Diagnosis and treatment of uncomplicated and complicated surgical infections

Diagnosis and treatment of uncomplicated and complicated surgical infections Dr Nichols. The clinical presentation of surgical infections involving skin and subcutaneous tissue is one that should be fairly straightforward. However, it is an area of some difficulty for physicians. Let us begin with a brief discussion of the presentation of these simpler infections and the recommended treatment approach. Dr Martone, what are the organisms associated with surgical wound infections? Dr Martone. Most of the surveillance data we use are from the Centers for Disease Control and Prevention’s (CDC) National Nosocomial Infection Surveillance program. The most common organisms associated with these infections are gram-positive bacteria, particularly Staphylococcus aureus (Table I). Dr Nichols. Surgical wound infections are heralded by the 5 classic signs of local inflammation: calor, dolor, rubor, tumor, and loss of function. Typically, these infections simply require drainage and surgical packing. The use of antibiotics depends on the appearance of the infection and evidence of local spread or systemic toxicity; the choice of antimicrobial agent will depend, in part, on local patterns of antimicrobial resistance (Figure). INFECTIONS ASSOCIATED WITH FOREIGN BODIES Dr Nichols. Dr Wilson, in the past we worried about these uncomplicated infections when they were associated with foreign bodies, such as in patients with arthroplasties or vascular grafts. However, there are newer studies that suggest we do not need to routinely remove the prostheses or the graft. What is your approach to these patients? Dr Wilson. The decreased incidence of infection in elective implant surgery is caused by several factors. These factors include (1) same-day admission for surgery so that patients are not colonized by hospital flora before they have their operation, (2) povidone-iodine skin preparation and antiseptic impregnated plastic drapes, (3) appropriate selection and timing of antimicrobial prophylaxis, (4) maintenance of normothermia, and Surgery 2000; 128:S19-S30. Copyright © 2000 by Mosby, Inc. 0039-6060/2000/$12.00 + 0 doi:10.1067/msy.2000.110236

11/0/110236

Table I. Nosocomial bloodstream infections Pathogen

% of surgical site infection

S aureus Coagulase-negative staphylococci Enterococcus spp E coli Pseudomonas aeruginosa Enterobacter spp Other

18.9 13.6 13.6 8.0 7.8 6.5 31.6

Data from Martone WJ, et al. Incidence of endemic and epidemic nosocomial infections. In: Hospital infections. Bennett JV, Brachman PS, editors. Philadelphia: Lippincott-Raven; 1998.

(5) decreased use of blood transfusions. However, the apparent decrease in the incidence of uncomplicated infections has been more than made up for by an increased number of complicated infections associated with foreign bodies and intravenous catheters. For example, the subgroup of dialysis patients is particularly at risk for gram-positive infections. This is a major problem in the one-quarter million patients on chronic hemodialysis and who have revision of these grafts every 1 to 2 years. Dr Nichols. We now know that these low-virulence organisms can be associated with chronic graft infection, protected by the biofilm that is produced by the organism. Consequently, with appropriate local care—debridement, irrigation, moving in viable tissue such as tissue flaps, use of effective antimicrobials—the graft need not always be sacrificed. That is a major advance in the management of the infected foreign body. There was a recent article in the Journal of the American Medical Association about a study with rifampin and leaving prosthetic devices in place.1 Dr Chambers. This was a study looking at the combination of ciprofloxacin and rifampin. Drug therapy was initially given parenterally, followed by an early transition to oral therapy. The study considered whether the addition of rifampin was beneficial in preventing relapse. The investigators followed up patients for a period of several months. The patient group had early infections rather than late infections. There was microbiologic data because some of the devices were pins that were removable; thus in some cases the therapy could be stopped and the pin was removed. SURGERY S19

S20 Panel discussion: Complicated/uncomplicated surgical infections

Surgery October 2000

Figure . Wound infection algorithm. The selection of antimicrobial agents will depend on the local pathogen profile and resistance patterns.

Those patients who received the combination of ciprofloxacin and rifampin, had no failure, and those who received single drug therapy had a 65% failure rate, which was highly statistically significant.1 Dr Nichols. This is a concept that can be used to study other drugs in infections caused by gram-positive pathogens. Is it possible to preserve the graft by adding a drug such as rifampin? One of the worst things that happens to older people who have placement of synthetic prostheses is the removal of the prosthesis and the need to start again. WHEN TO CULTURE: UNCOMPLICATED INFECTIONS Dr Nichols. When do you culture what looks like an uncomplicated abscess without a prosthesis? Dr Fry. If the patient has an uncomplicated infection and does not have evidence of severe invasive cellulitis or wound necrosis from the infection, I drain it, but I do not culture it. Culturing it in 99% of patients will have no influence whatsoever on any subsequent strategy. Dr Nichols. What if that patient with an uncomplicated infection comes back 2 days later? Now you see little fever and what you think is advancement to the fascia. What do you do then? Dr Fry. At that juncture, I would probably culture it, but that is an extraordinarily unusual course of events. Dr Wilson. I respectfully disagree with Dr Fry.

We do not culture for the 95% to 99% of patients who are going to do very well; we culture for the 1% to 5% who may progress. If you wait 2 to 3 days before you culture in those patients, when you start your antimicrobial therapy you are treating empirically. It is very important to know the susceptibility of that organism. If you had taken the original culture, you would be about 72 hours ahead and have precise data. Dr Nichols. Studies like the ones we did in the New England Journal of Medicine and the Journal of Infectious Diseases many years ago showed that when we routinely cultured the peritoneal cavity in cases of appendicitis or penetrating abdominal trauma, it did not help us identify the organism that eventually caused the secondary infection.2,3 It didn’t help, so we stopped culturing. Dr Dunn. What are we going to do in 10 years when we do not have any epidemiologic data? How are we going to obtain those data? I think we need to deal with those two issues. Dr Gorbach. Several years ago, there was a study from Foothills Hospital in Calgary, Alberta, that found that more than 50% of wounds were not cultured.4 The incidence of wound infection was reported to be very low until they began to look for them. So I disagree strongly with my eminent surgical colleague. First, I think if you culture out an organism like Streptococcus pyogenes, which you get back within 24 hours, you would immediately start antibiotics. In contrast, if the culture grew out

