6. | Principles of Surgery, Companion Handbook

Chapter 5 Surgical Infections

Principles of Surgery Companion Handbook

CHAPTER

5
SURGICAL INFECTIONS

General Considerations
	Principles of Therapy
	Determinants of Infection
Types of Surgical Infections
	Soft Tissue Infections
	Body Cavity Infections
Surgical Microbiology
	Bacteria
	Fungi
	Viruses
Antimicrobial Therapy
	Distribution of Antimicrobial Agents
	Use of Antibiotics in Surgery
	Drug Administration
	Immunotherapy and Biologic Therapy of Infection

GENERAL CONSIDERATIONS

Surgical infections can be defined conveniently as infections that require operative treatment or result from operative treatment. Infections that require operative treatment include (1) necrotizing soft tissue infections, (2) body cavity infections such as peritonitis, suppurative pericarditis, and empyema, (3) confined tissue, organ, or joint infections such as abscess and septic arthritis, and (4) prosthetic device–associated infections. With the possibility of patient-to-surgeon and surgeon-to-patient spread of viral infections such as from the human immunodeficiency virus (HIV) and hepatitis viruses, infections in health care workers also have become of interest to surgeons.

Infections that result from operative treatments include wound infections, postoperative abscesses, postoperative (tertiary) peritonitis, other postoperative body cavity infections, prosthetic device–related infections, and other hospital-acquired infections, among which are pneumonias, urinary tract infections, and vascular catheter–related infections. Immunocompromised patients are subject to viral and fungal infections that seldom cause infection in the normal host.

Principles of Therapy

The patient's own host defenses and antibiotic therapy are adequate to overcome most infections. Nonoperative treatments can assist recovery from some infections. Chest physiotherapy is useful in patients with pneumonia, especially those with thickened secretions. Increasing fluid intake and thus increasing urine flow is helpful in patients with urinary tract infections. Immobilization and elevation can relieve pain and reduce the swelling of an extremity afflicted with cellulitis or lymphangitis.

Operative treatment generally is required when host defenses cannot function properly or when there is continuing contamination with microorganisms: Infected fluid collections must be drained, infected necrotic tissue must be debrided, and infected foreign bodies must be removed. Infected fluid collections such as abscesses must be drained because phagocytic cells cannot function properly with the metabolic conditions usually present. Antibiotics are not very effective against bacteria in abscesses because they penetrate abscesses poorly and because antibiotics work best on actively dividing bacteria—and most bacteria in abscesses are not actively dividing. Drainage also is salutary because necrotic tissue and foreign bodies inhibit the proper functioning of host defenses.

Defects in the gastrointestinal (GI) tract provide a continuing source of bacteria that rapidly overwhelms host defenses. Operation is required to end this source by closing the defect in the GI tract or by bringing the defect to the outside as an ileostomy or colostomy.

Determinants of Infection

The development of surgical infection depends on several factors: (1) microbial pathogenicity and number, (2) host defenses, (3) the local environment, and (4) surgical technique (for postoperative infections).

Microbial Pathogenicity The ability of a microbe to cause infection is a balance between host defenses and microbial pathogenicity. Some microbes that have no ability to cause infection in the normal host can cause lethal infection in an individual with compromised host defenses.

Many bacteria (Streptococcus pneumoniae, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Salmonella typhi) and fungi (Histoplasma capsulatum, Candida albicans, Cryptococcus neoformans) have thick capsules that make them resistant to phagocytosis (see Surgical Microbiology, below). Other microbes (Mycobacterium tuberculosis, Aspergillus flavus, Toxoplasma gondii) resist intracellular killing after they have been phagocytosed when lysosomes that contain enzymes that digest microbes do not fuse with the phagosome. Other microbes successfully resist digestion by lysosomal enzymes.

Some bacteria can elaborate toxins, many of which are enzymes that injure or kill cells or promote spread within tissues. Exotoxins play an important role in the pathogenicity of Clostridium species, Staph. aureus, and Strep. pyogenes. Other bacteria (Clostridium tetani, C. botulinum) elaborate neurotoxins that alter normal neural transmission.

Endotoxins are lipopolysaccharide-protein complexes that are normal constituents of the cell wall of gram-negative bacteria. These molecules activate many biologic pathways, including the complement and coagulation systems, and cause release of cytokines and other biologic mediators from macrophages, release of hormones, and alterations in metabolism.

Host Defenses Local host defenses are important in preventing microbial penetration into the tissues. Systemic host defenses are needed to rid the tissues of microbes once penetration has occurred.

Local Host Defenses Tissues are protected from microbial invasion by a layer of epithelium. The epithelium of the skin, nasopharynx, oral cavity, esophagus, and genitourinary tract are multilayered. At other sites (the tracheobronchial tree, GI tract, and eye), a single layer of epithelium protects the underlying tissues. Each site also provides a local environment that is not conducive to microbial attachment and growth. Among these local environmental features may be lack of moisture (skin), the flushing action of tears and urine, cilia (trachea, bronchi), peristalsis, mucus, pH (GI tract), and local immunity (IgA).

Systemic Host Defenses Host defenses consist of phagocytic cells, the immune system, and other molecular cascades such as the complement system, the coagulation system, and the kinin system. Phagocytic cells that can ingest and kill microbes include polymorphonuclear leukocytes (PMNs) and tissue macrophages (monocytes in the blood). Through a complex set of interactions of microbes with complement and other activation molecules, PMNs adhere to vascular endothelium, migrate across the endothelium and move in the direction of the microbes (chemotaxis), attach to the microbes (which may involve immunoglobulins or other opsonins), and phagocytose the microbes. Finally, lysosomes containing a variety of enzymes fuse with the phagosome, and the microbe is rapidly digested. The initiation of this process and its attendant chemical, cellular, and physiologic changes result in inflammation.

Macrophages are phagocytic cells found throughout the body tissues: in liver (Küpffer cells), spleen, lymphoid tissue, lung (alveolar microphages), brain (glial cells), connective tissue (histiocytes), and pleura and peritoneum. Macrophages also can move toward microbes in response to chemotactic agents and phagocytose and kill them. In addition, macrophages are important in initiating the immune response and can elaborate cytokines, tissue necrosis factor, interferon, and other biologically active molecules. Humoral and cellular immunity are important systemic host defense mechanisms for many microbial agents. The complement system, clotting system, kinin system, leukotrienes, cytokines, and other biologically active molecules also are activated by microbial agents and have an important role in host defenses.

Host defenses are altered in malnourished individuals, trauma patients, postoperative patients, burn patients, patients with malignant neoplasms, and patients receiving drugs such as cancer chemotherapeutic agents, immunosuppressive agents to prevent transplant rejection, steroids, or other agents that have immunosuppressive effects.

Local Environmental Factors Some environmental factors inhibit systemic host defenses from being fully effective. A traumatic wound that normally would heal without infection has a greatly increased likelihood of becoming infected if the trauma has resulted in devitalization of tissue or if foreign bodies have been deposited in the wound. Phagocytic cells do not function effectively in the presence of devitalized tissue or foreign bodies. A suture can reduce the number of Staph. aureus required to produce a subcutaneous infection. Fluid collections and edema also increase the likelihood of infection because they inhibit phagocytosis.

Peripheral vascular disease and shock contribute to soft tissue infection by preventing blood and the systemic host defenses that it contains from reaching the site of microbial contamination. Vascular disease and shock, by lowering tissue oxygen tension (PO₂), inhibit the function of phagocytic cells and promote the growth of anaerobes.

Surgical Technique Surgeons can decrease the likelihood of postoperative infection by handling tissues gently; removing devitalized tissues, blood, and other substances that promote the growth of microbes; and using drains appropriately (and avoiding inappropriate use).

