SBP Recnt advances

 

Recent Advances in Spontaneous Bacterial Peritonitis: A Comprehensive Review

Dr Neeraj Manikath, Claude.ai

Abstract

Spontaneous bacterial peritonitis (SBP) remains a significant complication in patients with cirrhosis and ascites, associated with substantial morbidity and mortality. Despite advances in antimicrobial therapy and management strategies, mortality rates remain high, particularly in patients with advanced liver disease. This review provides an updated perspective on the epidemiology, pathophysiology, diagnosis, and management of SBP, with a focus on recent advances and emerging concepts. The evolving microbiological landscape, including shifts in causative organisms and increasing antimicrobial resistance, presents new challenges in the management of SBP. Novel biomarkers for early diagnosis, risk stratification tools, and innovative therapeutic approaches including albumin administration strategies and potential microbiome modulation are discussed. This review also addresses emerging challenges such as multidrug-resistant infections and healthcare-associated SBP, providing evidence-based recommendations for contemporary clinical practice.

Introduction

Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of ascitic fluid in the absence of an intra-abdominal surgically treatable source of infection[1]. It remains one of the most common and life-threatening complications in patients with cirrhosis and ascites, with an in-hospital mortality rate ranging from 20-40% despite appropriate treatment[2,3]. The one-year mortality rate following an episode of SBP can exceed 60% in patients with advanced liver disease[4].

The landscape of SBP has evolved considerably over the past decade. Changes in the microbiological profile, increasing antimicrobial resistance, and the emergence of healthcare-associated infections have dramatically altered the approach to diagnosis and management[5]. Concurrently, advances in our understanding of the pathophysiology, development of new diagnostic techniques, and implementation of novel treatment strategies have provided opportunities to improve outcomes in patients with SBP.

This review aims to provide a comprehensive update on recent advances in SBP, focusing on evolving concepts in pathophysiology, innovations in diagnostic approaches, and emerging therapeutic strategies that have the potential to transform clinical practice.

Epidemiology and Risk Factors

Changing Epidemiology

The incidence of SBP among hospitalized patients with cirrhosis and ascites ranges from 10-30%[6]. However, recent studies suggest that the epidemiological landscape is changing, particularly in terms of the causative organisms and antimicrobial resistance patterns[7].

Healthcare-associated (HCA) and nosocomial SBP have become increasingly prevalent, accounting for approximately 30-50% of SBP cases[8]. These infections are often caused by multidrug-resistant organisms (MDROs), particularly extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant organisms[9,10]. A multicenter study by Piano et al. demonstrated that MDROs were responsible for 23% of SBP episodes in Italy, with significantly higher rates in nosocomial infections (35%) compared to community-acquired infections (12%)[11].

Risk Factors for SBP

Several risk factors have been identified for the development of SBP:

1. Advanced liver disease: Higher Child-Pugh and MELD scores are associated with increased risk of SBP[12].
2. Low ascitic fluid protein: Ascitic fluid protein concentration <1.5 g/dL is a well-established risk factor, reflecting impaired local immune defenses[13].
3. Previous episodes of SBP: Recurrence rates within one year range from 40-70% without prophylaxis[14].
4. Gastrointestinal bleeding: Associated with a 3.5-fold increased risk of SBP[15].
5. Proton pump inhibitor (PPI) use: Recent meta-analyses have confirmed that PPI use is associated with an increased risk of SBP (OR 2.17, 95% CI 1.46-3.23)[16,17].
6. Genetic factors: Polymorphisms in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll-like receptor 2 (TLR2) genes have been associated with increased susceptibility to SBP[18].
7. Dysbiosis: Alterations in gut microbiota composition have been increasingly recognized as contributing to bacterial translocation and SBP risk[19].

Recent evidence has highlighted additional risk factors, including:

8. Sarcopenia: A prospective study by Kim et al. demonstrated that sarcopenia is independently associated with SBP development (HR 2.06, 95% CI 1.07-3.98)[20].
9. Vitamin D deficiency: Low vitamin D levels have been associated with increased susceptibility to SBP, possibly due to vitamin D's role in immune function and maintaining intestinal barrier integrity[21].
10. Beta-blocker non-response: Patients who do not achieve a hemodynamic response to non-selective beta-blockers appear to have a higher risk of developing SBP[22].

