Peritonitis is an inflammation of the peritoneum, the thin serous membrane that lines the abdominal cavity and covers most of the abdominal organs, typically resulting from bacterial or fungal infection and often leading to severe abdominal pain and potential life-threatening complications if untreated.[1][2]The condition is classified into primary (or spontaneous) peritonitis, which occurs without an identifiable source of infection in the abdomen, often in patients with ascites due to liver cirrhosis or other chronic conditions, and secondary peritonitis, which arises from a breach in the gastrointestinal tract or other abdominal structures.[1][2] Primary peritonitis, such as spontaneous bacterial peritonitis, is commonly associated with fluid accumulation in the abdomen from liver disease, heart failure, or certain cancers, allowing bacterial translocation from the gut.[2][3] In contrast, secondary peritonitis frequently stems from perforation of organs like the appendix, stomachulcer rupture, diverticulitis, or trauma, leading to contamination of the peritoneal cavity with gastrointestinal contents.[1][2] Additional risk factors include peritoneal dialysis, recent abdominal surgery, or immunocompromised states, with an annual incidence of spontaneous bacterial peritonitis ranging from 7% to 30% in patients with ascites.[1][3]Symptoms of peritonitis typically develop rapidly and include severe abdominal tenderness and pain that worsens with movement, fever, chills, nausea, vomiting, bloating, and reduced bowel sounds or urine output.[1][2] In patients undergoing peritoneal dialysis, signs may manifest as cloudy dialysate fluid or the presence of fibrin strands.[1]Diagnosis involves a physical examination revealing a rigid, tender abdomen, supported by blood tests showing leukocytosis, imaging such as X-rays or CT scans to identify free air or fluid, and paracentesis to analyze peritoneal fluid for infection markers like elevated neutrophil counts greater than 250 cells per microliter.[2][3]Treatment requires urgent intervention, beginning with broad-spectrum intravenous antibiotics to target common pathogens such as Escherichia coli, Klebsiella pneumoniae, or anaerobes. For primary peritonitis, management is primarily medical; for secondary peritonitis, it often includes surgical exploration to repair the underlying cause, drain abscesses, or lavage the peritoneal cavity.[4][3][5] Supportive care includes fluid resuscitation, pain management, and monitoring for sepsis in a hospital setting, with peritoneal dialysis-related cases potentially managed by adjusting dialysis techniques or switching to hemodialysis.[4][2] Complications can escalate to septic shock, multi-organ failure, abscess formation, or death, particularly if diagnosis is delayed, underscoring the need for prompt recognition and management to improve outcomes.[1][3]
Overview
Definition and Classification
Peritonitis is defined as an inflammation of the peritoneum, the thin serosal membrane that lines the abdominal cavity and covers the abdominal organs.[6] The peritoneum consists of two layers: the parietal peritoneum, which lines the abdominal wall (anteriorly and laterally), the retroperitoneum (posteriorly), the pelvis (inferiorly), and the diaphragm (superiorly); and the visceral peritoneum, which directly covers the abdominal viscera, forming a potential space known as the peritoneal cavity that normally contains less than 50 mL of fluid to facilitate organ movement.[6] This membrane, composed of mesothelial cells overlying loose connective tissue with vascular, lymphatic, and immune-competent elements, plays a key role in containing and lubricating abdominal fluids while providing a barrier against infection.[6]Peritonitis is primarily classified based on etiology into primary and secondary forms. Primary peritonitis, also known as spontaneous peritonitis, occurs without an identifiable intra-abdominal source of contamination, often arising from hematogenous or lymphatic spread of microorganisms, and is commonly seen in patients with cirrhosis or those undergoing peritoneal dialysis.[6] In contrast, secondary peritonitis results from direct contamination of the peritoneal cavity due to perforation of a hollow viscus, trauma, or postoperative complications, making it the most frequent type.[6] Additional classifications distinguish infectious peritonitis, caused by bacteria, fungi, or other pathogens, from noninfectious forms such as chemical peritonitis (e.g., due to bile, gastric acid, or pancreatic enzymes) or sterile peritonitis (e.g., from foreign bodies or blood).[1] Peritonitis can also be categorized by extent as generalized, involving the entire peritoneal cavity, or localized, confined to a specific region such as in appendicitis or diverticulitis.[6]A notable subtype of primary peritonitis is spontaneous bacterial peritonitis (SBP), particularly in patients with cirrhotic ascites, where diagnostic criteria include an ascitic fluid polymorphonuclear leukocyte (PMN) count exceeding 250 cells/mm³ in the absence of an intra-abdominal surgically treatable source of infection.[7] This threshold, supported by fluid analysis via paracentesis, guides presumptive diagnosis and empiric antibiotic therapy, with common pathogens including Escherichia coli and streptococcal species.[6]
Epidemiology
Peritonitis represents a substantial public health burden globally, with acute generalized peritonitis serving as a frequent surgical emergency and a leading cause of non-trauma-related mortality in emergency settings. [8] Reported incidence rates for acute peritonitis vary by region, with one study in a West African health district documenting 12.4 cases per 100,000 population annually. [9] These figures underscore the condition's role as a major contributor to morbidity, particularly in resource-limited environments where access to timely intervention is constrained.In specific high-risk populations, peritonitis prevalence is markedly elevated. Among patients undergoing peritoneal dialysis (PD), the incidence ranges from 0.2 to 0.6 episodes per patient-year, corresponding to an approximate risk of 18-45% for at least one episode annually, assuming a Poisson distribution, which remains a primary cause of technique failure and mortality in 15-16% of affected individuals. [10][11] Similarly, in patients with cirrhosis and ascites, spontaneous bacterial peritonitis (SBP) affects 10-30% of hospitalized cases and 1.5-3.5% of outpatients, with a global pooled prevalence of approximately 17%. [12][13]Demographic patterns reveal disparities in occurrence. Peritonitis is more common in males, who comprise 54-69% of cases across various cohorts, and incidence rises with age, particularly among those over 65 years, where older age independently predicts higher risk. [14][15][16] These trends are exacerbated in elderly populations due to comorbidities and delayed diagnosis.Geographically, peritonitis rates are higher in low- and middle-income countries, where delayed care for underlying conditions like appendicitis or peptic ulcers contributes to increased perforation and secondary peritonitis. [8] In contrast, high-income settings report lower SBP prevalence (around 11%) compared to middle-income regions (20%). [13]From 2020 to 2025, epidemiological trends show declining peritonitis rates in high-income countries, attributed to advances in surgical techniques, antibiotic stewardship, and infection prevention; for instance, PD-associated rates fell from 0.6 episodes per patient-year in 1992 to 0.3 by 2019, with further reductions observed during the COVID-19 period due to enhanced hygiene measures. [17][18] However, in PD populations, rates have shown variability, with some low-resource settings reporting increases to 0.96 episodes per patient-year amid socioeconomic challenges. [11]
