Intra-abdominal Infections: Appendicitis and Infections of the Liver and Biliary System

Peritonitis and Intraperitoneal Abscesses

Author

Russell Lewis

Published

2026-03-01

Lecture part 1.

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IDSA guidelines
Surgical Infection Society Guidelines

Lecture part 2.

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Lecture 1: Notes

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SHORT VIEW SUMMARY

Definition

Intraabdominal infections represent a spectrum of conditions involving contamination of the peritoneal cavity or intraabdominal organs with microorganisms. The key clinical concepts include:

Peritonitis: An inflammatory response within the peritoneal cavity resulting from contamination with microorganisms, chemicals, or both
Classification: Infections are classified as diffuse or localized; primary (spontaneous), secondary, or tertiary; and community-acquired or healthcare-acquired
Primary peritonitis: No intraabdominal surgical source of infection
Secondary peritonitis: Presence of an identifiable intraabdominal source of infection (perforation, ischemia, etc.)
Complicated infections: Extend beyond the organ of origin with spillage into the peritoneal space; uncomplicated infections are contained within a single organ
Risk stratification: Community-acquired infections are subdivided into low-risk and high-risk based on probability of drug-resistant organisms and severity (mild, moderate, severe)
Tertiary peritonitis: Persistent or recurrent infection without a surgically treatable focus, often involving less virulent organisms

Epidemiology

Primary peritonitis accounts for approximately 1% of all peritonitis cases
Secondary peritonitis is the most common intraabdominal infection (80-90% of cases)
Primary peritonitis occurs primarily in cirrhotic patients with ascites; risk increases with coexisting gastrointestinal hemorrhage, low ascitic protein (<1.5 g/dL), and elevated serum creatinine
Tertiary peritonitis is associated with disturbance of host immune response and occurs in critically ill patients without an obvious surgically treatable focus
Continuous ambulatory peritoneal dialysis (CAPD) peritonitis represents a major complication with recurrence in 20-30% of patients, often prompting switch to hemodialysis
Intraperitoneal abscesses occur secondarily following diseased organs, penetrating trauma, or surgical procedures

Microbiology

Primary peritonitis: Monomicrobial infection in >95% of cases; gram-negative enteric bacteria in 69% of cirrhotic patients (predominantly Escherichia coli)
Secondary peritonitis: Characteristically polymicrobial with both facultative and obligate anaerobes; depends on site and prior antibiotic exposure
Key organisms: Facultative gram-negative bacilli (E. coli, Klebsiella, Enterobacter), obligate anaerobes (Bacteroides fragilis, other Bacteroides spp., Clostridium spp.), and gram-positive cocci (streptococci, enterococci)
CAPD peritonitis: Gram-positive organisms in 60-80% (primarily coagulase-negative staphylococci); gram-negative bacteria in 15-30%
ESBL prevalence: Extended-spectrum beta-lactamase-producing gram-negative bacilli increasingly encountered in both healthcare-associated and community-acquired infections
Enterococci: Found in 15-20% of secondary peritonitis; treatment indicated in select high-risk patients
Candida species: Present in ~20% of acute GI perforations; more common in healthcare-associated settings with prior antibiotics

Diagnosis

Primary peritonitis: Diagnosed by excluding primary source with ascitic fluid analysis (WBC count, protein, Gram stain, culture)
Serum-ascitic albumin gradient >1.1 g/dL: Suggests nonperitoneal cause (e.g., portal hypertension)
Ascitic fluid findings suggestive of peritonitis: ≥250 PMN cells/mm³ (Ref11?) with positive culture or clinical symptoms
Secondary peritonitis: Requires imaging (CT or ultrasound) to identify source and assess for abscess formation
CAPD peritonitis: >100 WBC/mm³ (predominantly PMN cells) in dialysate with microorganism isolation in 90-95% of cases
Culture methods: Inoculating blood culture bottles with ascitic fluid at bedside improves culture sensitivity (Ref33?)

Therapy

Primary peritonitis: Empirical antibiotics based on likely pathogens with 5-7 days recommended duration (oral transition after 48 hours if improved)
Albumin supplementation: 1.5 g/kg within 6 hours of diagnosis plus 1 g/kg on day 3 for patients with serum creatinine >1 mg/dL or bilirubin >4 mg/dL significantly reduces acute kidney injury and mortality (16% vs 35% mortality)
Secondary peritonitis: Requires antibiotics, source control (Ref183?), abscess drainage, and supportive care
CAPD peritonitis: Intraperitoneal antibiotics for 14-21 days; catheter removal necessary in 10-20% of cases
Antifungal therapy: Indicated for invasive Candida infections; echinocandins preferred first-line
Intraperitoneal abscesses: Require drainage (percutaneous or surgical), targeted antibiotics, and source control

Prevention

Primary peritonitis prophylaxis:
- Short-term: Ceftriaxone 1 g daily for 7 days during gastrointestinal hemorrhage in cirrhotic patients
- Long-term: Ciprofloxacin 500 mg daily, norfloxacin 400 mg daily (Ref101?), or double-strength trimethoprim-sulfamethoxazole daily
Indications for long-term prophylaxis: Prior episode of primary peritonitis or high-risk factors (ascitic protein <1.5 g/dL, creatinine ≥1.2 mg/dL, BUN ≥25 mg/dL, sodium ≤130 mEq/L, or hepatic failure with MELD ≥9)

PERITONITIS OVERVIEW

Anatomy and Physiology

The peritoneal cavity is a complex anatomic space that accommodates multiple organs and facilitates motion while containing normal fluid. The anatomic relationships are critical in determining routes of infection spread:

The peritoneal cavity extends from the diaphragm to the pelvic floor, containing the stomach, small intestine, colon, liver, gallbladder, and spleen
The transverse mesocolon divides the peritoneal cavity horizontally into upper and lower spaces
The greater omentum extends from the transverse mesocolon and provides additional compartmentalization
The lesser sac, the largest recess, is surrounded by the pancreas, kidneys (posteriorly), stomach (anteriorly), and liver/spleen (laterally); its limited communication via the foramen of Winslow allows isolated suppuration
Anatomic spaces at risk for abscess formation include: subphrenic spaces, subhepatic spaces, paracolic gutters, Morison pouch (hepatorenal fossa), lesser sac, rectovesical/rectouterine pouch, and interloop spaces

The peritoneum is a serous membrane composed of a monolayer of mesothelial cells beneath which are lymphatic vessels, blood vessels, and nerve endings. Normal peritoneal fluid (approximately 100 mL) is clear yellow with low specific gravity and protein content (typically <3 g/dL), containing few leukocytes (<250/mm³, predominantly mononuclear). The peritoneal membrane has high permeability and facilitates both fluid exudation and absorption.

Anatomy of the peritoneal cavity showing key anatomic spaces relevant to intraabdominal infection.

Classification and Definitions

Peritonitis is classified based on:

Origin: Primary (spontaneous), secondary (from intraabdominal source), or tertiary (persistent/recurrent after treatment)
Extent: Diffuse or localized
Chronicity: Acute or chronic
Acquisition: Community-acquired (~80%) or healthcare-associated
Risk stratification: Low-risk vs high-risk based on pathogen probability and severity

Pathophysiology

Local Response

The peritoneum responds to contamination with characteristic inflammatory reactions:

Dramatic outpouring of protein-rich fluid (>3 g/dL) into the peritoneal cavity
Recruitment of polymorphonuclear leukocytes for bacterial phagocytosis and killing
Fibrinogen polymerization forming fibrinous exudate plaques that localize infection
Formation of fibrinous adhesions between bowel, mesentery, and omentum
Inhibition of intestinal motility in involved segments

The extent and rate of spread depend on bacterial virulence, volume and nature of exudate, and effectiveness of localization mechanisms. Potential outcomes include: spontaneous resolution if defenses are adequate, formation of a confined abscess, or progressive diffuse peritonitis if defenses are overwhelmed.

Systemic Response

The inflammatory response involves multiple cytokine mediators:

Tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, interferon-γ (IFN-γ), and soluble adhesion molecules released in response to bacterial products and tissue trauma
Cytokine concentrations are dramatically higher in peritoneal exudate than in serum
Systemic manifestations mediated by cytokine translocation via mesenteric lymph channels
Renal insufficiency develops in approximately 30% of patients with primary peritonitis and is the most sensitive predictor of mortality

PRIMARY PERITONITIS (SPONTANEOUS BACTERIAL PERITONITIS)

Etiology

Primary peritonitis (spontaneous bacterial peritonitis, SBP) represents infection of the peritoneal cavity without an evident intraabdominal source. It occurs in patients with predisposing conditions that result in ascites:

Cirrhosis and portal hypertension: The most common predisposing condition (prevalence 10-30% in hospitalized cirrhotic patients with ascites) (Ref12?; Ref22?)
Cirrhosis type: Alcoholic cirrhosis, postnecrotic cirrhosis, chronic active hepatitis, acute viral hepatitis
Other conditions: Congestive heart failure, metastatic malignancy, systemic lupus erythematosus, nephrotic syndrome, lymphedema, or rarely no underlying disease
Risk factors for SBP in cirrhotic patients:
- High-volume ascites (advanced cirrhosis, MELD >9)
- Concurrent gastrointestinal hemorrhage
- Prior episode of primary peritonitis
- Low ascitic protein (<1 g/dL)
- Elevated serum bilirubin (>2.5 mg/dL)
- Proton pump inhibitor use (Ref26?; Ref38?)

Tense ascites in a cirrhotic patient — a major risk factor for the development of SBP.

The common pathogenic link is the presence of ascites, likely due to impaired reticuloendothelial clearance of bacteria and reduced opsonic activity in ascitic fluid (Ref41?).

Cirrhosis with portal hypertension is the most common predisposing condition for SBP, present in 10–30% of hospitalized cirrhotic patients with ascites.

