and proliferation of inflammatory cells. Macrophage cytokine synthesis is upregulated. Secretion of tumor necrosis factor-alpha (TNF-α), of interleukins (IL)-1β, 6, and 8; and of gamma interferon (IFN-γ) occurs within the tissue milieu, and, depending on the magnitude of the host defense response, the systemic circulation.¹² Concurrently, a counterregulatory response is initiated consisting of binding protein (TNF-BP), cytokine receptor antagonists (e.g., IL-1ra), and anti-inflammatory cytokines (IL-4 and IL-10).

The interaction of microbes with these first-line host defenses leads to microbial opsonization (C1q, C3bi, and IgFc), phagocytosis, and both extracellular (C5b6-9 membrane attack complex) and intracellular microbial destruction (via cellular ingestion into phagocytic vacuoles). Concurrently, the classical and alternate complement pathways are activated both via direct contact with and via IgM>IgG binding to microbes, leading to the release of a number of different complement protein fragments (C3a, C4a, C5a) that are biologically active, acting to markedly enhance vascular permeability. Bacterial cell wall components and a variety of enzymes that are expelled from leukocyte phagocytic vacuoles during microbial phagocytosis and killing act in this capacity as well.

Simultaneously, the release of substances to which polymorphonuclear leukocytes (PMNs) in the bloodstream are attracted takes place. These consist of C5a, microbial cell wall peptides containing N-formyl-methionine, and macrophage secretion of cytokines such as IL-8. This process of host defense recruitment leads to further influx of inflammatory fluid into the area of incipient infection, and is accompanied by diapedesis of large numbers of PMNs, a process that begins within several minutes and may peak within hours or days. The magnitude of the response and eventual outcome generally are related to several factors: (a) the initial number of microbes, (b) the rate of microbial proliferation in relation to containment and killing by host defenses, (c) microbial virulence, and (d) the potency of host defenses. In regard to the latter, drugs or disease states that diminish any or multiple components of host defenses are associated with higher rates and potentially more grave infections.

Definitions

Several possible outcomes can occur subsequent to microbial invasion and the interaction of microbes with resident and recruited host defenses: (a) eradication, (b) containment, often leading to the presence of purulence—the hallmark of chronic infections (e.g., a furuncle in the skin and soft tissue or abscess within the parenchyma of an organ or potential space), (c) locoregional infection (cellulitis, lymphangitis, and aggressive soft tissue infection) with or without distant spread of infection (metastatic abscess), or (d) systemic infection (bacteremia or fungemia). Obviously, the latter represents the failure of resident and recruited host defenses at the local level, and is associated with significant morbidity and mortality in the clinical setting. In addition, it is not uncommon that disease progression occurs such that serious locoregional infection is associated with concurrent systemic infection. A chronic abscess also may intermittently drain and/or be associated with bacteremia.

Infection is defined by the presence of microorganisms in host tissue or the bloodstream. At the site of infection the classic findings of rubor, calor, and dolor in areas such as the skin or subcutaneous tissue are common. Most infections in normal individuals with intact host defenses are associated with these local manifestations, plus systemic manifestations such as elevated temperature, elevated white blood cell (WBC) count, tachycardia, or tachypnea. The systemic manifestations noted previously comprise the systemic inflammatory response syndrome (SIRS). A documented or suspected infection with some of the findings of SIRS define sepsis.¹³

SIRS can be caused by a variety of disease processes, including pancreatitis, polytrauma, malignancy, transfusion reaction, as well as infection (Fig. 6-1). There are a variety of systemic manifestations of infection, with the classic factors of fever, tachycardia, and tachypnea, broadened to include a variety of other variables (Table 6-1).¹³ Sepsis (SIRS caused by infection) is mediated by the production of a cascade of proinflammatory mediators produced in response to exposure to microbial products. These products include lipopolysaccharide (endotoxin, LPS) derived from Gram-negative organisms; peptidoglycans and teichoic acids from gram-positive organisms; many different microbial cell wall components, such as mannan from yeast and fungi; and many others.