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Panel discussion: Complicated/uncomplicated surgical infections S21

Escherichia coli, you might not. I think the nature of the organism is important. More important, it requires us—particularly with these rapid discharges—to keep track of our wound infection rate. Without culturing, we are simply not going to have any sense of what individual surgeons are doing, what a unit is doing, and we will not be able to detect epidemics from organisms such as Pseudomonas spp or an unusual fungus. This is particularly important among outpatients because we are moving our inpatients to the outpatient setting more quickly. I can’t imagine going back to the early 19th century when we never cultured wounds and did not know what was in a wound. Dr Christou. I think what you said is important, but we have to keep in mind what really happens in clinical practice. I believe there are very few people who are just going to drain an abscess. You may have quite a few physicians who culture an infection, but there are even more physicians who start an unnecessary antibiotic in that wound infection. Dr Condon. The reality is that few of these superficial subcutaneous wound infections need to get cultured. Most of them do not. Most of these infections present in an absolutely typical fashion and have predictable microbiologic characteristics. In my opinion, in those cases you are just wasting time and money culturing them. However, some wounds have more cellulitis than you would expect, some patients have more pain than you would expect, and if you wash out the wound there’s a little more necrosis than you would expect. I think these somewhat unusual wounds ought to be cultured. There is no need for antibiotics in this context. Dr Newell. We have been talking about standard wounds and standard patients. The flip side of this is standard wounds and nonstandard patients. I do not do much outpatient surgery, but almost all the patients I see are severely immunocompromised. We routinely culture all our wounds because frequently a wound infection in our patients belies something deeper, and knowing the culture result helps us a great deal. Dr Nichols. The use of antibiotics has always been a “plus/minus.” Most of us do not use antibiotics unless there is evidence of systemic toxicity or local spread. PERIRECTAL ABSCESS: TREATMENT APPROACH Dr Nichols. What about perirectal abscess? Do you wait for it to localize and prescribe sitz baths and antibiotics? What is your approach to this problem? Dr Dellinger. I think giving sitz baths and antibiotics to a patient with a perirectal abscess is a way to

make a small abscess a large abscess. When you suspect it, you should operate on it. There’s another important element I think we have missed. Although we acknowledge that approximately 99% of practitioners will use antibiotics when they see a wound infection, we neglected to say that a shocking number of them will use antibiotics and not drain the wound infection! We should emphasize the importance of drainage, with or without antibiotics. Dr Nichols. So you cut through normal tissue to find it, even though you don’t feel fluctuance? Dr Wilson. Certain abscesses do not have fluctuance. For example, deep perirectal abscesses will not point. Breast abscesses may present with just pain and swelling without pointing. Deep neck infections can be difficult to recognize. Dr Nichols. So if you suspect an abscess, do you put a needle in? Dr Wilson. This should be done under anesthesia. KEY STATEMENT REGARDING PERIRECTAL ABSCESS The definitive management of perirectal abscess is prompt surgical intervention. Antibiotics, if indicated, are used as an adjunct. Treatment failures in patients with perirectal abscess are those in whom the abscess is not recognized or in whom treatment consists of antimicrobial agents alone. NECROTIZING FASCIITIS Dr Nichols. What about the fulminant infections? Streptococcus spp is an organism that seems to be causing more than cellulitis and lymphangitis today. What has happened—is it the host, or has the organism become more virulent? Dr Rotstein. It is the organism, the Streptococcus spp. Dr Chambers. For reasons that are not clear, there has been an increased prevalence of strains that are toxigenic.5 Dr Gorbach. The M groups have changed. There has been a shift in streptococcal serotypes over the last 15 years.6 It is usually group A S pyogenes, and it occurs in a normal host who is usually approximately 50 years of age. However, these infections can occur in young patients with a very minor traumatic injury that’s just barely remembered. Dr Christou. This is a very confusing subject, and we have to start helping people sort this out. We have heard streptococcal infections, cellulitis, necrotizing fasciitis. I think you have to take them individually in terms of describing them. In terms of treating them, they’re probably all going to be

S22 Panel discussion: Complicated/uncomplicated surgical infections

treated very similarly because of the aggressiveness of the disease. Dr Nichols. Cellulitis is treated with antibiotics and warm packs, whereas necrotizing or gangrenous infections require surgical interventions in addition to the use of efficacious parenteral antibiotics. Dr Condon. It depends on the context. A practicing physician sees these necrotizing infections at a critical time. Their choices can alter the course of the infection. The first 4 to 6 hours of the development of these infections is the critical period.7 None of us sitting around this table ever sees those infections within that time frame. We talk about black skin and things that are late effects. The real watershed is to try as best you can to determine whether this is an infection that is limited to the subcutaneous tissues and may respond to antibiotic therapy alone, or whether this is an infection causing tissue necrosis that needs immediate and early debridement. That’s the watershed issue. I don’t care what kind of gangrene you call it. My view is you just ought to recognize that there are infections that cause necrosis of deep fat, muscle fascia, and muscle. They can be streptococcal or they can be clostridial, it doesn’t matter because they get the same antibiotics and they get the same surgical treatment. How does a person recognize a developing necrotizing infection? It’s easy for us in the operating room because the tissue doesn’t bleed, it’s necrotic. How does the primary care physician know that this is the infection that is going to spread rapidly? He or she tries to make a clinical determination, but if there is any doubt, it is best to make an incision and look. Dr Christou. These people have extremely high fevers and tachycardia. Dr Chambers. I think there are 3 useful elements to prompt you to think about this. One symptom is pain out of proportion to the physical findings. The second is fever that would not be explained by the physical findings and other systemic signs of infection that are out of proportion. We are talking about a toxin-mediated disease. The third symptom that should make you think of one of these potentially serious infections is very high white blood cell count. However, I think that is less useful because it’s unpredictable.8 Dr Nichols. Sometimes these patients are so sick that their white blood cell count is actually suppressed. Dr Chambers. I agree that they’re hard to recognize and I think that is the nature of the disease. But there are clues that push you to do additional studies such as CT or MRI.