Bacteriologic Characteristics

Primary peritonitis is characteristically a monomicrobial infection, with microorganisms of presumed enteric origin:

Most common pathogens: E. coli (most frequent), Klebsiella pneumoniae, other Enterobacterales, Streptococcus pneumoniae, and other streptococcal species
Percentage distribution (in cirrhotic patients):
- Gram-negative enteric bacteria: 69%
- Streptococcus species: 15%
- Staphylococcus aureus: 2-4% (unusual; may occur with umbilical hernia erosion)
Rare pathogens: Pseudomonas aeruginosa, fungi, anaerobes (less than 1%)

Variants of Primary Peritonitis

Three distinct variants have been described:

Monomicrobial nonneutrocytic bacterascites: Positive cultures but <250 neutrophils/mm³; may represent early bacterial colonization; 62-86% resolve spontaneously, remainder progress to SBP
Culture-negative neutrocytic ascites: >250 neutrophils/mm³ with negative cultures (in absence of prior antibiotics); occurs in 35% of clinically suspected SBP; blood cultures positive in one-third of cases (Ref32?)
Polymicrobial bacterascites: Due to traumatic paracentesis (Ref34?) with bowel entry (<1% of procedures); transient in most cases if protein >1 g/dL and opsonic activity adequate

Note

Diagnostic Pearl: The finding of >250 neutrophils/mm³ in peritoneal fluid warrants empirical antibiotic therapy even with negative cultures if SBP is clinically suspected, as blood cultures are positive in one-third of culture-negative cases.

Pathogenesis

The route of infection in primary peritonitis is typically not apparent, but several mechanisms have been proposed:

Routes of Bacterial Entry

Hematogenous/lymphogenous: Bacteria from intestinal translocation enter portal circulation; hepatic reticuloendothelial system is primary site for clearance
Transmural migration: Enteric bacteria traverse intact bowel wall (demonstrated with hypertonic peritoneal solutions in animal models)
Vaginal ascension: Transfallopian spread in prepubertal females; associated with intrauterine devices
Distant foci: Hematogenous seeding from skin, soft tissues, urinary tract, respiratory tract, or odontogenic infections

Host Factors Facilitating Infection

Impaired reticuloendothelial clearance: Cirrhosis is associated with impaired hepatic bacterial clearance
Reduced opsonization: Low complement and immunoglobulin levels in ascitic fluid, particularly in cirrhosis and nephrotic syndrome
Impaired phagocytosis: Alcohol abuse and cirrhosis cause reduced intracellular killing by monocytes and neutrophils
Intestinal bacterial overgrowth: Proton pump inhibitors may increase bacterial overgrowth and translocation risk
Portosystemic shunts: Allow portal blood to bypass hepatic filtering

Clinical Manifestations

Primary peritonitis often presents insidiously in cirrhotic patients with minimal or nonspecific symptoms:

Symptoms

Abdominal pain (often mild or absent)
Fever (variable, may be absent)
Change in mental status (hepatic encephalopathy)
Malaise, fatigue
Nausea and vomiting

Warning

Clinical Pearl: Primary peritonitis may present with only fever and a decline in mental status without marked peritoneal signs; a low threshold for paracentesis is essential in cirrhotic patients with ascites.

Physical Findings

Mild abdominal tenderness (may be absent)
Decreased rebound tenderness compared to secondary peritonitis
Absence of classic peritoneal signs in many cases
Jaundice and stigmata of cirrhosis

Laboratory Findings

Peritoneal Fluid Analysis

WBC count: ≥250 cells/mm³ (predominantly PMN); cultures positive in 40-60% of cases
Protein concentration: Usually reflects serum levels (low in cirrhotic patients)
Gram stain: Positive in only 10-15% of cases
Culture: Positive in 40-60%; single organism in >95%
Blood cultures: Positive in 75% of patients with aerobic bacterial peritonitis

Note

Diagnostic Technique: Inoculation of blood culture bottles with 10-20 mL of ascitic fluid at bedside improves culture yield, particularly for fastidious organisms.

Bedside paracentesis for ascitic fluid sampling — essential for diagnosis of SBP. Inoculation of blood culture bottles at the bedside improves culture sensitivity.

Additional Studies

Serum-ascitic albumin gradient >1.1 g/dL: Suggests portal hypertension (not peritonitis)
Ascitic glucose: May be low in secondary peritonitis or tuberculous peritonitis
Ascitic amylase and LDH: May help distinguish primary from secondary peritonitis
Blood chemistry: Assess renal function (creatinine), liver function (bilirubin, INR)

Diagnosis

Primary peritonitis is diagnosed by:

Clinical suspicion in patient with ascites and signs of infection
Paracentesis with ascitic fluid cell count ≥250 PMN/mm³
Exclusion of a primary intraabdominal source of infection (clinical exam, imaging if needed)
Positive ascitic fluid or blood culture

Note

Diagnostic Criteria for SBP: - Ascitic fluid PMN count ≥250 cells/mm³ - Positive ascitic or blood culture with single organism - No evidence of secondary peritonitis (perforation, pancreatitis, etc.)

Prognosis

Prognosis in primary peritonitis is significantly influenced by the presence of complications:

Mortality: Historically 30-40% in hospitalized patients; improved with early diagnosis and therapy
Renal failure: Develops in 30-40% of patients and is the major cause of death
Recurrence: 69% at 1 year if prophylaxis not given after first episode
Albumin administration: Meta-analysis of four controlled trials demonstrated significant mortality reduction (16% vs 35%) and reduction in acute kidney injury (8% vs 31%) when albumin given with antibiotics

Therapy

Antimicrobial Therapy

Empirical therapy should be initiated immediately after paracentesis upon clinical suspicion:

Warning

Indications for Initiation of Antimicrobial Therapy: - Temperature >37.8°C (100°F) - Abdominal pain and/or tenderness - Unexplained change in mental status - Laboratory abnormalities (renal failure, acidosis, peripheral leukocytosis) - Ascitic fluid PMN count ≥250 cells/mm³

First-Line Regimens

Organism	Preferred Agent
S. pneumoniae or Group A streptococci	High-dose penicillin, ceftriaxone, or cefotaxime
Penicillin-resistant pneumococci	Vancomycin ± fluoroquinolone
Methicillin-sensitive S. aureus	Nafcillin or first-generation cephalosporin (cefazolin)
Methicillin-resistant S. aureus	Vancomycin, daptomycin, telavancin, or linezolid
P. aeruginosa	Antipseudomonal penicillin, ceftazidime, cefepime, carbapenem ± aminoglycoside or fluoroquinolone
ESBL-producing gram-negative bacilli	Carbapenem (preferred)

Duration and Route of Therapy

Duration: 5-7 days is standard for most cases
Transition to oral: After 48 hours of intravenous therapy if clinical improvement demonstrated and effective oral agent available
Clinical improvement: ≥25% decline in ascitic PMN count at 24-48 hours indicates adequate therapy
Repeat paracentesis: Consider if:
- Unusual organism isolated
- Lack of expected clinical response
- Elevated PMN count on follow-up

Albumin Administration

Albumin is indicated to prevent renal insufficiency and reduce mortality:

Dosing: 1.5 g/kg IV within 6 hours of diagnosis, then 1 g/kg on day 3
Indications:
- Ascitic fluid PMN ≥250 cells/mm³
- Serum creatinine >1 mg/dL, BUN >30 mg/dL, or total bilirubin >4 mg/dL
Mechanism: Maintains effective arterial blood volume and prevents acute kidney injury
Evidence: Reduces mortality from 35% to 16% and acute kidney injury from 31% to 8%

Albumin infusion reduces renal vasoconstriction and prevents acute kidney injury in SBP — a key adjunct to antibiotic therapy.

Vasopressor Consideration

Beta-blockers associated with increased mortality in SBP; should be discontinued in hypotensive or hyponatremic patients

Prevention

Tip

Prophylaxis Reduces Mortality: Antibiotic prophylaxis has been proven in randomized controlled trials to decrease infection episodes and lower mortality in high-risk patients.

Short-Term Prophylaxis (Acute Gastrointestinal Bleeding)

Agent: Intravenous ceftriaxone 1 g daily
Duration: 7 days inpatient
Transition: Change to oral double-strength trimethoprim-sulfamethoxazole, ciprofloxacin 500 mg twice daily, or norfloxacin 400 mg twice daily once bleeding cessation and clinical stability achieved

Long-Term Prophylaxis

Indication	Preferred Agents
Prior episode of SBP	Ciprofloxacin 500 mg daily, norfloxacin 400 mg daily, or double-strength TMP-SMX daily
Ascitic protein <1.5 g/dL AND one of:	Same as above
- Serum creatinine ≥1.2 mg/dL
- BUN ≥25 mg/dL
- Serum sodium ≤130 mEq/L
- Hepatic failure (MELD ≥9, bilirubin ≥3 mg/dL)
High-risk GI bleeding	Ciprofloxacin or norfloxacin

Note

Alternative Agent: Rifaximin has been shown effective in reducing SBP occurrence, though routine use data are insufficient at present.

SECONDARY AND TERTIARY PERITONITIS

Etiology

Secondary peritonitis results from spillage of gastrointestinal or genitourinary microorganisms into the peritoneal cavity following loss of mucosal integrity. It accounts for 80-90% of intraabdominal infections and is the most common.

Causes by Organ

Organ	Cause of Peritonitis
Distal esophagus	Boerhaave syndrome, malignancy, trauma, iatrogenic perforation
Stomach	Peptic ulcer perforation, malignancy, trauma, iatrogenic injury
Duodenum	Peptic ulcer perforation, trauma, iatrogenic injury
Biliary tract	Cholecystitis, stone perforation, malignancy, trauma, iatrogenic injury
Pancreas	Pancreatitis (alcohol, drugs, gallstones), trauma, iatrogenic injury
Small bowel	Ischemic bowel, incarcerated hernia, Crohn disease, malignancy, Meckel diverticulum, trauma
Large bowel and appendix	Ischemic bowel, diverticulitis, malignancy, inflammatory bowel disease, appendicitis, volvulus, penetrating trauma, iatrogenic injury
Uterus/salpinx/ovaries	Pelvic inflammatory disease, tubo-ovarian abscess, ovarian cyst rupture, malignancy, trauma, iatrogenic injury

Special Populations

Immunocompromised patients: Typhlitis (neutropenic enterocolitis), an inflammation of the cecum with potential progression to perforation and secondary peritonitis, represents a significant risk.

Microbiologic Characteristics

Secondary peritonitis is characteristically polymicrobial, with both facultative and obligate anaerobes. The specific microflora depends on the site of origin and may be altered by prior antibiotic therapy, other medications affecting gastric acidity, and host factors.