TYPES OF SURGICAL INFECTIONS

Soft Tissue Infections

Infection of the soft tissues—skin, subcutaneous fat, fascia, and muscle—usually can be treated by antibiotics unless an abscess has formed or tissue necrosis has developed.

CELLULITIS AND LYMPHANGITIS

Cellulitis is a spreading infection of the skin and subcutaneous tissues. There may or may not be evidence of injury to the skin. It is characterized by local pain and tenderness, edema, and erythema. The border between infected and uninvolved skin usually is indistinct. Erysipelas, which is caused by Strep. pyogenes, is characterized by intense erythema with a sharp line of demarcation between involved and uninvolved skin. Cellulitis may be accompanied by systemic manifestations such as fever, chills, malaise, and toxic reaction.

Cellulitis can be caused by numerous bacteria in addition to Strep. pyogenes, such as Staph. aureus, Strep. pneumoniae, other streptococci, Hemophilus influenzae, and aerobic and anaerobic gram-negative bacteria. Lymphangitis, inflammation of the lymphatic channels in the subcutaneous tissues, presents as visible red streaks. Bacteria may reach the lymph nodes and cause lymphadenitis.

Cellulitis and lymphangitis can be treated by antibiotics alone, but surgery may be needed to treat the source. Treatment includes immobilization and elevation to reduce pain and swelling.

SOFT TISSUE ABSCESS

Surgical treatment usually is required when soft tissue infection results in abscess or tissue necrosis. Furuncles and carbuncles (boils), breast abscesses, and perirectal abscesses require surgical incision and drainage and usually antibiotic therapy. A carbuncle is a subcutaneous abscess usually formed by a confluent infection of multiple contiguous hair follicles. A felon is a purulent collection in the distal phalanx of the fingers that causes intense pain and pressure in that compartment. Swelling may be minimal because of the fibrous bands between the skin and bone. Treatment requires incision and drainage. A lateral incision is used to avoid a painful scar on the fingertip. Breast abscess usually is caused by Staph. aureus but can be a result of gram-negative bacteria as well. It frequently occurs in nursing mothers. Treatment consists of incision and drainage and antibiotics. Perirectal abscess begins as an infection of one of the crypt glands that then extends into the perirectal space and may present subcutaneously near the anus. It is caused by aerobic and anaerobic gram-negative bacteria that are normal residents of the colon. Incision and drainage and antibiotic therapy are the appropriate initial treatment. Up to 50 percent of perirectal abscesses may result in a fistula communicating with the anal crypt and may require later treatment.

NECROTIZING SOFT TISSUE INFECTIONS

Soft tissue infections that cause necrosis are more serious because of their propensity for extensive tissue destruction and high mortality rates. Terms such as necrotizing fasciitis, streptococcal gangrene, gas gangrene, bacterial synergistic gangrene, clostridial myonecrosis, and Fournier's gangrene are used commonly. Necrotizing fasciitis rarely is limited to fascia, and myonecrosis frequently is not limited to muscle.

Most necrotizing soft tissue infections are caused by mixed aerobic and anaerobic gram-negative and gram-positive bacteria. Clostridium species, of which C. perfringens, C. novyi, and C. septicum are the most common, cause infections with rapid progression, early toxic conditions, and high mortality rates. The term gas gangrene has become synonymous with clostridial infection. However, the presence of gas in tissue simply means that anaerobic bacterial metabolism has produced insoluble gases such as hydrogen, nitrogen, and methane. Both facultative and obligate anaerobes are capable of such metabolic activity. Aerobic bacteria also can produce gas.

Diagnosis is not difficult when skin necrosis or bullae are present, but occasionally the clinical findings are subtle until extensive necrosis has occurred. The presence of cutaneous necrosis, bullae, or crepitus strongly suggests a necrotizing infection, and surgical exploration is warranted.

Surgical treatment requires debridement of all necrotic tissue. Amputation may be required for myonecrosis of the extremities. The wound must be inspected daily until the surgeon can be sure that there is no further necrosis. The goal of treatment is to remove all necrotic tissue. Initially, broad-spectrum antibiotics including penicillin should be administered. A Gram stain of the tissue and fluid should be done to look for gram-positive rods (Clostridium species) or cocci (Streptococcus species). The use of hyperbaric oxygen to treat necrotizing soft tissue infections is controversial.

TETANUS

Tetanus is caused by Clostridium tetani, a large gram-positive spore-forming bacillus. Currently, there are approximately 50 cases of tetanus reported per year. C. tetani usually is acquired by implantation of the organisms into tissues by means of breaks in the mucosal or skin barriers. Tetanus can appear after surgical wounds, injections, and in patients who have no apparent injury at all. Organisms have virtually no capacity for causing an invasive infection. Clinical tetanus is as much an intoxication as an infection.

The median incubation period for both fatal and nonfatal cases of tetanus is 7–8 days. Tetanus usually appears in generalized form but occasionally appears as localized tetanus with increased muscle tone and spasms confined to muscles near the wound and without systemic signs.

Some patients have symptoms of restlessness, headache, or a stiff neck. In other patients the first symptoms are muscle spasms with vague discomfort in the neck, lumbar region, and jaws. Spasm of the pharyngeal muscles makes swallowing difficult. Progressively, other muscle groups become involved until the spasms become generalized. Generalized convulsions are frequent, exhausting, and unpredictable. Any slight external stimulus and internal stimuli (e.g., cough, swallow, or distended bladder) may trigger generalized convulsions. These convulsions may involve the laryngeal and respiratory muscles and result in fatal acute asphyxia. Throughout these spasms the patient remains mentally alert. The pulse is elevated, and there is profuse perspiration. Fever may or may not be present. Diagnosis of tetanus is based on the clinical picture associated with no prior history of immunization. Even with adequate treatment, the mortality rate can exceed 50 percent.

Initially therapy consists of administration of tetanus immune globulin (TIG) 500–10,000 units as soon as the diagnosis is made. Nursing care must be provided constantly in an intensive care unit setting. Patients may require tracheostomy if they need a respirator for a prolonged period. Pulmonary emboli can be a problem in patients who have minimal movement. Cardiac exhaustion and circulatory disruption can occur from sympathetic overstimulation. Hyperbaric oxygen treatment is not recommended because it is ineffective.

The wound must be treated to remove as much of the C. tetani and nonviable tissue as possible. Debridement of all necrotic tissue should be done. Penicillin G should be administered.

Active immunization with tetanus toxoid is a safe and effective way of preventing tetanus (Table 5-1). One month after the diagnosis of tetanus is made, tetanus toxoid immunization should be begun. The amount of tetanus toxin released during an infection is so small that the patient does not make antibody.

TABLE 5-1 SUMMARY OF IMMUNIZATION PRACTICES ADVISORY COMMITTEE RECOMMENDATIONS FOR TETANUS PROPHYLAXIS IN ROUTINE WOUND MANAGEMENT

Body Cavity Infections

PERITONITIS AND INTRAABDOMINAL ABSCESS

Primary peritonitis is caused by a single organism and occurs most commonly in young children and in adults with ascites or with renal failure that is being treated by peritoneal dialysis. Primary peritonitis can be treated with antibiotics and other medical measures.