Pathophysiology: Recent Insights

Gut-Liver Axis and Bacterial Translocation

The pathogenesis of SBP centers on bacterial translocation (BT) from the intestinal lumen to mesenteric lymph nodes and the systemic circulation, with subsequent colonization of the ascitic fluid. Recent advances in our understanding of this process have identified several key factors:

1. Intestinal dysbiosis: Patients with cirrhosis exhibit significant alterations in gut microbiota composition, characterized by reduced microbial diversity, decreased beneficial bacteria (Lachnospiraceae, Ruminococcaceae), and overgrowth of potentially pathogenic bacteria (Enterobacteriaceae, Streptococcaceae)[23,24]. Qin et al. used metagenomic analysis to demonstrate that patients with cirrhosis have enrichment of oral microbiota in the gut microbiome, which correlated with disease severity and risk of complications including SBP[25].

2. Intestinal barrier dysfunction: The intestinal epithelial barrier, comprising tight junctions, mucus layer, and antimicrobial peptides, is compromised in cirrhosis due to oxidative stress, inflammation, and portal hypertension. Recent studies have identified zonulin, a protein that regulates tight junction permeability, as a potential biomarker for intestinal barrier dysfunction and predictor of SBP risk[26].

3. Impaired local immune defenses: The ascitic fluid normally contains opsonins and immunoglobulins that facilitate bacterial clearance. In advanced cirrhosis, the synthesis of complement components is reduced, and the ascitic fluid protein concentration is low, impairing opsonization and phagocytosis[27].

4. Bile acid dysregulation: Recent evidence suggests that altered bile acid metabolism in cirrhosis contributes to intestinal dysbiosis and barrier dysfunction. Decreased bile acid synthesis leads to reduced antimicrobial activity in the intestine, promoting bacterial overgrowth[28].

Immune Dysfunction in Cirrhosis

Cirrhosis-associated immune dysfunction (CAID) is characterized by both systemic inflammation and immunodeficiency[29]. Recent studies have provided insights into the immunological mechanisms underlying SBP:

1. Impaired neutrophil function: Neutrophils from patients with cirrhosis exhibit defective chemotaxis, phagocytosis, and oxidative burst capacity[30].

2. MAIT cell depletion: Mucosal-associated invariant T (MAIT) cells, which play a crucial role in antimicrobial immunity, are significantly depleted in cirrhosis. The severity of MAIT cell depletion correlates with the risk of bacterial infections, including SBP[31].

3. Macrophage dysfunction: Kupffer cells and peritoneal macrophages show impaired pathogen recognition and clearance in cirrhosis. Recent studies have identified defects in pattern recognition receptors, particularly toll-like receptors (TLRs) and NOD-like receptors, contributing to reduced bacterial clearance[32].

4. Increased inflammatory response: Paradoxically, despite immunodeficiency, patients with cirrhosis exhibit an exaggerated inflammatory response to bacterial stimuli, with excessive production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β)[33]. This "cytokine storm" can lead to septic shock and multi-organ failure in SBP.

Role of the Microbiome

The gut microbiome has emerged as a central player in the pathogenesis of SBP. Beyond quantitative changes, functional alterations in the microbiome contribute to increased bacterial translocation:

1. Metabolomic changes: Metagenomic studies have identified enrichment of genes involved in ammonia production, endotoxin biosynthesis, and virulence factors in the gut microbiome of patients with cirrhosis[34].

2. Short-chain fatty acid (SCFA) depletion: SCFAs, particularly butyrate, maintain intestinal barrier integrity and regulate immune responses. Reduced SCFA-producing bacteria in cirrhosis contribute to barrier dysfunction[35].

3. Microbiome-bile acid interactions: The gut microbiota influences bile acid composition through biotransformation, while bile acids shape the microbiota through antimicrobial effects. This bidirectional relationship is disrupted in cirrhosis, contributing to dysbiosis and increased susceptibility to SBP[36].

Diagnostic Advances

Traditional Diagnostic Criteria

The diagnosis of SBP traditionally requires an elevated polymorphonuclear leukocyte (PMN) count ≥250 cells/mm³ in the ascitic fluid, regardless of culture results[37]. However, this approach has limitations, including limited sensitivity, the need for trained personnel for cell counting, and delays in obtaining results.

Advances in Microbiological Diagnosis

1. Automated cell counting: Automated flow cytometry-based cell counters can provide rapid and accurate PMN counts in ascitic fluid, potentially reducing the time to diagnosis[38].