Clinical Presentation
Signs and Symptoms
The hallmark symptom of peritonitis is diffuse, severe abdominal pain resulting from peritoneal irritation, which often intensifies with movement, coughing, or palpation.[1][19][2]Associated symptoms frequently include fever and chills, reflecting the systemic inflammatory response; gastrointestinal disturbances such as nausea, vomiting, anorexia, constipation, or diarrhea; and in advanced cases, tachycardia or hypotension signaling dehydration or early shock.[1][19][3][2]On physical examination, patients typically exhibit abdominal tenderness, involuntary guarding or rigidity of the abdominal wall, rebound tenderness upon release of pressure, and diminished or absent bowel sounds indicative of ileus; signs of dehydration, such as dry mucous membranes, or overt shock may also be evident in severe presentations.[1][19][3][2]Symptom severity varies by type: primary peritonitis, often spontaneous bacterial in origin, may present with milder or even absent abdominal pain in up to 30% of cases, particularly in patients with cirrhosis, whereas secondary peritonitis typically features a more rapid onset of intense pain due to underlying visceral perforation.[20][3]In pediatric patients, presentations can be atypical, with irritability, lethargy, or nonspecific distress substituting for clear verbalization of pain, alongside common features like fever and vomiting.[21][22][23]Elderly individuals may exhibit subdued or atypical manifestations, such as confusion, minimal fever, or reduced pain perception due to age-related physiological changes, potentially delaying recognition.[24][25][26]
Complications
Peritonitis, if untreated or severe, can lead to a range of acute complications stemming from the systemic inflammatory response and bacterial dissemination. Sepsis occurs when the infection triggers a dysregulated host response, potentially progressing to septic shock characterized by profound hypotension and tissue hypoperfusion.[27]Septic shock is a frequent outcome in generalized peritonitis, with mortality rates reaching 35% in affected patients.[28] This can escalate to multi-organ dysfunction syndrome (MODS), where multiple organs fail due to widespread inflammation and microvascular injury, often involving the kidneys, liver, and lungs.[29]Acute respiratory distress syndrome (ARDS) is another critical acute complication, arising in up to 40% of septic shock cases and contributing to high mortality through severe hypoxemia and lung inflammation.[30]Local complications arise from persistent infection and inflammatory scarring within the peritoneal cavity. Intra-abdominal abscesses form as localized collections of pus, commonly following perforation or inadequate source control, and can prolong recovery if not drained.[31] Adhesions, fibrous bands resulting from peritoneal injury, may develop and lead to bowel obstruction by kinking or compressing intestinal loops.[32]Fistula formation, an abnormal connection between organs or to the skin, is another risk, often complicating severe cases with ongoing leakage of intestinal contents.[31]Chronic sequelae can persist long after the acute episode, particularly from adhesion-related changes. These adhesions are implicated in chronic abdominal or pelvic pain due to ongoing irritation and entrapment of nerves or viscera.[33] In women, pelvic adhesions may cause infertility by distorting fallopian tubes or ovaries, representing a significant long-term impact.[34] Extensive bowel resection, sometimes required in necrotizing peritonitis, can result in short bowel syndrome, characterized by malabsorption, diarrhea, and nutritional deficiencies due to insufficient intestinal length.[35]Overall mortality in secondary peritonitis varies but can reach 20-40% in cases with delayed treatment or severe sepsis, driven by the rapid progression to shock and organfailure.[36] Complications differ by peritonitis type; for instance, perforated appendicitis carries a higher risk of intra-abdominal abscess formation, occurring in up to 39% of perforated cases compared to non-perforated ones.[37] In spontaneous bacterial peritonitis (SBP), particularly in cirrhotic patients, hepatic encephalopathy may worsen as a complication, exacerbating neurological dysfunction through ammonia buildup and systemic inflammation.[38]
Etiology
Infectious Causes
Infectious causes of peritonitis are predominantly bacterial, arising either from direct contamination of the peritoneal cavity or spontaneous bacterial translocation in susceptible individuals. Secondary peritonitis, the most common form, results from perforation or rupture of a hollow viscus in the gastrointestinal tract, allowing luminal contents to spill into the peritoneum. Common precipitating conditions include appendicitis, diverticulitis, peptic ulcer perforation, and abdominal trauma.[6][3] This leads to polymicrobial infection, typically involving a mix of enteric Gram-negative aerobes such as Escherichia coli and Klebsiella species, anaerobes like Bacteroides fragilis, and occasionally Gram-positive organisms.[6] Anaerobes are particularly prominent in cases of bowel perforation due to their prevalence in the colonic flora.[39]Primary peritonitis, also known as spontaneous bacterial peritonitis (SBP), occurs without an identifiable intra-abdominal source of contamination and is often monomicrobial. It is most frequently associated with cirrhotic patients who have ascites, where bacteria translocate from the gut lumen into the bloodstream and subsequently seed the ascitic fluid.[3] Predominant pathogens include Gram-negative enteric bacteria such as E. coli (accounting for up to 40% of cases) and Klebsiella pneumoniae, alongside Gram-positive species like Streptococcus pneumoniae.[6] In patients undergoing peritoneal dialysis, primary peritonitis can present as polymicrobial, reflecting contamination via the dialysis catheter, with organisms including skin flora and enteric bacteria.[40] The mechanism involves hematogenous spread or direct ascension through disrupted barriers in immunocompromised states.[41]Fungal causes are less common but significant in immunocompromised hosts, those on prolonged broad-spectrum antibiotics, or peritoneal dialysis patients. Candida species, particularly C. albicans and C. parapsilosis, predominate and often arise as a complication of bacterial overgrowth suppression or catheter-related biofilm formation.[42] In peritoneal dialysis, fungal peritonitis accounts for about 4-10% of episodes and carries higher morbidity due to poor response to therapy.[43]Tuberculous peritonitis, caused by Mycobacterium tuberculosis, is a rare but important infectious etiology in endemic regions or among immigrants from high-prevalence areas. It typically manifests through hematogenous dissemination from a primary pulmonary focus, leading to chronic granulomatous inflammation of the peritoneum.[44] This form is more prevalent in patients with underlying cirrhosis or HIV, where it presents insidiously with ascites and constitutional symptoms.[45]