Secondary bacterial peritonitis usually is the result of a defect in the GI tract and requires operative intervention. The goals of surgery are to control the source of contamination, to remove bacteria and adjuvant materials from the peritoneal cavity, and to prevent postoperative abscess or recurrent peritonitis. Antibiotics effective against aerobic and anaerobic enteric bacteria have an important role in treating patients with secondary bacterial peritonitis but should not replace operative intervention. Peritonitis occurring (or persisting) after initial operation for secondary peritonitis is persistent peritonitis. Tertiary peritonitis is a peritonitis-like syndrome occurring late as a result of a disturbance in the host's immune response and is characterized by peritonitis without evidence of pathogens or peritonitis caused by fungi or low-grade pathogenic bacteria. Percutaneous or operative drainage along with antibiotic therapy is necessary for the treatment of intraabdominal abscesses.

EMPYEMA

Empyema usually is a result of pneumonia. Other causes include pulmonary infarction, septic emboli to the lung, tracheal or bronchial fistula, leaking esophageal anastomosis, hepatic abscess, subphrenic abscess, trauma, leaking bronchial closure, infected hemothorax, and paravertebral abscess.

Empyema may be encapsulated and localized or may involve the entire pleural cavity. Initially the fluid in the chest is thin, but with increasing numbers of PMNs and fibrin deposition, the fluid becomes thicker, and the visceral peritoneum and parietal peritoneum adhere to each other. The clinical manifestations of empyema initially resemble those of pneumonia, with pleuritic chest pain and fever. Chronic empyema can be manifested by dysp-nea, fatigue, anemia, debility, and clubbing of the fingers.

Treatment of empyema is aimed at evacuation of the empyema contents and expansion of the lung. Most empyemas can be treated by tube thoracostomy, especially in early empyema when the fluid is thin, and antibiotic therapy. The tube may be converted to open drainage after 2–3 weeks when the visceral and parietal pleura have become adherent so that the lung does not collapse. Open drainage should be used if there are multiple pus pockets, if the pus is very thick, or if the empyema is inadequately drained by tube thoracostomy. In some cases a decortication procedure may be necessary to reexpand the lung, or if a bronchopleural fistula is present, a thoracoplasty may be required.

OTHER CLOSED-SPACED INFECTIONS

Purulence in closed spaces usually requires drainage and tetanus toxoid immunization and antibiotic therapy. Antibiotic therapy alone may be sufficient to treat early septic arthritis. If the diagnosis is delayed, surgical treatment is required to preserve joint function and to eradicate the infection.

Antibiotic therapy alone may be sufficient to treat some early cases of pericarditis, but operative therapy is usually required once suppuration has occurred.

PROSTHETIC DEVICE–ASSOCIATED INFECTIONS

Infections in prosthetic devices, such as cardiac valves, pacemakers, vascular grafts, and artificial joints, are associated with great morbidity. Although intensive antibiotic therapy alone occasionally can cure the infection, frequently it can be eradicated only by complete removal of all foreign material and antibiotic therapy. Vascular grafts have been salvaged occasionally without graft removal by treatment with debridement, povidone-iodine–soaked dressings, and antibiotic therapy when the suture line has not been infected. Infected prosthetic joints and pacemakers have been salvaged occasionally by antibiotic irrigation of the joint or pacemaker.

HOSPITAL-ACQUIRED (NOSOCOMIAL) INFECTIONS

Each year in the United States there are an estimated 2 million hospital-acquired infections that result in 150,000 deaths. Hospital-acquired infections add an average of 1.5 days to the hospital stay of patients who develop lymphangitis, 14.8 days for patients with septicemia, and 16.6 days for patients who have infections at multiple sites. Infection rates were greatest on the surgical service, at 44.3 per 1000 discharges. On surgical services, urinary tract infections are most common, followed by wound infections, lower respiratory infections, bacteremia, and cutaneous infections. Vascular catheter–related infections are frequently classified under bacteremia or cutaneous infections.

WOUND INFECTIONS

Classification Wounds have been classified into four categories according to the theoretical number of bacteria that contaminate wounds: clean, clean-contaminated, contaminated, and dirty. Wound infection rates in large series are approximately 1.5–3.9 percent for clean wounds, 3.0–4.0 percent for clean-contaminated wounds, and approximately 8.5 percent for contaminated wounds. Dirty wounds generally are left open, but wound infection rates for dirty wounds of 28 and 40 percent have been reported. Wound infections encompass infections of the wound that occur above the fascia (superficial wound infections) and those which occur below the fascia (deep wound infections).

Definition of Surgical Wound Infection An incisional (superficial) wound infection occurs at an incision site within 30 days after operation and involves skin or subcutaneous tissue above the fascial layer and any of the following:

There is purulent drainage from the incision or a drain located above the fascial layer.
An organism is isolated from culture of fluid that has been aseptically obtained from a wound that was closed primarily.
The wound is opened deliberately by the surgeon, unless the wound is culture-negative.

Deep surgical wound infection occurs at the operative site within 30 days after operation if no prosthesis was permanently placed and within 1 year if an implant was placed, and infection involves tissues or spaces at or beneath the fascial layer and any of the following:

The wound spontaneously dehisces or is deliberately opened by the surgeon when the patient has a fever (>38°C) and/or there is localized pain or tenderness, unless the wound is culture-negative.
An abscess or other evidence of infection directly under the incision is seen on direct examination, during operation, or by histopathologic examination.
The surgeon diagnoses infection.

Bacteria can gain entrance to the wound from endogenous or exogenous sources. Most infections in clean-contaminated and contaminated wounds and also in the majority of clean wounds are caused by endogenous bacteria present on the skin or mucosal surfaces.

PROPHYLAXIS

Operating Room Environment Air-handling systems are designed to reduce the number of airborne microbes. Special laminar flow systems with high-efficiency particulate air (HEPA) filters frequently are used when prosthetic joints are implanted to reduce the likelihood of airborne contamination.

Instruments and Drapes If drapes become wet, bacteria can move from underneath the drapes to the surgical field by capillary movement. Disposable drapes with plastic liners and cloth drapes with tighter weaves are designed to minimize this type of bacterial contamination. Adhesive plastic drapes do not lower the incidence of wound infection.

Hand Washing Hand washing with soap and an antiseptic agent reduces the number of microbes on the skin. Although tradition calls for scrubbing for 10 min and using two brushes, washing for 5 min and using one brush accomplishes equal reduction in skin bacterial counts. Hexachlorophene, povidone-iodine, and chlorhexidine are the antiseptics most commonly used for hand washing.

Gloves Thirty percent of gloves have defects in them by the end of the operation. Surgeons are potentially exposed to infectious agents harbored by their patients when blood enters through these holes and gets onto their skin. Some advocate wearing two pairs of gloves to reduce the likelihood of exposure to patient's blood.

Other Barriers Caps prevent hair and skin scales (and adherent bacteria) from falling into the patient's wound, masks prevent droplets produced during speaking or coughing from entering the patient's wound, and gowns prevent desquamated skin and other particles from entering the patient's wound. There are no data that demonstrate unequivocally that wearing these barriers lowers the wound infection rate.

Preoperative Stay Patients who have longer preoperative hospitalizations are more likely to develop postoperative wound infections.

Preoperative Shower Cruse reported that the infection rate was 1.3 percent for patients who took a preoperative shower with soap containing hexachlorophene, 2.1 percent for those who took a shower with ordinary soap, and 2.3 percent for those who did not shower. However, another study of 5536 patients found no reduction in wound infection rates in patients who had a preoperative shower with 4% chlorhexidine detergent.

Remote Infections Remote infections can triple the rate of wound infection. Elective operations generally should be delayed until the infection has been eliminated. Elective operations should be delayed until the dermatitis is treated, especially if the skin incision is near or through such regions.

Hair Removal Nicks and cuts caused by shaving are sites where bacteria can proliferate.When shaving is done the night before operation, there is ample time for bacterial proliferation in any nicks or cuts, and the wound infection rate is higher than when shaving is done in the operating room immediately before operation. When hair is removed by clipping with an electric clipper, the wound infection rate can be reduced further.