Severe sepsis is characterized as sepsis (defined previously) combined with the presence of new-onset organ failure. Severe sepsis is the most common cause of death in noncoronary critical care units and the 11^th most common cause of death overall in the United States, with a mortality rate of 10.3 cases/100,000 population in 2010.¹⁴ A number of organ dysfunction scoring systems have been described.^15,16,17 With respect to clinical criteria, a patient with sepsis and the need for ventilatory support, with oliguria unresponsive to aggressive fluid resuscitation, or with hypotension requiring vasopressors should be considered to have developed severe sepsis. Septic shock is a state of acute circulatory failure identified by the presence of persistent arterial hypotension (systolic blood pressure <90 mm Hg) despite adequate fluid resuscitation, without other identifiable causes. Septic shock is the most severe manifestation of infection, occurring in approximately 40% of patients with severe sepsis; it has an attendant mortality rate of 30% to 66%.^18,19

While classification of severity of shock has been successful in driving efforts to improve patient outcomes, staging of sepsis by other patient characteristics remains in its infancy. The impetus for development of such a scheme is related to the heterogeneity of the patient population developing sepsis, an example of which would include two patients, both in the intensive care unit (ICU), who develop criteria consistent with septic shock. While both have infection and sepsis-associated hypotension, one might expect a different outcome in a young, healthy patient who develops urosepsis than in an elderly, immunosuppressed lung transplant recipient who develops invasive fungal infection. One schema for providing such a classification is the predisposition, infection, response and organ failure (PIRO) classification.²⁰ This scheme has borrowed from the tumor-node-metastasis staging scheme developed for oncology. The PIRO staging system stratifies patients based on their predisposing conditions (P), the nature and extent of the infection (I), the nature and magnitude of the host response (R), and the degree of concomitant organ dysfunction (O). Clinical trials using this classification system have confirmed the validity of this concept.^21,22

A partial list of common pathogens that cause infections in surgical patients is provided in Table 6-2.

Bacteria

Bacteria are responsible for the majority of surgical infections. Specific species are identified using Gram’s stain and growth characteristics on specific media. The Gram’s stain is an important evaluation that allows rapid classification of bacteria by color. This color is related to the staining characteristics of the bacterial cell wall: gram-positive bacteria stain blue and Gram-negative bacteria stain red. Bacteria are classified based upon a number of additional characteristics, including morphology (cocci and bacilli), the pattern of division (e.g., single organisms, groups of organisms in pairs [diplococci], clusters [staphylococci], and chains [streptococci]), and the presence and location of spores.

Gram-positive bacteria that frequently cause infections in surgical patients include aerobic skin commensals (Staphylococcus aureus and epidermidis and Streptococcus pyogenes) and enteric organisms such as Enterococcus faecalis and faecium. Aerobic skin commensals cause a large percentage of surgical site infections (SSIs), either alone or in conjunction with other pathogens; enterococci can cause nosocomial infections (urinary tract infections [UTIs] and bacteremia) in immunocompromised or chronically ill patients, but are of relatively low virulence in healthy individuals.

There are many pathogenic Gram-negative bacterial species that are capable of causing infection in surgical patients. Most Gram-negative organisms of interest to the surgeon are bacilli belonging to the family Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Enterobacter, Citrobacter, and Acinetobacter spp. Other Gram-negative bacilli of note include Pseudomonas spp., including Pseudomonas aeruginosa and fluorescens and Xanthomonas spp.

Anaerobic organisms are unable to grow or divide poorly in air, as most do not possess the enzyme catalase, which allows for metabolism of reactive oxygen species. Anaerobes are the predominant indigenous flora in many areas of the human body, with the particular species being dependent on the site. For example, Propionibacterium acnes and other species are a major component of the skin microflora and cause the infectious manifestation of acne. As noted previously, large numbers of anaerobes contribute to the microflora of the oropharynx and colon.

Infection due to Mycobacterium tuberculosis was once one of the most common causes of death in Europe, causing one in four deaths in the seventeenth and eighteenth centuries. In the nineteenth and twentieth centuries, thoracic surgical intervention was often required for severe pulmonary disease, now an increasingly uncommon occurrence in developed countries. This organism and other related organisms (M avium-intracellulare and M leprae) are known as acid-fast bacilli. Other acid-fast bacilli include Nocardia spp. These organisms typically are slow-growing, sometimes necessitating observation in culture for weeks to months prior to final identification, although deoxyribonucleic acid (DNA)-based analysis is increasingly available to provide a means for preliminary, rapid detection.

Fungi

Fungi typically are identified by use of special stains (e.g., potassium hydroxide (KOH), India ink, methenamine silver, or Giemsa). Initial identification is assisted by observation of the form of branching and septation in stained specimens or in culture. Final identification is based on growth characteristics in special media, similar to bacteria, as well as on the capacity for growth at a different temperature (25°C vs. 37°C). Fungi of relevance to surgeons include those that cause nosocomial infections in surgical patients as part of polymicrobial infections or fungemia (e.g., Candida albicans and related species), rare causes of aggressive soft tissue infections (e.g., Mucor, Rhizopus, and Absidia spp.), and so-called opportunistic pathogens that cause infection in the immunocompromised host (e.g., Aspergillus fumigatus, niger, terreus, and other spp., Blastomyces dermatitidis, Coccidioides immitis, and Cryptococcus neoformans). Agents currently available for antifungal therapy are described in Table 6-3.