Surgery October 2000

Dr Ginzburg. This is really a spectrum of disease because it can start as a cellulitis and burrow down into the soft tissues and then spread into the actual fascial planes. We see a significant amount of necrotizing fasciitis at the University of Miami because of our inner city and immigrant patient populations. When the infection is below the knee, we don’t often see it spreading down in to the fascial planes. As soon as you get up into the upper thigh, perineum, upper abdomen, we either get a CT scan, which has been very helpful in showing subcutaneous tissue gas and/or thickening of the fascia, or retroperitoneal extension. If this is seen, we then take the patient to the operating room. Otherwise, that patient is started on IV antibiotics and is observed in the hospital. Once there is even a suspicion of this type of infection, we take those patients straight to the operating room and open them up. If you wait just those 2, 3, 4, or 6 hours, you may literally be making decisions about the mortality of that patient. In other words, that patient may die with extensive disease. Dr Fry. In New Mexico, we see approximately 30 cases of group A streptococcal infection a year. There seems to a higher incidence of the more virulent strains of group A streptococci in the high altitude, arid west.9 Similarly, there are a number of cases each year in Idaho.10 We now see these cases within 4 hours because we have got the private community sensitized to the issue. I would emphasize what Dr Chambers said. Pain out of proportion to the size of the apparent infection is an important clue. Secondly, the thinness of the patient may also be a clue. In thinner patients, true cellulitis is still a very soft disease when you feel the wound. Therefore, when you have induration, you need to be seriously thinking about going to the operating room. This does not always apply because obesity and diabetes are clearly risk factors in patients with necrotizing soft tissue infection. We have seen cases of infection on thighs and on the trunks of some of our Native American patients, and they came in almost immediately because there has been a public service program to educate people. Dr Rotstein. I just wanted to expand a little bit on what Dr Fry said with respect to early identification of high-risk patients. When you think about it, the morbidity rates of exploring an area of severe cellulitis are very low. If the finding is negative, the worst you are going to get is an incision and no debridement at all. If the finding is positive, then you have taken a very important step to intervening early and aborting the development of the whole disease.

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Panel discussion: Complicated/uncomplicated surgical infections S23

Dr Hardin. One of the things that I think we need to point out is that in young patients we also see variants of these necrotizing infections. The most significant is omphalitis seen in the newborn. This can progress into a necrotizing infection and be rapidly fatal. It has the same presentation, but we do not have the luxury of being able to evaluate pain out of proportion. In this population, we look for early signs of systemic illness, and we have a high index of suspicion. We are very aggressive about operating on these children and doing early debridement. Dr Nichols. I have told many doctors that you don’t get sued for making an incision and looking for evidence of deep tissue involvement and necrotic or gangrenous changes. Now you have a patient, but you are not sure if he or she has one of these virulent infections unless you surgically explore the wound. It isn’t a straightforward situation as it is when you have a patient with black spots of the scrotum, indicating Fournier’s gangrene. How long do you use antibiotics before you turn to surgical exploration? Dr Condon. First, let us remember that not every little bit of erythema is going to get into this classification. Also, Dr Fry made an important point: The subcutaneous infection, the cellulitis, may not produce induration, may not produce pain out of proportion, may not produce toxicity, even when it is caused by Clostridium spp or virulent streptococci. You must have a high index of suspicion. I think that antibiotics need to be given in high doses and early. You can always reduce the dose, but the usual mistake is to start late, to start with only one drug, and not to give enough. Patients with the possibility of serious cellulitis or deep necrotizing infection ought to be put on high-dose penicillin, a very broad-spectrum agent such as meropenem—in preference to imipenem—and ought to receive clindamycin. If there is Clostridium there, clindamycin turns off the production of A toxin. Then you can begin to sort out the real nature of the infection and tailor the subsequent antibiotic therapy to the documented microbiology. Dr Nichols. What do you do for S aureus, which accounts for a very large number of the isolates along with the streptococci? Dr Chambers. I don’t think penicillin adds much, actually. I think it has absolutely no usefulness if you use other drugs at a high enough dose. You could do that many ways. I think you need to cover streptococci and staphylococci. In some patients, you may have a very high index of suspicion for an anaerobic infection. If a patient is diabetic, an injection drug user, or if the infection has

an abdominal presentation, you may be dealing with a complex microbiology, and it may be more than just a group A streptococcal cellulitis. Consequently, whatever regimen you use should be directed toward those potential pathogens.11,12 Dr Fry. I agree with the choice of clindamycin because it does shut off the toxin production. The issue of toxin production in these patients is really a serious concern. Thus, whether or not there are staphylococci or an anaerobe, high-dose clindamycin is an essential component of the treatment of these types of patients. Dr Nichols. I think it is important to reiterate that a black spot on the scrotum is pathognomonic of Fournier’s disease. Most of these necrotizing infections are polymicrobial, caused by both aerobes and anaerobes; a few are streptococcal only. In 1994, McHenry and Malangoni’s paper in American Surgeon described a syndrome that has confused many physicians.13 This is the syndrome with group A streptococci, in which there is no obvious portal of entry and no break of the skin. Infection is spread to a soft tissue area by hematogenous spread from unknown sources, perhaps the oropharynx. Dr Malangoni, would you address this problem because we should stress the importance of these infections in people with no apparent portal of entry? Dr Malangoni. I think one of the key points is that unexplained, disproportionate pain was found in most of these patients. Many of them had fever, many of them had an elevated white blood cell count. The dominant organism was Streptococcus pyogenes, but it was present in only 55% to 60% of cases.13 There were a variety of other pathogens. Although these are unusual infections, it is important to remember a portal of entry is not required, nor is an incision, nor must you have a sore that’s festered. Dr Nichols. It seems to be very common today. What is the source? Dr Fry. I think it comes from the pharynx. If it is in a postoperative infection or a blood stream infection, group A Streptococcus is a reportable disease to the Department of Health in New Mexico. Twenty percent of the patients have no portal of entry. They will have acute streptococcal bacteremia without a site of infection. The Ontario (Canada) study in the New England Journal of Medicine in 1996 reported on 323 cases of invasive streptococcal infection.14 Nineteen percent of patients had no portal of entry. I think these are very similar to the patients with postsplenectomy sepsis who get a pneumococcus that probably came