2. Blood culture bottles: Inoculation of ascitic fluid directly into blood culture bottles significantly increases the sensitivity of bacterial detection compared to conventional culture methods (45-60% vs. 25-40%)[39]. A recent meta-analysis confirmed that bedside inoculation of ascitic fluid into blood culture bottles improves the diagnostic yield by approximately 20%[40].

3. Molecular techniques: Multiplex PCR and next-generation sequencing have shown promise in the rapid identification of pathogens in culture-negative SBP[41]. Friedrich et al. demonstrated that 16S rRNA gene sequencing could identify bacteria in 80% of culture-negative samples from patients with PMN counts ≥250 cells/mm³[42].

4. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS): This technique allows rapid identification of bacteria from positive culture bottles within minutes, facilitating early organism-directed therapy[43].

Novel Biomarkers

Several biomarkers have been investigated for the early diagnosis of SBP:

1. Calprotectin: Ascitic fluid calprotectin, a calcium-binding protein released from neutrophils, has shown promising results as a point-of-care test for SBP. A meta-analysis of 7 studies demonstrated a pooled sensitivity of 93% and specificity of 94% at a cutoff of 1.57 μg/mL[44]. The strip-based test provides results within minutes, potentially facilitating rapid diagnosis in the emergency setting.

2. Lactoferrin: Ascitic fluid lactoferrin, another neutrophil-derived protein, has shown high diagnostic accuracy for SBP, with sensitivity and specificity exceeding 90%[45].

3. Inflammatory cytokines: Ascitic fluid levels of IL-6, TNF-α, and IL-1β are significantly elevated in SBP. A cutoff value of 20 pg/mL for IL-6 provided 87% sensitivity and 92% specificity for SBP diagnosis in a recent study[46].

4. Bacterial DNA: Detection of bacterial DNA in ascitic fluid and serum by PCR has shown promise as a marker of bacterial translocation and predictor of SBP development[47].

5. Procalcitonin: Serum procalcitonin has demonstrated utility in differentiating SBP from non-infectious ascites, with a recent meta-analysis reporting a pooled sensitivity of 86% and specificity of 80% at a cutoff of 0.58 ng/mL[48].

6. Leukocyte esterase reagent strips (LERS): LERS provide a rapid, point-of-care assessment for SBP. However, a recent Cochrane review found that while specificity was high (97%), sensitivity was inadequate (45%), limiting its utility as a stand-alone test[49].

7. Platelet indices: Recent studies have suggested that platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) may have utility in predicting SBP[50].

Emerging Imaging Modalities

1. Contrast-enhanced ultrasound (CEUS): CEUS can detect increased vascularity and permeability of the peritoneum in SBP, potentially providing a non-invasive diagnostic approach[51].

2. Positron emission tomography/computed tomography (PET/CT): Early studies suggest that 18F-FDG PET/CT may help identify sites of inflammation in the peritoneum and differentiate SBP from secondary peritonitis[52].

Treatment Strategies: Current Recommendations and Novel Approaches

Empirical Antibiotic Therapy

The choice of empirical antibiotic therapy for SBP has evolved in response to changing antimicrobial resistance patterns:

1. Community-acquired SBP: Third-generation cephalosporins (cefotaxime 2g IV every 8 hours or ceftriaxone 2g IV daily) remain the first-line treatment, with documented efficacy in 70-90% of cases[53]. Amoxicillin-clavulanic acid (IV followed by oral) has also shown comparable efficacy in randomized trials[54].

2. Healthcare-associated and nosocomial SBP: For patients with healthcare-associated risk factors or in settings with high prevalence of ESBL-producing organisms, broader-spectrum antibiotics should be considered:

   • Piperacillin-tazobactam (4.5g IV every 6 hours)
   • Carbapenems (meropenem 1g IV every 8 hours)
   • Ceftazidime-avibactam for settings with high prevalence of carbapenem-resistant organisms[55,56]

3. De-escalation strategy: Once culture results and susceptibility testing are available, antibiotic therapy should be narrowed to the most appropriate agent[57].