Skin Preparation Painting the operation site with an alcohol solution of povidone-iodine, which can be accomplished in less than 1 min, is as effective as a 5-min scrub with povidone-iodine followed by painting with povidone-iodine solution.

Reduction of Colonic Bacteria Colon procedures potentially expose the wound to numerous bacteria. Colonic bacteria can be greatly reduced by cleansing the colon of feces. A variety of enemas or cathartics such as magnesium citrate solution or electrolyte solutions in polyethylene glycol can be used. These agents should be used before all elective colon surgery. Oral antibiotics can further reduce the number of colonic bacteria. A combination of neomycin and erythromycin base is used most commonly, but other antibiotics also are effective.

Improving Host Defenses Any malnutrition should be corrected to restore the patient's resistance to infection toward normal. Weight reduction lowers the risk of wound infection and pulmonary complications. Uremia and diabetes should be corrected as far as possible. Patients who smoke should cease smoking before the operation.

Surgical Technique The incision should be made in such a way to injure as little tissue as possible and to prevent the accumulation of agents that facilitate bacterial growth or inhibit host defense such as devitalized tissue, foreign bodies, blood, and serum. Blood in the incision provides a good environment for bacterial growth.

There is no solid evidence that local antibiotics lessen the likelihood of infection. There are no definitive studies that provide data on whether subcutaneous sutures affect the risk of wound infection. If the surgeon is concerned about the possibility of a wound seroma such as might occur in the subcutaneous tissue of an extremely obese patient, a closed-suction drain should be used. Latex rubber (Penrose) drains should not be used because bacteria can enter the wound through the drain tract. All devitalized tissue and foreign bodies should be removed from traumatic wounds. Irrigation with saline solution can facilitate the removal of small particles. When complete removal of devitalized tissue and foreign bodies cannot be ensured, or when the wound is heavily contaminated with bacteria, it can be left open and closed secondarily.

Prophylactic Antibiotics Prophylactic antibiotic therapy should be directed against the bacteria likely to contaminate the wound. For clean operations for which antibiotic prophylaxis is appropriate, Staph. aureus, Staph. epidermidis, and gram-negative enteric bacteria are the most likely bacteria to cause wound infections. Gram-negative enteric bacteria are the most likely causes of wound infection after gastroduodenal and biliary tract procedures, colorectal surgery, appendectomy, and gynecologic surgery.

The antibiotics usually should be given intravenously 30–60 min before operation so that adequate blood and tissue levels are present at the time that the skin incision is made. The antibiotic dose should be repeated if the operation lasts longer than 4 h or twice the half-life of the antibiotic or if blood loss has been great. With many operations now being performed on patients who are not in a hospital before surgery, oral antibiotic prophylaxis also may be suitable. Prophylactic antibiotics should not be continued beyond the day of operation. The most commonly violated principle is giving the antibiotic longer than is actually needed, which increases costs and the likelihood of antibiotic resistance among hospital strains of bacteria.

Cephalosporins are the most commonly used antibiotics for prophylaxis because of their broad antibacterial spectrum, which provides activity against gram-positive pyogenic cocci and gram-negative enteric bacteria, and because of their low toxicity. Cefazolin, a first-generation cephalosporin, is an effective antibiotic prophylaxis for indicated clean gastroduodenal, biliary tract, and head and neck operations and traumatic wounds. Vancomycin can be substituted in patients who are allergic to penicillins or cephalosporins. For colorectal procedures, oral neomycin plus erythromycin base and/or cefoxitin or cefotetan provides effective coverage. First- or second-generation cephalosporins provide effective prophylaxis for gynecologic surgery and cesarean section.

Indications Prophylactic antibiotics are indicated when bacterial contamination of the wound is likely or for patients having clean operations in which a prosthetic device is placed. Studies indicate that prophylactic antibiotics can lower the incidence of all infectious complications in clean surgery (hernia and breast surgery), but the incidence of wound infection is not reduced. The bacteria in the stomach are increased in patients who have gastric outlet obstruction, decreased gastric acidity (achlorhydria, antacid or H₂-receptor blocker therapy), or gastric cancer, and prophylactic antibiotics are indicated for these patients. Jaundice, bile duct obstruction, stones in the common bile duct, reoperative biliary tract operation, acute cholecystitis, and age greater than 70 years also are indications for prophylaxis in biliary tract operations.

OTHER HOSPITAL-ACQUIRED INFECTIONS

Urinary Tract Infection Urinary tract infection (UTI) accounts for 40 percent of hospital-acquired infections. Two-thirds of patients with hospital-acquired UTI have had an operation on the lower urinary tract, instrumentation of the bladder, or catheterization. Catheter-associated UTIs cause bacteremia in 2–4 percent of patients and are associated with a case-fatality rate three times as high as that of nonbacteremic patients. Bacteriuria occurs in 1–5 percent of patients after a single short-term catheterization. The risk of infection is higher in pregnant patients, in elderly or debilitated patients, and in patients with urologic abnormalities. The risk of bacteriuria in patients with long-term indwelling catheters is approximately 5–10 percent for each day the catheter is in place. Urinary catheters should be placed only when necessary and should be removed as soon as possible. If prolonged urinary tract catheterization is required, suprapubic or condom catheters can be used to reduce the risk of infection.

Lower Respiratory Tract Infection Anesthesia, operations on the head and neck, and postoperative endotracheal intubation interfere with the normal protective cough reflex and may permit aspiration of contaminated material. Pain associated with thoracic or upper abdominal operations and trauma interferes with coughing and deep breathing and promotes the collection of material in the tracheobronchial tree and atelectasis, which in turn predispose to infection. Pulmonary edema or adult respiratory distress syndrome resulting from cardiac failure, trauma, sepsis, renal failure, or inhalation of hot gases by burn patients also predisposes to pulmonary infection.

Hospitalized patients may have gram-negative bacteria as part of their oral flora. These bacteria may be aspirated into the lungs during the postoperative period. Tracheostomies and respiratory care devices also predispose to the entry of bacteria into the lower respiratory tract. Lower respiratory tract infections are common in intubated patients in intensive care units, occurring in as many as 20–25 percent of patients.

The most common causative organisms of lower respiratory tract infection in hospitalized patients are Staph. aureus, Pseudomonas aeruginosa, Klebsiella species, Escherichia coli, and Enterobacter species. These bacteria, especially in the intensive care unit setting, may be resistant to commonly used antibiotics. Specially protected specimen swabs can be introduced into the lungs through a flexible bronchoscope, with sensitivity rates for diagnosing the pneumonia between 70 and 90 percent. Bronchoalveolar lavage has increased the accuracy of bronchoscopic diagnosis.

Vascular Catheter–Related Infection Central venous catheters have a higher infection rate than peripheral venous catheters, and polyethylene catheters have a higher infection rate than Silastic catheters. The most common source of catheter sepsis is believed to be microorganisms at the skin exit site that follow the catheter into the vein rather than microorganisms originating from a distant site that colonize the catheter via the bloodstream. Staph. aureus and Staph. epidermidis usually originate from the skin and cause most catheter-related infections. Most yeast vascular-access infections result from hematogenous dissemination from another site. Gram-negative enteric bacteria also may infect catheters hematogenously.

The duration of catheterization, the number of catheter manipulations, inexperience of the inserter, violations of aseptic technique, and use of multilumen catheters are all associated with an increased risk of infection. There are no data proving that practices such as changing catheters at intervals, changing infusion tubing every 24–48 h, and using in-line filters reduce the risk of infection.