S24 Panel discussion: Complicated/uncomplicated surgical infections

from the hypopharynx. In some patients, the infections appear as metastatic infections. We had one patient in whom I took 40% of his body surface and did a forequarter amputation after he fell and just bruised his flank. He then developed metastatic infection without even breaking the skin surface. If you create a microenvironment of a bruise, contusion or hematoma after some event that occurred in the home and the patient has one of these primary bacteremias without a portal of infection, you can end up with a metastatic necrotizing infection from group A streptococci. Dr Nichols. Dr Ledger, group A streptococci has always been a significant issue in obstetrics and gynecology. Dr Ledger. That’s right. I think there are more cases now, and I think this is part of the fluctuations that we see. There are two problems for obstetrician/gynecologists. It may be the same for all doctors. One is that our practice has moved out of the hospital into the outpatient setting, and I don’t know whether we teach the young practitioners as well. We don’t have the organized inpatient rounds where they would see these cases and talk about them. The other problem is that even when we do talk about them and let everyone know about it, the next case that comes in is missed again. Physicians don’t recognize it. Group A streptococcal infection is certainly something we’re seeing more frequently in our area. In these cases, I think clindamycin is very, very important. It is a much better drug for these patients. Dr Barie. We should not leave the issue of necrotizing faciitis without reemphasizing that the majority of these patients (about 80%) have polymicrobial infections, not just those with fasciitis of the perineum (Fournier-type). Typically, the flora in these mixed infections consists of gram-positive cocci (usually staphylococci), aerobic gram-negative bacilli, and anaerobes. Antibiotic therapy must be broad initially, and can be narrowed for confirmation of a monomicrobic gram-positive infection. KEY STATEMENTS REGARDING NECROTIZING FASCIITIS Like perirectal abscess, the optimum treatment for necrotizing fasciitis is prompt surgical therapy. This may involve frequent trips to the operating room for debridement. Appropriate antibiotic therapy must also be given. Early recognition and aggressive intervention are essential. It is important to note that although the prevalence of necrotizing fasciitis is increasing, it remains an uncommon problem. Most physicians will see several cases during their practice lifetime, but rarely will this experience be

Surgery October 2000

sufficiently frequent to permit easy recognition. A high index of suspicion is key. TOXIC SHOCK SYNDROME Dr Nichols. Let me ask you about toxic shock syndrome that we saw in 1979. It used to be menstrual toxic shock. This rare infection was characterized by fever, an erythematous rash, desquamation of the palms and soles of the feet late in the disease, multiple organ failure, and most importantly hypotension. Now there are surgical wounds that cause these same types of devastating infections.15 Dr Ledger. I think it is a specific organism, S aureus, and patients who do not have antibodies against toxic shock syndrome toxin-1 are susceptible. Whether it is the presence of a tampon in the vagina for a long period of time, or a surgical wound infection caused by this strain of Staphylococcus, it is these patients who are susceptible to this type of infection from these virulent pathogens. Dr Christou. Toxic shock syndrome may also be caused by streptococci. The Ontario study group has reported extensively about the other characteristic of some of these streptococci: they initiate superantigen production.16 An antigen will stimulate 1 in 100 T cells, a superantigen will stimulate at 1 in 10,000 or 1 in 100,000. Thus intravenous immunoglobulin has been suggested as an adjunct to the treatment of these people. Early surgery is very important, as is high-dose antibiotic therapy, as an initial measure. One can sort out the details after getting microbiology test results. Dr Dellinger. I think it is worth mentioning that the wound that is the cause of toxic shock can look extremely innocent. We have had a couple of striking cases. Dr Nichols. That’s right. It can be a simple hematoma that later gets infected through the blood stream and goes on to produce the often lethal toxin. Dr Fry. Commonly, the infection is not really an invasive infection in toxic shock, in which you have the microbe proliferating in the foreign body. Only 3% of patients with toxic shock have blood cultures that are positive for staphylococci. In contrast, 80% of patients will have a positive blood culture with the invasive group A streptococci.9 The last point I would like to emphasize is that there is considerable chemical homology between the traditional toxic shock toxin now and the group A streptococci. This has led some people to speculate that there may have been genetic transfer between the 2 species.9 We are very interested in this in New Mexico as a possible explanation for

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Panel discussion: Complicated/uncomplicated surgical infections S25

the seemingly more virulent kinds of streptococcal infections we are seeing now. KEY STATEMENTS REGARDING TOXIC SHOCK SYNDROME Toxic shock syndrome is caused by a specific species of S aureus or group A Streptococcus and occurs in patients with no antibodies to the toxic shock syndrome toxin-1. It results in a severe symptom complex, most often without significant clinical infection. The treatment is symptomatic and antibiotics are given to suppress the offending microorganism. INTRA-ABDOMINAL ABSCESS Dr Nichols. What about intra-abdominal sepsis in general surgical and obstetric/gynecologic practice? Dr Ledger. In gynecology, there has been a trend in the last 3 to 4 years of using laparoscopy and draining abscesses with needles under direct visualization.17 We are seeing fewer pelvic abscesses and fewer people who require operations in which pelvic organs are removed.18 The early work done in France was an observational study. That study was very suggestive that these patients get better quicker and do very well. Also, because of Sherwood Gorbach and his group of investigators, there is an increased awareness of the importance of gram-negative anaerobes.19,20 Patients with these infections are placed on antibiotics effective against gram-negative anaerobes very early so that the ruptured tuboovarian abscess that was a common event 20 to 30 years ago is really very uncommon today. When they do occur, everyone talks about them because they are such a rare event. Dr Condon. Very severe pelvic inflammatory disease is now an uncommon presentation, and I believe that the absolute incidence of tubo-ovarian abscess of any size has also decreased dramatically. Why is that? Dr Ledger. I think it’s because these patients are recognized early and are treated right from the beginning with antibiotics that are effective against gram-negative anaerobes. Gynecologists used to write about sterile abscesses and that we had to operate on everyone; one could not cure an abscess. At that time, they were treating patients with penicillin and an aminoglycoside that was ineffective against the gram-negative anaerobes. When we’ve started treatment immediately, as happens now, we rarely see patients with abscesses. Dr Gorbach. The same thing is happening in intra-abdominal infection. Altemeier published his classic paper on approximately 750 cases of intra-

