6
Principles of Infection: Prevention and Treatment
John M. Davis
Objectives
1. To learn which operative procedures require pro- phylactic antibiotics.
2. To learn the proper timing and duration of pro- phylactic antibiotics.
3. To learn the proper conduct in the Operating Room (OR) and the scientific basis for the proce- dures done in the OR to prevent infections.
4. To learn the diagnosis and management of soft tissue infections.
5. To learn the diagnosis and management of intraabdominal infections.
Cases
Case 1
A 69-year-old woman is admitted with right upper quadrant pain and tenderness and known gallstones found incidentally during an ultra- sound for uterine fibroids. Subsequent to the diagnosis, she had an attack of biliary colic requiring an outpatient visit to her local emer- gency room. Her blood work in the emergency room included a fasting blood glucose level that was elevated at a level of 240 mg/dL. Out- patient blood testing prior to her surgery revealed a direct bilirubin level of 3.5 mg/dL.
Case 2
You are a third-year medical student beginning your third-year clerk- ship with surgery. You are instructed by the course director to have the chief resident orient you to your duties. The chief resident tells you to come to the operating room quickly to help on an emergency opera- tion. When you arrive at the operating room, you are given a scrub suit
99
and are faced with a variety of head covers and shoe covers. Some sur- geons are putting on shoe covers while others are putting on dirty, old running shoes and not using shoe covers. The head nurse tells you that you are in violation of hospital code by not wearing a head cover in the hallways outside the operating room. When you reach the operat- ing room, the surgeon and the chief resident already are at the operat- ing table, having washed their hands for less than 2 minutes. You are left to scrub by yourself. What soap should you use? For how long should you scrub?
Case 3
An obese 55-year-old man had an emergency colectomy for perforated diverticulitis. At surgery, a large segment of sigmoid colon was involved with the infectious process. The colon was thickened by chronic inflammation, surrounded by a watery exudate, with omentum and small bowel adherent to the sigmoid colon. An end colostomy was constructed after the segment of diseased colon was removed. The distal end of the colon was closed with a stapler. The patient had no significant medical history, but on admission he had significant hyper- tension and a blood sugar of 340 mg/dL. The wound was closed, including the skin, and the patient was transferred to the intensive care unit. Now, on postoperative day three, he is febrile with a peak tem- perature of 39°C (102.2°F), and has a heart rate of 105 bpm. The wound is erythematous, swollen, and tender.
Introduction
Control of infection in the surgical patient should be considered in three components as indicated in Algorithm 6.1. The preoperative (pre- hospital) component consists of whatever medical conditions the patient brings to the hospital. Evaluation of this component dictates a careful review of the patient’s general health, so that appropriate antibiotics, when necessary, may be administered in a timely fashion.
Other health conditions, such as smoking, should be stopped so that they have minimum effect during the surgical procedure. The second component is the operative environment. Care of the patient during this phase involves following appropriate conduct in the OR in order to minimize contamination and taking full advantage of the modern concepts regarding surgical infection. In this component, the timing of antibiotics and possible re-dosing of antibiotics need to be considered.
The third component is microbial factors. Here, the local hospital bac- terial flora is important. The transmission of resistance organisms or the particular infestation of a highly virulent organism is the factor that determines whether a patient develops an infection. For this compo- nent, the surgeon needs to consider the antibiotic sensitivities so that proper antibiotics are given.
An infection manifests itself when local or systemic host factors, environmental factors, and the microbes overwhelm the host. When this occurs in the postoperative period, the patient needs to be evalu- 100 J.M. Davis
ated carefully. The wound needs to be assessed with respect to the post- operative signs of sepsis, specifically, fever, elevated white blood count, wound erythema, and wound tenderness. An early diagnosis of a postoperative infection can minimize its impact on the speed of recuperation. Delay in the diagnosis and management of an infection can result in devastating, if not life-threatening, complications.
Preoperative Antibiotics
The second half of the 20th century ushered in the “antibiotics era.”
Since the introduction of antibiotics, it increasingly has become evident that most operative infections are caused by bacteria from the patient’s own body that reach the wound at the time of the surgery. Consequently, for antibiotics to work effectively, they have to be “on board” at the time of this inoculation in order to prevent the infection. The risk that any postoperative wound will get infected is based on the complexity and duration of the operation. Since clean operations do not violate bacterial-bearing organs, the infection rate is very low. A wound classification system was devised in the 1970s that identifies the infection risk following surgery. Table 6.1 shows the
INFECTION
HOST FACTORS
ENVIRONMENTAL FACTORS
MICROBIAL FACTORS Disease
process
Immune competence
Genenal health of the patient
Wound
classification Resistant
organisms
Virulent organisms
Appropriate antibiotic
use
OR environment well maintained
Healthcare workers wash hands prior to patient encounters
Algorithm 6.1. The risk factors for developing a wound infection: the susceptibility of the host, the vir- ulence of the invasive bacteria, and the environmental conditions in which the wound is made.
wound classification, specific indications for antibiotic therapy, and the recommended drug of choice.
Clean Cases
Prophylactic antibiotics generally are not recommended for those patients having clean operative procedures, since the minimal benefit that might result is equivalent to the risk of a side effect from the antibiotic.The routine use of antibiotics in operative procedures in which there is no identifiable benefit, such as breast biopsies, is not advised. Antibiotics are given only in operations that require the implantation of a foreign body, such as an orthopedic device, prosthetic mesh, or a vascular graft. Therefore, antibiotics are not recommended routinely in clean cases.