Noninfectious Causes
Noninfectious peritonitis, also known as sterile or chemical peritonitis, arises from non-microbial irritants that trigger an inflammatory response in the peritoneal cavity without bacterial involvement.[6] This condition often presents with symptoms mimicking infectious peritonitis, such as abdominal pain and tenderness, but peritoneal fluid cultures remain negative for organisms.[46] Differentiation typically relies on clinical history, imaging, and laboratory analysis confirming the absence of infection.[47]Chemical peritonitis commonly results from the leakage of irritating substances due to organ perforation or rupture. Bile spillage from gallbladderperforation, as seen in acute cholecystitis or trauma, induces a potent inflammatory reaction owing to its caustic properties on the peritoneum.[48] Similarly, gastric acid from a perforated peptic ulcer can cause severe peritoneal irritation, leading to rapid onset of inflammation shortly after perforation.[19] Pancreatic enzymes leaking into the peritoneal space during acute pancreatitis provoke autodigestion and sterile inflammation, often complicating severe cases with elevated amylase levels in ascitic fluid.[49]Sterile peritonitis can also stem from hemoperitoneum, where blood accumulation from trauma, ruptured ectopic pregnancy, or vascular injury acts as an irritant, potentially leading to secondary complications like adhesions if untreated.[50] In neonates, meconium peritonitis occurs due to in utero bowel perforation, allowing sterile meconium to spill into the peritoneal cavity and cause chemical inflammation, often detected prenatally via calcifications on ultrasound.[51]Iatrogenic causes are prominent in patients undergoing peritoneal dialysis, where noninfectious peritonitis may arise from reactions to dialysate components, such as icodextrin-induced chemical irritation or eosinophilic responses to allergens in the solution.[52] Post-procedural events, including endoscopy or surgery, can introduce sterile irritants like barium from contrast studies, exacerbating peritoneal inflammation.[6]Rarely, autoinflammatory disorders contribute to recurrent sterile peritonitis. Familial Mediterranean fever (FMF), an autosomal recessive condition, manifests with episodic serositis, including acute peritoneal attacks simulating peritonitis, driven by MEFV gene mutations and responsive to colchicine therapy.[53] Other entities, such as systemic lupus erythematosus, can similarly produce aseptic peritoneal inflammation through immune-mediated mechanisms.[54]
Risk Factors
Peritonitis development is influenced by various individual and procedural factors that compromise the peritoneal barrier or immune defenses. Patients with liver cirrhosis and ascites are at heightened risk for spontaneous bacterial peritonitis (SBP), a subtype of primary peritonitis, due to impaired immune function and translocation of gut bacteria across the intestinal wall. Immunosuppression, such as that seen in HIV infection or from chemotherapy, further exacerbates this vulnerability by reducing the body's ability to combat bacterial invasion in the peritoneal cavity.[55] Diabetes mellitus independently increases the risk of SBP in cirrhotic patients with ascites, likely through hyperglycemia-induced immune dysfunction and endothelial damage.[56] Similarly, obesity, often measured by higher body mass index, correlates with elevated peritonitis rates, possibly due to associated metabolic inflammation and reduced peritoneal clearance.[57]Procedural interventions also predispose individuals to peritonitis. Peritoneal dialysis, commonly used in chronic kidney disease, carries a significant risk from catheter-related infections, with patients experiencing approximately 0.2 to 0.5 episodes per patient-year at risk, though rates can vary by facility and adherence to protocols.31105-9/fulltext) Recent abdominal surgery introduces contamination risks during the procedure or postoperative period, allowing bacterial entry into the peritoneum.[19] Endoscopic procedures, such as colonoscopy in dialysis patients, have been linked to peritonitis episodes, potentially from transient bacteremia or mucosal disruption.[58]Lifestyle factors contribute to peritonitis susceptibility, particularly in vulnerable populations. Chronic alcoholism promotes liver cirrhosis and ascites formation, thereby elevating SBP risk through portal hypertension and gut barrier impairment. Intravenous drug use indirectly heightens risk by increasing the likelihood of hepatitis C acquisition, leading to cirrhosis and subsequent SBP predisposition.[59] In peritoneal dialysis patients, poor hygiene practices, including inadequate handwashing or improper equipment handling, significantly contribute to infection rates.[1]Certain comorbidities amplify peritonitis risk beyond isolated conditions. Chronic kidney disease necessitates peritoneal dialysis, inherently exposing patients to recurrent infection threats.[60]Inflammatory bowel disease, exemplified by Crohn's disease, predisposes to secondary peritonitis through chronic intestinal inflammation and potential fistulas.[1]
Pathophysiology
Inflammatory Mechanisms
Peritonitis involves the activation of peritoneal mesothelial cells as the initial response to inflammatory stimuli, where these cells rapidly release proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), along with chemokines like IL-8, to orchestrate the local immune defense.[61] This cytokine release induces endothelial activation and increases vascular permeability, marking the onset of acute inflammation in the peritoneal cavity.[62]The immune cascade follows, characterized by the recruitment of neutrophils via chemokine gradients, which migrate into the peritoneal space to perform phagocytosis of invading pathogens.[63] Complement activation occurs concurrently, enhancing opsonization and amplifying the phagocytic activity of neutrophils and macrophages, thereby facilitating pathogen clearance but also contributing to tissue damage through the release of reactive oxygen species.[64] Macrophages further propagate the response by secreting additional cytokines and promoting the resolution phase once the threat is neutralized.[61]Fluid dynamics are profoundly altered during peritonitis, with cytokine-mediated vasodilation and increased capillary permeability leading to exudative fluid accumulation in the peritoneal cavity, resulting in ascites formation.[62] This third-spacing of fluid can cause hypovolemia and hemodynamic instability, as plasma volume shifts into the peritoneal compartment, exacerbating systemic physiological stress.[63]In severe cases, the inflammatory process escalates systemically through a cytokine storm, where elevated levels of IL-1, TNF-α, and IL-6 spill over into the bloodstream, triggering systemic inflammatory response syndrome (SIRS) with widespread endothelial dysfunction and potential multi-organ involvement.[64]Resolution of the inflammatory response depends on the balance between pro- and anti-inflammatory signals; anti-inflammatory cytokines like IL-10 promote neutrophil apoptosis and efferocytosis by macrophages, aiding clearance.[63] However, if unresolved, excessive fibrin deposition occurs due to impaired fibrinolysis, leading to adhesion formation and progressive peritoneal fibrosis characterized by extracellular matrix accumulation driven by transforming growth factor-beta (TGF-β).[61]