abdominal abscess in an 11-year period.21 At Cook County Hospital at the same time, we were seeing 50 to 75 cases a year. Now these infections have become very uncommon. Interestingly, when an intra-abdominal abscess is found, it is often in a later stage, with unusual organisms. I have been impressed with the number of Candida abscesses. I think not only has there been a real shift in the number of infections, but also, very importantly, in the microbiology of those infections.22 If I see a late abscess, I would not think of starting conventional antibiotics the way we have done in the past. I would be looking for Candida, Pseudomonas, or vancomycin-resistant enterococci and would treat accordingly. Dr Malangoni. This raises the subject of the importance of culturing. I’d like to ask Dr Fry about an article from the University of New Mexico suggesting that in some of these infections, culture may not help in making initial therapeutic decisions.23 Dr Fry. If you operate on a patient and see fecal contamination, why should you expect anything other than stool microflora? In the community, as opposed to many tertiary care centers where we practice, the laboratory may not correctly represent what is present in the abdomen. Therefore I believe that when we culture acute communityacquired bacterial peritonitis such as an acute perforated diverticulum or an acute perforated appendix, we can expect what the organisms will be. We need to treat aerobes and anaerobes with conventional, appropriate therapy. For the reasons that Dr Gorbach mentioned, treatment failures in 1999 are commonly from very bizarre organisms, and you may need to reculture at the time you have a treatment failure. Dr Nichols. How many people on this panel routinely culture intra-abdominal or pelvic infection where there is no leak of bowel or trauma with a leak? Dr Condon. If a patient presents from the community with acute bacterial peritonitis of whatever cause, the flora are predictable. We demonstrated that the antibiotic susceptibilities are also predictable and stable over time.23 The community reservoir of organisms that you will find in the abdomen has not changed over the last 2 decades. One starts antibiotics and goes to surgery. I wouldn’t culture that patient. Dr Malangoni. I think I would agree with that circumstance with one exception. You cannot include the nursing home patient as part of the community because these individuals frequently harbor nosocomial flora.

S26 Panel discussion: Complicated/uncomplicated surgical infections

KEY STATEMENT REGARDING INTRA-ABDOMINAL ABSCESS Appropriate early surgical intervention is the best treatment. The early use of parenteral antibiotics aimed at colonic aerobes and anaerobes, or antibiotics effective against identified (cultured) pathogen(s) may be necessary. Pelvic abscesses from gram-negative anaerobes are much less frequent today. The early use of antibiotics effective against gram-negative anaerobes is at least one factor in this development. TREATMENT APPROACHES TO POSTOPERATIVE INFECTIONS Dr Nichols. Now, would we all culture the patient who comes acutely to the hospital from the home or from the community and who has an obvious leak of microflora? Having ordered a culture, how would you approach the patient with a postoperative infection? Dr Malangoni. There are a variety of choices. You should make a decision based on whether this is a community-acquired infection, whether the patient has been in a nursing home and acquired a secondary bacterial peritonitis or fasciitis, or whether it is a more complicated problem such as a postoperative abscess. There may be some specific situations in which the choice of antibiotics may be limited. For example, the soft tissue infections seen on the upper extremities of black tar heroin addicts are different from the flora seen in other necrotizing infections. Dr Rotstein. In the management of peritonitis, it is important to define or distinguish the different types of peritonitis; that is, primary, secondary, and tertiary peritonitis. In secondary and tertiary peritonitis, one sees polymicrobial flora. The management approach to those infections is far different from the approach that is used for primary peritonitis. In general, patients with tertiary peritonitis are the sickest and have the highest probability of dying. They have had several interventions and multiple doses of antibiotics, and their flora is far different than the standard polymicrobial anaerobic/aerobic type. Instead of E coli or Bacteroides fragilis, these infections involve Staphylococcus epidermidis, Candida species, Enterococcus spp, or Pseudomonas spp and should be treated quite differently than our standard regimen for treating aerobes and anaerobes. From an antimicrobial standpoint, those microbes are not necessarily resistant microbes. John Marshall wrote a paper more than a decade ago in which he prospectively looked at the microflora of the GI tract in ICU patients.24 He maintained that there is a significant correlation with the unusual microbes elsewhere. In the reviews