Several factors affect on the patient’s risks for postoperative surgi- cal infection. Many of the following factors are based on a wound sur- veillance protocol that was initiated by Peter Cruse in the early 1970s1: age of the patient, nutritional status, diabetes, smoking, obesity, 102 J.M. Davis
Table 6.1. Choice of antibiotics by wound classification.
Wound Approximate
classification infection rate Indications Drug of choice
Clean 1% Foreign-body implantation Cefazolin 1–2 g IV
Coronary bypass Peripheral vascular
Clean-contaminated 5–8% Gastroduodenal Cefazolin 1–2 g IV
Perforated Obstructed Bleeding
Biliary tract Cefazolin 1–2 g IV
>70 years old Acute cholecystitis Obstructive jaundice Common duct stones Nonfunctioning
gallbladder
Colorectal Neo/erythro (PO) or
cefotetan 1–2 g IV
Genitourinary Ciprofloxacin
400 mg IV
Ob-Gyn Cefotetan 1–2 g IV
Contaminated 15% Penetrating abdominal trauma Cefotetan 1–2 g IV Accidental spillage during
elective surgery
Dirty 50% Drainage of an abscess Dependent on site
and likely etiology of infection
1Cruse, PJ, Foord R. A five-year prospective study of 23,649 surgical wounds. Arch Surg 1973;107:206–210.
existing infections, colonization of the wound of the skin with microorganisms, length of preoperative stay of the patient, and altered immune status. In Case 1, the patient has an elevated white blood count (WBC) and serum bilirubin indications that the gallblad- der contains an active bacterial infection. These factors have been iden- tified by multivariant or univariant analysis as increasing the risk of a wound infection. However, these risk factors are not necessarily inde- pendent predictors of a wound infection, which means that, by defi- nition, a longer operative time involves more dissection, more blood loss, more dead space, and, therefore, a number of other factors that may increase the risk of a wound infection. Recent prospective studies indicate that the use of blood transfusions increases the risk of a wound sepsis by severalfold. Diabetes frequently is seen in patients who are overweight and elderly. Therefore, all three factors (age, obesity, and diabetes) may be dependent on one another. Table 6.2 summarizes the evidence-based guidelines for the prevention of surgical site infection.
The emergence of vancomycin-resistant enterococcus (VRE) in the early 1990s has led to national guidelines recommending the restricted use of this antimicrobial agent in an attempt to minimize the emergence of resistant strains. In patients undergoing open-heart surgery, van- comycin should be used only when the incidence of methicillin- resistant Staphylococcus aureus (MRSA) as a cause of postoperative wound infections is in the range of 15% to 20%. With this exception, and in penicillin-allergic patients, vancomycin should not be used for antibiotic prophylaxis.
Clean-Contaminated Cases
Since clean-contaminated surgery, which is defined as an operation in which a hollow viscus is opened in planned surgery, has a higher infection risk than clean surgery, prophylactic antibiotics are advised in most situations.As with antibiotic prophylaxis in clean operations, the critical features for antibiotic use in clean-contaminated surgery are short duration, correct dosing-time interval, narrow spectrum of activity with equivalent safety, and a good safety profile. While studies consistently show that clinical practice patterns favor the use of post- operative antibiotics, no scientific data have shown an advantage to prolonged therapy of prophylactic antibiotics after surgery. A second dose of antibiotics may be given in surgery when the operation lasts over 4 hours or when significant blood loss has occurred.
Examples of clean-contaminated operations include surgery of the stomach, gallbladder, small intestine, colon, and uncomplicated appendicitis.In each situation, preoperative preparation of the patient and consideration of their condition might entail a different approach.
For example, when performing a cholecystectomy on a patient with known gallstones who has had a single attack in the several weeks prior to surgery, the surgeon does not need to administer prophylactic antibiotics, especially since this operation is amenable to a laparoscopic procedure. The wounds are small and are unlikely to become contam- inated and result in a wound infection. However, for patients who have
Table 6.2. Summary of evidence-based guidelines for the prevention of surgical site infection (wound infection).a
Preparation of the patient
Level I: Identify and treat all infections remote to the surgical site before elective operations. Postpone elective operations until the infection has resolved.
Do not remove hair preoperatively unless hair at or near the incision site will interfere with surgery. If hair is removed, it should be removed immediately beforehand, preferably with electric clippers.
Level II: Control the blood glucose concentration in all diabetic patients.
Encourage abstinence from tobacco for a minimum of 30 days before surgery.
Indicated blood transfusions should not be withheld as a means to prevent surgical site infection.
Patients should shower or bathe with an antiseptic agent at least the night before surgery.
Wash and clean the incision site before antiseptic skin preparation.
Hand/forearm antisepsis Level II: Keep nails short.
Scrub the hands and forearms up to the elbows for at least 2–5 min with an appropriate antiseptic.
Antimicrobial prophylaxis
Level I: Administer antibiotic prophylaxis only when indicated.
Administer the initial dose intravenously, timed such that a bactericidal
concentration of the drug is established in serum and tissues when the incision is made. Maintain therapeutic levels of the agent in serum and tissues for the duration of the operation. Levels should be maintained only until, at most, a few hours after the incision is closed.
Before elective colon operations, additionally prepare the colon mechanically with enemas or cathartic agents. Administer nonabsorbable oral antimicrobial agents in divided doses on the day before surgery.
For high-risk cesarean section, administer the prophylactic antibiotic agent immediately after the umbilical cord is clamped.
Level II: Do not use vancomycin routinely for surgical prophylaxis.
Surgical attire and drapes
Level II: A surgical mask should be worn to cover fully the mouth and nose for the duration of the operation, or while sterile instruments are exposed.
