Background
Peritonitis can be defined in a variety of ways. Primary peritonitis is an infection of the peritoneal cavity usually occurring in patients with preexisting ascites that is not related to diseases of the abdominal or retroperitoneal viscera. Secondary peritonitis, the most common form of peritonitis, can occur due to spontaneous perforation of the gastrointestinal tract, intestinal ischemia, or following an operation. Tertiary peritonitis is a recurrent infection of the peritoneal cavity that follows an episode of either primary or secondary peritonitis [
1,
2]. Peritonitis can also be classified as diffuse or localized. Over time, peritoneal infection can coalesce to form an intraabdominal abscess. These two forms of peritonitis are often referred to collectively as intraabdominal infection.
There are a variety of factors influencing the reduction in mortality from peritonitis over the last century. Safer anesthetic techniques, improved understanding of perioperative fluid management, the advent of blood banking, improvements in critical care, more rapid and accurate diagnostic studies, and more effective antibiotics are some of the factors that have led to a reduction in mortality from peritonitis. On the other hand, a variety of challenges have arisen that threaten to offset these advances. Patients with intraabdominal infection are older, more commonly have comorbid diseases, often have associated immune suppression due to chronic diseases or their treatment, and more frequently have decreased physiologic reserve with either sub-clinical or evident organ failure. Although the bacterial flora of the gastrointestinal tract has remained relatively consistent over time, the widespread presence of antimicrobial resistance among patients with nosocomial as well as community-acquired infections has presented another challenge. This is particularly true for patients who have received previous antimicrobial treatment, inappropriate therapy, or have developed tertiary peritonitis where the pathogens are commonly resistant to front- line agents [
2‐
5].
Much of what has been learned about the management of peritonitis has come from prospective randomized clinical trials. A number of important concepts have developed from these studies. We recognize that patients with appendicular sources of peritonitis have a lower mortality and improved outcomes compared to patients with non-appendicular sources [
6]. Pancreatic necrosis incites a unique systemic inflammatory response, which is commonly associated with respiratory failure as well as other organ failures. Although pancreatic necrosis was once treated commonly with operation, non-operative management of sterile necrosis has become the norm due to the use of long-term prophylactic antibiotics to prevent infection and recognition than uninfected necrosis will usually resolve over time [
7]. Pancreatic necrosis is thus excluded from most reviews of peritonitis as it will be from the present review.
The successful management of intraabdominal infection is predicated on the use of appropriate operative measures to address peritoneal infection. Prospective clinical trials have also taught us the importance of the concept of "source control" [
2]. Source control encompasses all of the measures that eradicate the focus of infection, prevent continuing contamination, and restore functional anatomic relationships. This generally involves: 1) drainage of abscesses or infected fluid collections; 2) débridement of necrotic or infected tissues; and 3) definitive measures to control the source of contamination and to restore anatomy and function.
The response to intraabdominal infection depends upon the complex interaction of a variety of factors. The degree of microbial contamination, the site of origin of contamination and whether contamination is localized or diffuse are important. Previous operations or diseases can result in adhesions that may help localize infections. The systemic response to infection depends upon immune status as well as innate genetically coded responses to infection.
The diagnosis of intraabdominal infection is usually based on history and physical examination. Many patients will have abdominal computed tomography (CT) scanning to establish the diagnosis. CT is also useful to identify patients with localized abscesses who are candidates for percutaneous drainage rather than operation.
The treatment of intraabdominal infections is based on the restoration of normal homeostasis. Treatment principles include: 1) restoration of fluid and electrolyte imbalances; 2) administration of appropriate empiric antimicrobial therapy; 3) control of the source of infection; and 4) physiologic support of organ systems. Failure to address any of these important areas can lead to increased mortality, an increased incidence of organ failure, and prolonged hospital stay.
This article will review the recent advances in the treatment of intraabdominal infections in the Western world. Emphasis will be on the emergence of newer developments upon the outcome of treatment.
Management of localized peritonitis
Patients with a localized intraabdominal abscess are often candidates for percutaneous drainage. This is usually done under CT or ultrasound guidance. Percutaneous drainage is most successful for patients with single abscesses that are accessible by a safe route. Patients with multiple abscesses, complex or multilocular abscesses, associated necrotic tissue, or who require resection of a neoplasm are usually better candidates for open drainage [
20].