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of tertiary peritonitis that have been done, quite frequently the GI tract is open and the peritoneal cavity is colonized through that mechanism as well. Dr Nichols. You are talking about gram-positive pathogens. Given the high rate of resistance among these organisms now, we know that patients with infections from these organisms often have a difficult course. Infections from S epidermidis or enterococcal sepsis are associated with increases in the number of days spent in the ICU. When resistance is noted, there are some newer antimicrobial agents such as quinupristin/dalfopristin that may have an important role. Dr Rotstein. In a tertiary care hospital, the problem of resistant gram-positive infections is one of our major issues. Indeed, most patients, when they come to our hospital from another institution, are cultured to see if they need to be isolated. Dr Nichols. These gram-positive pathogens have become important in the transplant centers. Dr Linden, what are your observations about resistance patterns of gram-positive pathogens and the therapeutic implications? Dr Linden. In the liver transplant units, one sees multiple scenarios. We see the patient who has had a long length of stay, who has had a long wait in the ICU or in the hospital for a suitable donor organ, and who invariably goes into his transplant surgery already colonized with vancomycin-resistant enterococcus (VRE). This patient has a lung or liver transplant and a high transfusion load and develops postoperative peritonitis that is monomicrobial. It is interesting to note that so much VRE infection is monomicrobial. In the vancomycin-sensitive era, it was difficult to attribute poor outcome to the Enterococcus because there were usually also gramnegative bacteria present. Now, the only pathogen one often finds is VRE because it persists. These patients with VRE have not had successful percutaneous drainages or multiple trips to the operating room. Often they have secondary complications because they have a fistula, or their abdomen is left open, or invasive aspergillosis develops. Thus there is an extended course of negative sequelae from as many as 5 trips to the operating room in a few weeks—even if the only thing that is done is debridement. I think the patient with an abscess does better than the patient with a diffuse peritonitis. My bigger concern is the patients without a technical complication who have early VRE peritonitis develop, which is a breakthrough phenomenon. Dr Nichols. How do you treat those patients? Dr Linden. It has been a work in progress. Like

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a lot of other clinicians, we initially reached for the antiquated antimicrobials, which were novobiocin, chloramphenicol, and whatever worked in the test tube. Invariably they were bacteriostatic and had some unwanted toxicities. Dr Nichols. What do you use parenterally? Dr Linden. We’ve used quinupristin/dalfopristin (Synercid) in about 150 patients since about 1993. We are involved in studying some other investigational agents for gram-positive infections as well. We no longer use much chloramphenicol. Our chloramphenicol susceptibilities have gone from about 95% down to about 60% to 70%. Not surprisingly, rifampin susceptibilities have gone from the 90% range down to the 70% range. There are very few drugs available. Dr Newell. If you look at our published experience in the early 1990s, the 2 most common organisms were Enterobacter and Enterococcus.25,26 Through changes in antibiotics, we have now selected grampositive pathogens. We see several different presentations. First, we see the late infection that is more often related to technical problems. Second, we encounter the early infections with gram-positive organisms and, unlike the reports from Pittsburgh of abscesses and discrete infections, we see a diffuse infectious process. There is nothing that you can easily drain. We lavage fluids wherever the various organisms are found. However, it is not rewarding because you don’t feel you’ve found the source of the problem. Perhaps it is a host problem in which these patients are compromised from the outset. In addition to the resistant Enterococcus faecium (20%), we are very commonly finding Candida there as well. FUNGAL INFECTIONS: RECOGNITION AND MANAGEMENT Dr Nichols. How do you treat massive enterococcal and fungal infections? Do you use amphotericin and quinupristin/dalfopristin? Dr Newell. That is the approach we are using most frequently. I would like to ask the group what are the recommendations for patients who have tertiary peritonitis and the possibility of a fungal infection? Do you use empiric treatment for fungus? Dr Gorbach. There are certain organisms that are not mysterious; if they are present, they grow in culture. S epidermidis and S aureus easily grow in culture. If a fungus is present in tissue or the peritoneal cavity, it will grow in culture. In such chronic cases, or so-called tertiary peritonitis, I recommend waiting for a positive culture so that appropriate treatment can be given.

With regard to treatment of fungal peritonitis, my experience with fluconazole has been singularly unproductive. So we use low-dose amphotericin, approximately 20 mg/day, with a total dose of about 200 mg. Dr Linden. We use low-dose amphotericin and it seems to work. There appears to be a protective effect both in terms of documented Candida infections and cases in which a Candida infection is suspected. We use 10 mg to 20 mg/day for approximately 7 to 14 days. The UCLA group did a placebo-controlled trial on the use of fluconazole in liver transplant recipients. It was found to be effective.27 Dr Gorbach. Richard Wenzel has reported development of resistance in Candida species when using a lot of fluconazole.28 Dr Dunn. With respect to prophylaxis and treatment in the immunosuppressed transplant patients, there are 2 groups: long-term infections not associated with the immediate surgical problem and short-term infectious issues. We use prophylactic trimethoprim/sulfamethoxazole to prevent the emergence of organisms such as Legionella spp, Pneumocystis carinii, Nocardia spp, and other pathogens that cause significant infections in these patients. Antiviral prophylaxis is another topic that is controversial. I think it is clear that you can prevent most types of cytomegalovirus, with the exception of primary cytomegalovirus, with standard acyclovir or ganciclovir prophylaxis. With respect to treatment of tertiary peritonitis, I think the paper that Dr Rotstein published in the Canadian Journal of Surgery really set the standard for retrospective trials looking at mortality rate.29 In that study, mortality rate was reported to be approximately 50%. It was not affected by treatment with either vancomycin to treat gram-positive organisms or amphotericin B to treat the fungi. We may be dealing with at least 2 subsets of patients: patients who are colonized, have cultures obtained, and are given fluconazole to eradicate the fungi. The other subset are patients who actually have tertiary peritonitis and probably require re-exploration. Dr Rotstein. One of the interesting things about transplant recipients who get tertiary peritonitis is that they skip secondary peritonitis. We believe this is because we define the patient with tertiary peritonitis as someone who is immunosuppressed and who has had a lot of antibiotics and/or other interventions. In general, we should not be giving blind broad-spectrum antimicrobial agents to these immunocompromised patients. One needs to treat the pathogen recovered from your cultures.