A cap or hood should be worn to cover fully hair on the head and face.
Wear sterile gloves after donning a sterile gown.
Do not wear shoe covers for the prevention of surgical site infection.
Use surgical gowns and drapes that are effective barriers when wet.
Change scrub suits that are visibly soiled or contaminated by blood or other potentially infectious materials.
Asepsis and surgical technique
Level I: Adhere to principles of asepsis when placing intravascular devices or when dispensing or administering intravenous drugs.
Level II: Handle tissue gently, maintain hemostasis, minimize devitalized or charred tissue and foreign bodies, and eradicate dead space at the surgical site.
Use delayed primary skin closure or allow incisions to heal by secondary intention if the surgical site is contaminated or dirty.
Use closed suction drains when drainage is necessary, placing the drain through a separate incision distant from the operative incision. Remove drains as soon as possible.
Postoperative incision care
Level II: A sterile dressing should be kept for 24–48 h postoperatively on an incision closed primarily. No recommendation is made regarding keeping a dressing on the wound beyond 48 h.
Wash hands before and after dressing changes and any contact with the surgical site. Use sterile technique to change dressings.
Educate the patient about surgical site infections, relevant symptoms and signs, and the need to report them if noted.
* Centers for Disease Control and Prevention, 1999; level III guidelines excluded.
Source: Adapted from Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infec- tion, 1999, with permission. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epi- demiol 1999;20:250–278. Reprinted from Barie PS. Perioperative management. In: Norton JA, Bollinger RR, Chang AE, et al, eds. Surgery: Basic Science and Clinical Evidence. New York: Springer-Verlag, 2001, with permission.
had a recent attack of cholecystitis, suspected cholangitis, or common duct stones, are elderly (>70 years of age), or have diabetes, prophy- lactic antibiotics are used. The patient presented in Case 1 would benefit from prophylactic antibiotics based not only on the suspicion of common duct stones as evidenced by the elevated bilirubin, but also on the fact of the current attack of pain.
In the case of colon surgery, the bowel needs to be cleansed mechan- ically, and appropriate antibiotics need to be given either orally or intravenously (IV). It is controversial whether both intravenous and oral antibiotics should be given. Some evidence suggests that there is a slightly lower infection rate when antibiotics are given by both routes.
In urologic surgery, prophylactic antibiotics should be given when a urinary catheter is in place or if the urine is culture-positive. The drug of choice is ciprofloxacin, since it is well concentrated in the urine and covers the enteric gram-negative bacilli, which are the common pathogens. Culture results should direct appropriate prophylaxis if resistant organisms are identified. When performing a transrectal prostate biopsy, prophylaxis with antianaerobic coverage needs to be given. Similarly, head and neck surgery generally does not require prophylactic antibiotics unless the sinuses, nasal, oral, pharynx, or hypopharynx is entered.
In patients undergoing gastric surgery for an obstructive stomach, a bleeding ulcer, or gastric cancer, prophylactic antibiotics need to be considered carefully. Since gastric cancer is known to spread to con- tiguous organs, the possibility of a colon resection needs to be consid- ered. Patients should have a mechanical bowel preparation with appropriate antibiotics prior to surgery. In addition, a patient with an obstructing gastric cancer would require antibiotic coverage of anaer- obic and aerobic colonization of the stomach. When surgery is confined to the upper gastrointestinal tract for benign peptic ulcer disease, the patient would need antibiotics covering only the aerobic flora. It should be remembered that the stomach poses as a barrier to bacterial colo- nization of the small intestine, so that when gastric pH increases as a result of antacid therapy, bacterial overgrowth occurs. A single dose of prophylactic antibiotics to cover gram-negative and gram-positive flora is considered appropriate.
For surgery of the small intestine, such as for Crohn’s disease or primary tumors of the small bowel, a single dose of an antibiotic to cover the gram-negative aerobes is appropriate. When the stomach or small intestine is obstructed, the flora changes dramatically so that 1 mL of small bowel contents contains the same density of aerobic and anaerobic bacteria as 1 mL of feces. Antibiotics, therefore, need to be altered appropriately to include coverage against anaerobes.
Contaminated Cases
The difference in the management of patients with contaminated abdominal wounds compared to patients with dirty wounds is that in contaminated wounds there is bacterial soilage even though there is no active infection. Because there is no established pathogen in the
wound, a short course of antibiotics is appropriate.For example, in a patient with a penetrating abdominal wound with injured bowel, a short course of antibiotics (two to three doses) is as effective as longer therapy. Evidence indicates that shortened administration of perioper- ative antibiotics reduces the infection rate without increasing the emer- gence of resistant organisms. In addition, a short course of antibiotics reduces the incidence of side effects from the antibiotics.
Dirty Cases
When pus is encountered during an intraabdominal operative pro- cedure, prolonged antibiotic therapy is advised in order to contain the cellulitic component of the infectious process.Standard drug reg- imens are recommended for uncomplicated infections that arise outside of the hospital setting. Second-generation cephalosporins, cefoxitin, cefotetan, and ticarcillin-clavulinic acid are safe single-agent drugs that are extremely effective against most community-acquired infections. These agents all are derived from penicillin, and therefore carry the risk of an allergic reaction in patients who are allergic to penicillin.