Any evidence of phlebitis or cellulitis or any suspicion of septic complications caused by intravenous cannulas should lead to prompt removal of the cannulas. Because many central venous catheters are used in compromised hosts who are prone to fever, these catheters generally should not be removed because of fever alone until other potential sources of fever have been eliminated. When an infected catheter is removed and another central venous catheter is immediately inserted at the same site, infection of the new catheter usually does not occur.

Catheter infections caused by Staph. epidermidis occasionally can be treated with antibiotics alone or by removal of the catheter. If antibiotics are used, a short course (3–7 days) is recommended. Vascular-access infections caused by Staph. aureus always require antibiotic therapy for a 2–3-week course. Vascular catheter infection caused by yeasts should always be treated by catheter removal and administration of an antifungal agent if cultures remain positive after removal or if there is infection elsewhere.

SURGICAL MICROBIOLOGY

Bacteria

Bacteria can be classified according to staining characteristics with Gram stain (positive or negative), shape (cocci, rods, spirals), and ability to grow without oxygen (aerobic, facultative, anaerobic) or according to a combination of these characteristics. Gram-positive cocci, gram-negative aerobic and facultative rods, and anaerobic bacteria are three groups into which most bacteria-causing surgical infections can be placed.

GRAM-POSITIVE COCCI

Staphylococcus and Streptococcus species are the gram-positive cocci that cause primary surgical infections and postoperative infections. The genus Staphylococcus is composed of facultatively anaerobic gram-positive cocci that are found on moist areas of the body, the anterior nares, and mucous membranes. In addition, these bacteria can be found on the body surfaces of many species of mammals and birds, in the air and dust of occupied buildings, and in milk, food, and sewage.

Staph. aureus is the most common pathogen isolated from wound infections. An enterotoxin is responsible for food poisoning. Epidermolytic toxin can cause a variety of skin lesions; the most characteristic are the diffuse exfoliative bullae seen in children with the scalded-skin syndrome. Another exotoxin, TSS toxin-1, is responsible for toxic shock syndrome. Other extracellular products make Staph. aureus resistant to H₂O₂-mediated intracellular killing (catalase) and cause cell death (leukocidin, alpha toxin, beta toxin).

Staph. epidermidis, a member of the flora of the skin and mucous membranes, causes infection in the presence of foreign bodies such as plastic catheters, ventricular shunts, and prosthetic joints and heart valves. Surgically important members of the genus Streptococcus include Strep. pyogenes, Strep. pneumoniae, and the viridans group, which includes Strep. mutans, Strep. mitior, Strep. salivarius, Strep. sanguis, and Strep. milleri.

Group A streptococci have cell surface components and extracellular products that inhibit host defenses or promote spread of the bacterium. Streptococci can cause postoperative infections, including cellulitis, wound infection, endocarditis, UTI, and bacteremia. These bacteria also can cause primary necrotizing soft tissue infections and abscesses. Strep. pyogenes is an uncommon cause of necrotizing soft tissue infections.

Enterococcus faecalis, E. faecium, and E. durans formerly were classified as members of the genus Streptococcus, but a separate genus is now recognized. They are part of the normal flora of the GI tract and vagina. They are found commonly in patients with peritoneal and pelvic infections as part of the mixed flora typical of these infections. Enterococcal bacteremia has a poor prognosis when associated with intraabdominal or pelvic infection and is found most often in patients who have been hospitalized for a long time.

AEROBIC AND FACULTATIVELY ANAEROBIC GRAM-NEGATIVE BACILLI

There are numerous gram-negative rods that can cause human disease, but relatively few are of surgical significance. Their cell walls have common chemical constituents, most prominent of which is lipopolysaccharide or endotoxin, which is responsible for most of the biologic effects of these bacteria. Most are members of the family Enterobacteriaceae that are inhabitants of the GI tract. The genera Escherichia, Klebsiella, Proteus, Enterobacter, Serratia, and Providencia frequently can be cultured from patients with intraabdominal and pelvic peritonitis and abscess, postoperative wound infection, pneumonia, and UTI.

The family Pseudomonadaceae is composed of obligate aerobes that lack the ability to ferment sugars, unlike members of the Enterobacteriaceae. Pseudomonas aeruginosa is the species in this family responsible for most surgical infections. They cause infections similar to those of gram-negative enteric bacteria in association with GI disease, pneumonia, UTI, and burns. They are found frequently in immunologically compromised patients, especially if they have been hospitalized for some time. They cause necrotizing infections, especially pneumonia and vasculitis.

ANAEROBIC BACTERIA

Anaerobic bacteria require reduced oxygen tension for growth. They are found predominantly in the mouth, vagina, and GI tract, where they greatly outnumber the aerobic bacteria. Anaerobic bacteria, which are pathogenic, can tolerate an initial exposure of up to 3% oxygen. Vascular disease, cold, shock, edema, trauma, devitalized tissue, operation, foreign bodies, and malignant disease can lower the oxidation-reduction potential and predispose to infection with these organisms.

In most infections with anaerobic bacteria, facultative or aerobic bacteria are also present. Aerobic or facultative bacteria make conditions favorable for anaerobic bacteria by lowering the oxidation-reduction potential. The aerobic bacteria also may supply a growth factor necessary for another organism or may interfere with local or systemic host resistance.

Anaerobes such as the Bacteroides fragilis group have an endotoxin, but it differs chemically from the endotoxin of the enteric facultative or aerobic gram-negative bacilli, and it exhibits poor biologic activity. The cell wall of anaerobic bacteria is important in abscess formation.

The genus Clostridium is the most virulent of all anaerobes. Clostridium, which can be found in soil and stool, can cause necrotizing soft tissue infection. The exotoxins produced by these bacteria are believed to be responsible for most of the local and systemic manifestations. C. perfringens, C. septicum, and C. novyi, which can cause necrotizing infections, produce toxins that can destroy cell membranes and lyse red blood cells, collagenase, hyaluronidase, and other enzyme toxins that enhance the spread of the infection through the tissues.

C. perfringens and C. difficile both produce an enterotoxin. C. difficile causes pseudomembranous colitis and occurs in patients treated with antibiotics. It produces a cytotoxin that is cytopathic for almost all tissue culture cell lines. C. tetani and C. botulinum produce neurotoxins that cause muscle spasms and paralysis, respectively.

In the colon the ratio of anaerobic bacteria to aerobic bacteria is between 300:1 and 1000:1. The most common pathogens in the colon are members of the genera Bacteroides, Fusobacterium, and Peptostreptococcus. Of these, Bacteroides is the most commonly cultured genus in patients with intraabdominal infections. The B. fragilis group, composed of B. fragilis, B. thetaiotaomicron, B. distasonis, B. ovatus, and B. vulgatus, accounts for most infections with this genus. Colonic anaerobes almost never cause infections by themselves but only as part of a mixed flora, often with facultative enteric gram-negative bacilli.

Fungi

Fungi can be grouped as primary pathogens, which can cause disease in individuals with intact host defenses, and opportunists, which cause disease in patients with compromised host defenses. Among the primary pathogens are Histoplasma, Coccidioides, and Blastomyces. Candida, Cryptococcus, Aspergillus, and the phycomycetes (Mucor, Absidia, and Rhizopus) cause most of the opportunistic infections.

In surgical patients, opportunists cause most infections. Candida albicans and other Candida species are by far the most common. They cause infections in patients being treated with broad-spectrum antibiotics and in those receiving steroids and other immunosuppressive agents, in malnourished patients, in patients with malignant neoplasms, and in other compromised hosts. In these patients they can cause vascular catheter–related infections, bacteremia, intraabdominal infections, pneumonia, and UTIs. These infections can be treated by stopping antibiotic administration, correcting host defenses, and therapy with amphotericin B or one of the azole antifungal agents.