Albumin Administration

The use of intravenous albumin in SBP has evolved beyond volume expansion:

1. Standard indications: Current guidelines recommend albumin administration (1.5 g/kg on day 1, followed by 1 g/kg on day 3) in patients with SBP who have:

   • Serum creatinine >1 mg/dL
   • Blood urea nitrogen >30 mg/dL
   • Total bilirubin >4 mg/dL[58]

2. Universal administration: A recent randomized controlled trial by Fernández et al. suggested that all patients with SBP benefit from albumin administration, regardless of risk factors for renal dysfunction, with a reduction in mortality (rate ratio 0.78, 95% CI 0.63-0.97)[59].

3. Mechanisms of action: Beyond volume expansion, albumin exerts pleiotropic effects in SBP:

   • Binding and clearance of endotoxins and pro-inflammatory molecules
   • Immunomodulatory effects, reducing the inflammatory response
   • Antioxidant properties, protecting against oxidative stress
   • Preservation of endothelial function and microcirculation[60]

4. Alternative albumin formulations: The potential benefit of albumin dialysis using the molecular adsorbent recirculating system (MARS) in patients with SBP and acute-on-chronic liver failure is being investigated[61].

Management of Acute Kidney Injury (AKI) in SBP

SBP-associated AKI carries a poor prognosis, with mortality exceeding 50%[62]. Recent advances in management include:

1. Early identification: Implementation of the International Club of Ascites (ICA) criteria for AKI in cirrhosis allows earlier recognition and intervention[63].

2. Terlipressin plus albumin: The combination of terlipressin (1-2 mg IV every 4-6 hours) and albumin has shown efficacy in reversing hepatorenal syndrome precipitated by SBP[64].

3. Continuous renal replacement therapy (CRRT): Early initiation of CRRT in patients with severe AKI and hemodynamic instability may improve outcomes[65].

4. Novel biomarkers: Urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) allow earlier detection of tubular injury in SBP-associated AKI[66].

Emerging Therapeutic Approaches

1. Granulocyte colony-stimulating factor (G-CSF): A small randomized trial showed that G-CSF administration in SBP improved survival by enhancing immune function and promoting hepatic regeneration[67].

2. Non-selective beta-blockers (NSBBs): While traditionally contraindicated in SBP due to concerns about hemodynamic compromise, recent data suggest that NSBBs may reduce bacterial translocation and SBP incidence by decreasing intestinal permeability and modulating gut motility[68]. The PREDESCI trial demonstrated that maintaining NSBBs in responders with acute decompensation did not increase mortality[69].

3. Farnesoid X receptor (FXR) agonists: FXR agonists such as obeticholic acid improve intestinal barrier function and reduce bacterial translocation in experimental models[70]. Clinical trials evaluating their effect on SBP prevention are ongoing.

4. Rifaximin: Beyond its established role in hepatic encephalopathy, rifaximin may reduce SBP incidence by modulating gut microbiota and reducing bacterial translocation. A meta-analysis of observational studies showed a significant reduction in SBP risk with rifaximin (OR 0.47, 95% CI 0.33-0.67)[71].

5. Fecal microbiota transplantation (FMT): Preliminary studies suggest that FMT may restore gut microbial diversity and reduce bacterial translocation in cirrhosis[72]. A small pilot study demonstrated that FMT reduced hospitalizations and serious adverse events in patients with recurrent hepatic encephalopathy[73].

6. Toll-like receptor modulators: TLR4 antagonists are being investigated for their potential to reduce the inflammatory response in SBP without compromising bacterial clearance[74].

Prevention Strategies

Primary Prophylaxis

Primary prophylaxis is recommended for patients at high risk of SBP:

1. Established indications:

   • Cirrhosis with gastrointestinal bleeding: Short-term prophylaxis with ceftriaxone 1g IV daily or norfloxacin 400 mg twice daily for 7 days[75]
   • Cirrhosis with low ascitic fluid protein (<1.5 g/dL) and at least one additional risk factor (serum creatinine ≥1.2 mg/dL, blood urea nitrogen ≥25 mg/dL, serum sodium ≤130 mEq/L, or Child-Pugh score ≥9 with bilirubin ≥3 mg/dL): Long-term prophylaxis with norfloxacin 400 mg daily or trimethoprim-sulfamethoxazole DS 1 tablet daily[76]

2. Emerging indications:

   • Patients with MELD score ≥20 or those awaiting liver transplantation[77]
   • Patients with hepatocellular carcinoma (HCC), who have been shown to have a higher incidence of SBP[78]

