In peritonitis caused by bacteria, the physiologic response is determined by several factors, including the virulence of the contaminant, the size of the inoculum, the immune status and overall health of the host (eg, as indicated by the Acute Physiology and Chronic Health Evaluation II [APACHE II score!, and elements of the local environment, such as necrotic tissue, blood, or bile"[# Intra$abdominal sepsis from a perforated viscus (ie, secondary peritonitis or suppurative peritonitis! results from direct spillage of luminal contents into the peritoneum (eg, perforated peptic ulcer, diverticulitis, appendicitis, iatrogenic perforation!" %ith the spillage of the contents, gram$negative and anaerobic bacteria, including common gut flora, such as Escherichia coli and Klebsiella pneumoniae, enter the peritoneal cavity" Endoto&ins produced by gram$negative bacteria lead to the release of cyto'ines that induce cellular and humoral cascades, resulting in cellular damage, septic shoc', and multiple organ dysfunction syndrome (()*+!" ,he mechanism for bacterial inoculation of ascites has been the sub-ect of much debate since Harold Conn first recognized it in the ./01s" Enteric organisms have traditionally been isolated from more than /12 of infected ascites fluid in spontaneous bacterial peritonitis (+3P!, suggesting that the 4I tract is the source of bacterial contamination" ,he preponderance of enteric organisms, in combination 5ith the presence of endoto&in in ascitic fluid and blood, once favored the argument that +3P 5as due to direct transmural migration of bacteria from an intestinal or hollo5 organ lumen, a phenomenon called bacterial translocation" Ho5ever, e&perimental evidence suggests that direct transmural migration of microorganisms might not be the cause of +3P" An alternative proposed mechanism for bacterial inoculation of ascites suggests a hematogenous source of the infecting organism in combination 5ith an impaired immune defense system" 6onetheless, the e&act mechanism of bacterial displacement from the 4I tract into ascites fluid remains the source of much debate" A host of factors contributes to the formation of peritoneal inflammation and bacterial gro5th in the ascitic fluid" A 'ey predisposing factor may be the intestinal bacterial overgro5th found in people 5ith cirrhosis, mainly attributed to decreased intestinal transit time" Intestinal bacterial overgro5th, along 5ith impaired phagocytic function, lo5 serum and ascites complement levels, and decreased activity of the reticuloendothelial system, contributes to an increased number of microorganisms and decreased capacity to clear them from the bloodstream, resulting in their migration into and eventual proliferation 5ithin ascites fluid" Interestingly, adults 5ith +3P typically have ascites, but most children 5ith +3P do not have ascites" ,he reason for and mechanism behind this is the source of ongoing investigation" FibrinolysisAlterations in fibrinolysis (through increased plasminogen activator inhibitor activity! and the production of fibrin e&udates have an important role in peritonitis" ,he production of fibrin e&udates is an important part of the host defense, but large numbers of bacteria may be se7uestered 5ithin the fibrin matri&" ,his may retard systemic dissemination of intraperitoneal infection and may decrease early mortality rates from sepsis, but it also is integral to the development of residual infection and abscess formation" As the fibrin matri& matures, the bacteria 5ithin are protected from host clearance mechanisms"%hether fibrin ultimately results in containment or persistent infection may depend on the degree of peritoneal bacterial contamination" In animal studies of mi&ed bacterial peritonitis that e&amined the effects of systemic defibrinogenation and those of abdominal fibrin therapy, heavy peritoneal contamination uniformly led to severe peritonitis 5ith early death (8 9: h! because of over5helming sepsis"Bacterial load3acterial load and the nature of the pathogen also play important roles" +ome studies suggest thatthe number of bacteria present at the onset of abdominal infections is much higher than originally believed (appro&imately # ; .1: Cm?, much higher than the @ ; .1@ Cm? inocula routinely used for in vitro susceptibility testing!" ,his bacterial load may over5helm the local host defense" Bacterial virulence3acterial virulence factors[A that interfere 5ith phagocytosis and 5ith neutrophil$mediated bacterial 'illing mediate the persistence of infections and abscess formation" Among these virulence factors are capsule formation, facultative anaerobic gro5th, adhesion capabilities, and succinic acid production" +ynergy bet5een certain bacterial and fungal organisms may also play an important role in impairing the hostBs defense" )ne such synergy may e&ist bet5een Bacteroides fragilis and gram$negative bacteria, particularly E coli (see the image belo5! , 5hereco$inoculation significantly increases bacterial proliferation and abscess formation" 4ram$negative Escherichia coli" EnterococciEnterococci may be important in enhancing the severity and persistence of peritoneal infections" In animal models of peritonitis 5ith E coli and B fragilis, the systemic manifestations of the peritoneal infection and bacteremia rates 5ere increased, as 