Viruses

Members of the herpesvirus family, especially cytomegalovirus (CMV), herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus, can cause infections in immunosuppressed patients such as organ transplant recipients. CMV causes most viral infections in organ transplant recipients. In these patients, CMV can cause ulcerative lesions of the GI tract leading to bleeding or perforation for which operations might be required. Epstein-Barr virus is implicated as the cause of a polyclonal B-cell lymphoma in transplant recipients. Hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) are of importance to surgeons because of the possibility that they can become infected from patient exposure and that patients can potentially be infected by physicians who harbor these viruses. Hepatitis B prophylaxis is available should a health care worker sustain a percutaneous or permucosal exposure (Table 5-2).

TABLE 5-2 RECOMMENDATIONS FOR HEPATITIS B PROPHYLAXIS AFTER PERCUTANEOUS OR PERMUCOSAL EXPOSURE

HUMAN IMMUNODEFICIENCY VIRUS

CD4+ cells infected with the retrovirus HIV are not able to carry out their normal immune functions, which leads to opportunist infections and the development of Kaposi's sarcoma. The development of opportunist infections and tumors (Kaposi's sarcoma and lymphomas) is accompanied by a decrease in the number of T cells to less than 200/mm³. The most recent definition of AIDS includes all patients infected with HIV who have a CD4+ count of less than 200 cells/mm³.

Epidemiology The Centers for Disease Prevention and Control (CDC) estimates that for every person with AIDS there are approximately eight persons with HIV infection who have not yet developed clinical AIDS. There are approximately 5 million people infected with HIV in the United States. Approximately 30.6 million people are infected with HIV worldwide.

HIV has been isolated from blood, semen, saliva, tears, vaginal secretions, alveolar fluid, cerebrospinal fluid, breast milk, synovial fluid, and amniotic fluid. Only blood and blood products, semen, vaginal secretions, and breast milk have been linked to transmission. The groups at highest risk for HIV infection are (1) homosexual and bisexual men, (2) intravenous drug abusers, (3) persons with hemophilia and other coagulation disorders, (4) heterosexual contacts of the individuals in the three previous categories, and (5) children born to HIV-positive mothers. Recipients of transfusions of blood and blood products from HIV-positive donors have approximately a 95 percent chance of developing HIV infection. The CDC has estimated that the number of cases of transfusion-acquired AIDS could eventually reach 12,000. Since testing blood donors for evidence of HIV became mandatory in 1985, transfusion-acquired HIV infection has been virtually eliminated. The current risk of transmission of HIV by screened blood in the United States is estimated to be between 1 in 450,000 and 1 in 660,000.

Serologic Events Patients infected with HIV develop viremia accompanied by a generalized lymphadenopathy, fever, and malaise. Approximately 6–12 weeks after infection, antibody to HIV develops. During this time, the viral titer in blood decreases markedly from 10⁴/mL to 10–100/mL. A low virus titer persists until the patient develops AIDS approximately 7–9 years after infection. When AIDS develops, the virus titer rapidly increases to a level of 10⁴/mL. Serologic testing examines antibody to HIV, and seroconversion usually occurs within 12 weeks of infection but has been known to take as long as 6 months. During this period (the “window”), it is possible for patients to have circulating virus and to be potentially infectious to those around them and yet test negative for HIV.

Surgery in HIV-Infected Patients Patients with HIV infection and AIDS generally do not require any extra preoperative preparation. Malnutrition associated with HIV infection may require correction if time permits. Perioperative antimicrobial therapy is given for the same indications as for patients without HIV infection. These patients generally do not have difficulty with wound healing and do not have a higher rate of wound infections or other postoperative hospital-acquired infections. Drains and open wounds require precaution to avoid contamination with HIV-infected blood and other body fluids.

HIV and AIDS in Health Care Workers As of June 30, 1997, 166 health care workers (HCWs) had developed HIV infection as a result of occupational exposure, most as a result of exposure to blood from HIV-infected patients. Most of the infected HCWs are nurses or technicians, and 6 are surgeons.

Risk of HIV Seroconversion in Health Care Workers Of 1948 HCWs in 12 reports who sustained a total of 1051 mucous membrane exposures to blood or blood-containing body fluids from HIV-infected patients, 6 (0.29 percent per exposure) seroconverted. Risk of HIV infection is associated with deep injury, visible blood on the device, a procedure involving a needle placed directly in a vein or artery, terminal illness in the source patient, and no postexposure use of zidovudine (AZT). Most exposures are to the skin, and their numbers can be minimized by wearing two pairs of gloves and face shields.

Prevention of Blood-Borne Infections in Health Care Workers The CDC issued guidelines designed to minimize the risk of transmission of HIV in the health care setting (Table 5-3). Although universal precautions were issued to reduce the transmission of HIV in health care settings, they also are appropriate for reducing the transmission of other blood-borne viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), and the recently described hepatitis G virus (HGV).

TABLE 5-3 GUIDELINES TO PREVENT TRANSMISSION OF HIV

Compliance in a large inner-city hospital emergency room was found to be only 18 percent, and it fell to 5 percent if the patient was bleeding from an external injury. The rates of noncompliance with universal precautions are reported to be 74 percent in the surgical intensive care unit and 34 percent on the surgical wards.

Testing Patients for Blood-Borne Pathogens The CDC does not recommend routine HIV testing of all patients. HIV testing of patients is recommended for management of HCWs who sustain parenteral or mucous membrane exposure to blood or other body fluids from a patient, for patient diagnosis and management, and for counseling associated with efforts to prevent and control HIV transmission in the community.

Management of HCWs Exposed to Patients' Blood and Other Body Fluids The Department of Labor and the CDC have published detailed employer responsibilities in protecting workers from acquisition of blood-borne diseases in the workplace. Now that a serologic test is available for HCV, the patient also should be tested for that virus (and probably also for HGV when testing becomes available).

HIV Postexposure Management If an HCW is exposed percutaneously or by a splash to the eye or mucous membrane from a patient who has HIV infection or AIDS or who refuses to be tested, the worker should be counseled regarding the risk of infection and be evaluated clinically and serologically for evidence of HIV infection as soon as possible after the exposure. The worker should be advised to report and seek medical evaluation for any acute febrile illness that occurs within 12 weeks after exposure. After the initial test at the time of exposure, seronegative workers should be retested 6 weeks, 12 weeks, and 6 months after exposure to determine whether transmission has occurred. During this period, the worker should refrain from blood or semen donation and should use appropriate protection during sexual intercourse. If the source individual is found to be seronegative, baseline testing of the exposed worker with follow-up 12 weeks later may be performed if desired or recommended by the health care provider.

AZT is used to treat patients with HIV infection and has been proposed as chemoprophylaxis to prevent occupational infection in HCWs. Postexposure AZT use by HCWs is associated with a lower risk of HIV transmission. The CDC now recommends that HCWs exposed to blood from HIV-infected individuals be treated with AZT and lamivudine (3TC). If the exposure is high risk (a large volume of blood containing a high titer of HIV), the protease inhibitor indinavir also should be given. Prophylaxis should be given within 1–2 h of exposure. If the HIV status of the source patient is unknown, the use of postexposure prophylaxis should be decided on a case-by-case basis. A dilemma arises when the source individual refuses to be tested; some states permit testing blood specimens obtained for another purpose if an HCW has been exposed to a patient's blood or other body fluid and the patient refuses testing. AZT prophylaxis protocols generally advise administering 200 mg AZT every 4 h for 28–42 days. Some protocols skip the 4:00 A.M. dose.