If the patient has a history of a serious penicillin allergy or an imme- diate anaphylactic reaction, a combination of antibiotics may be used (Table 6.3). The disadvantage of some of these combinations is increased toxicity. The aminoglycosides are associated with renal and ototoxicity. Perhaps, more importantly, it has been recognized that this gentamicin has an altered volume of distribution and an altered half- life in the septic patient. This results in the likelihood of providing an inadequate dose of antibiotic to a septic patient, but still exposing the patient to the risk of a toxic side effect. One way to minimize these risks is to give the patient a single daily dose of gentamicin rather than three divided doses. The drug continues to be effective because of the phe- nomenon called the postantibiotic effect. The postantibiotic effect of a drug is realized when a drug continues to kill microbes even when measurable tissue levels are not present. If gentamicin is given once a 106 J.M. Davis
Table 6.3. Therapeutic antibiotics for abdomi- nal sepsis.
Single agents Cefoxitin Cefotetan
Ticarcillin-clavulinic acid Combinations
Ciprofloxicillan+ metranidazole/(clindamycin) Aztreonam+ metranidazole/(clindamycin) Gentamicina+ metronidazole/(clindamycin)
aMay also use amikacin or tobramycin.
Source: Adapted from Bohnen JMA, Solomkin JS, Dellinger EP, Bjornson HS, Page CP. Guidelines for clinical care: anti- infective agents for intraabdominal infections. Arch Surg 1992;127:83. Copyright © 1992, American Medical Associa- tion. All rights reserved.
day, then the renal function of the patient must be normal (normal cre- atinine). The combination of ciprofloxacin with flagyl, an antianaerobe, also is a combination therapy for penicillin-allergic patients and has the advantage of efficacy with low toxicity. Aztreonam plus flagyl is another recommended combination for penicillin-allergic patients.
Aztreonam has a cross-reactivity with penicillin because it is derived from the penicillin molecule, and therefore it should not be prescribed for someone with an anaphylactic reaction to penicillin.
The decision to terminate antibiotics is a critical one. Antibiotic therapy should not be ordered for a prescribed period of time, such as 7, 10, or 14 days. Two separate studies showed that the return of gas- trointestinal function, the defervescence of fever, and the return of a white count to normal value all were deemed good evidence for the termination of antibiotics. When these criteria are not met, the risk of recurrent infection was 40%, while the infection rates were less than 3%
if these criteria were met.
The use of antibiotic cultures in the face of intraabdominal pus recently has been questioned. Evidence indicates that surgeons are not inclined to adjust antibiotic therapy based on culture reports, especially if the patient is doing well. However, the intraperitoneal culture report is invaluable when an unusual pathogen is encountered, such as Pseudomonas aeruginosa, requiring specific antibiotic therapy.
Conduct in the Operating Room
Shoe Covers, Caps, Masks, Gowns, and Gloves
Operating room (OR) conduct combines procedures that are ritualistic, with no scientific basis, and activities that have been studied exten- sively and are of paramount importance in preventing transmission of infection in the operating field (Case 2). The use of shoe covers is a ritual from the era of flammable anesthetic gases. Because a spark from static electricity potentially could cause an explosion, specially designed nonconductive shoes that did not conduct an electric current were made for operating room personnel. For the visitor without special nonconductive shoes, shoe covers were available. Ether and cyclopropane especially were inflammable. Occasional explosions in the operating room were devastating events. By the mid-1970s, while explosive anesthetic agents were a thing of the past, shoe covers remained part of the accoutrements of the surgeon, along with caps and masks. However, current evidence suggests that the use of shoe covers actually may enhance the transmission of bacteria from the soles of one’s shoes to the surgical wound. This is likely to occur especially if one does not wash one’s hands after putting on the shoe covers.
With respect to barrier precaution, the use of cap, gown, mask, and OR gloves by the operating staff in the operating room to cover areas of their body that harbor a high density of potentially pathogenic bacteria is of paramount importance. However, data indicating the degree to which these barriers fail, resulting in infection, are seriously lacking. For example, the failure of gloves in the OR has been docu-
mented; however, their failure has never been coordinated with the risk of postoperative infection, even though it has been estimated that a glove failure results in inoculation of 105organisms per glove failure.
This may have to do with the relative differences of bacterial density in different parts of the body. The scalp hair and face, especially around the nares, are areas of high bacterial density; bacteria easily can contaminate the wound, resulting in a wound infection. Adequate coverage of these areas is imperative to prevent infection in the surgical environment.
Preoperative Shower
Over the past 20 years, there has been a revolution in the access of patients to the surgical environment. In 1980, 90% of surgical patients came to the hospital the day before surgery. Currently, 80% to 90% of patients stay at home the night prior to surgery. The preoperative man- agement of these patients with respect to bathing, out of necessity, has been reevaluated. While a routine preoperative shower was standard in the 1970s, there is little evidence to indicate that this makes a dif- ference in a patient’s risk of wound infection postoperatively.
Remote-Site Infection and Shaving
The presence of a remote-site infection, whether it is a pustule, an upper respiratory infection, or urinary tract infection, needs to be identified and treated prior to any surgical intervention. Similarly, the routine shave of the operating field done either in the OR imme- diately prior to surgery or the night before is not recommended.A patient whose surgical site has been shaved has an infection rate two to three times higher than patients who are not shaved. The reason for this increased risk of postoperative infection is based on numerous prospective trials, as well as on scanning electron microscopy showing small injuries to the skin of experimental animal models. These injuries show heavy bacterial colonization and inflammatory cells. The need for shaving a surgical site should be considered not for sanitary reasons but only for the convenience of the patient’s wound care.