Primary Versus Secondary Peritonitis
Peritonitis is classified into primary and secondary forms based on the underlying etiology and presence of an identifiable intra-abdominal source of infection. Primary peritonitis, also known as spontaneous bacterial peritonitis (SBP), arises without a detectable breach in the gastrointestinal or genitourinary tract, typically resulting from bacterial translocation across the gut mucosa or hematogenous spread in susceptible individuals.[36] It is commonly observed in patients with ascites due to liver cirrhosis, where fluid accumulation facilitates bacterial seeding, or in those undergoing peritoneal dialysis, where the procedure introduces risk without an intra-abdominal perforation.[1] Microbiologically, primary peritonitis is usually monomicrobial; in SBP associated with cirrhosis, it typically involves aerobic gram-negative enteric bacteria such as Escherichia coli or gram-positive organisms like streptococci, whereas in peritoneal dialysis-associated cases, gram-positive cocci such as coagulase-negative staphylococci or Staphylococcus aureus predominate due to catheter contamination.[65][66]In contrast, secondary peritonitis develops from direct contamination of the peritoneal cavity due to visceral perforation, such as from appendicitis, diverticulitis, or trauma, or from intra-abdominal inflammatory processes like pancreatitis.[36] This form is the most prevalent type of peritonitis in non-cirrhotic patients and is characterized by polymicrobial infection, encompassing a mix of aerobic and anaerobicbacteria from the gastrointestinal flora, depending on the site of perforation.[67] Unlike primary peritonitis, secondary cases often involve a surgically treatable source, such as a ruptured viscus, necessitating intervention beyond antimicrobial therapy.[65]
Diagnosis
Clinical Assessment
The clinical assessment of suspected peritonitis begins with a detailed history taking to evaluate the onset, location, and character of abdominal pain, which is typically sudden and severe, often becoming diffuse as the condition progresses.[1] Associated symptoms such as fever, nausea, vomiting, and anorexia are commonly reported, helping to distinguish peritonitis from other acute abdominal conditions.[19] Relevant risk factors, including recent abdominal surgery, peritoneal dialysis, liver cirrhosis, or immunocompromise, are elicited to guide suspicion toward primary or secondary etiologies.[3]Physical examination starts with vital signs assessment, revealing tachycardia, fever, and potentially hypotension in advanced cases indicative of systemic inflammatory response.[6] Abdominal inspection may show distension and diminished bowel sounds, while palpation elicits marked tenderness, often with guarding, rigidity, and rebound tenderness upon release of pressure, reflecting peritoneal irritation.[4] Systemic signs such as altered mental status or dehydration further support the diagnosis.[19]Severity assessment may include tools like the Acute Physiology and Chronic Health Evaluation II (APACHE II) score for risk stratification in complicated intra-abdominal infections.[68]Differential diagnosis encompasses mimics of acute abdomen, including acute pancreatitis (presenting with epigastric pain radiating to the back), ruptured aortic aneurysm (with sudden severe pain and hemodynamic instability), and lower lobe pneumonia (causing referred abdominal pain via diaphragmatic irritation).[3] In cases where appendicitis is suspected as the underlying cause of secondary peritonitis, the Alvarado score—a clinical tool incorporating symptoms like right lower quadrant pain, anorexia, and rebound tenderness, along with signs such as fever and leukocytosis—can help stratify risk and inform urgency of intervention.[69]Due to the high mortality risk, ranging from 6% overall to 35% in patients developing sepsis, clinical assessment must be expedited, with immediate hospitalization and further evaluation prioritized to mitigate rapid deterioration.[6]
Laboratory Tests
Laboratory tests play a crucial role in confirming the diagnosis of peritonitis, assessing its severity, and guiding therapeutic decisions by providing objective evidence of infection, inflammation, and organ dysfunction.[3] Blood tests are typically the initial step, revealing systemic responses to the inflammatory process. A complete blood count often shows leukocytosis, characterized by an elevated white blood cell count greater than 11,000 cells/μL, frequently with a left shift indicating neutrophilia, which supports the presence of an acute bacterial infection.[4][3] Inflammatory markers such as C-reactive protein (CRP) and procalcitonin are commonly elevated; CRP levels above 10 mg/L indicate inflammation, while procalcitonin greater than 0.5 ng/mL suggests a bacterial etiology and helps differentiate from non-infectious causes.[3] In cases of suspected sepsis, serum lactate levels are measured, with values exceeding 2 mmol/L signaling tissue hypoperfusion and poor prognosis.[3] Additionally, electrolyte panels and blood urea nitrogen (BUN)/creatinine ratios evaluate dehydration and renal impairment, as peritonitis can lead to third-spacing of fluids and acute kidney injury, often showing elevated BUN (>20 mg/dL) and creatinine (>1.2 mg/dL).[3]Paracentesis, the aspiration of peritoneal or ascitic fluid, is the gold standard for direct evaluation in patients with ascites or suspected intra-abdominal fluid collections, prompted by clinical signs such as abdominal tenderness.[4] Analysis of the fluid includes a cell count, where a polymorphonuclear leukocyte (PMN) count greater than 250 cells/μL is diagnostic for spontaneous bacterial peritonitis (SBP), a common subtype, even in the absence of positive cultures.[70][3] The total nucleated cell count exceeding 500 cells/μL with a predominance of degenerative neutrophils further confirms an exudative inflammatory process.[71] Biochemical assessment measures protein levels (typically >2.5 g/dL in exudates), lactate dehydrogenase (LDH > upper limit of normal serum value), and glucose, where low peritoneal fluid glucose (<60 mg/dL) or a fluid-to-blood glucose ratio less than 0.4 strongly suggests bacterial infection due to bacterial consumption.