Transmission of Blood-Borne Pathogens from HCWs to Patients HIV, HBV, and HCV can be transmitted potentially to a patient during invasive procedures when a surgeon sustains a percutaneous injury with a needle or sharp instrument that then recontacts the patient. Only HBV and HCV have been demonstrated to be transmitted from physicians to patients. One dentist has transmitted HIV to six patients; the mechanism of transmission is unclear, however. More than 9000 patients cared for by more than 75 HCWs with AIDS have been followed, and no cases of transmission by HCW to patient have been reported.

Management of the HIV-, HBV-, or HCV-Infected HCW The report of a dentist's having passed HIV to his patients sparked considerable discussion in the scientific and popular press about the HIV-positive HCW, especially surgeons and dentists, since they are most likely to participate in invasive procedures. The CDC first issued guidelines for the management of HIV-infected personnel in 1985. It subsequently issued guidelines for management of HIV-infected HCWs who participate in invasive procedures. The CDC recommended that HCWs who are otherwise fit for duty and who do not participate in invasive procedures be allowed to perform their regular duties. The CDC recommended that HIV-infected personnel who do participate in invasive procedures be evaluated on a case-by-case basis.

ANTIMICROBIAL THERAPY

Antimicrobial therapy is only an adjunct in treating surgical infection; operative treatment (or percutaneous radiologically guided drainage of infected material) is more important. The goal of antimicrobial therapy is to prevent or treat infection by reducing or eliminating organisms until the host's own defenses can get rid of the last pathogens.

Efficacy is the most important consideration in choosing an antimicrobial agent. Effective antimicrobial agents must be active against the pathogens causing the infection and must be able to reach the site of infection in adequate concentrations. All antibiotics have potential toxicity. Toxic effects may be idiosyncratic, such as allergy or the rare instances of bone marrow aplasia caused by chloramphenicol. They also can cause damage to tissues and organs, such as in the renal toxicity or ototoxicity seen with the aminoglycosides or amphotericin B. Antimicrobial agents also exert selective pressures on the microbial ecology of the hospital that lead to resistant microbes, a problem that is especially important in intensive care units. Cost is the final consideration in the selection of antimicrobial agents. Determining the costs of antimicrobial therapy includes more than just the cost of the drug. Drug administration charges, nursing time, intravenous fluid and lines, and monitoring costs also must be considered. Additionally, any increased hospital time that occurs when an inexpensive agent that is less effective or that causes more toxicity is used ultimately makes that agent a more expensive antimicrobial.

Distribution of Antimicrobial Agents

Successful treatment of localized infections with systemic antimicrobial agents requires that an adequate concentration of drug be delivered to the site of infection. Ideally, the tissue concentration of antibiotics should exceed the minimum inhibitory concentration. Tissue penetration depends in part on protein binding of antibiotics. Only the unbound form of antibiotics will pass through the capillary wall or act to inhibit bacterial growth. Therapeutic outcome, on the other hand, does not appear to be correlated with protein affinity, presumably because protein binding is easily reversible. Lipid solubility of antibiotics is also an important factor in tissue penetration. It determines the ability of antibiotics to pass through membranes by non-ionic diffusion or into wounds, bone, cerebrospinal fluid, the eye, endolymph of the ear, vegetations of bacterial endocarditis, and abscesses.

Blood Rapidity of excretion and protein binding are two main determinants of blood concentration of antimicrobial agents. Protein binding affects the rapidity of excretion. Antibiotics that are highly protein bound are not excreted as rapidly as those with a low binding affinity and thus have longer half-lives. Therefore, highly protein-bound antibiotics generally do not have to be given as frequently as those with low protein binding. The efficacy of penicillins, cephalosporins, and other antibiotics that affect bacterial cell wall synthesis depends on the amount of time during which serum levels are above the minimum inhibitory concentrations rather than their peak serum concentration. The efficacy of aminoglycosides, on the other hand, is related to achieving peak serum concentrations that are four to eight times the minimum inhibitory concentration. Monitoring of serum aminoglycoside concentrations usually is necessary to ensure that these concentrations have been achieved. Some antimicrobial agents such as nitrofurantoin and norfloxacin are excreted so rapidly in the urine that they never achieve blood (or tissue) levels sufficient to reach effective antibacterial concentrations. They do, however, reach high urinary concentrations and are effective agents for treating UTIs.

Urine Most commonly used antibiotics (sulfonamides, penicillins, cephalosporins, aminoglycosides, tetracyclines, quinolones, and azoles) are excreted principally in the urine and achieve high urinary concentrations—up to 50–200 times their serum concentrations. Notable exceptions are erythromycin and chloramphenicol. Because concentrating ability is severely compromised in patients with renal disease, infections of the urinary tract are more difficult to treat in these patients. The pH of urine can be changed to facilitate antibiotic activity. For instance, aminoglycosides are more active in an alkaline medium, whereas other urinary antibacterial agents (tetracyclines, nitrofurantoin, methenamine mandelate) are more active in an acidic environment. The antimicrobials most commonly used to treat UTIs have antimicrobial activity across a broad pH range.

Bile Besides urine, only bile regularly has antibiotic concentrations higher than serum levels. The biliary concentrations of many of the penicillins (especially nafcillin, piperacillin, mezlocillin, and azlocillin), cephalosporins (especially cefazolin, cefamandole, ceforanide, cefoxitin, cefoperazone, and cefadroxil), tetracyclines, and clindamycin frequently are several times their serum concentrations. Nafcillin and rifampin achieve biliary concentrations 20–100 times those of serum. Aminoglycoside antibiotics enter bile less well, especially in the presence of liver disease, and their biliary concentrations usually are lower than serum levels.

Interstitial Fluid and Tissue High, prolonged serum concentration and low protein binding favor diffusion of antibiotics from serum into extravascular tissue. Absolute tissue levels may not accurately reflect the therapeutic potential of the antibiotic, however, because the agent may be tightly bound to tissue and thus be unavailable for binding to bacteria.

Abscesses The generalization that no antibiotics penetrate abscesses is not true. While the penicillins, cephalosporins, and some other antibiotics penetrate mature abscesses poorly, others such as metronidazole, chloramphenicol, and clindamycin can achieve inhibitory concentrations in abscesses.

A separate problem is whether, after penetration, an antibiotic can retain its antimicrobial efficacy under the conditions that exist in an abscess. The acidic pH, the low oxidation-reduction potential, and the large numbers of microbial and tissue products that can bind antibiotics all serve to reduce antimicrobial efficacy. Multiple types of bacteria within an abscess make it more likely that one type will inactivate an agent effective against it or another bacterium. The lack of efficacy of penicillins and cephalosporins in treating most abscesses may be a result of the high concentrations of beta-lactamases that accumulate there. Metronidazole and clindamycin can enter abscesses and retain antibacterial activity, but they are not effective against the aerobic gram-negative bacteria that usually are present together with the anaerobic bacteria against which they are effective.

An additional reason that antibiotics alone are seldom effective in treating abscesses is that antibiotics are most effective against actively metabolizing, rapidly dividing bacteria. Conditions in abscesses usually are unfavorable for bacterial growth, so the antibiotic is not able to enter and be active against the bacteria. For all these reasons antibiotics alone should not be relied on for the treatment of most abscesses. Drainage is the mainstay of treating abscess.

Use of Antibiotics in Surgery

Prophylactic Antibiotics Antibiotics frequently are administered prophylactically to patients undergoing operation to prevent wound infection when the likelihood of infection is high (e.g., when the tissues have been exposed to bacteria such as occurs during colon surgery) or when the consequences of infection are great even though the risk of infection is low (e.g., when a prosthetic device is implanted). Antibiotic prophylaxis should be administered to patients with previously placed prosthetic devices such as cardiac valves or artificial joints who are having any operation or dental procedure.