Hand Washing
With respect to the surgeon’s handwashing, 30 years ago a 10-minute wash was considered the standard. However, increasingly shorter washes have been recommended by both the American College of Surgeons and the Centers for Disease Control. An initial wash of 5 minutes before the first surgery of the day is considered the standard, with subsequent preps of 2 minutes or less. One of the reasons for these decreasing skin prep times is the recognition that the soaps are harmful to the surgeon’s skin; a surgeon with a chronic skin condition can be a greater risk to the patient with respect to postoperative infec- tion than the duration of the skin prep. Three types of soaps currently are used: an iodophor-based soap, one with chlorhexidine and one with hexachlorophene (Table 6.4). Alcohol-based skin preps, which are 108 J.M. Davis
being used in Europe and have just been introduced in the U.S., offer the advantage that they require only topical application to clean skin, resulting in shorter skin prep times and less toxicity than soaps. In all of these considerations, it is important to recognize that the greater source of infection and contamination is the nail beds of the surgeon and the grossly evident contamination on the skin and arms.
Core Body Temperature
A recent, carefully controlled series of experiments clearly showed that the presence of the cold environment in the operating room reduces the patient’s core body temperature. This reduction in the patient’s core temperature significantly increases the risk of postoperative infection. This requires meticulous attention to keeping the patient warm while in the operating room and not allowing the patient to come into the OR and remain there for long periods of time prior to the ini- tiation of surgery.
Postoperative Care
Causes of Postoperative Fever
Postoperative fever is an important parameter to monitor after surgery since it can indicate that the patient has a serious post- operative infection. A temperature is abnormal if it is one degree Fahrenheit or one half of a degree centigrade above the normal core temperature. Depending on the patient population studied, the inci- dence of a postoperative fever in surgical patients may range from 15%
to 75%. The decision of whether or not to evaluate a patient with expen- sive blood and radiographic tests needs to be made in the context of whether or not these tests are likely to yield helpful results. Since half of postoperative fevers do not have an infectious etiology, the timing, duration, and clinical setting of a fever are important clues in indicat- ing whether or not further tests are necessary.
A postoperative fever occurring in the first 2 days after surgery is very unlikely to have an infectious cause.After general anesthesia, Table 6.4. Mechanism of action of the agents effective against both G+ and G- organisms.
Antifungal
Agent Mode of action activity Comments
Chlorhexidine Cell wall Fair Poor against
distruction tuberculosis/toxicity
(eye/ear) Iodine/iodophor Oxidation Good Broad spectrum/I
absorption skin irritation Alcohols Denaturation of Good Rapid action/short
protein duration/flammable
pulmonary atelectasis causes activation of the pulmonary alveolar macrophage, resulting in endogenous pyrogen release. Early postop- erative fever is believed to be due to this cytokine release. If, however, a fever occurs after postoperative day 3 or persists for more than 5 days, there is a high likelihood that an underlying infection is the cause.In this setting, before subjecting the patient to a battery of expen- sive laboratory tests, a careful clinical evaluation needs to be done to look for a wound infection. The most common nosocomial infections are urinary tract infections (UTIs), wound infections, and pneumonia.
The clinical setting is important, since most nosocomial UTIs follow instrumentation of the urinary tract. Similarly, nosocomial pneumonias frequently follow prolonged endotracheal intubation.
Surgical Wound Management and Surgical Wound Infection Care What is the correct definition of a surgical wound infection? The rigid criterion of pus from a wound is only one sign of wound sepsis. The Centers for Disease Control and Prevention (CDC) expanded the defi- nition in 1992 to include additional criteria.2Organisms isolated asep- tically from a wound, pain and tenderness, localized swelling, and redness in a wound that is deliberately opened by a surgeon all meet the criteria of a surgical site infection (Case 3). In addition, the diag- nosis of a superficial wound infection by the surgeon or attending physician meets the CDC criteria for a surgical site infection. Con- sequently, the intention to treat a wound with antibiotics meets the criteria of a wound infection.
Postoperative management of a wound is dictated by the wound classification.A dirty wound, in which pus was encountered at the time of surgery, is left open to prevent a wound infection. While there is no prospective randomized trial to support this approach, the inci- dence of a wound infection is at least 50%. By leaving the wound open and letting it heal by secondary intent (allowing it to granulate in) or by delayed primary closure (pulling the wound closed with sutures placed but not tied in the operating room or by Steri-Strips), the risk of a wound infection significantly is reduced. Since a wound closed by delayed primary closure still has a risk of becoming infected, diligent wound surveillance is required by the surgeon. This approach is not applied universally to all surgical patients. In the pediatric population, wound approximation by delayed primary closure or by secondary intent generally is not done because of the very minimal amount of subcutaneous tissue and because the mechanics of local wound care are difficult in the pediatric age group. In this case, a loosely closed wound or a wound closed over a drain may help reduce a postopera- tive wound infection.
110 J.M. Davis
2Horan TC, Gaynes RP, Martore WJ, Jarvis WR, Emori G. CDC definitions of nosoco- mial surgical site infections, 1992: a modification of CDC definition of surgical wound infections. Infect Control Hosp Epidemiol 1992;13:606.
If the wound results from a clean or clean-contaminated surgery, a sterile dressing is applied for the first 24 to 48 hours. After this time period, once the wound has sealed, the risk of bacterial invasion from the external environment is eliminated, and the use of a dressing is optional. When the postoperative signs of sepsis (fever, elevated white blood count, tachycardia)occur in the presence of a swollen and tender wound, the possibility of a wound infection needs to be con- sidered. If the wound is only erythematous in the early postoperative period, then a trial of antibiotics is reasonable until the erythema sub- sides. A clinical response should be seen within 24 to 48 hours. If the patient fails to respond, the wound must be explored. Some of the stitches should be removed at the site of the most erythematous area of the wound, and, if pus is encountered, the wound should be opened further and packed with gauze.