[70][71]Microbiological evaluation of the peritoneal fluid is essential for identifying pathogens and determining antibiotic sensitivity. Gram staining provides rapid preliminary identification of bacterial morphology, though it has low sensitivity (10-30%) and is positive in only a minority of cases.[3] Cultures of the fluid, ideally inoculated at the bedside into blood culture bottles to enhance yield, detect organisms such as Escherichia coli or Klebsiella pneumoniae in up to 40-60% of SBP cases; fungal cultures are pursued if bacterial cultures are negative and risk factors like immunosuppression are present.[70][3] For culture-negative cases, molecular techniques such as 16S rRNA PCR can detect bacterial DNA directly from ascitic fluid, improving identification in up to 20-30% of cases and associating with poorer prognosis.[72] Emerging point-of-care tests, including IL-6-based lateral flow assays on peritoneal effluent, provide rapid diagnosis (within 5 minutes) with high sensitivity (97.6%) and negative predictive value (98.3%), particularly useful in peritoneal dialysis-associated peritonitis.[73] Additionally, artificial intelligence and machine learning models using clinical and laboratory variables offer predictive scoring for SBP with sensitivities up to 94.7% as of 2025.[72] Sensitivity testing on positive isolates guides targeted antimicrobial therapy. Blood cultures should be obtained concurrently in all patients to assess for bacteremia, which occurs in approximately 20-40% of peritonitis cases with systemic involvement, particularly in those with elevated temperature or suspected resistant organisms.[4][3][68]Other laboratory tests help exclude alternative diagnoses. Serum amylase and lipase levels are checked to rule out pancreatitis, with elevations above three times the upper limit of normal (amylase >300 U/L, lipase >180 U/L) indicating possible pancreatic involvement rather than primary peritonitis.[3] Interpretation of results must consider the clinical context, as isolated elevations in blood markers may occur in non-peritoneal infections, while fluid analysis provides the most specific evidence; for instance, a PMN count between 100-250 cells/μL warrants close monitoring and repeat testing.[70][71]
Imaging Modalities
Imaging plays a crucial role in the diagnosis of peritonitis by visualizing structural abnormalities such as free fluid, abscesses, perforations, and the underlying source of infection or inflammation.[74] While clinical assessment and laboratory tests provide initial clues, imaging modalities help confirm the presence of peritonitis and guide management decisions, particularly in distinguishing primary from secondary causes.[4]Plain abdominal radiography, often performed as an upright chest-abdomen X-ray, is a rapid initial imaging tool used to detect free intraperitoneal air, which indicates gastrointestinal perforation as a common cause of secondary peritonitis.[74] The classic finding is subdiaphragmatic free air, appearing as a crescent-shaped lucency under the diaphragm on upright views, with a sensitivity of approximately 89% for pneumoperitoneum in cases of gastric or duodenal perforation but lower for other sites.[75] However, its overall sensitivity is limited, missing small amounts of free air or non-perforative causes of peritonitis, and it rarely identifies abscesses or fluid collections directly.[76]Ultrasound serves as a first-line imaging modality, particularly in hemodynamically unstable patients, pregnant individuals, or resource-limited settings, due to its portability, lack of ionizing radiation, and ability to detect free peritoneal fluid or abscesses in real time.[74] Key findings include echogenic free fluid exceeding 100 mL, loculated collections with internal debris suggesting abscesses (e.g., perihepatic or pelvic), and bowel wall thickening or peristalsis abnormalities; it also guides diagnostic paracentesis.[77] Its accuracy reaches about 83% for peritonitis diagnosis, outperforming clinical impression alone, though it is operator-dependent and hindered by bowel gas or obesity.[77] Per 2024 IDSA guidelines, ultrasound is recommended as initial imaging for suspected appendicitis or cholecystitis in children and pregnant patients.[68]Computed tomography (CT) is considered the gold standard imaging modality for peritonitis, offering high sensitivity (up to 100%) for detecting small volumes of free fluid, pneumoperitoneum, abscesses, bowel wall thickening, and the precise source of perforation or inflammation.[74] Contrast-enhanced CT protocols enhance visualization of peritoneal enhancement, vascular complications like ischemia, and loculated collections (e.g., subhepatic abscesses), aiding in preoperative planning and percutaneous drainage.[78] It excels in evaluating complex cases, such as identifying smooth peritoneal thickening in infectious peritonitis versus nodular patterns in malignancy mimics.[78] The 2024 IDSA guidelines suggest CT as initial imaging for appendicitis in adults.[68]Magnetic resonance imaging (MRI) is rarely employed in acute peritonitis due to its limited availability, longer acquisition time, and unsuitability for critically ill patients, but it may be useful in complex or chronic cases, such as suspected encapsulating peritoneal sclerosis, or when CT is contraindicated (e.g., renal impairment).[74] Findings include decreased T1 signal and increased T2 signal in fluid collections with rim enhancement on gadolinium-enhanced sequences, providing detailed soft-tissue characterization comparable to CT for peritoneal abnormalities.[79]MRI is recommended after inconclusive ultrasound for appendicitis in children and pregnant patients per 2024 guidelines.[68]Despite their utility, imaging modalities have limitations including radiation exposure from X-ray and CT (a concern in younger patients or repeated scans), variable availability in emergency settings, and potential delays in definitive surgical intervention if over-relied upon when clinical diagnosis is evident.[74] Ultrasound's effectiveness can be reduced in distended bowels, while MRI's high cost and contraindications (e.g., pacemakers) restrict its routine use.[74]
Pathological Examination
In gross pathological examination of peritonitis, the peritoneal cavity often contains variable amounts of purulent or fibrinous fluid, with congestion and hyperemia of the peritoneal surfaces evident.[80] In cases of secondary peritonitis due to organ perforation, such as appendiceal rupture or bowel perforation, a focal site of perforation is typically identified, surrounded by adherent inflammatory exudate and possibly localized abscess formation.[80] Fibrinous exudates may form shaggy, yellow-white plaques over visceral and parietal peritoneum, while purulent fluid appears thick and creamy, reflecting bacterial contamination in infectious etiologies.[71]Microscopically, acute peritonitis demonstrates dense neutrophilic infiltration within the submesothelial connective tissue and overlying the peritoneum, often with fibrin deposition on the surface.[81] Mesothelial cells show reactive changes including denudation, hyperplasia, or sloughing due to inflammatory damage, contributing to impaired barrier function.