Distribution of Organisms

Organism	Percentage (%)
Aerobic/Facultative Gram-Negative Bacilli
Escherichia coli	71
Klebsiella spp.	14
Pseudomonas aeruginosa	14
Proteus mirabilis	5
Enterobacter spp.	5
Anaerobes
Bacteroides fragilis	35
Other Bacteroides spp.	71
Clostridium spp.	29
Prevotella spp.	12
Peptostreptococcus spp.	17
Fusobacterium spp.	9
Eubacterium spp.	17
Gram-Positive Aerobic Cocci
Streptococcus spp.	38
Enterococcus faecalis	12
Enterococcus faecium	3
Staphylococcus aureus	4

Overall Pattern

Aerobes only: 17%
Anaerobes only: 1%
Anaerobes + aerobes: 82%

Warning

Polymicrobial Synergy: Obligate anaerobes protect aerobic bacteria from phagocytic killing and antibiotic effects through beta-lactamase production. Bacteroides species are responsible for late abscess formation, while E. coli drives early mortality.

Emerging Resistance Patterns

ESBL-producing E. coli and Klebsiella(Ref115?; Ref116?) spp.: Increasing prevalence in both community-acquired and healthcare-associated infections
AmpC-producing organisms: Enterobacter, Serratia, Citrobacter, Providencia, Morganella, and Acinetobacter spp. with resistance to third-generation cephalosporins
Carbapenem-resistant Enterobacterales (CRE): Emerging threat with multiple resistance mechanisms
MRSA: More prevalent in healthcare-associated infections
Enterococci: Increasing frequency with vancomycin resistance increasingly documented
Candida species: Present in 20% of acute GI perforations, more common with upper GI sources and prior antibiotics

Pathogenesis

Establishment of Infection

Anaerobic infections require: - Low oxygen tension - Low oxidation-reduction potential - Abundant nutrients - Sometimes specific growth factors (vitamin K, arginine, serum, blood pigments, bile)

These conditions are met in tissue devitalized by ischemia, trauma, or neoplasia.

Bacterial Synergy

Mixed infections involve both pathogenic and nonpathogenic organisms whose presence together creates pathogenicity:

Environmental modification: Facultative organisms reduce oxygen tension, creating conditions favorable for obligate anaerobes
Growth factor generation: One organism produces essential factors for another (e.g., vitamin K production for Prevotella by diphtheroids)
Antibiotic protection: Anaerobes protect aerobes from phagocytic killing and antibiotic effects via beta-lactamase production
Differentiated roles: E. coli responsible for early mortality; B. fragilis (with E. coli) responsible for late abscess formation

Pathophysiologic Responses

Local Response

Following peritoneal contamination, a characteristic local inflammatory response occurs:

Exudative response: High protein content (>3 g/dL) with many cells, primarily PMN leukocytes that phagocytose organisms
Fibrinous exudate: Fibrinogen polymerization forming plaques on inflamed surfaces
Adhesion formation: Exudate glues together adjacent bowel, mesentery, and omentum
Motility inhibition: Impaired intestinal motility in involved loops aids localization

Outcome depends on interplay of factors: - Greater bacterial virulence → spread - Larger volume/duration of contamination → spread - Impaired host defenses → spread

Possible outcomes: spontaneous resolution, localized abscess, or diffuse progressive peritonitis.

CT imaging demonstrating peritonitis with bowel wall thickening, mesenteric stranding, and free fluid characteristic of secondary peritonitis.

Systemic Response

Cytokines mediate systemic manifestations:

Major cytokines: TNF-α, IL-1, IL-6, IFN-γ, and soluble adhesion molecules
Source: Macrophages and host cells responding to bacteria, bacterial products (endotoxin), and tissue trauma
Concentration: Dramatically higher in peritoneal exudate than serum
Translocation: Via mesenteric lymph channels into systemic circulation
Consequences:
- Reduction of effective arterial blood volume
- Activation of renin-angiotensin system
- Renal insufficiency (associated with mortality)
- Multi-organ failure

Clinical Manifestations

Symptoms

The presentation varies depending on acuity and extent of contamination:

Acute onset (perforation): Sudden severe abdominal pain
Gradual onset (perforated viscus, ischemia): Progressive pain
Constitutional: Fever, chills, malaise
GI: Nausea, vomiting, loss of appetite, constipation
Systemic: Tachycardia, tachypnea, confusion (sepsis)

Physical Findings

Peritoneal signs: Rebound tenderness, guarding, rigidity
Absent bowel sounds: Due to ileus
Abdominal distension: From fluid accumulation and bowel distension
Hypotension: Indicates sepsis and need for urgent intervention
Altered mental status: Indicates severe sepsis/shock

Diagnostic Studies

Imaging

Computed Tomography (CT): Gold standard for diagnosis

Identifies primary source (perforation, abscess)
Shows free air, free fluid, bowel dilatation
Assesses for abscess requiring drainage
Guides percutaneous drainage

Ultrasound: Alternative in some settings

Bedside capability
Less sensitive than CT for free air and early peritonitis
Better for ascites quantification

CT abdomen showing intraperitoneal abscess — CT is the gold standard for identifying the source of peritonitis and guiding percutaneous drainage.

Bedside ultrasound demonstrating free intraperitoneal fluid — useful when CT is not immediately available.

Laboratory Studies

CBC: Leukocytosis (though may be normal in some cases)
Chemistries: Electrolyte abnormalities, elevated creatinine, elevated LDH
Coagulation studies: Assess for DIC if severe sepsis
Lactate: Elevated in sepsis; correlates with severity
Blood cultures: Positive in 50-80% of cases with bacteremia

Peritoneal Fluid Analysis

Cell count and differential: PMN predominance
Gram stain: Often negative but should be performed
Culture: Essential for organism identification and susceptibility
pH: Low pH suggests bacterial contamination
Glucose: Low in secondary peritonitis
Lactate: Elevated in bacterial peritonitis

Prognosis

Prognosis depends on multiple factors:

Mortality: Ranges from 5-15% in low-risk, uncomplicated cases to 30-40% in high-risk, severe cases
Tertiary peritonitis: Worst prognosis with mortality of 30-64%
Factors worsening prognosis:
- Delayed source control
- Inadequate initial antimicrobial therapy
- Multiple organ failure
- Immunocompromised status
- Severity of illness (APACHE II score)
- Presence of resistant pathogens

Therapy

Antimicrobial Therapy Principles

Tip

Key Principle: Empirical therapy must cover both aerobic gram-negative bacilli (especially E. coli) and obligate anaerobes (B. fragilis) based on animal models showing necessity of treating both.

Timing: Initiate immediately after appropriate specimens (blood, peritoneal fluid) obtained for culture.

Duration: 4-7 days for uncomplicated secondary peritonitis; longer for complicated cases or delayed source control.

Adjustments: Modify based on culture and susceptibility results to ensure coverage of predominant pathogens.

Recommended Antimicrobial Regimens

For Mild-to-Moderate Community-Acquired Infections (Low-Risk)

Agent	Dosing
Single Agent
Ertapenem	1 g IV daily
Moxifloxacin	400 mg IV daily
Combination Therapy
Cefotaxime (Ref64?; Ref77?) or ceftriaxone	1-2 g IV Q8H +
+ metronidazole	500 mg IV Q6-8H
Ciprofloxacin	400 mg IV Q12H +
+ metronidazole	500 mg IV Q6-8H

For High-Risk or Severe Community-Acquired, Healthcare-Associated, and Tertiary Infections

Agent	Dosing
Single Agent
Imipenem-cilastatin	500 mg IV Q6H
Meropenem	1 g IV Q8H
Tigecycline	100 mg IV once, then 50 mg Q12H
Eravacycline	1 mg/kg IV Q12H
Combination Therapy
Cefepime or ceftazidime	2 g IV Q8-12H +
+ metronidazole	500 mg IV Q6-8H
Piperacillin-tazobactam	3.375-4.5 g IV Q6-8H
Ceftazidime-avibactam	2.375 g IV Q8H + metronidazole
Ceftolozane-tazobactam	1.5 g IV Q8H + metronidazole

Warning

Resistance Considerations: - Tigecycline: NOT recommended as empirical therapy for healthcare-associated or tertiary infections due to inactivity against P. aeruginosa - Fluoroquinolones: Resistance becoming common; use only if institutional surveys show ≥90% E. coli susceptibility - Piperacillin-tazobactam: Reduced susceptibility with ESBL and AmpC producers; reserved primarily for high-risk patients

New Agents Against Resistant Gram-Negative Bacilli

Agent	ESBL	AmpC	CRE	CRAB	CRPA	FDA-cIAI	Notes
Plazomicin	✓	✓	✓	X	X	X	R-enterococci, gram-pos cocci
Eravacycline	✓	✓	✓	✓	X	✓	Not R-P. mirabilis, Morganella, Providencia
Tigecycline	✓	✓	✓	✓	X	✓	Not R-P. mirabilis, Morganella, Providencia
Cefiderocol	✓	✓	✓	✓	✓	X	R-enterococci, gram-pos cocci; UTI/VAP only approved
Ceftazidime-avibactam	✓	✓	✓	X	±	✓	R-enterococci
Ceftolozane-tazobactam	✓	X	X	X	✓	✓	R-enterococci
Meropenem-vaborbactam	✓	✓	✓	X	X	X
Imipenem-relebactam	✓	✓	✓	X	X	✓

Legend: ✓ = Active; X = Not active; ± = Variable/partial activity

Special Pathogen Considerations

Enterococci

The role of enterococci in polymicrobial intraabdominal infection remains controversial:

Prevalence: Found in ~20% of intraabdominal infections
Clinical significance:
- Animal models show they enhance abscess formation, bacteremia, and mortality
- Clinical reports document enterococcal superinfection when initial therapy lacks enterococcal coverage
- However, selective therapy against E. coli and B. fragilis may be sufficient in some cases
Indications for anti-enterococcal coverage:
- Healthcare-associated or postoperative infections
- Prior broad-spectrum cephalosporin or fluoroquinolone exposure
- Immunocompromised patients
- Prosthetic heart valves or valvular disease
- Septic shock
- High APACHE II score, advanced age, or prolonged preinfection hospitalization
Agents: Beta-lactam agents (ampicillin-sulbactam), glycopeptides (vancomycin), or newer agents (daptomycin, tigecycline, eravacycline) for VRE

Candida Species

The optimal management of Candida in polymicrobial intraabdominal infection remains controversial:

Prevalence: Isolated from 20% of acute GI perforations
Risk factors for invasive candidemia:
- Upper GI tract perforation/disruption
- Surgical treatment of pancreatitis
- Previous antibiotic therapy
- Multiple perforations
- Immunosuppression (chemotherapy, transplantation)
- Postoperative or recurrent intraabdominal infection
Indications for antifungal therapy:
- Candida in blood culture (indicates invasive disease)
- Candida as sole organism in residual/recurrent infection
- Candida as predominant organism on Gram stain of peritoneal exudate
- Severe community-acquired or healthcare-associated IAI with Candida isolation (expert recommendation)
First-line agent: Echinocandin (caspofungin, micafungin, anidulafungin)
Alternative: Fluconazole 400-800 mg daily (if non-neutropenic, no recent azole exposure, no azole-resistant species)

Note

Management Algorithm: Most authorities recommend antifungal therapy only for invasive disease (positive blood culture or sole organism), though many experts support treatment for Candida in severely ill patients with community-acquired or healthcare-associated infections.