Viruses

Due to their small size and necessity for growth within cells, viruses are difficult to culture, requiring a longer time than is typically optimal for clinical decision making. Previously, viral infection was identified by indirect means (i.e., the host antibody response). Recent advances in technology have allowed for the identification of the presence of viral DNA or ribonucleic acid (RNA) using methods such as polymerase chain reaction. Similarly to many fungal infections, most clinically relevant viral infections in surgical patients occur in the immunocompromised host, particularly those receiving immunosuppression to prevent rejection of a solid organ allograft. Relevant viruses include adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and varicella-zoster virus. Surgeons must be aware of the manifestations of hepatitis B and C virus, as well as human immunodeficiency virus infections, including their capacity to be transmitted to health care workers (see General Principles section). Prophylactic and therapeutic use of antiviral agents is discussed in Chap. 11.

General Principles

Maneuvers to diminish the presence of exogenous (surgeon and operating room environment) and endogenous (patient) microbes are termed prophylaxis, and consist of the use of mechanical, chemical, and antimicrobial modalities, or a combination of these methods.

As described previously, the host resident microflora of the skin (patient and surgeon) and other barrier surfaces represent a potential source of microbes that can invade the body during trauma, thermal injury, or elective or emergent surgical intervention. For this reason, operating room personnel are versed in mild mechanical exfoliation of the skin of the hands and forearms using antibacterial preparations, and the intraoperative aseptic technique is employed. Similarly, application of an antibacterial agent to the skin of the patient at the proposed operative site takes place prior to creating an incision. Also, if necessary, hair removal should take place using a clipper rather than a razor; the latter promotes overgrowth of skin microbes in small nicks and cuts. Dedicated use of these modalities clearly has been shown to diminish the quantity of skin microflora, and although a direct correlation between praxis and reduced infection rates has not been demonstrated, comparison to infection rates prior to the use of antisepsis and sterile technique makes clear their utility and importance.

The aforementioned modalities are not capable of sterilizing the hands of the surgeon or the skin or epithelial surfaces of the patient, although the inoculum can be reduced considerably. Thus, entry through the skin, into the soft tissue, and into a body cavity or hollow viscus invariably is associated with the introduction of some degree of microbial contamination. For that reason, patients who undergo procedures that may be associated with the ingress of significant numbers of microbes (e.g., colonic resection) or in whom the consequences of any type of infection due to said process would be dire (e.g., prosthetic vascular graft infection) should receive an antimicrobial agent.

Source Control

The primary precept of surgical infectious disease therapy consists of drainage of all purulent material, débridement of all infected, devitalized tissue, and debris, and/or removal of foreign bodies at the site of infection, plus remediation of the underlying cause of infection.²³ A discrete, walled-off purulent fluid collection (i.e., an abscess) requires drainage via percutaneous drain insertion or an operative approach in which incision and drainage take place. An ongoing source of contamination (e.g., bowel perforation) or the presence of an aggressive, rapidly spreading infection (e.g., necrotizing soft tissue infection) invariably requires expedient, aggressive operative intervention, both to remove contaminated material and infected tissue (e.g., radical débridement or amputation) and to remove the initial cause of infection (e.g., bowel resection). Other treatment modalities such as antimicrobial agents, albeit critical, are of secondary importance to effective surgery with regard to treatment of surgical infections and overall outcome. Rarely, if ever, can an aggressive surgical infection be cured only by the administration of antibiotics, and never in the face of an ongoing source of contamination. Also, it has been repeatedly demonstrated that delay in operative intervention, whether due to misdiagnosis or the need for additional diagnostic studies, is associated with increased morbidity and occasional mortality.²⁴

Appropriate Use of Antimicrobial Agents

A classification of antimicrobial agents, mechanisms of action, and spectrum of activity is shown in Table 6-4. Prophylaxis consists of the administration of an antimicrobial agent or agents prior to initiation of certain specific types of surgical procedures in order to reduce the number of microbes that enter the tissue or body cavity. Agents are selected according to their activity against microbes likely to be present at the surgical site, based on knowledge of host microflora. For example, patients undergoing elective colorectal surgery should receive antimicrobial prophylaxis directed against skin flora, gram negative aerobes, and anaerobic bacteria. There are a wide variety of agents that meet these criteria with recently published guidelines.²⁵