[82] In infectious cases, bacterial colonies may be visible within the exudate or tissue, particularly in secondary peritonitis from gastrointestinal perforation.[71]In resolving or chronic peritonitis, pathological features shift toward fibrosis of the submesothelial layer, with collagen deposition leading to peritoneal thickening and adhesions.[83]Granulation tissue may appear in areas of organization, featuring proliferating fibroblasts, new blood vessels, and mixed inflammatory cells as the acute response subsides.[83]Special stains play a key role in identifying causative organisms; Gram staining highlights bacterial morphology and aids in classifying infectious peritonitis, while acid-fast bacilli (AFB) stains, such as Ziehl-Neelsen, detect Mycobacterium tuberculosis in tuberculous peritonitis, often revealing caseating granulomas.[84]Biopsy of peritoneal tissue, obtained intraoperatively during laparotomy or laparoscopy, or post-mortem, confirms the diagnosis by demonstrating the above features and distinguishing peritonitis from mimics like malignancy; imaging-guided sampling may occasionally assist but is less common for direct pathological evaluation.[3]
Management
Initial Medical Therapy
Initial medical therapy for peritonitis primarily involves prompt initiation of broad-spectrum intravenous antibiotics to cover the most likely pathogens, including Gram-negative aerobes, anaerobes, and enterococci, pending culture results.[85] For community-acquired secondary peritonitis in adults, recommended empirical regimens include monotherapy with piperacillin-tazobactam (3.375 g IV every 6 hours) or a carbapenem such as meropenem (1 g IV every 8 hours), which provide adequate coverage for enteric bacteria and anaerobes. In high-risk patients, such as those with healthcare-associated infections or recent antibiotic exposure, broader coverage with addition of an agent active against resistant organisms, like vancomycin for methicillin-resistant Staphylococcus aureus, may be necessary.[86] Therapy should be de-escalated to narrower agents based on microbiological cultures and sensitivities, typically within 48-72 hours, to minimize resistance and toxicity.[85]For primary peritonitis, particularly spontaneous bacterial peritonitis (SBP) in patients with cirrhosis, empirical therapy consists of a third-generation cephalosporin such as cefotaxime (2 g IV every 8 hours) or ceftriaxone (2 g IV every 24 hours), which effectively targets common Gram-negative pathogens like Escherichia coli. The standard duration for SBP treatment is 5 days, provided clinical response is observed and complications are absent. Adjunctive albumininfusion is recommended in SBP to prevent renal impairment: 1.5 g/kg body weight on day 1 and 1 g/kg on day 3, reducing the risk of hepatorenal syndrome by improving effective circulating volume.For peritoneal dialysis-associated peritonitis, empirical intraperitoneal antibiotics are recommended per International Society for Peritoneal Dialysis guidelines, typically vancomycin (15-30 mg/L per exchange) or cefazolin (15 mg/L) plus ceftazidime (250 mg/L loading dose, then 125 mg/L maintenance) for Gram-positive and Gram-negative coverage, respectively, with intermittent dosing in automated peritoneal dialysis. Therapy is adjusted based on effluent cultures; total duration is 14-21 days for most organisms, with catheter removal indicated for refractory peritonitis (no response after 5 days) or fungal/relapsing cases to prevent recurrence.[87]Empirical antifungal therapy is reserved for cases with suspected fungal involvement, such as in peritoneal dialysis-associated peritonitis or immunocompromised patients with risk factors like recent broad-spectrum antibiotics; fluconazole (400 mg IV/PO daily) or an echinocandin like caspofungin (70 mg IV loading dose, then 50 mg daily) is used if Candida is suspected.[88] For secondary peritonitis, antibiotic duration is generally 4-7 days after source control, as shorter courses (e.g., 4 days) are noninferior to longer ones (8-10 days) in resolving infection without increasing recurrence.[89] These recommendations align with the 2024 World Society of Emergency Surgery (WSES) guidelines on intra-abdominal infections, emphasizing early empirical coverage and stewardship.[86]
Surgical Interventions
Surgical interventions are the cornerstone of managing secondary peritonitis, particularly when source control is required to eliminate the infectious focus, such as in cases of gastrointestinal perforation, anastomotic dehiscence, or failure of initial medical therapy to resolve diffuse infection or sepsis.[90] Indications typically arise in patients with generalized peritonitis exhibiting signs like abdominal rigidity, rebound tenderness, or systemic inflammatory response, where non-operative approaches are inadequate.[36] These procedures aim to interrupt the cycle of ongoing contamination and bacterial proliferation, thereby supporting resuscitation and antimicrobial therapy.[91]The primary procedures involve either open laparotomy or laparoscopic exploration to identify and address the underlying pathology. For instance, in perforated appendicitis, an appendectomy is performed, while colonic perforations from diverticulitis may necessitate resection with or without colostomy formation; abscesses are drained percutaneously or surgically as needed.[92]Laparotomy remains the standard for most emergency cases due to its reliability in extensive exploration and control of contamination, though laparoscopy is increasingly favored for stable patients with localized disease, such as uncomplicated cholecystitis or early appendicitis, offering reduced morbidity when expertise is available.[90] Intraoperative peritoneal lavage with copious saline irrigation is routinely incorporated to remove purulent material and debris.[36]In critically ill patients with sepsis or hemodynamic instability, damage control surgery is employed as a staged technique, focusing on rapid source control through resection of necrotic bowel, thorough washout of the peritoneal cavity, and temporary closure of the abdomen to prevent abdominal compartment syndrome.[92] Open abdomen management may follow, utilizing negative pressure wound therapy or mesh-mediated traction to facilitate relaparotomy on demand—guided by clinical deterioration rather than scheduled reoperations—while minimizing fistula formation and evisceration risks.[91] These approaches are complemented by broad-spectrum antibiotics initiated preoperatively.[90]Timing of intervention is critical, with source control ideally achieved emergently upon diagnosis, particularly within 12-24 hours for diffuse peritonitis, as delays beyond this threshold are associated with increased mortality rates exceeding 30% in severe cases.[36] Early surgery in the setting of sepsis recognition allows for better hemodynamic stabilization and reduces the progression to multi-organ failure.[92]Complications from these interventions include wound infections, occurring in up to 20% of open procedures, and anastomotic leaks, which can necessitate reoperation and prolong recovery.[90] Other risks encompass enteric fistulas (10-20% in open abdomen cases) and incisional hernias, underscoring the need for meticulous technique and postoperative monitoring.[91]