ESBL-Producing Organisms

Extended-spectrum beta-lactamase-producing Enterobacterales require special consideration:

Prevalence: Increasing from 1.7% (E. coli) and 3.2% (Klebsiella) in 2005 to 7.3% and 13.1% respectively in 2012 in North America
Mechanism: Hydrolysis of extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, cefepime)
Risk factors: Healthcare-associated infections, prior antimicrobial exposure
Detection: Nonsusceptibility to ceftriaxone (MIC ≥2 mcg/mL) with cefoxitin susceptibility suggests ESBL
Therapy:
- Preferred: Carbapenem (imipenem or meropenem)
- Alternatives: Ceftolozane-tazobactam or ceftazidime-avibactam (plus metronidazole)
- Carbapenem-sparing: Current IDSA (Ref1?) 2022 guidelines recommend reserving carbapenems when possible

Individual Antimicrobial Agents

Chloramphenicol - Broad anaerobic coverage (>99% at 16 μg/mL) - Activity against gram-positive cocci and many Enterobacterales - P. aeruginosa resistant - Risk of aplastic anemia limits use - Largely replaced by better-tolerated agents - May be option in resource-limited settings

Clindamycin - Activity against anaerobes: >95% (at 8 μg/mL) but increasing resistance documented - 15% of Clostridium spp. (except C. perfringens) and rare Fusobacterium strains resistant - Activity: S. aureus, Streptococcus pyogenes (but not enterococci or Enterobacterales) - Risk of C. difficile-associated diarrhea: 2-20% incidence, with pseudomembranous colitis in half - No longer recommended except when other options contraindicated or intolerable

Metronidazole - Bactericidal against strict anaerobes: B. fragilis, Fusobacterium, Clostridium spp. - Unique bactericidal action against B. fragilis and C. perfringens - Resistance among B. fragilis to metronidazole: rare - Limitation: Poor activity against aerobes and microaerophiles; must combine with agent active against facultative pathogens - Lower incidence of C. difficile infection compared to clindamycin

Tetracyclines

Older tetracyclines (tetracycline, doxycycline, minocycline): Limited utility due to resistance, particularly among anaerobes

Newer tetracyclines: - Tigecycline (glycylcycline): - Broad spectrum: Anaerobes, gram-positive/negative aerobes, ESBL, AmpC, CRE, MRSA, VRE - Approved as monotherapy for cIAI - NOT active against P. aeruginosa, Proteus mirabilis, Morganella, Providencia - Black box warning: Pooled analysis showed increased mortality vs comparators - Recommendation: Use high-dose (100 mg IV once, then 100 mg IV Q12H); lower doses associated with higher mortality - Alternative for CRE when beta-lactams contraindicated

Eravacycline (halogenated tetracycline):
- 2-4 fold more potent than tigecycline
- Broad spectrum similar to tigecycline
- Approved as monotherapy for cIAI
- NOT active against P. aeruginosa, Proteus mirabilis, Morganella, Providencia
- Emerging alternative to tigecycline with potentially better safety profile

Beta-Lactams (Penicillins)

Older agents (penicillin G, ampicillin, amoxicillin, piperacillin): Inactivated by beta-lactamases; no longer recommended alone

Beta-lactam/beta-lactamase inhibitor combinations: - Ampicillin-sulbactam: Previously FDA-approved for IAI, now no longer recommended due to emerging resistance - Amoxicillin-clavulanate: Oral formulation may complete therapy but not recommended for empirical treatment - Piperacillin-tazobactam: - Spectrum: Gram-positive and many gram-negative aerobes and anaerobes - Recommended for severe community-acquired cIAI - Limitations: Does not inhibit AmpC beta-lactamases or carbapenem-resistant (Ref194?) organisms; high-inoculum ESBL infections may overcome beta-lactamase inhibition - Recent CLSI changes: Lowered susceptible breakpoint from ≤16 to ≤8 μg/mL; introduced SDD category at 16 μg/mL - Current recommendation: Reserve for high-risk patients with close monitoring of susceptibilities

Temocillin - 6-α-methoxy derivative of ticarcillin - Stable against ESBLs, KPC carbapenemases, and AmpC beta-lactamases - Available in UK and EU but not FDA-approved in US - Limitation: Borderline activity against KPC and AmpC; may be inadequate for systemic infections despite UTI activity - Interest renewed as carbapenem-sparing option

Cephalosporins

First and second-generation (cefazolin, cefuroxime): Resistant B. fragilis; require metronidazole; limited recent evidence

Cephamycins (cefoxitin, cefotetan): Increased resistance at many medical centers; cannot be recommended

Third and fourth-generation (cefotaxime, ceftriaxone, ceftazidime, cefepime): - Better activity against Enterobacterales - Ceftazidime and cefepime: Activity against P. aeruginosa - Poor anaerobic activity: Require metronidazole addition - ESBL resistance: Emerging problem; can be selected under antimicrobial pressure - Increasingly resistant; higher prevalence in healthcare-associated infections

New cephalosporin combinations: - Ceftazidime-avibactam: - Avibactam: New beta-lactamase inhibitor blocking ESBLs, AmpC, and some carbapenemases - Effective against ESBL and AmpC producers - IDSA 2022: Reserve for CRE (not routine ESBL use to preserve activity) - Must add metronidazole for anaerobic coverage

Ceftolozane-tazobactam:
- Active against drug-resistant P. aeruginosa
- Not affected by common P. aeruginosa resistance mechanisms
- Limitations: Limited ESBL and AmpC coverage; lacks gram-positive and enterococcal activity
- Requires metronidazole addition for anaerobes
- SIS 2017: Recommended for high-risk patients with ESBL or P. aeruginosa
Cefiderocol:
- Siderophore-conjugated cephalosporin
- Active against CRE, CRPA, CRAB despite resistance mechanisms
- Limitations: FDA approved for UTI/VAP only, not cIAI; variable anaerobic activity; lacks gram-positive activity
- Requires metronidazole if used for cIAI

Carbapenems - Treatment of choice for serious ESBL-producing infections - Imipenem-cilastatin: 500 mg IV Q6H - Meropenem: 1 g IV Q8H - Broad spectrum including anaerobes and beta-lactamase producers - Emerging resistance: CRE increasingly encountered

Newer carbapenem combinations: - Imipenem-relebactam: Relebactam blocks AmpC and some carbapenemases; FDA-approved for cIAI - Meropenem-vaborbactam: Vaborbactam blocks AmpC and some carbapenemases - Reserve for high-risk or confirmed resistant pathogens per IDSA 2022

Aztreonam (Monobactam) - Gram-negative activity including P. aeruginosa; lacks gram-positive and anaerobic activity - Used in combination: Aztreonam + vancomycin + metronidazole - Option for patients with severe beta-lactam allergy

Aminoglycosides - Limited role in modern therapy - Nephrotoxicity and ototoxicity significant concerns - Once-daily dosing preferred over divided dosing - Current recommendation: Avoid routine use; reserve for specific situations with careful monitoring - Synergistic with beta-lactams but single agent inactive against anaerobes

Fluoroquinolones - Ciprofloxacin or levofloxacin: Gram-negative activity (including P. aeruginosa) - Limitations: Poor anaerobic coverage; resistant B. fragilis; requires metronidazole addition - Resistance: Fluoroquinolone-resistant E. coli increasingly common in some communities - Current recommendation: Use only if institutional surveys show ≥90% E. coli susceptibility

Polymyxins - Colistin (polymyxin E) and polymyxin B: Last-resort agents for multidrug-resistant organisms - Activity: CRE, CRPA, CRAB - Nephrotoxicity and neurotoxicity are significant concerns - Reserved for infections resistant to all other agents

Additional Therapeutic Measures

Source Control

Source control is essential and often determines outcome:

Prompt identification and repair of perforation or damaged viscus
Resection of necrotic or irreversibly damaged tissue
Drainage of purulence, feces, blood, and other foreign material
Peritoneal irrigation: Optimal technique remains controversial; some favor running water irrigation
Repeat exploration: May be necessary in severe cases (planned relaparotomy or damage control)

Gastrointestinal Decompression

Nasogastric tube: Useful in acute peritonitis with ileus to prevent vomiting and aspiration
Fluid management: Careful balance to maintain perfusion while avoiding overload

Fluid Management

Initial resuscitation: Aggressive IV hydration in sepsis
Monitoring: Urine output, hemodynamics, response to therapy
Vasopressors: Consider if hypotensive despite fluids

Respiratory Support

Close monitoring for signs of respiratory failure
Mechanical ventilation if necessary for severe sepsis/ARDS

Prevention of Secondary Peritonitis

Not typically applicable as secondary peritonitis is managed reactively once it develops.