5ere bacterial concentrations in the peritoneal fluid and rate of abscess formation" 6evertheless, the role of Enterococcus organisms in uncomplicated intra$abdominal infections remains unclear" Antibiotics that lac' specific activity against Enterococcus are often used successfully in the therapy of peritonitis, and the organism is not often recovered as a blood$borne pathogen in intra$abdominal sepsis" Fungi,he role of fungi in the formation of intra$abdominal abscesses is not fully understood" +ome authors suggest that bacteria and fungi e&ist as nonsynergistic parallel infections 5ith incompletecompetition, allo5ing the survival of all organisms" In this setting, treatment of the bacterial infection alone may lead to an overgro5th of fungi, 5hich may contribute to increased morbidity" Abscess formationAbscess formation occurs 5hen the host defense is unable to eliminate the infecting agent and attempts to control the spread of this agent by compartmentalization" ,his process is aided by a combination of factors that share a common feature, ie, impairment of phagocytotic 'illing" (ostanimal and human studies suggest that abscess formation occurs only in the presence of abscess$potentiating agents" Although the nature and spectrum of these factors have not been studied e&haustively, certain fiber analogues (eg, bran! and the contents of autoclaved stool have been identified as abscess$potentiating agents" In animal models, these factors inhibit opsonization andphagocytotic 'illing by interference 5ith complement activation" Cytokines,he role of cyto'ines in mediation of the bodyBs immune response and their role in the development of the systemic inflammatory response syndrome (+IC+! and multiple organ failure(()or an elevated %3C count may be the only signs present" As many as #12 of patients 5ith +3P demonstrate very subtle signs and symptoms" 6e5 onset or deterioration of e&isting encephalopathy may be the only sign of the infection at the initial presentation" (ost patients 5ith ,P demonstrate vaguesymptoms and may be afebrile" ,horacic processes 5ith diaphragmatic irritation (eg, empyema!, e&traperitoneal processes (eg, pyelonephritis, cystitis, acute urinary retention!, and abdominal 5all processes (eg, infection, rectus hematoma! may mimic certain signs and symptoms of peritonitis" Al5ays e&amine the patient for the presence of e&ternal hernias to rule out intestinal incarceration"According to Adler and 4asbarra, the follo5ing should be considered in the differential diagnosis[: D Chemical irritants (eg, bile, blood, gastric -uice, barium, enema or douche contents! Chronic peritoneal dialysis Chylous peritonitis Eosinophilic peritonitis L? or greater" ,his may happen in as many as @12 of patients 5ith +3P and may not actually represent a distinctly different disease entity" Cather, it may be the result of poor culturing techni7uesor late$stage resolving infection" 6onetheless, these patients should be treated -ust as aggressively as those 5ith positive culture results" (onomicrobial nonneutrocytic bacterascites e&ists 5hen a positive culture result coe&ists5ith a P(6 count #@1 cells>L? or greater" Although this may often be the result of contamination of bacterial cultures, A:2 of these patients develop +3P" ,herefore, monomicrobial nonneutrocytic bacterascites may represent an early form of +3P" All study patients described 5ho eventually developed +3P 5ere symptomatic" d?, ?*H level greater than /1 =>m?, and predominantly mononuclear cell count of more than @11 cells>L? should raise the suspicion of ,P, but specificity for the diagnosis is limited" ?aparoscopy 5ith visualization of granulomas on peritoneal biopsy and specific culture (5hich re7uires 9$0 5'! may be needed for definitive diagnosis" Peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAP*! is indicated by contamination of the dialysis catheterF cloudy effluent, total fluid %3C count of greater than .11 neutrophils>L?, or presence of organisms on 4ram stain" Coutine intraoperative peritoneal fluid cultures in defined acute disease entities (ie, gastric or duodenal ulcer perforation, appendicitis, diverticulitis or perforation of the colon caused by obstruction or ischemia! are controversial" +everal studies found no significant difference in patients 5ith appendicitis, diverticulitis, and other common etiologies for bacterial peritonitis 5ith regard to postoperative complication rates or overall outcomes" ,he antibiotic regimen 5as altered only :$.12 of the time based on operative culture data" In patients 5ho had previous abdominal operations or instrumentation (eg, peritoneal dialysis catheter, percutaneous stents! and patients 5ith prolonged antibiotic therapy, critical illness, and>or hospitalization, these cultures may reveal resistant or unusual organisms that should prompt alteration of the antibiotic strategy" ,he current approach to peritonitis and peritoneal abscesses targets correction of the underlying process, administration of systemic antibiotics, and supportive therapy to prevent or limit secondary complications due to organ system failure" ,reatment success is defined as ade7uate source control 5ith resolution of sepsis and clearance of all residual intra$abdominal infection" Early control of the septic source is mandatory and can be achieved by