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Table II. Medical management of methicilin-resistant Staphylococcus aureus in hospitalized patients Colonized or nasal carriage state • Preventive measures: careful, repeated hand-washing in healthcare workers, isolation of patients, removal of colonized catheters ± eradication of nasal carriage with mupirocin (?) • Eradication of carriage: may be indicated for recurrent infections or presence of an epidemic strain in a potential source case. Mupirocin ointment for 5-7 days, or a regimen including rifampin and another drug to which the strain is susceptible Systemic infections from methicilin-resistant Staphylococcus aureus • Vancomycin for bacteremia, skin and soft tissue infection, native valve endocarditis* • Vancomycin + rifampin for bone and joint infection, meningitis • Vancomycin + rifampin + gentamicin for prosthetic valve endocarditis Alternative and future therapies • Quinupristin/dalfopristin • Linezolid • Newer fluoroquinolones (eg, trovafloxacin, clinafloxacin, levofloxacin (± rifampin) • Daptomycin (?) • LY333328 (?) *Some authorities suggest adding low-dose gentamicin (ie, 1 mg/kg per 8 h) or rifampin (600 mg/d) to vancomycin. However, data supporting improved outcome with combination therapy are lacking, and vancomycin and gentamicin in combination are more nephrotoxic and ototoxic than either drug alone. Adapted from Michel M, Gutmann M. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: therapeutic realities and possibilities. Lancet 1997;349:1901-6. Copyright by The Lancet Ltd.

However, that is not the whole answer to the problem. What is also needed is a more controlled approach to determining not only the optimal antimicrobial therapy, but also the specific interventional therapy (percutaneous vs operative). Dr Dunn. One of the things that we often do in these patients is to reduce the dosage of the antibacterial agent(s) as well as immunosuppression. Sometimes we find that these seriously ill patients are on full dose immunosuppression, and there is a request to add an antifungal agent. For example, the patient may be on imipenem, cilastatin, and vancomycin. I think the solution is to truncate the antibacterial agent therapy, reduce the immunosuppression, and reculture. We have a very large pancreas transplant service, and this is a heavily contaminated case group. Care must be taken not to make the situation worse. For example, in an effort to reduce superficial and deep wound infection rates, the use of a β-lactam antibiotic, vancomycin and fluconazole for 7 to 10 days, will select for VRE with no substantial decrement in overall outcome. We need to think very carefully about the implications of our antimicrobial therapies because as we learned, one can promulgate resistance without changing overall patient outcomes. Dr Malangoni. There are data that show that if you do pick the right antibiotic and it matches your cultures, then those patients have a better outcome than if the selected empiric therapy does not match the culture report. The weakness of these papers is that they were not risk-stratified.

The second comment I would make is that we are beginning to see some of these same problems in the nontransplant patient in whom, after an operation, tertiary peritonitis develops. Much like the transplant patient, this is not localized, usual bacterial flora that is purulent, but a more murkylooking fluid that does not have a high degree of contamination but on CT scan or at operation has a clearly identifiable cavity with bacteria growing in it. This is very different from the traditional abscess. I think we are going to see more of this as we begin to treat more of these patients whose disease is more advanced and who have had multiple operations. Dr Fry. I think that sometimes we chase our tails trying to treat things as infections where the bugs are in fact just the surrogate marker for the fact that the host defense has collapsed. We end up rotating our organisms as a function of the antimicrobials we use and we sort of go from one bug to the next. I think that’s why we see some of the data in the studies to which Dr Rotstein referred. We constantly add more and more drugs, but I’d like to make the argument for perhaps deleting one category of antimicrobial coverage: anaerobes. When they are in soft tissue and in the peritoneal cavity, they are very genuine synergistic pathogens and cause real disease, but anaerobes that are in the human colon, that colonize the human gut, I believe have very real and very positive host defense benefits. Dr Newell. In the last several years, I don’t believe we’ve seen a significant anaerobic infection

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Panel discussion: Complicated/uncomplicated surgical infections S29

in our patients; we never treat for it. If you view some of these as a host problem, withdrawing immunosuppression is a first step. Surprisingly, we have people who are on minimal doses of steroids after transplantation; it is very uncommon for them to reject their transplanted organ. CONCLUSION Dr Nichols. In recent years, because of the rising prevalence of resistance to penicillin and other βlactam agents among gram-positive organisms, surgeons have turned to vancomycin for prophylaxis and treatment of surgical wound infections. It is recommended that surgeons follow the suggested approach of the Hospital Infection Control Practices Advisory Committee (HICPAC) concerning the appropriate use of antimicrobial agents, particularly the use of vancomycin (1995). One prospective study has reported that a survey of a tertiary care hospital found that only one third of the orders for vancomycin were consistent with HICPAC guidelines.30 Unfortunately, there have been several recent reports on the emergence of resistance to glycopeptides among enterococci and staphylococci. Reports of isolates with vancomycin MICs of 8 µg/mL, classified as intermediate resistance, have been reported in the United States. A recent report in Infection Control and Hospital Epidemiology found reduced susceptibility to vancomycin among coagulase-negative staphylococci.31,32 Because staphylococci are commonly identified organisms associated with surgical wound infections and pneumonia, the specter of glycopeptide resistance is very disturbing. Recently, several new agents have been developed that may provide some hope for critically ill patients in whom vancomycin resistance would be catastrophic. Streptogramins or oxazolidinones may be helpful. I have reported on our experience with quinupristin/dalfopristin that produced an equivalent clinical efficacy rate as standard therapies.33 In summary, the prevention of surgical wound infections is of paramount importance. Applying standard infection control measures, practicing careful and exacting surgical techniques, understanding the factors that increase a patient’s risk of infection (such as T-time and type of surgery), and the individual patient’s risk factors are extremely important considerations. The clinician must use the prevalence and susceptibility data from his or her institution concerning those organisms in selecting both prophylactic and therapeutic antimicrobial regimens. Knowing the spectrum of action