While a postoperative infection is a nuisance and, in the past, has been associated with high costs if treated in the hospital, the more serious consequence of postoperative wound sepsis is a necrotizing soft tissue infection. Finding gas on a roentgenogram in the soft tissues or crepitance on physical exam is a sign of necrotizing infection. Necro- tizing fasciitis and clostridial myonecrosis are two terms for life- threatening infections that frequently result from neglected wounds.
While these infections are rare and not subject to extensive clinical or laboratory study, it is believed that these infections are part of a con- tinuum of a septic wound. It is clear that a clostridial infection requires an inoculum of a clostridia species, an anaerobic environment, and muscle necrosis. The term necrotizing fasciitis is defined more poorly, but similarly requires an anaerobic environment. Whether tissue necro- sis occurs depends on the extent of the infection and the host’s ability to resist. Mortality has been related to several medical risk factors, including diabetes mellitus, hypertension, and peripheral vascular disease.
Necrotizing soft tissue infections can arise outside of the hospital setting. Trivial infections in a partially compromised host may result in a serious infection. Retrospective reviews indicate that in up to half of patients with these infections, there is no identifiable cause. In some cases, a chronic wound suddenly becomes the source of a devastating infection. Illicit drug use with infected needles has been a frequent cause in hospitals located in high drug abuse areas. Fournier’s gan- grene is an infection initially described in the male perineum in the 1890s. The cause initially was due to a perineal soft tissue infection originating from chronic gonococcal urethritis. Since gonorrhea has become an infrequent infection with the advent of antibiotics, other causes more commonly trigger this infection. Neglected perirectal abscess or neglected hydradenitis suppurativa are currently the more common causes and can occur in women as well as men.
Aggressive surgical debridement is the mainstay of therapy in patients with necrotizing infections, with antibiotics serving as an important adjunct to therapy. Because the wounds are anaerobic, opening them to the air and removing necrotic tissue destroys the bac- teria’s ability to proliferate. The use of hyperbaric oxygen has been
advocated, with some evidence indicating its efficacy. The risk of middle ear damage and decompression sickness make its practical use ineffective.
Drains
Drains are a very controversial issue with regard to infection. A recent study evaluating their effectiveness in draining elective colon resec- tions shows no increased risk of infection or other complications with a drain as opposed to without one. Additionally, however, there is no clear advantage to placing a drain as opposed to not placing it. Routine use of drainage after axillary dissection has been subjected to prospec- tive randomized trial. Again, no distinct advantage with respect to infection could be seen with the presence or absence of drains. The presence of drains resulted in fewer postoperative visits and a greater subjective evaluation of postoperative pain. In general, the use of drains should be restricted to those situations in which there is a spe- cific indication, and the duration of drainage should be determined and limited as much as possible.
Antibiotic Therapy
Prior to the 1940s, the only antibiotic agents available were the sul- fonamide drugs. These antibiotics are the prototype antimetabolite;
their mechanism of action is inhibiting the production of microbial folic acid. The fact that they were not microbicidal and they were not effec- tive against common gram-positive species led to the need for the development of more potent antibiotics with a broader spectrum.
Penicillin initially was administered to a British policeman, and, subsequently, in the United States, it was given to a deathly ill woman with postpartum puerperal sepsis. The miraculous survival of these patients as a result of this natural antibiotic derived from Penicillium notatum and discovered accidentally by Sir Alexander Fleming, gave rise to an entire class of B-lactam antibiotics (Table 6.5). These antibac- terial agents are related to penicillin by the presence of the active chem- ical component, the B-lactam ring. This structure kills the bacteria by the competitive binding of the enzymes, known as penicillin binding proteins, responsible for the transpeptidation and transglycosylation process during cell wall polymerization. This step is critical to the integrity of the cell wall.
Bacterial resistance to penicillin began to be reported in the 1950s, necessitating the development of chemically altered derivatives of the original molecule. Methicillin was developed in an effort to effect therapy for bacteria resistant to penicillin. This antibiotic subsequently has become known for identifying a class of bacteria that is resistant to methicillin, methicillin-resistant Staphylococcus aureus (MRSA).
Major side chains added to certain B-lactam–derived antibiotics altered the effectiveness and spectrum of activity of the penicillin mol- ecule. By adding the side chains, such as clavulanate, sulbactam, or tazobactam, B-lactamase, an enzyme secreted by bacteria resistant to the penicillin molecule, may be inhibited.
112 J.M. Davis
The cephalosporins are related to the penicillin molecule by the pres- ence of the B-lactam ring, but they were derived from a naturally occur- ring fungus that, like penicillin, was discovered accidentally. This molecule has given rise to a large group of drugs that have been sub- classified as first-generation, second-generation, or third-generation cephalosporin. These agents, as they increase in their evolution from the first generation, lose their gram-positive efficacy and increase their effectiveness against gram-negative agents, so that cefazolin, a first- generation agent, has good gram-positive coverage, cefoxitin, a second- generation cephalosporin, has good gram-negative coverage and moderate gram-positive coverage, and ceftriaxone, a third-generation cephalosporin, has excellent gram-negative coverage but very poor gram-positive effectiveness.
The major antibiotic in the glycopeptide group is vancomycin, an antibiotic that, like the B-lactam agents, inhibits cell wall synthesis.
Vancomycin disrupts cell wall synthesis through a different mechanism from the B-lactam antibiotics. The recent emergence of resistant strains of MRSA to vancomycin has led to the development of a new gly- copeptide, teicoplanin, an agent with less renal toxicity and longer dosing intervals than vancomycin.