operative and nonoperative means")perative management addresses the need to control the infectious source and to purge bacteria and to&ins" ,he type and e&tent of surgery depends on the underlying disease process and the severity of intra$abdominal infection" *efinitive interventions to restore functional anatomy involve removing the source of the antimicrobial contamination and repairing the anatomic or functional disorder causing the infection" ,his is accomplished by surgical intervention" )ccasionally, this can be achieved during a single operationF ho5ever, in certain situations, a second or a third procedure may be re7uired" In some patients, definitive intervention is delayed until the condition of the patient improves and tissue healing is ade7uate to allo5 for a (sometimes! lengthy procedure" ,o see complete information on the +urgical Approach to Peritonitis and Abdominal +epsis, please go to the main article by clic'ing here" 6onoperative interventions include percutaneous abscess drainage, as 5ell as percutaneous and endoscopic stent placements" If an abscess is accessible for percutaneous drainage and if the underlying visceral organ pathology does not clearly re7uire operative intervention, percutaneousdrainage is a safe and effective initial treatment approach" %ith percutaneous treatment, the definition of success includes the avoidance of further operative intervention and, in some cases, the delay of surgery until after resolution of the initial sepsis" ,he general principles guiding the treatment of[.A infections are 9$fold, as follo5sD ." Control the infectious source#" Eliminate bacteria and to&insA" (aintain organ system function9" Control the inflammatory process,he treatment of peritonitis is multidisciplinary, 5ith complementary application of medical, operative, and nonoperative interventions" (edical support includes the follo5ingD +ystemic antibiotic therapy Intensive care 5ith hemodynamic, pulmonary, and renal support 6utrition and metabolic support Inflammatory response modulation therapyEarly control of the septic source is mandatory and can be achieved by operative and nonoperative means" 6onoperative interventional therapies include percutaneous drainage of abscesses and percutaneous and endoscopic stent placements" ,reatment of peritonitis and intra$abdominal sepsis al5ays begins 5ith volume resuscitation, correction of potential electrolyte and coagulation abnormalities, and empiric broad$spectrum parenteral antibiotic coverage" Antibiotic therapy is used to prevent local and hematogenous spread of infection and to reduce late complications"[.0 +everal different antibiotic regimens are available for the treatment of intra$abdominal infections"[.0 3oth single$agent broad$spectrum therapy and combination therapies have been used" Ho5ever, no specific therapy has been found to be superior to another therapy" Infection of the abdominal cavity re7uires coverage for gram$positive and gram$negative bacteria, as 5ell as for anaerobes" Antipseudomonal coverage is recommended in patients 5ho have had previous treatment 5ith antibiotics or 5ho have had a prolonged hospitalization" ,he optimal duration of antibiotic therapy must be individualized and depends on the underlying pathology, severity of infection, speed and effectiveness of source control, and patient response to therapy" Antibiotics can be discontinued once clinical signs of infection have resolved" Cecurrence is a concern 5ith certain infections, such as those from Candida and Staphylococcus aureus, and treatment should be continued for #$A 5ee's" Complications of peritonitis include tertiary peritonitis, infection or dehiscence of the surgical site, enterocutaneous fistula, abdominal compartment syndrome, and enteric insufficiency" Enterocutaneous fistulae can lead to ongoing (potentially large! volume, protein, and electrolyte lossesF inability to use the gut for nutritional supportF and associated long$term complications of intravenous alimentation" Abdominal compartment syndrome is a 5ell$recognized disease entity related to acutely increased abdominal pressure (ie, intra$abdominal hypertension! and is associated 5ith the development of multiple organ dysfunction" E&tensive initial (gastrointestinal! disease, chronic recurrent infections, and associated reoperations may lead to enteric insufficiency because of short gut, pancreatic insufficiency, or hepatic dysfunction",he goals of pharmacotherapy in patients 5ith peritonitis and abdominal sepsis are to reduce morbidity and prevent complications" ,he agents used are antimicrobials such as cefota&ime, gentamicin, ampicillin, and sulfametho&azole" Empiric antimicrobial therapy must be comprehensive and should cover all li'ely pathogens in the conte&t of the clinical setting" ,raditionally, a combination of an aminoglycoside and ampicillin 5as used to treat +3P" ,his regimen affords e&cellent empiric coverage of more than /12 of +3P cases caused by gram$negative aerobes or gram$positive cocci" (ore recently, the third$generation cephalosporin cefota&ime has been demonstrated to be as effective as the ampicillin>aminoglycoside combination, and it does not carry the increased ris' of nephroto&icityin cirrhotic patients" Cefota&ime does not cover enterococci, 5hich are the pathogen in up to @2 of cases"