and toxicity profile of the available drugs will enable one to make intelligent, appropriate therapeutic choices in effectively treating infection and in reducing the possibility of resistance in the institution (Table II). REFERENCES 1. Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA 1998;279:1537-41. 2. Nichols RL, Smith JW, Klein DB, Trunkey DD, Dooper RH, Adinolfi MF, et al. Risk of infection after penetrating abdominal trauma. N Engl J Med 1984;311:1065-70. 3. Browder W, Smith JW, Vivoda LM, Nichols RL. Nonperforative appendicitis: a continuing surgical dilemma. J Infect Dis 1989;159:1088-94. 4. Cruse PJE, Foord R. The epidemiology of wound infection: A 10-year prospective study of 62,939 wounds. Surg Clin North Am 1980;60:1. 5. Kaul R, McGeer A, Low DE, Green K, Schwartz B. Population-based surveillance for group A streptococcal necrotizing fasciitis: clinical features, prognostic indicators, and microbiological analysis of sevety-seven cases. Ontario Group A Streptococcal Study. Am J Med 1997;103:18-24. 6. Schwartz B, Facklam RR, Breiman RF. Changing epidemiology of group A streptococcal infection in the USA. Lancet 1990;336:1167-7. 7. Condon RE. Necrotizing skin and soft tissue infections. In: Conn’s current therapy. Rakel R, editor. Philadelphia: WB Saunders; 1998. p. 87-90. 8. Eriksson B, Andersson J, Holm SE, Norgren M. Epidemiological and clinical aspects of invasive group A streptococcal infection and the streptococcal toxic shock syndrome. Clin Infect Dis 1998;27:1428-36. 9. Fry DE. Toxic shock syndrome. In: Surgical infection. Fry DE, editor. Boston: Little Brown; 1995. p. 569-76. 10. Stevens DL, Tanner MH, Winship J, Swarts R, Ries KM, Schlievert PM, et al. Severe group A streptococcal infection associated with a toxic shock-like syndrome and scarlet fever toxic. N Engl J Med 1989;321:1. 11. Lewis RT. Soft tissue infections. World J Surg 1998;22:14655. 12. Brown G, Chamberlain R, Goulding J, Clarke A. Ceftriaxone verseus cefazolin with probenecid for severe skin and soft tissue infections. J Emerg Med 1996;14:547-51. 13. McHenry CR, Brandt CP, Piotrowski JJ, Jacobs DG, Malangoni MA. Idiopathic necrotising fasciitis: recognition, incidence and outcome of therapy. Am Surg 1994;60:490-4. 14. Davies HD, McGeer A, Schwartz B, Green K, Cann D, Simor AE, et al. The Ontario Group A Streptococcal Study Group. Invasive group a streptococcal infections in Ontario, Canada. N Engl J Med 1996;335:547-54. 15. Bartlett P, Reingold AL, Graham DR, Dan BB, Selinger DS, Tank GW, et al. Toxic shock syndrome associated with surgical wound infection. JAMA 1982;247:1448-50. 16. Norrby-Teglund A, Low DE, McGeer A, Kotb M. Superantigenic activity produced by group A streptococcal isolates is neutralized by plasma from IVIG-treated streptococcal toxic shock syndrome patients. Adv Exp Med Biol 1997;418:563-6. 17. Reich H, McGlynn F. Laparoscopic treatmentof tubo-ovarian and pelvic abscess. J Reprod Med 1984;29:579-82.

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18. Ledger WJ. A historical review of pelvic infections. Am J Obstet Gynecol 1988;158:687-93. 19. Thadepalli H, Gorbach SL, Keith L. Anaerobic infections of the female genital tract: bacteriologic and therapeutic aspects. Am J Obstet Gynecol 1973;117:1034-40. 20. Weinstein WM, Onderdonk AB, Gorbach SL, Bartlett JG. Experimental intra-abdominal abscesses in rats: development of an experimental model. Infect Immun 1974;10:1250-5. 21. Altemeier WA, Culbertson WR, Fullen WD, Shook CD. Intra-abdominal abscesses. Am J Surg 1973;125:70-9. 22. Gorbach SL. Intra-abdominal infections. Clin Infect Dis 1993;17:961-7. 23. Krepel CJ, Gohr CM, Edmiston CE, Condon RE. Surgical sepsis: constancy of antibiotic susceptibility of causative organisms. Surgery 1995;117:505-9. 24. Marshall JC, Christou NV, Horn R, Meakins JL. The microbiology of multiple organ failure. The proximal gastrointestinal tract as an occult reservoir of pathogens. Arch Surg 1988;123:309-15. 25. Arnow PM, Zachary KC, Thistlethwaite JR, Thompson KD, Bova JL, Newell KA. Pathogenesis of early operative site infections after orthotopic liver transplantation. Transplantation 1998;65:1500-3. 26. Newell KA, Millis JM, Arnow PM, Bruce DS, Woodle ES, Cronin DC, et al. Incidence and outcome of infection by vancomycin-resistant Enterococcus following orthotopic liver transplantation. Transplantation 1998;65:439-42.

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27. Linden P, Kramer DJ, Mazariegos G, Marsh W, Casavilla A, Pinna A, et al. Low-dose amphotericin B for the prophylaxis of serious Candida infection in high-risk liver recipients. Proceedings of the 36th International Conference on Antimicrobial Agents and Chemotherapy. New Orleans, La, September 1996. Abstract #J-47, p. 227. 28. Wenzel RP. Nosocomial candidemia: risk factors and attributable mortality. Clin Infect Dis 1995;20:1531-4. 29. Rotstein OD, Pruett TL, Simmons RL. Microbiologic features and treatment of persistent peritonitis in patients in the intensive care unit. Can J Surg 1986;29:247-50. 30. Hospital Infection Control Practices Advisory Committee (HICPAC).Recommendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol 1995;16:105-13. 31. Garrett DO, Jochimsen E, Murfitt K, Hill B, McAllister S, Nelson P, et al. The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis. Infect Control Hosp Epidemiol 1999;20:167-70. 32. Wong SS, Ho PL, Woo PC, Yuen KY. Bacteremia caused by staphylococci with inducible vancomycin heteroresistance. Clin Infect Dis 1999;29:760-7. 33. Nichols RL. Graham DR, Barriere SL, Rogers A, Wilson SE, Zervos M, et al. Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: two randomized multicenter studies of quinupristin—dalfopristin versus cephazolin, oxacillin, or vancomycin. J Antimicrobial Chemo 1999;44:263-73.