Quinupristine-dalfopristine is a new drug in the streptogramin class of agents that works by inhibiting protein synthesis. Similar to the glycopeptides, it is active against gram-positive organisms and was developed to treat resistant strains of staphylococcal species.
The macrolide antibiotics, such as erythromycin, inhibit protein syn- thesis by reversible binding to the 50S ribosomal subunit. Azithromycin and clarithromycin are broader spectrum agents with anaerobic effi- cacy especially good for penicillin-allergic patients. Clindamycin and chloramphenicol are unrelated structurally but have a similar mecha- nism of action as the macrolides. Because the mechanism of action involves reversible binding, these agents are not bactericidal but bacteriostatic.
The aminoglycosides, similar to the macrolide antibiotics, bind to the ribosomal subunit, but, unlike macrolide antibiotics, this binding is not reversible. Consequently, these agents are bactericidal. While the aminoglycosides were the only effective antibiotic for the Enterobacte- riaceae in the 1970s, their renal and ototoxicity, combined with esti- mating appropriate dosing regimen, have made them unacceptable as a first-line agent for gram-negative infections.
Quinolonestarget the DNA synthesis by binding to one of the bac- teria’s DNA synthetase enzymes. They are effective primarily against gram-negative aerobes, but they also are effective against gram- positive organisms. Their usefulness is enhanced because therapeutic drug tissue levels may be achieved with oral administration as well as with the intravenous route.
Metronidazole, like the quinolones, impairs microbial growth by blocking DNA synthesis. Although its spectrum of activity is limited to the gram-negative anaerobes, it is highly effective against this group of microbes. It is well absorbed orally so that parenterally and enter- ally administered drugs both result in therapeutic levels in the serum.
114 J.M. Davis
Table 6.5. Activity of selected antimicrobial agents.a
Streptococcus Staphylococcus Staphylococcus
pyrogenes aureus epidermidis
b-Lactam agents Penicillins
Penicillin G +++++ + +
Methicillin +++++ ++ +
Ticarcillin +++ ++ +
Ampicillin ++ + +
Penicillin agent + b-lactamase inhibitors
Piperacillin + + —
Ampicillin-sulbactam ++ ++ +
Ticarcillin-clavulanate +++ ++ +
Piperacillin-tazobactam + + —
First-generation cephalosporins +++ ++++ ++
Second-generation cephalosporinsb ++ ++ ++
Cefoxitin ++ ++ ++
Cefaperazone ++ ++ ++
Third-generation cephalosporinsb ± ± —
Cefotaxime + ± —
Cefotetan + + —
Ceftazadime + + —
Ceftriaxone + + —
Fourth-generation cephalosporin
Cefapime ± ± —
Aztreonam
Carabapenems ++ + +
Vancomycin +++++ +++++ +++++
Quinupristine-dalfopristine ++++ ++++ ++++
Erythromycin ++++ ++ ++
Aminoglycosides + + +
Quinolonesb V V V
Naladixic acid — — —
Norfloxacin — — —
Ciprofloxacin + — —
Moxifloxacin + + +
Trimethoprim-sulfamethoxazole — — —
Clindamycin +++ ++ +
Metronidazole — — —
a+++++ indicates maximal activity; — indicates none.
b V indicates variability within the group, as denoted by the difference in activity among specific agents for certain types of organisms. Source: from Dunn DL. Diagnosis and Treatment of Infection. In: Norton JA, Bollinger RR, Chang AE, et al, eds. Surgery: Basic Science and Clinical Evidence. New York: Springer-Verlag, 2001, with permission.
Summary
Prevention of a surgical infection requires a thorough understanding of the three component parts (factors) that may contribute to a post- operative infection: the host, the environment, and the bacteria (see Algorithm 6.1). The severity and likelihood of an infection are depen- dent on the relative balance of these three factors. Since most infections come from the patient’s own body, knowing the infectious risk of an operation, using the appropriate antibiotics, and conducting a timely and efficient surgery are the most significant factors in preventing a postoperative infection. The success of treating an established infection
Table 6.5. Continued
Enterococcus Enterococcus Escherichia Pseudomonas
fecalis fecium coli aeruginosa Anaerobes
+ + — — —
+ + — — —
++ ++ ++ ++ —
+++ +++ + — —
+++ +++ +++ ++++ +
+++ +++ ++ ++ ++++
++ ++ ++ ++ ++++
+++ +++ ++++ ++++ ++++
— — — — —
— — +++ ++ V
— — +++ ++ +++
— — +++ ++ —
— — +++++ V V
— — +++++ ++ —
— — ++++ + +++
— — +++++ +++++ —
— — +++++ ++ ++++
— — +++++ ++++ —
+ + +++++ ++++ ++++
++++ ++++ — — —
— ++++ — — —
+ + — — ++
++ + +++++ ++++ —
V V V V V
— — ++ + —
— — +++ ++
++ ++ ++++ ++++
++ ++ ++++ ++++ +++
— — ++++ ++ —
++ ++ — — ++++
— — — — +++++
Source: Reprinted from Dunn DL. Diagnosis and treatment of infection. In: Norton JA, Bollinger RR, Chang AE, et al, eds. Surgery: Basic Science and Clinical Evidence. New York: Springer-Verlag, 2001, with permission.
requires an understanding of both the microbes involved and the spec- trum of antibiotics to treat these microbes. Finally, the operating room environment may compromise the patient’s ability to resist infection in a variety of ways. The patient’s internal milieu is exposed to bacteria where the natural host defense mechanism is not effective. Keeping the patient’s core body temperature in a normal range is a significant factor in preventing infection. Finally, understanding the nature and types of resistant organisms present in the specific hospital, how they are spread, and what antibiotics are recommended to treat these organisms are important both for preventing the dissemination of these organisms and for curing the patient.