PERITONEAL DIALYSIS-ASSOCIATED PERITONITIS

Long-Term Peritoneal Dialysis

Peritoneal dialysis (PD) is used in chronic kidney disease management due to advantages of preserving residual renal function and cardiovascular hemodynamics. Continuous ambulatory peritoneal dialysis (CAPD) uses patient-performed exchanges 3-4 times daily. Peritonitis represents a major complication occurring in 12-56% of patients annually depending on technique and patient factors.

Microbiology

The microbiology of CAPD peritonitis differs from other intraabdominal infections:

Gram-positive organisms: 60-80% of cases
- Coagulase-negative staphylococci (most common, ~40-50%)
- Staphylococcus aureus (~10-15%)
- Streptococcus spp. (various species)
- Enterococcus spp.
Gram-negative bacteria: 15-30%
- Enterobacterales (various species)
- Pseudomonas aeruginosa (associated with poor outcomes)
- Acinetobacter spp.
- Origin: Urinary tract, bowel, skin, contaminated water
Fungal: 5-10% (particularly Candida spp.)
- Associated with worse prognosis than bacterial peritonitis
- May represent disseminated candidiasis
- Requires immediate catheter removal
Mycobacterial: Occasional (tuberculous peritonitis)
Polymicrobial peritonitis: Suggests bowel perforation; requires investigation

Pathogenesis

The route of infection in CAPD peritonitis is usually:

Touch contamination: Most common; improper technique during exchange
Catheter tunnel infection: Biofilm formation on catheter
GI translocation: Intact bowel wall passage of bacteria
Ascending infection: Via catheter from exit site
Bloodstream seeding: Hematogenous route (less common)
Bowel perforation: Polymicrobial flora; medical emergency

Diagnosis

Clinical Presentation

Abdominal pain: Variable severity; may be mild
Fever: May be absent even with peritonitis
Cloudy dialysate: Most reliable clinical sign
Nausea/vomiting: Variable
Diarrhea or constipation: May worsen outcome

Note

Diagnostic Criteria for CAPD Peritonitis: - Peritoneal fluid WBC count >100 cells/mm³ (predominantly PMN) - Cloudy dialysate fluid - Positive culture (90-95% of cases) - At least one of: fever, abdominal pain, cloudy dialysate

Laboratory Findings

Finding	Details
WBC Count	>100 cells/mm³ (optimal: >400 cells/mm³ for diagnosis)
Differential	>50% PMN neutrophils
Culture	Positive in 90-95% of cases
Gram stain	Positive in ~10% of cases (low sensitivity)
Blood cultures	Not routinely helpful

Table 76.7: Updated 2022 ISPD Peritonitis Diagnosis Criteria

Criterion	Details
Probable CAPD peritonitis	Symptoms + cloudy dialysate + elevated WBC (>100 cells/mm³)
Confirmed peritonitis	Probable diagnosis + positive culture
Culture-negative peritonitis	Probable diagnosis + negative culture after 5 days
Contamination	Positive culture on single exchange only
Relapsing peritonitis	Episode within 4 weeks of completing therapy for prior peritonitis with same organism
Repeat peritonitis	Episode >4 weeks after completing therapy for prior peritonitis
Tunnel infection	Subcutaneous track infection with or without peritonitis

Prognosis

Prognosis in CAPD peritonitis depends on organism, promptness of treatment, and patient factors:

CAPD continuation: 50-70% of patients continue CAPD after peritonitis episode
Catheter removal: Necessary in 10-20% of patients
- Higher rates: Fungal peritonitis (>70%), nontuberculous mycobacterial infections
- Lower rates: Gram-positive cocci (5-10%), gram-negative bacteria (15-20%)
Mortality: 1-3% directly attributable to peritonitis; higher with fungal infections
Relapse/recurrence: More common with gram-negative organisms than gram-positive

Warning

Poor Prognostic Indicators: - Fungal peritonitis (requires immediate catheter removal) - Polymicrobial infections (suggests bowel perforation) - Pseudomonas aeruginosa peritonitis - Delayed initiation of therapy - Relapsing or repeat episodes

Therapy

Antimicrobial Therapy Approach

Intraperitoneal (IP) administration of antibiotics is preferred in CAPD peritonitis:

Duration: 14-21 days per 2022 ISPD guidelines (previously 10-21 days)
Route: Intraperitoneal administration at therapeutic levels in dialysate
Monitoring: Repeat peritoneal fluid analysis at 2-3 days if inadequate response
Culture-guided therapy: Adjust based on susceptibilities

Tip

Intraperitoneal Administration: IP dosing achieves high local concentrations while minimizing systemic toxicity, making it preferred over IV therapy for CAPD peritonitis.

Antimicrobial Regimens

Organism	Typical Regimen	Dosing
Gram-Positive Cocci
Staphylococcus spp. (uncomplicated)	Cefazolin OR vancomycin	Cefazolin 500 mg IP Q8H; Vancomycin 15-30 mg/L in dialysate
S. aureus (methicillin-resistant)	Vancomycin	15-30 mg/L in each exchange
Gram-Negative Bacilli
E. coli, Klebsiella, other	Ceftazidime OR ciprofloxacin	Ceftazidime 500 mg IP Q8H; Ciprofloxacin 100 mg IP daily
Pseudomonas aeruginosa	Ceftazidime + gentamicin	Ceftazidime 500 mg IP Q8H + gentamicin or tobramycin IP
Anaerobes	Clindamycin OR metronidazole	IP administration

Special Considerations

Fungal Peritonitis

Indication for therapy: Positive culture or compelling clinical evidence
Treatment: Systemic antifungal agents preferred over IP
First-line agents:
- Echinocandins: Caspofungin, micafungin, anidulafungin (preferred)
- Fluconazole: 400-800 mg daily (alternative for non-immunosuppressed, no recent azole exposure)
- Voriconazole: Alternative option
Catheter removal: MANDATORY; necessary in >70% of cases
Timing: Catheter removal within 48 hours of diagnosis or if no improvement within 4-7 days of therapy
Prognosis: Poor; high discontinuation of CAPD (>70%)

Warning

Fungal Peritonitis Pearls: - Immediate catheter removal is essential - fungal peritonitis is NOT compatible with CAPD continuation - Systemic antifungal therapy is necessary; IP administration alone is inadequate - Risk factors: Prior antibiotic exposure, catheter colonization, immunosuppression

Mycobacterial Peritonitis

Nontuberculous mycobacteria (Mycobacterium avium complex, others): 5-10% of CAPD peritonitis
Mycobacterium tuberculosis: Less common but indicates serious infection
Treatment: Prolonged therapy (months) with appropriate antimycobacterial regimens
Catheter removal: Often necessary
Diagnosis: Delayed; requires special stains and culture

Culture-Negative Peritonitis

Occurs in ~5-10% of CAPD peritonitis
Causes:
- Inadequate sampling technique
- Prior antibiotic exposure
- Atypical organisms (fungi, mycobacteria, fastidious bacteria)
Management: Continue empirical therapy if clinical peritonitis present; repeat peritoneal fluid analysis
Outcome: Usually favorable with continued therapy

Acute Peritoneal Dialysis (Acute PD)

In acute kidney injury, peritonitis may occur with acute PD use:

Risk factors: Same as CAPD but acute presentation
Management: Similar to CAPD peritonitis
Consideration: May switch to hemodialysis if peritonitis uncontrolled
Outcome: Depends on underlying acute kidney injury severity and organism

INTRAPERITONEAL ABSCESSES

Etiology

Intraperitoneal abscesses represent focal collections of pus that complicate peritonitis:

Secondary complication: Result from inadequate localization of primary or secondary peritonitis
Formation: Develops when peritoneal defenses (fibrin, adhesions, omentum) encapsulate infection
Location: Determined by primary disease site and dependent peritoneal drainage
Multiple abscesses: Common; average 2.3 per patient
Common sites: Pelvis (most common in females), paracolic gutters, perihepatic spaces, lesser sac, Morison pouch, retroperitoneal spaces

Common Locations by Condition

Appendicitis: Right lower quadrant, paracolic gutter, pelvis
Diverticulitis: Left lower quadrant, paracolic gutter, pelvis
Perforated peptic ulcer: Paracolic gutter, perihepatic spaces
Cholecystitis: Perihepatic, right paracolic gutter
Pelvic inflammation: Pelvis, pouch of Douglas
Post-surgical: Depends on operative site; anastomotic sites at risk

Bacteriologic Findings

Intraperitoneal abscesses are characteristically polymicrobial:

Composition: Identical to the polymicrobial flora of secondary peritonitis
Obligate anaerobes: Bacteroides fragilis and other Bacteroides spp., Clostridium spp., Prevotella spp., peptostreptococci, fusobacteria
Facultative gram-negative bacilli: E. coli, Klebsiella, Enterobacter, Proteus, Pseudomonas
Gram-positive cocci: Streptococci, enterococci, staphylococci
Emerging organisms: ESBL-producing gram-negative bacilli, Candida spp., resistant pathogens

Pathogenesis

Abscess formation requires:

Localization of infection: Peritoneal defenses (fibrin, adhesions, omentum) compartmentalize contamination
Bacterial survival: Obligate anaerobes require low oxygen tension, achievable in enclosed spaces with devitalized tissue
Synergistic interactions: Polymicrobial communities with protective mechanisms (anaerobes protect aerobes from antimicrobials)
Time: Progressive accumulation of pus within loculated space
Barrier: Host tissue forms capsule limiting abscess spread but also limiting antibiotic penetration

Clinical Manifestations

Symptoms

The presentation depends on abscess size, location, and host factors:

Fever: May be persistent or spiking
Abdominal pain: Location-specific; may be subtle
Constitutional symptoms: Malaise, anorexia, weight loss
Sepsis: May present with tachycardia, hypotension, altered mental status
GI symptoms: Nausea, vomiting, diarrhea (depend on location)
Urinary symptoms: Dysuria, frequency (if pelvic abscess)
Gynecologic symptoms: Vaginal discharge, abnormal menses (if tubo-ovarian or pelvic)

Physical Findings

Fever: Usually present but may be absent in debilitated patients
Localized tenderness: Over abscess site
Mass: May be palpable, particularly with larger abscesses
Peritoneal signs: Variable; may be minimal if abscess well-loculated
Sepsis signs: If abscess ruptures or infection spreads

Diagnosis

Imaging

Computed Tomography (CT): Gold standard for diagnosis

Sensitivity: 90-95% for intraperitoneal abscesses
Findings:
- Fluid collection with enhancing rim
- Air-fluid levels
- Associated inflammation in surrounding tissues
- Loculation or multiple locules
- Gas within abscess (suggesting anaerobic infection)
Capabilities: Identifies location, size, relationship to organs, guides drainage approach
Limitations: May miss very small abscesses (<5 mm)

Ultrasound: Alternative for mobile patients

Sensitivity: 80-90% for larger abscesses
Advantages: Bedside capability, no radiation
Limitations: Operator-dependent; limited by bowel gas

MRI: Excellent soft tissue contrast

Reserved for complex cases or when CT contraindicated
May be particularly useful for pelvic abscesses

Laboratory Findings

CBC: Leukocytosis (though may be normal)
Chemistry: Electrolyte abnormalities, elevated creatinine
Blood cultures: Positive in 20-30% of cases
Lactate: Elevated in severe infections

Abscess Fluid Characteristics

Gram stain: Positive in 30-50% (shows polymicrobial flora)
Culture: Should be obtained; multiple organisms isolated
Sensitivity testing: Essential for appropriate directed therapy
Cell count: Many PMN, variable organisms

CT scan showing intraperitoneal abscess with drainage catheter in situ.