Supportive Measures
Supportive measures in peritonitis management focus on stabilizing hemodynamics, preventing organ dysfunction, and promoting recovery through ancillary care, often provided in an intensive care unit (ICU) setting. These interventions address the systemic inflammatory response and complications such as shock, which can exacerbate the condition. Early and aggressive supportive therapy is essential to improve outcomes in critically ill patients.[93]Fluid resuscitation is a cornerstone of supportive care, particularly in cases of septic shock associated with peritonitis. At least 30 mL/kg body weight of intravenous crystalloids, such as normal saline or lactated Ringer's solution, should be administered within the first 3 hours to restore intravascular volume and maintain tissue perfusion. If hypotension persists despite adequate fluid loading, vasopressors like norepinephrine or inotropes such as dobutamine are initiated to achieve a mean arterial pressure greater than 65 mmHg. Monitoring to guide therapy includes dynamic parameters such as passive leg raise or stroke volume variation for further fluid administration, urine output (>0.5 mL/kg/hour), and lactate clearance to detect ongoing hypoperfusion.[94][3]Nutritional support is initiated early to counteract catabolism and support immune function, with enteral nutrition preferred when gastrointestinal function allows, typically via nasogastric or nasojejunal tubes. This approach helps maintain gut barrier integrity and reduces bacterial translocation. In patients with ileus or bowel rest, total parenteral nutrition (TPN) is used to provide adequate calories (approximately 25-30 kcal/kg/day) and protein (1.2-1.5 g/kg/day), though it carries risks of hyperglycemia and line infections. Perioperative nutritional supplementation has been shown to shorten hospital stays and enhance recovery in abdominal infection cases.[93][95]Pain management is crucial for patient comfort but must be balanced to avoid masking clinical signs of deterioration. Opioids, such as morphine or fentanyl, are commonly employed as first-line agents for severe abdominal pain, administered intravenously in the acute phase. These can be safely used without significantly impairing diagnostic accuracy in acute abdominal conditions. Multimodal analgesia, including non-opioid adjuncts like acetaminophen, may be incorporated to minimize opioid requirements and mitigate side effects such as respiratory depression.[4][96]Organ support is tailored to specific failures, with mechanical ventilation using low tidal volumes (6-8 mL/kg) recommended for acute respiratory distress syndrome (ARDS), which occurs in up to 30% of severe peritonitis cases. For acute kidney injury, continuous renal replacement therapy or hemodialysis is employed to manage fluid overload, electrolyte imbalances, and uremia. These measures, often in conjunction with vasopressor support, aim to sustain vital organ function during the inflammatory cascade.[93][3]Close monitoring in the ICU involves serial abdominal examinations to assess for worsening peritonitis, vital signs tracking, and laboratory evaluations of inflammatory markers and organ function. Repeat imaging, such as computed tomography or ultrasound, is performed as needed to evaluate response to therapy and detect complications. Severity scoring systems like APACHE II help stratify risk and guide resource allocation.[93]
Prognostic factors in peritonitis significantly influence patient survival and recovery, encompassing clinical, microbiological, and patient-specific elements that determine outcomes following diagnosis and intervention. Early diagnosis and prompt source control, ideally achieved within 24 hours of symptom onset, are critical positive predictors, substantially improving survival rates by limiting the progression to severe sepsis and multi-organ dysfunction.[97] Monomicrobial infections, particularly those caused by single gram-negative organisms, also correlate with better prognosis compared to more complex cases, as they respond more effectively to targeted antimicrobial therapy.[98]Conversely, several negative factors adversely affect outcomes. Delayed treatment beyond the initial 24-hour window markedly increases mortality risk, often due to escalating systemic inflammation and organ failure.[99] Polymicrobial infections, common in secondary peritonitis, are associated with higher complication rates and poorer resolution, as they complicate antimicrobial management and promote persistent intra-abdominal contamination.[100] Advanced age, typically over 65 years, serves as an independent risk factor, with elderly patients exhibiting reduced physiological reserve and higher susceptibility to decompensation.[101] Comorbidities such as chronic kidney disease, cardiovascular disease, diabetes mellitus, and cirrhosis further worsen prognosis by impairing immune response and increasing vulnerability to septic shock.[100] Elevated severity scores, including a high APACHE II score (greater than 15), strongly predict adverse events, reflecting acute physiological derangements and chronic health burdens. Recent validations of such scores, along with emerging machine learning models for risk stratification as of 2025, have enhanced predictive accuracy in intensive care settings.[102][103]Mortality rates vary by peritonitis type and severity. Primary peritonitis, often spontaneous and community-acquired, carries a lower mortality of approximately 10-20% at 30 days, primarily in non-cirrhotic patients without shock.[104] Secondary peritonitis, resulting from perforation or postoperative complications, has higher rates of 20-50%, driven by the need for surgical source control and frequent polymicrobial involvement.[105] In cases complicated by septic shock, mortality can range from 30-50%, underscoring the role of rapid hemodynamic stabilization.[106]Long-term outcomes include risks of recurrence and diminished quality of life. In peritoneal dialysis-associated peritonitis, recurrence or relapse occurs in 20-30% of cases within the first year, often necessitating catheter removal and technique failure.[107] Survivors frequently experience persistent abdominal symptoms, reduced physical function, and psychological impacts, contributing to overall morbidity beyond the acute phase.[108]As of 2025, outcomes have improved in high-resource settings through standardized protocols like those from the International Society for Peritoneal Dialysis, which emphasize early empirical antibiotics and audit-driven care, reducing peritonitis rates to below 0.40 episodes per patient-year.[52] However, in low-resource areas, mortality remains elevated at approximately 25-30% due to delayed access to surgery and antimicrobial resistance challenges.[109]
Preventive Strategies