Selected Readings
Aly R, Maibach HI. Comparative antibacterial efficacy of a 2-minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and chloroxylenol sponge-brushes. Am J Infect Control 1988;16:173–177.
Ayliffe GA. Role of the environment of the operating suite in surgical wound infection. Rev Infect Dis 1991;13(suppl 10):S800–804.
Ayliffe GA, Noy MF, Babb JR, Davies JG, Jackson J. A comparison of pre- operative bathing with chlorhexidine-detergent and non-medicated soap in the prevention of wound infection. J Hosp Infect 1983;4:237–244.
Barie PS. Perioperative management. In: Norton JA, Bollinger RR, Chang AE, et al., eds. Surgery: Basic Science and Clinical Evidence. New York: Springer- Verlag, 2001.
Bohnen JMA, Solomkin JS, Dellinger EP, Bjornson HS, Page CP. Guidelines for clinical care: antiinfective agents for intraabdominal infections. Arch Surg 1992;127:83.
Centers for Disease Control and Prevention. National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986–April 1997, issued May 1997. Am J Infect Control 1997;25:477–487.
Condon RE, Bartlett JG, Greenlee H, et al. Efficacy of oral and systemic anti- biotic prophylaxis in colorectal operations. Arch Surg 1983;118:496–502.
Cruse PJ, Foord R. A five-year prospective study of 23,649 surgical wounds.
Arch Surg 1973;107:206–210.
Deshmukh N, Kramer JW, Kjellberg SI. A comparison of 5-minute povidone- iodine scrub and 1-minute povidone-iodine scrub followed by alcohol foam.
Milit Med 1998;163:145–147.
Dineen P, Drusin L. Epidemics of postoperative wound infections associated with hair carriers. Lancet 1973;2(7839):1157–1159.
Dougherty SH, Simmons RL. The biology and practice of surgical drains. Part 11. Curr Prob Surg 1992;29(9):635–730.
Dunn DL. Diagnosis and treatment of infection. In Norton JA, Bollinger RR, Chang AE, et al., eds. Surgery: Basic Science and Clinical Evidence. New York: Springer-Verlag, 2001.
Ford CR, Peterson DE, Mitchell CR. An appraisal of the role of surgical face masks. Am J Surg 1967;113:787–790.
Hambraeus A. Aerobiology in the operating room—a review. J Hosp Infect l988;11(suppl A):68–76.
Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori G. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definition of surgical wound infections. Infect Control Hosp Epidemiol 1992;13:606.
Humphreys H, Marshall RJ, Ricketts VE, Russell AJ, Reeves DS. Theatre over- shoes do not reduce operating theatre floor bacterial counts. J Hosp Infect 1991;17:117–23.
Jensen LS, Kissmeyer-Nielsen P, Wolff B, Qvist N. Randomized comparison of leucocyte-depleted versus buffy-coat-poor blood transfusion and complica- tions after colorectal surgery. Lancet 1996;348:841–845.
Jonsson K, Hunt TK, Mathes SJ. Oxygen as an isolated variable influences resis- tance to infection. Ann Surg 1988;208: 783–787.
Kaiser AB, Kernodle DS, Barg NL, Petracek MR. Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers. Ann Thorac Surg 1988;45:35–38.
Krizek TJ, Robson MC. Evolution of quantitative bacteriology in wound man- agement. Am J Surg 1975;130:579–584.
116 J.M. Davis
Lennard ES, Hargiss CO, Schoenknecht FD. Postoperative wound infection sur- veillance by use of bacterial contamination categories. Am J Infect Control 1985;13:147–153.
Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgi- cal site infection, 1999. Hospital Infection Control Prectices Advisory Com- mittee. Infect Control Hosp Epidemiol 1999;20:250–278. Reprinted from Barie PS. Perioperative Management. In Norton JA, Bollinger RR, Chang AE, et al., eds. Surgery: Basic Science and Clinical Evidence. New York: Springer- Verlag, 2001.
Nichols RL, Smith JW, Robertson GD, et al. Prospective alterations in therapy for penetrating abdominal trauma. Arch Surg 1993;128:55–64.
Page CP, Bohnen JM, Fletcher JR, McManus AT, Solomkin JS, Wittmann DH.
Antimicrobial prophylaxis for surgical wounds. Guidelines for clinical care.
Arch Surg 1993;128(l):79–88.
Pitt HA, Postier RG, MacGowan AW, et al. Prophylactic antibiotics in vascular surgery. Topical, systemic, or both? Ann Surg 1980;192:356–364.
Rotter ML, Larsen SO, Cooke EM, et al. A comparison of the effects of pre- operative whole-body bathing with detergent alone and with detergent containing chlorhexidine gluconate on the frequency of wound infections after clean surgery. The European Working Party on Control of Hospital Infections. J Hosp Infect 1988;11:310–320.
Seropian R, Reynolds BM. Wound infections after preoperative depilatory versus razor preparation. Am J Surg 1971;121:251–254.
Sessler DI, McGuire J, Hynson J, Moayeri A, Heier T. Thermoregulatory vaso- constriction during isoflurane anesthesia minimally decreases cutaneous heat loss. Anesthesiology 1992;76:670–675.
Sharma LK, Sharma PK. Postoperative wound infection in a pediatric surgical service. J Pediatr Surg 1986;21:889–891.
Vamvakas EC, Carven JH, Hibberd PL. Blood transfusion and infection after colorectal cancer surgery. Transfusion 1996;36:1000–1008.