Therapeutic Use of Antibiotics Many infections can be treated successfully with oral antibiotics on an outpatient basis. Severe surgical infections should be treated with intravenous antibiotics. Initial antibiotic therapy usually is empiric, because it should not be postponed until microbiotic studies are complete. Antibiotic therapy generally should be initiated before cultures are obtained in patients with peritonitis, abscesses, and necrotizing soft tissue infections.

Empiric Therapy Rational empiric antibiotic therapy requires familiarity with the microbes most likely to cause infection at the involved site and antibiotic susceptibility patterns in the hospital or intensive care unit. Intraabdominal surgical infections are nearly always caused by mixed gram-negative and gram-positive aerobic and anaerobic bacteria.

Most necrotizing soft tissue infections, especially those originating after an intraabdominal operation or occurring below the waist, also are a result of a mixed bacterial flora, and broad-spectrum empiric therapy should be initiated. Because clostridia or streptococci also can cause these infections, penicillin G generally should be included. Once Gram stain and culture results are available, antibiotic therapy can be modified.

Prosthetic device infections usually progress much more slowly than intraabdominal or necrotizing soft tissue infections. Gram-positive cocci, especially Staph. aureus and Staph. epidermidis, play a prominent role in these infections, but they also can be caused by gram-negative bacteria.

Numerous single and combination antimicrobials are available for initial and empiric therapy. The Surgical Infection Society (SIS) recommends against using drugs such as cefazolin and other first-generation cephalosporins, penicillin, cloxacillin and other antistaphylococcal penicillins, ampicillin, erythromycin, and vancomycin because these drugs do not provide adequate coverage for both aerobic and anaerobic organisms.

Metronidazole and clindamycin should not be used as single agents for mixed infection because they lack activity against aerobic enteric organisms. Other antibiotics, such as aminoglycosides, aztreonam, cefuroxime, cefonicid, cefamandole, ceforanide, cefotetan, cefotaxime, ceftizoxime, cefoperazone, ceftriaxone, ceftazidime, and polymyxin, should not be used alone because of the inadequate coverage of anaerobic gram-negative bacilli. Because of inadequate clinical data documenting efficacy and concerns about resistance, the SIS also recommends against using as single agents for empiric therapy antibiotics such as piperacillin, mezlocillin, azlocillin, ticarcillin, and carbenicillin despite their relative safety and broad in vitro antibacterial activity. Chloramphenicol has an appropriate in vitro spectrum of activity but is not acceptable because it can produce serious side effects.

Acceptable agents for community-acquired intraabdominal infections include cefoxitin, cefotetan, cefmetazole, and ticarcillin/ clavulanic acid. These antibiotics should not be used for patients whose abdominal infection develops in the hospital after previous antibiotic therapy. For these infections and serious intraabdominal infections, antibiotics such as imipenem-cilastatin (Primaxin) should be used. Combination therapy such as metronidazole or clindamycin plus an aminoglycoside or an antianaerobic antibacterial agent plus a third-generation cephalosporin or clindamycin plus a monobactam is acceptable. The combination of an antianaerobic antibiotic plus an aminoglycoside plus penicillin or ampicillin is recommended only if enterococcal infection is suspected on the basis of a Gram stain or thought to be clinically relevant (e.g., associated with Enterococcus bacteremia). Community-acquired intraabdominal infections are seldom associated with serious Enterococcus infection.

Definitive Therapy Antimicrobial therapy may have to be altered when the results of Gram stain, culture, and sensitivity data are available. Sensitivity data may determine that one of the antibiotics currently being used is not active against one of the bacteria isolated. In addition, change to a less toxic or less costly antimicrobial agent may be possible once laboratory results are available.

Infections originating in the intensive care unit are frequently caused by antibiotic-resistant bacteria. This especially is true for hospital-acquired Staph. aureus, which often is resistant to methicillin. For hospital-acquired staphylococcal infections, vancomycin generally should be initiated if methicillin-resistant Staph. aureus is a problem in the hospital until definitive sensitivity data are available. If the Staph. aureus is sensitive to penicillin G or methicillin, these agents should be used because they are more effective and less costly than vancomycin. Two drugs generally are used to treat P. aeruginosa infections, an antipseudomonal beta-lactam drug such as mezlocillin or ceftazidime in combination with an aminoglycoside, in an attempt to prevent development of resistance and to take advantage of possible synergism.

Drug Administration

Route For seriously ill surgical patients, the antimicrobial agent should be administered intravenously to ensure adequate serum levels. Absorption by other routes is inconsistent in seriously ill patients whose GI tract is not functioning properly and who have problems maintaining blood pressure. If patients need prolonged antimicrobial therapy, other routes can be used once they have begun to recover, or long-term IV antimicrobial therapy can be given on an outpatient basis.

Recommendations provided by the manufacturer should be used as guidelines for appropriate doses of antimicrobial agents. In general, there is a wide margin between therapeutic and toxic concentrations with drugs such as the penicillins and cephalosporins. Other agents, such as the aminoglycosides, have a much narrower margin between therapeutic and toxic levels. For these antibiotics, the calculated dose in adults is based on lean body weight.

Duration Most surgical infections can be treated effectively in 5–7 days of antibiotic therapy. It generally is safe to stop antibiotics as long as the patient is making clinical progress and has a normal temperature and white blood cell count, and GI function has returned in patients with peritonitis. If clinical improvement is not evident within 4–5 days after operation and fever or leukocytosis persists after more than 5 days of therapy, a reason for the apparent treatment failure should be sought.

Treatment Failure Although failure of a bacterial infection to respond to a particular antibiotic is commonly regarded as evidence that the wrong antibiotic was selected, usually other factors are responsible. Patients with intraabdominal infections who remain febrile or have persistent leukocytosis usually have recurrent (tertiary) peritonitis or an intraabdominal abscess that requires drainage. Patients with necrotizing soft tissue infections may have persistent infections. Other causes of fever such as pneumonia, UTI, vascular catheter–related infection, drug fever, and thrombophlebitis should be investigated. The antibiotic may be the wrong antibiotic, or it may have been given in an inadequate dose or by an inappropriate route. The bacteria may not be susceptible to the antibiotic at the concentration achievable at the site of infection, or the site may have become superinfected by another bacterium not sensitive to the antibiotic.

Drug Toxicity Normally antibiotics are excreted primarily by the kidneys and accumulate in the serum of patients with impaired renal function. Therefore, with many antibiotics it is necessary to reduce the dose or to increase the interval between doses in patients with renal failure. Toxic drugs such as the aminoglycosides should either not be used in patients with renal failure or impaired renal function or, if used, their serum or plasma concentrations must be obtained frequently to verify that toxic levels are not being reached. The general approach to antibiotic usage in patients with renal failure is to give a first dose of 80–100 percent of the usual amount and then to estimate the timing and the amount of the second dose according to various schedules based on the normal half-life of the antibiotic.

Immunotherapy and Biologic Therapy of Infection

Antibodies to bacterial products and to mediators of sepsis are new (and extremely costly) therapeutic modalities that are currently being evaluated. Results thus far have been disappointing. There are no currently approved immunotherapeutic agents for treating infections. A previously approved antiendotoxin antibody (HA-1A) has been taken off the market. Other molecules or antagonists of molecules of the inflammatory or septic response are being investigated in the laboratory or undergoing clinical trials.

For a more detailed discussion, see Howard RJ: Surgical Infections, chap. 5 in Principles of Surgery, 7th ed.