3. Novel risk stratification tools:

   • The MATIC score incorporates serum bilirubin, platelet count, and ascitic fluid protein to identify patients who would benefit most from prophylaxis[79]
   • Measurement of intestinal permeability using the lactulose/mannitol ratio may identify patients at high risk for bacterial translocation[80]

Secondary Prophylaxis

Secondary prophylaxis is recommended for all patients who have recovered from an episode of SBP:

1. Standard approach: Norfloxacin 400 mg daily or trimethoprim-sulfamethoxazole DS 1 tablet daily until liver transplantation, resolution of ascites, or death[81]. In settings with high prevalence of fluoroquinolone resistance, ciprofloxacin 500 mg weekly or rifaximin 550 mg twice daily may be considered[82].

2. Antimicrobial resistance concerns: In patients with prior infections by multidrug-resistant organisms, prophylaxis should be guided by susceptibility testing[83].

3. Combination approaches: The combination of norfloxacin and rifaximin has shown promise in preventing recurrent SBP in small studies, but larger trials are needed[84].

Non-antibiotic Approaches to Prophylaxis

Given concerns about antimicrobial resistance, non-antibiotic approaches to SBP prophylaxis are being investigated:

1. Probiotics: A meta-analysis of 12 randomized trials suggested that probiotics may reduce the incidence of SBP and overall infections in cirrhosis, but heterogeneity in probiotic formulations limits definitive conclusions[85].

2. Zinc supplementation: Zinc deficiency is common in cirrhosis and contributes to intestinal barrier dysfunction. Small studies suggest that zinc supplementation may reduce bacterial translocation and infection risk[86].

3. Vitamin D supplementation: Preliminary evidence suggests that vitamin D may enhance antimicrobial peptide production and maintain intestinal barrier integrity. A randomized trial is ongoing to evaluate its effect on SBP prevention[87].

4. Simvastatin: Beyond its lipid-lowering effects, simvastatin improves portal hypertension and may reduce bacterial translocation. The LIVERHOPE trial is evaluating the combination of simvastatin and rifaximin for the prevention of complications in cirrhosis, including SBP[88].

Special Considerations

Multidrug-Resistant (MDR) Infections

The increasing prevalence of MDR infections in SBP presents significant challenges:

1. Epidemiology: The prevalence of MDR organisms in SBP ranges from 15-45%, with higher rates in nosocomial infections, patients with previous antibiotic exposure, and those with multiple hospitalizations[89].

2. Risk assessment: Several risk scores have been developed to predict MDR infections, including the ESBL-GPCS score (prior ESBL infection, current/recent ICU stay, recent β-lactam antibiotic use)[90] and the Piano score (nosocomial origin, healthcare-associated origin, recent infection by MDR bacteria, recent use of β-lactams)[91].

3. Treatment approaches: For patients with suspected MDR infections, combination therapy (e.g., carbapenem plus glycopeptide or daptomycin) may be necessary until susceptibility results are available[92]. In settings with high prevalence of carbapenem-resistant organisms, newer antibiotics such as ceftazidime-avibactam, ceftolozane-tazobactam, or meropenem-vaborbactam should be considered[93].

4. Antimicrobial stewardship: Implementation of antimicrobial stewardship programs in hepatology units is essential to preserve antibiotic efficacy[94].

Culture-Negative Neutrocytic Ascites (CNNA)

CNNA is defined as an ascitic fluid PMN count ≥250 cells/mm³ with negative culture results, occurring in approximately 30-40% of suspected SBP cases[95]:

1. Diagnostic approach: In patients with CNNA, repeat paracentesis after 48 hours should be considered if there is no clinical improvement. Molecular techniques (PCR, 16S rRNA sequencing) may identify bacteria in culture-negative samples[96].

2. Management: CNNA should be treated with the same antibiotic regimens as culture-positive SBP, with duration guided by clinical response and follow-up ascitic fluid analysis[97].

SBP in the Setting of Acute-on-Chronic Liver Failure (ACLF)

SBP is a common precipitant of ACLF, characterized by rapid deterioration of liver function and multiple organ failure[98]:

1. Diagnosis and risk assessment: The PREDICT score incorporates clinical and laboratory parameters to predict ACLF development in patients with SBP[99].