CT showing liver abscesses with percutaneous drains.

CT showing percutaneous drainage of intraperitoneal abscess.

Prognosis

Prognosis depends on:

Abscess size: Larger abscesses have worse prognosis
Location: Difficult-to-drain locations (lesser sac, multiple loculations) carry higher risk
Organism: ESBL/AmpC producers, fungi, resistant pathogens worsen prognosis
Host factors: Immunocompromised patients, advanced age, comorbidities
Treatment delay: Delayed drainage or inadequate source control increases mortality
Underlying disease: Severity of original process affecting prognosis
Overall mortality: Ranges from 5-15% with appropriate therapy to 30-40% in severe/delayed cases

Therapy

Drainage

Drainage is essential for cure; antibiotics alone are insufficient:

Percutaneous Drainage (Preferred approach) - CT or ultrasound-guided: Allows safe placement with visualization - Catheter selection: Size depends on abscess contents (larger bore for thick debris) - Technique: Trocar or Seldinger technique - Advantages: Minimally invasive, avoids operative risk, allows repeated access if needed - Outcomes: Success rate 80-95% depending on abscess characteristics - Complications: Perforation of adjacent organs, creation of fistulae (rare)

Surgical Drainage - Indications: - Failure of percutaneous drainage - Multiple complex loculations not amenable to percutaneous approach - Associated perforation or source requiring operative repair - Immunocompromised host with poor response - Approach: Dependent on location; laparotomy most common - Associated procedures: Source control, resection of necrotic tissue, repair of perforation

Antibiotic Therapy

Antibiotics should be guided by culture results but empirical therapy essential initially:

Empirical Therapy - Must cover polymicrobial flora: gram-negative bacilli, anaerobes, gram-positive cocci - Duration: 4-7 days minimum after drainage; continued until clinical resolution - Route: IV initially; may transition to oral after improvement

Culture-Directed Therapy - Adjust based on susceptibility results - Target most virulent pathogens: B. fragilis + E. coli model - Special considerations for resistant organisms

Regimen Selection (Similar to secondary peritonitis) - For community-acquired, low-risk: Cefotaxime/ceftriaxone + metronidazole or ertapenem - For high-risk: Piperacillin-tazobactam, carbapenem, or newer agents based on susceptibilities - For resistant organisms: Tailored based on resistance pattern

Source Control

Beyond drainage, address the primary process:

Resection: Remove perforated viscus, necrotic tissue
Repair: Primary closure of perforations when possible
Diversion: Colostomy for certain colorectal perforations
Definitive treatment: Address underlying disease (appendectomy for appendicitis, colectomy for diverticulitis, etc.)

Follow-Up

Repeat imaging: If inadequate response (persistent fever, leukocytosis) at 3-5 days
Drain management: Leave in place until output minimal and patient clinically improved
Culture follow-up: Repeat if organisms recovered are unusual or slow to respond
Transition to oral: After fever resolves and clinical improvement documented

Special Situations

Hepatic Abscesses

Amebic: Entamoeba histolytica; treat with metronidazole ± luminal agents
Pyogenic: Polymicrobial; require drainage + antibiotics
Fungal: Candida spp.; require systemic antifungal ± drainage
Tuberculous: M. tuberculosis; prolonged therapy; drainage if large

Splenic Abscesses

Rare but serious; high mortality if untreated
Often require splenectomy given difficulty of drainage
May respond to antibiotics alone if small and hemodynamically stable

Pancreatic Abscesses

Complicate acute pancreatitis
Require drainage + antibiotics
Often polymicrobial with gas-forming organisms
May require multiple drainages

Perinephric Abscesses

Usually associated with urinary tract infection or stone
Require drainage + antibiotics
Urology consultation for underlying urologic pathology

Tubo-Ovarian Abscesses

Result of pelvic inflammatory disease
May respond to antibiotics alone (smaller lesions)
Require drainage if large or inadequate response to antibiotics
May require hysterectomy/oophorectomy if chronic recurrence

ANTIMICROBIAL AGENTS - DETAILED DISCUSSION

Agents for Anaerobic Infections

Metronidazole

Spectrum: Active against obligate anaerobes; inactive against aerobes

Indications - Combined with agent active against aerobic gram-negative bacilli - Beta-lactam/beta-lactamase inhibitor provides adequate anaerobic coverage - Carbapenems provide adequate anaerobic coverage - Fluoroquinolone combinations for specific scenarios

Dosing: 500 mg IV Q6-8H or 400-500 mg IV Q12H (higher doses more common)

Advantages - Excellent anaerobic coverage: B. fragilis, Clostridium spp., Fusobacterium, Prevotella - Unique bactericidal action against B. fragilis - Rare resistance among anaerobes - Oral formulation available for transition therapy - Lower C. difficile risk than clindamycin

Disadvantages - No aerobic coverage; must combine - Rare: Peripheral neuropathy with prolonged use - Metallic taste

Chloramphenicol

Spectrum: Broad anaerobic activity; some gram-positive and gram-negative coverage

Current Role: Largely replaced; reserved for resource-limited settings

Concerns: Risk of aplastic anemia (idiosyncratic reaction)

Agents for Aerobic Gram-Negative Coverage

Aminoglycosides (Gentamicin, Tobramycin, Amikacin)

Current Role: Limited in modern therapy

Advantages: Activity against gram-negative bacilli including P. aeruginosa

Disadvantages - No anaerobic activity - Nephrotoxicity and ototoxicity - Poor peritoneal penetration - Synergistic killing (not single-agent therapy)

Current Recommendation: Avoid routine use; reserve for specific scenarios

Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin)

Spectrum: Aerobic gram-negative (including P. aeruginosa with ciprofloxacin/levofloxacin); limited anaerobic

Indications - Low-risk community-acquired IAI (ciprofloxacin or levofloxacin + metronidazole) - Moxifloxacin monotherapy for mild-to-moderate IAI (includes anaerobes) - Oral step-down therapy option

Advantages - Good oral bioavailability - Tissue penetration - Lower cost

Disadvantages - Resistance increasingly common (E. coli resistance variable by region) - B. fragilis resistance necessitates metronidazole addition (except moxifloxacin) - QT prolongation with fluoroquinolones - Recent FDA warnings regarding safety profile

Current Recommendation: Use only if institutional surveillance shows ≥90% E. coli susceptibility

Specialty Agents for Resistant Organisms

Ceftazidime-Avibactam

Spectrum: ESBL, AmpC (at lower levels), some CRE

Avibactam: New beta-lactamase inhibitor effective against ESBLs, KPCs, AmpC

Indications: Reserve for CRE per IDSA 2022 to preserve activity

Limitations - Not active against all CRE - Requires metronidazole for anaerobes - Higher cost

Ceftolozane-Tazobactam

Spectrum: P. aeruginosa including drug-resistant strains; ESBL Enterobacterales

Advantages - Novel P. aeruginosa activity - Resistance mechanism evasion (efflux pumps, porin loss, chromosomal AmpC)

Limitations - Limited AmpC coverage - No anaerobic activity; requires metronidazole - No gram-positive/enterococcal activity - Higher cost

Eravacycline

Spectrum: Broad; includes anaerobes, gram-positive, gram-negative, ESBL, AmpC, CRE, VRE, MRSA

Advantages - Not active against P. aeruginosa (not disadvantage for all infections) - 2-4 fold more potent than tigecycline - Emerging as alternative to tigecycline

Dosing: 1 mg/kg IV Q12H

Limitations - Newer agent; less clinical data - Not active against P. aeruginosa

Tigecycline

Spectrum: Broad; anaerobes, gram-positive, gram-negative, resistant pathogens

Indications: CRE infections when beta-lactams contraindicated or resistant; high-risk complicated IAI

Dosing: 100 mg IV load, then 50 mg IV Q12H (high-dose recommended for infection)

Advantages - Broad spectrum - Activity against most resistant pathogens

Disadvantages - Black box warning: Increased mortality vs comparators in pooled analysis - Not active against P. aeruginosa, Proteus mirabilis, Morganella, Providencia - Not recommended as empirical therapy for healthcare-associated or tertiary infections - Higher costs

Important: Recommend high dosing to minimize mortality risk

Cefiderocol

Spectrum: ESBL, AmpC, CRE (including MBL), CRPA, CRAB

Mechanism: Siderophore-conjugated cephalosporin; iron-dependent bacterial uptake

Limitations - FDA approval limited to UTI and hospital-acquired/VAP (not cIAI) - No gram-positive/enterococcal activity; requires metronidazole - Variable anaerobic activity - Cost

Future Consideration: May be approved for cIAI in the future

CLINICAL GUIDELINES AND RECOMMENDATIONS

Surgical Infection Society 2017 Guidelines

Lower-Risk Community-Acquired IAI - Preferred: Cefotaxime or ceftriaxone + metronidazole OR ertapenem - Alternatives: Ciprofloxacin + metronidazole OR moxifloxacin