Preventive strategies for peritonitis focus on addressing underlying risk factors through early intervention, strict hygiene protocols, and targeted prophylaxis in vulnerable populations. Prompt recognition and treatment of abdominal infections, such as appendicitis or diverticulitis, can prevent perforation and subsequent secondary peritonitis by reducing bacterial translocation into the peritoneal cavity.[110]In surgical settings, adherence to evidence-based hygiene measures significantly lowers the risk of postoperative peritonitis arising from surgical site infections. Key practices include preoperative patient bathing with antimicrobial soap, alcohol-based chlorhexidine skin preparation, surgical hand antisepsis with alcohol-based rubs, and timely administration of prophylactic antibiotics within 120 minutes before incision.[110] For elective colorectal procedures, combining mechanical bowel preparation with oral antibiotics further mitigates contamination risks.[110]For patients undergoing peritoneal dialysis (PD), comprehensive training by experienced nurses on aseptic techniques, including hand hygiene and proper connection-disconnection methods, is essential to minimize contamination-related peritonitis.[111] Structured programs, often exceeding 15 hours of cumulative training, enhance self-care knowledge and behaviors, with home visits and retraining for non-compliance further supporting adherence.[112] Exit-site care protocols involve daily application of topical antibiotics like mupirocin or gentamicin cream, alongside antiseptic cleaning with chlorhexidine, which reduces Staphylococcus aureus-related exit-site infections and peritonitis by 40-70%.[111] Use of Y-connection or double-bag systems with flush-before-fill designs decreases peritonitis rates by approximately 33% compared to traditional spike systems.[111]Antibiotic prophylaxis at PD catheter insertion and before invasive procedures, such as colonoscopy, is recommended to prevent early infections.[111] Antifungal prophylaxis, such as fluconazole during systemic antibiotic courses, prevents secondary fungal peritonitis.[111] Overall, these catheter protocols and quality improvement initiatives can achieve peritonitis rates below 0.40 episodes per patient-year at risk.[52]In patients with cirrhosis and ascites, antibiotic prophylaxis targets spontaneous bacterial peritonitis (SBP), particularly in high-risk groups with ascitic fluid protein below 1.5 g/dL or prior episodes. Primary prophylaxis with norfloxacin (400 mg daily) or trimethoprim-sulfamethoxazole (one double-strength tablet daily) is advised for those without prior SBP, while secondary prophylaxis uses the same regimens post-resolution of an episode.[113] These interventions reduce SBP incidence by 50-70% and lower infection-related mortality.[114] Pneumococcal vaccination is also recommended for cirrhotics to prevent bacterial infections that may contribute to SBP.[113]Public health efforts emphasize education on early symptom recognition, such as abdominal pain and fever, to facilitate timely medical access and reduce peritonitis complications in at-risk communities.[112] In resource-limited settings, improving PD infrastructure and multidisciplinary training programs can lower peritonitis rates through better hygiene and self-care practices.[112]
History and Terminology
Historical Development
Peritonitis, an inflammation of the peritoneum, was first recognized in ancient medicine by Hippocrates in the 5th century BCE, who described symptoms including severe abdominal pain, fever, and rigidity, often leading to fatal outcomes without effective intervention.[115] Early observations in Greek texts noted similar symptoms of abdominal infection but lacked etiological understanding, attributing it to imbalances in bodily humors.[116]In the 19th century, surgical advancements were hampered by high rates of postoperative peritonitis due to infection, with mortality exceeding 80% in abdominal procedures. Joseph Lister's introduction of antiseptic techniques in 1867, using carbolic acid to sterilize wounds and instruments, dramatically reduced these infections by targeting microbial causes, as inspired by Pasteur's germ theory.[117] Concurrently, Hans Christian Gram developed the Gram staining method in 1884, enabling differentiation of bacterial pathogens—crucial for identifying causative agents in peritonitis samples and guiding early microbiological diagnosis.[118]The 20th century marked a turning point with the advent of antibiotics in the 1940s, which improved management of bacterial infections including peritonitis; sulfonamides and penicillin contributed to better outcomes in secondary peritonitis following appendicitis or perforation, though diagnostic delays continued to pose challenges.[119][120]Spontaneous bacterial peritonitis (SBP), particularly in cirrhotic patients, was initially reported in 1907 with cases of Escherichia coli infection in ascitic fluid, though its distinct pathophysiology was not clarified until the 1960s through studies confirming bacterial translocation without intra-abdominal sources.[121]From the 1980s onward, the adoption of laparoscopic surgery allowed minimally invasive exploration and source control in peritonitis, reducing operative trauma and complications compared to open laparotomy.[122] By the 2000s, evidence-based guidelines from organizations like the World Society of Emergency Surgery standardized multimodal approaches, integrating early antibiotics, imaging, and surgery, leading to improved outcomes—such as targets for technique survival exceeding 80% in peritoneal dialysis-related cases (as of 2022) and reduced overall mortality through refined protocols, including 2024 updates emphasizing antimicrobial stewardship.[123][52][124]
Etymology
The term peritonitis derives from the Greek peritonaion (περιτόναιον), referring to the peritoneum or abdominal membrane, combined with the suffix -itis, which denotes inflammation in medical terminology.[125] This etymological construction reflects the condition's core pathology: inflammation of the serous membrane lining the abdominal cavity.[126]The word peritoneum itself originates from the Greek roots peri- ("around") and teinein ("to stretch"), literally meaning "stretched around," alluding to the membrane's enveloping role over abdominal viscera; it entered Late Latin as peritonaeum before adoption into English in the early 15th century.[126] The full term peritonitis was coined in medical Latin around 1750 by the French pathologist François Boissier de Sauvages, marking its formal introduction into nosological classifications.[125]In early medical literature, peritonitis was often described using phrases like "peritoneal inflammation" to emphasize the localized inflammatory process within the abdominal cavity.[116] A related descriptor, "acute abdomen," emerged as a broader clinical term encompassing sudden-onset abdominal pain syndromes, including peritonitis, and gained traction in diagnostic contexts from the 19th century onward.[127]The modern usage of peritonitis became standardized during the 19th century amid advances in pathology and abdominal surgery, as detailed in seminal texts that clarified its association with perforations and infections.[128] As of 2025, no significant variants or alternative nomenclature have supplanted this term in international medical practice, maintaining its precision in describing peritoneal inflammation across subtypes.