Both percutaneous and open drainage of intraabdominal abscesses have a similar rate of success. There is no doubt that percutaneous drainage is associated with less morbidity and a shorter length of stay. Mortality appears to be similar for these two techniques.
Measures of successful treatment
Adequate source control can be achieved at initial operation in 90% or greater of patients. The need for reoperation in this group is less than 10%. When source control is not possible at the initial operation, the rate of reoperation is 30% or greater [
21,
22].
There is both a significant increase in mortality and worse long-term survival among patients with peritonitis who undergo planned relaparotomy compared to those who have relaparotomy on demand [
23]. Exceptions include patients with intestinal ischemia, advanced tertiary peritonitis, infected ascites, or those who need to have reestablishment of intestinal continuity at a second operation.
Role of antimicrobial therapy
The recommended antimicrobial regimens for patients with intraabdominal infections have been outlined by the Surgical Infection Society based on prospective randomized clinical trials (Table
1) [
24,
25]. Since this publication, additional antimicrobial regimens have been found to be of similar efficacy to these previously endorsed drugs [
26,
27]. Importantly, all of the recommended regimens are effective against gram negative enteric aerobic and anaerobic microorganisms. A recent review of prospective randomized studies of antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults from the Cochrane Colorectal Cancer Group concluded that 16 antibiotic regimens had similar rates of clinical success [
28]. There was no difference in mortality between any of these regimens.
Table 1
Recommended antimicrobial regimens for patients with intra-abdominal infection
Single agents |
Ampicillin/sulbactam |
Cefotetan |
Cefoxitin |
Ertapenem |
Imipenem/cilastatin |
Meropenem |
Moxifloxacin |
Piperacillin/tazobactam |
Ticarcillin/clavulanic acid |
Combination regimens
|
Aminoglycoside plus an antianaerobe agent (clindamycin or metronidazole) |
Aztreonam plus clindamycin |
Cefuroxime plus metronidazole |
Ciprofloxacin plus metronidazole |
Third-or fourth-generation cephalosporin (cefepime, cefotaxime, ceftazidime, ceftizoxime, or ceftriaxone) plus an antianaerobe |
The use of appropriate empiric antimicrobial treatment has been associated with improved survival in a variety of clinical settings [
5,
29]. A recent study by Baré et al. has demonstrated that selection of an appropriate treatment regimen as recommended by the Surgical Infection Society was associated with a significant and marked improvement in successful treatment [
5]. Mortality was not significantly reduced by the use of an appropriate regimen. This study was conducted retrospectively and only patients with community-acquired intraabdominal infections were included. These authors also identified colonic sites of infection, age ≥ 75 years, and a Charlson Index of one or greater as other factors associated with successful treatment.
It has been recognized for some time that patients who have intraabdominal infections and are treated with empiric antimicrobial therapy have a greater rate of treatment failure when resistant organisms are cultured [
30,
31]. The influence of
Candida cultured from the peritoneal fluid has been controversial, since this organism is not routinely treated by most empiric therapy regimens. Montravers and coworkers have demonstrated that the isolation of
Candida from peritoneal cultures of patients with nosocomial peritonitis appears to be an independent risk factor for mortality [
32]. In contrast, patients with community-acquired infections who have growth of
Candida on culture were not at greater risk for death.
There has not been a consensus about the appropriate duration of treatment for intraabdominal infections. Some believe that antibiotics can be stopped once fever and leukocytosis have resolved, and gastrointestinal function has returned [
25], while others recommend a specific duration of therapy [
24]. The development of effective oral antimicrobials for the treatment of intraabdominal infections has led to a number of prospective randomized trials that have advocated switching to oral antibiotics once patients can tolerate a diet. [
24,
25,
27] This has been advocated as a cost saving measure without clear data defining the duration of treatment. Taylor and colleagues have demonstrated that the use of postoperative oral antibiotics once intravenous antibiotics were stopped did not improve outcomes in patients with complicated appendicitis [
33]. This study questions whether continued antibiotics are needed in patients once gastrointestinal function has returned.
Competing interests
Dr. Malangoni has served as a consultant and received research funding from Astra-Zeneca, Bayer, Eli Lilly, Merck, Ortho-McNeill and Wyeth-Ayerst. Mr. Inui has no competing interests.
Authors' contributions
MM contributed to the conception and design, acquisition of data, analysis and interpretation of data, and final approval of the manuscript.
TI was involved in acquisition of data and drafting of the manuscript.
The authors have read and approved the final manuscript.