Higher-Risk Community-Acquired IAI - Preferred: Piperacillin-tazobactam OR imipenem-cilastatin OR meropenem OR cefepime + metronidazole - Alternatives: Ceftazidime + metronidazole OR aztreonam + metronidazole + vancomycin

ESBL-Producing Enterobacterales - Preferred: Carbapenem (imipenem or meropenem) OR ceftolozane-tazobactam OR ceftazidime-avibactam + metronidazole

AmpC-Producing Enterobacterales - Preferred: Carbapenem OR ceftazidime-avibactam + metronidazole

CRE - Carbapenem or ceftazidime-avibactam ± aminoglycoside/polymyxin/tigecycline

IDSA 2022 Guidance

ESBL-Producing Enterobacterales - Recommend carbapenem preference - Reserve ceftazidime-avibactam for CRE

AmpC-Producing Enterobacterales - Carbapenem or newer alternatives

CRE and CRPA - Tailored based on resistance mechanism - Consider combination therapy

World Society of Emergency Surgery (Ref171?) 2021 Guidelines

No MDR Risk - Piperacillin-tazobactam (continuous infusion), tigecycline, meropenem, or imipenem

High MDR Risk - Tigecycline or eravacycline + piperacillin-tazobactam - Or in critically ill: Meropenem or imipenem + vancomycin or teicoplanin

SUMMARY AND KEY TAKEAWAYS

Clinical Pearls

Primary peritonitis diagnosis: Low threshold for paracentesis in cirrhotic patients with ascites; can present with minimal peritoneal signs
Albumin administration: Critical in SBP to prevent renal failure and mortality; demonstrated 50% mortality reduction in meta-analysis
Polymicrobial coverage essential: Secondary peritonitis requires agents active against both E. coli and B. fragilis
Source control primacy: Drainage of intraperitoneal abscesses essential; antibiotics alone insufficient
Culture importance: Essential for organism identification and susceptibility; guides therapy optimization
Resistance emerging: ESBL, AmpC, CRE increasingly encountered; must consider institution-specific resistance patterns
Newer agents: Eravacycline, ceftazidime-avibactam, ceftolozane-tazobactam expand options for resistant pathogens
CAPD peritonitis management: Intraperitoneal antibiotics preferred; fungal peritonitis requires immediate catheter removal
Enterococcal coverage: Selective, not routine; indicated in high-risk patients with sepsis or prior broad-spectrum exposure
Fluoroquinolone caution: Use only with documented high institutional susceptibility

Warning Signs

Warning

Clinical Warning Signs Requiring Urgent Action: - Persistent fever despite appropriate antibiotics (consider resistant pathogen, inadequate source control, or abscess) - Rapid clinical deterioration (suggests perforation, rupture of abscess, or inadequate coverage) - Fungal peritonitis in CAPD (immediate catheter removal mandatory) - Polymicrobial CAPD peritonitis (suggests bowel perforation; investigate urgently) - Increasing renal dysfunction (prognostic indicator; support with albumin and aggressive management) - Recurrent/relapsing infections (consider relapse vs re-infection; repeat cultures essential)

References

Lecture 2: Notes

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PART I: APPENDICITIS

Introduction

In 1886, Fitz first described the natural course of acute inflammation of the appendix, coining the term appendicitis and advocating early surgical intervention (Fitz, 1886). With an incidence of 108 cases per 100,000 person-years in the United States and 100 to 150 cases per 100,000 person-years in most upper-middle-income countries, appendicitis is among the most common surgical emergencies of the abdomen (Addiss et al., 1990). Improvements in clinical assessment, antibiotic therapy, and surgical management have reduced the overall mortality rate of acute appendicitis to less than 1%, although rates increase to 5% or more in the elderly (Berry and Malt, 1984; Blomqvist et al., 2001; Körner et al., 1997).

Epidemiology

The lifetime risk for acute appendicitis is 8.6% in men and 6.7% in women in industrialized countries (Körner et al., 1997). In 2018, a total of 190,000 appendectomies were performed in the United States, constituting 1.3% of all operating room procedures (Bhangu et al., 2015); however, this represents a 42% decrease since 2011, likely because of the increasing adoption of nonoperative medical management of uncomplicated appendicitis (Flum et al., 2020).

Key Epidemiologic Point

Although the frequency of appendectomy surgery is declining, it is still ranked as the most common surgery for individuals aged 17 years and younger in the United States.

Appendicitis is rare in infants, but its incidence steadily increases through childhood and reaches a peak at 15 to 25 years of age for men and women (Berry and Malt, 1984; Blomqvist et al., 2001; Körner et al., 1997; Livingston et al., 2007). The incidence declines through adulthood, and less than 25% of cases occur in individuals older than 45 years. Men have slightly higher rates than women; the overall male-to-female rate ratio is 1.4:1 (Körner et al., 1997).

Similar to diverticulitis, the incidence of appendicitis is significantly lower in rural, nonindustrialized areas (Burkitt, 1971; Walker and Segal, 1995). Also like diverticulitis, appendicitis rates increase as societies become industrialized (Barker et al., 1986; Lee et al., 2010; Naaeder and Archampong, 1998).

Pathogenesis

Figure 1: Anatomy of the appendix showing its position relative to the cecum and terminal ileum.

The appendix is a tube-shaped structure, usually 5 to 10 cm long in adults, which arises 2 to 3 cm below the terminal part of the ileum along the medial posterior wall of the cecum (Schumpelick et al., 2000). Previously considered a vestigial organ, recent studies suggest that the appendix may contribute to the development and homeostasis of the gut microbiome and mucosal immune system (Randal Bollinger et al., 2007). Bacteria reside in the appendix within a mucus-rich biofilm that is intermittently shed into the intestinal tract at a rate of 2 to 3 mL per day (Randal Bollinger et al., 2007; Schumpelick et al., 2000).

Clinical Pearl

The appendix has been hypothesized to act as a microbial “sanctuary” that can repopulate the intestinal tract when needed, for example during recovery from acute diarrheal illnesses (Bollinger et al., 2007; Randal Bollinger et al., 2007).

Typically, the appendix lies in an ascending retrocecal position, but atypical positions (descending pelvic, transverse retrocecal, ascending postileal) are common and can alter the typical clinical features (Schumpelick et al., 2000).

Physical obstruction of the appendiceal lumen by fecaliths or other causes (e.g., foreign bodies, tumor, stricture, or parasites) has classically been thought to be the primary pathogenic mechanism (Arnbjörnsson, 1983; Singh and Mariadason, 2013; Wangensteen and Bowers, 1937). Mucus accumulates within the obstructed lumen, and intraluminal pressure increases, leading to compression of lymphatic and vascular drainage and causing ischemic damage of the mucosa, followed by microbial invasion and inflammation. If left untreated, this may lead to gangrene and eventual perforation. The pathologic hallmark of acute appendicitis is the presence of polymorphonuclear cells within the appendiceal wall, accompanied by edema and vascular congestion.

Figure 2: Classic pathogenesis model of appendicitis: luminal obstruction leads to mucus accumulation, increased intraluminal pressure, lymphatic and vascular compression, ischemic mucosal damage, microbial invasion, and potentially gangrene and perforation.

In recent years, this classic model has faced challenges. Most modern case series report that fecaliths or other causes of obstruction are found in only a minority of cases (Carr, 2000; Singh and Mariadason, 2013). The efficacy of medical rather than surgical treatment also suggests that physical obstruction may not be the primary mechanism. Alternative inciting etiologies include infectious agents, socioeconomic factors, genetic susceptibility, environmental factors, dietary fiber, and microbiome imbalances leading to lymphoid hyperplasia and inflammation (Lamps, 2010; Singh and Mariadason, 2013).

Role of Diet and Fiber

Interest in dietary fiber dates back over a century. Short, noting high rates of appendicitis in Great Britain compared with Africa in the early 20th century, suggested that “the cause is the relatively less quantity of cellulose [fiber] eaten” (Short, 1920). Burkitt and colleagues later hypothesized that dietary fiber acted as a bulking agent, reducing risk for appendicitis (Adamidis et al., 2000; Burkitt, 1971). The influence of diet, dietary fiber, and the gut microbiome has been increasingly recognized (Bhangu, 2014; Lamps, 2010).

Microbiology

Conventional cultures of inflamed or gangrenous appendixes typically yield 10 to 14 different organisms, which generally reflect the colonic microbiota. A mixture of colonic anaerobic and facultative bacteria is usually recovered, predominantly Escherichia coli, Bacteroides fragilis group, pigmented Prevotella spp., Bilophila wadsworthia, Peptostreptococcus spp., Enterobacteriaceae, and viridans streptococci, particularly the Streptococcus anginosus group (Bennion et al., 1990; Brook, 1980; Roberts, 1988). Pseudomonas aeruginosa has also been found in a minority of cases (4%–15%) but is less frequently sensitive to routinely used antibiotics (Guinane et al., 2013; Swidsinski et al., 2011).

Microbiome Insights

Culture-independent 16S rRNA gene amplicon sequencing-based studies have demonstrated that the microbial community of the appendix is remarkably diverse, consisting of more than a dozen phyla and hundreds of different species (Guinane et al., 2013; Jackson et al., 2014; Swidsinski et al., 2011; Zhong et al., 2014). The appendiceal microbiome is distinct in composition compared with elsewhere in the digestive tract (Rogers et al., 2016; Swidsinski et al., 2011).

A few taxa, including Fusobacterium, Peptostreptococcus, and Parvimonas—all typically considered to be oral commensal bacteria and occasional periodontal pathogens—are enriched in the inflamed appendix and are associated with disease severity (Swidsinski and Loening-Baucke, 2012; Zhong et al., 2014). This has led some investigators to hypothesize that rather than being caused by physical obstruction, acute appendicitis may be the consequence of dysbiosis (microbial imbalance) (Swidsinski et al., 2011; Zhong et al., 2014).