2. Management: Patients with SBP-triggered ACLF require:

   • Intensive care monitoring
   • Higher doses of albumin (1.5-2 g/kg/day)
   • Early renal replacement therapy for severe AKI
   • Vasopressors (norepinephrine, terlipressin) for hemodynamic support
   • Consideration for extracorporeal liver support (MARS, Prometheus) as a bridge to transplantation[100]

3. Granulocyte colony-stimulating factor: G-CSF has shown promise in improving survival in ACLF, particularly when initiated early[101].

4. Transplantation: Expedited liver transplantation evaluation should be considered for suitable candidates, as mortality remains high despite optimal medical therapy[102].

SBP in Non-cirrhotic Ascites

While uncommon, SBP can occur in patients with non-cirrhotic ascites, particularly in malignant ascites, nephrotic syndrome, and heart failure[103]:

1. Microbiological differences: Streptococcus species and Enterococcus are more common pathogens in non-cirrhotic SBP[104].

2. Diagnostic criteria: The diagnostic threshold of 250 PMN/mm³ has not been validated in non-cirrhotic ascites, and a lower threshold (≥100 PMN/mm³) may be appropriate in certain settings[105].

3. Treatment considerations: The optimal antibiotic regimen and duration have not been established. Treatment should be guided by the underlying condition, local antimicrobial resistance patterns, and clinical response[106].

Future Directions

Personalized Approaches to SBP Management

The heterogeneity of SBP in terms of causative organisms, host immune response, and clinical outcomes calls for personalized approaches:

1. Microbiome analysis: Characterization of the gut microbiome composition using metagenomic sequencing may identify patients at high risk for SBP and guide preventive strategies[107].

2. Host genetic factors: Genetic polymorphisms affecting intestinal barrier function, immune response, and antimicrobial peptide production may influence susceptibility to SBP and response to treatment[108].

3. Biomarker-guided therapy: Integration of multiple biomarkers (inflammatory markers, markers of bacterial translocation, organ dysfunction indices) may facilitate early intervention and guide treatment intensity[109].

4. Machine learning algorithms: Several predictive models incorporating clinical, laboratory, and microbiological data have been developed to predict SBP outcomes and guide management[110].

Novel Therapeutic Targets

Emerging molecular insights into SBP pathogenesis have identified potential therapeutic targets:

1. Intestinal barrier modulators: Compounds that enhance tight junction integrity, such as larazotide acetate (a tight junction regulator) and cobiprostone (a chloride channel activator), are being investigated for their potential to reduce bacterial translocation[111].

2. Microbiome-targeted therapies: Beyond probiotics, precision manipulation of the microbiome using engineered bacteria or bacteriophages targeting specific pathogens represents a promising approach[112].

3. Immunomodulatory strategies: Targeted immunotherapy to restore immune function while preventing excessive inflammation, such as checkpoint inhibitors and adoptive cell therapy, is being explored[113].

4. Anti-fibrotic agents: Reversing hepatic fibrosis may improve portal hypertension and reduce bacterial translocation. Several agents, including galectin inhibitors and lysyl oxidase-like 2 (LOXL2) inhibitors, are in clinical trials[114].

5. Cell-based therapies: Mesenchymal stem cells have shown promise in experimental models by reducing inflammation, enhancing antimicrobial responses, and promoting hepatic regeneration[115].

Conclusion

Spontaneous bacterial peritonitis remains a significant challenge in the management of patients with cirrhosis and ascites. The evolving landscape of causative organisms and increasing antimicrobial resistance necessitates a reevaluation of diagnostic and therapeutic approaches. Recent advances in our understanding of the gut-liver axis, microbiome alterations, and immune dysfunction in cirrhosis have provided insights into novel therapeutic targets.

The development of rapid, point-of-care diagnostic tests and biomarkers holds promise for early identification and intervention. Personalized antibiotic regimens based on local resistance patterns and individual risk factors, combined with optimal albumin administration, may improve outcomes in the short term. In the longer term, strategies targeting the microbiome, intestinal barrier function, and immune dysfunction may transform the prevention and management of this life-threatening complication.

While liver transplantation remains the definitive treatment for patients with decompensated cirrhosis, the high mortality associated with SBP underscores the urgent need for innovative approaches to bridge patients to transplantation or extend survival in those who are not transplant candidates. Multidisciplinary collaboration between hepatologists, infectious disease specialists, microbiologists, and critical care physicians is essential to optimize the management of this complex condition.

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