Specific Infectious Agents

In some instances, intestinal pathogens have been associated with acute appendicitis. Yersinia enterocolitica and Yersinia pseudotuberculosis are believed to have a causative role in some cases (Cover and Aber, 1989; Lamps, 2006; Lamps et al., 2003). More commonly, nonplague Yersinia causes ileocecitis or mesenteric adenitis, which mimics acute appendicitis with fever, leukocytosis, and acute right lower quadrant pain (Saebø and Lassen, 1992; Shorter et al., 1998). Similarly, Campylobacter and nontyphoidal Salmonella can cause pseudoappendicitis with ileocecitis and mesenteric adenitis (Mégraud, 1988; Puylaert et al., 1989). Appendiceal or ileocecal tuberculosis, actinomycosis, and histoplasmosis are more likely to cause subacute or recurrent disease (Butler, 1981; Salminen et al., 2018).

Viral causes of mesenteric adenitis and, rarely, appendicitis include measles, Epstein-Barr virus, cytomegalovirus, and adenovirus (Alder et al., 2010; Grynspan and Bhargava, 2013; Johnson, 1993). Amebiasis may also cause appendicitis (Gotoff, 1962). In many cases of mesenteric adenitis, an infectious cause is not identified but is probably present (Toorenvliet et al., 2011).

Clinical Manifestations

The clinical manifestations of acute appendicitis are distinctive and, in many cases, diagnostic. Appendicitis classically starts as colicky, visceral periumbilical pain that evolves for the next 6 to 24 hours to localized, somatic right lower quadrant abdominal pain after inflammation extends to the parietal peritoneum. If the inflamed appendix lies in the anterior position, tenderness is often maximal at or near the McBurney point, which lies two to three fingerbreadths above the right anterior superior iliac spine on a line with the umbilicus (Figure 3) (Wagner et al., 1996).

Figure 3: Location of the McBurney point — the point of maximal tenderness in anterior appendicitis.

Diagnostic Challenge

Pelvic appendixes can cause pelvic or left lower quadrant pain. Third-trimester pregnancy or intestinal malrotation may shift pain to the right upper quadrant. Diagnosis is more difficult in women of childbearing age, in whom gynecologic processes may mimic appendicitis.

Guarding is usually seen on examination. Rebound tenderness in the right lower quadrant with palpation of the left lower quadrant, known as the Rovsing sign, may be elicited (Figure 4). Other maneuvers include pain with active extension of the right hip (the psoas sign), and pain with internal rotation of the right hip (the obturator sign) (Figure 5). High fever or a sudden reduction in pain suggests perforation, whereas abdominal rigidity suggests diffuse peritonitis.

Figure 4: The Rovsing sign: right lower quadrant pain elicited by palpation of the left lower quadrant.

(a) Psoas sign — pain with active extension of the right hip

Diagnosis

Laboratory Studies

The white blood cell count is elevated in approximately 70% to 80% of adults with appendicitis, with a predominance of polymorphonuclear leukocytes. C-reactive protein (CRP) is also frequently elevated and may be particularly useful for identifying complicated appendicitis.

Imaging

Clinical diagnosis is enhanced using imaging, especially computed tomography and ultrasonography. CT scanning with intravenous contrast has become the imaging modality of choice in most centers, with reported sensitivity and specificity both exceeding 95% (Bixby et al., 2006).

Imaging Approach

Ultrasonography is often the initial imaging study of choice in children and pregnant women. CT is preferred in adults. Uncomplicated appendicitis typically shows a dilated (>6 mm) appendix with periappendiceal fat stranding on CT.

Scoring Systems

Scoring systems such as the Alvarado score and Appendicitis Inflammatory Response (AIR) score combine clinical, laboratory, and sometimes imaging findings to stratify patients by risk.

Therapy

Surgical Management

Surgical removal of the appendix, often performed laparoscopically, is curative. Laparoscopic appendectomy has become the standard of care and is associated with shorter hospital stays, less postoperative pain, and lower wound infection rates compared with open surgery.

Antibiotic Therapy

Adjunctive use of broad-spectrum antibiotics, such as piperacillin-tazobactam or ceftriaxone and metronidazole, may be required. For perforated appendicitis, a typical course of 3 to 5 days of intravenous antibiotics followed by oral therapy is standard.

Antibiotic-First Strategy

An “antibiotic first” strategy has emerged as a safe and effective nonoperative treatment option for acute uncomplicated appendicitis, with outcomes comparable to those of appendectomy. Several large randomized trials have demonstrated that initial antibiotic treatment can avoid surgery in approximately 60% to 70% of patients with uncomplicated appendicitis.

PART II: INFECTIONS OF THE LIVER AND BILIARY SYSTEM

Liver Abscess

Liver abscesses fall broadly into two categories: amebic and pyogenic. Amebic liver abscess represents a unique clinical entity caused by invasive Entamoeba histolytica infection, characterized by specific induction of hepatocyte apoptosis. Pyogenic liver abscess is the result of several distinct pathologic processes that cause a suppurative infection of the liver parenchyma.

Epidemiology and Etiology

Amebic Liver Abscess

In the United States, amebic liver abscess has become a rare disease found almost exclusively in travelers, immigrants, and men who have sex with men. In 1994, the last year in which incidence data were collected, there were only 2983 total cases of amebiasis (Stanley, 2003a). From 1993 through 2007, approximately 4100 patients were hospitalized in the United States with amebic liver abscess, with the annual incidence decreasing on average 2.4% annually (Guo et al., 2014).

Worldwide, contamination of food and drinking water has maintained E. histolytica infection second only to malaria as a cause of death from parasitic disease. The epidemiology has been greatly informed by the appreciation that Entamoeba dispar, a closely related nonpathogenic species, colonizes between 5% and 25% of persons (Clark and Diamond, 1993; Diamond and Clark, 1993; Haque et al., 2003).

Species Distinction

E. dispar has no apparent propensity for invasive disease. In industrialized countries, most asymptomatic individuals with Entamoeba in their stool are colonized with E. dispar, whereas in endemic regions, asymptomatic infection with E. histolytica may exceed the rate of E. dispar colonization.

Pyogenic Liver Abscess

The incidence of pyogenic liver abscess is about 1 to 4 cases per 100,000 individuals annually in the United States and Europe (Huang et al., 1996; Kaplan et al., 2004; Meddings et al., 2010; Rahimian et al., 2004; Tsai et al., 2008). This incidence has been relatively stable, albeit with a slight increasing trend in more recent case series. In Asia, the incidence may be 5- to 10-fold higher and is associated with the emergence of community-acquired Klebsiella pneumoniae infection (Fang et al., 2007; Wang et al., 1998a).

Pyogenic liver abscess is a disease of middle-aged persons, with a peak incidence in the fifth and sixth decades of life. About one-half of patients have a solitary abscess. Right-sided abscesses are most common, followed by left-sided and then abscesses involving the caudate lobe.

Routes of Hepatic Invasion

Table 1: Frequency of Route of Infection in Hepatic Abscess

Route of Infection	Frequency (%)
Biliary tree	40–50
Hepatic artery	5–10
Portal vein	5–15
Direct extension	5–10
Trauma	0–5
Cryptogenic	20–40

1. Biliary tree. Cholangitis is now the major identifiable cause of pyogenic liver abscess. The underlying biliary obstruction is usually a result of gallstone disease, but can also be caused by obstructing tumor, occluded stent, Ascaris lumbricoides migration, or overwhelming cryptosporidiosis.

2. Hepatic artery. Any systemic bacteremia (e.g., endocarditis, line sepsis) can spread to the liver via this route.

3. Portal vein. Pylephlebitis from diverticulitis, pancreatitis, omphalitis, inflammatory bowel diseases, or postoperative infection can result in pyogenic liver abscess. Untreated appendicitis was historically a major cause but has greatly diminished with the introduction of antibiotics.

4. Direct extension from a contiguous focus of infection. This may occur with cholecystitis or subphrenic, perinephric, or other intraabdominal abscesses.

5. Trauma. Any penetrating trauma to the liver, even as subtle as ingestion of a toothpick, can result in abscess formation. Blunt trauma, hepatic destruction from sickle cell disease, tumor necrosis, or cirrhosis can predispose to abscess formation.

Risk Factors for Pyogenic Liver Abscess

Diabetes imparts a greater than threefold risk of development of pyogenic liver abscess (Thomsen et al., 2007). Conditions of neutrophil dysfunction (e.g., chronic granulomatous disease) are associated with a marked predisposition for hepatic and other abscesses. Hemochromatosis conveys particular susceptibility to abscesses caused by Yersinia enterocolitica (Vadillo et al., 1994).

Pathogenesis and Pathophysiology

Amebic Liver Abscess

Infection with E. histolytica results from ingestion of cysts in fecally contaminated food or water. Excystation occurs in the intestinal lumen, and trophozoites migrate to the colon, where they adhere by means of a lectin that specifically binds galactose N-acetyl-D-galactosamine (the Gal/GalNAc lectin) on colonic epithelium and multiply by binary fission (Petri et al., 2002, 1987).

Figure 7: Life cycle of *Entamoeba histolytica* showing transmission via fecal-oral route, excystation, and tissue invasion.

A number of virulence factors have been implicated, including small proteins (amoebapores) that punch holes in lipid bilayers of target cells, cysteine proteases, and the Gal/GalNAc lectin (Ankri et al., 1999; Huston, 2004; Leippe, 1997; Que and Reed, 2000; Seigneur et al., 1998; Stanley, 2003b; Tillack et al., 2007).

E. histolytica induces apoptosis in hepatocytes and neutrophils, forming large, nonpurulent, “anchovy paste” abscesses that grow inexorably without treatment (Ghosh et al., 2003; Ragland et al., 1994). The mechanism by which E. histolytica induces apoptosis is unknown, but its importance is underscored by the resistance of caspase-3–deficient mice to amebic liver abscess formation (Huston et al., 2000; Yan and Stanley, 2001).

Figure 8: Characteristic “anchovy paste” material aspirated from an amebic liver abscess — the nonpurulent appearance results from *E. histolytica*-induced hepatocyte apoptosis rather than necrosis.

Predisposition to liver disease is influenced by host genetics. Individuals with the major histocompatibility complex haplotype HLA-DR3 have an increased frequency of amebic liver abscess (Arellano et al., 2005; Srivastava and Bhargava, 2005). Host factors in containment include complement, neutrophils, interferon-γ, nitric oxide, and adaptive immune responses (Begum et al., 2015; Haque et al., 2007; Houpt et al., 2002; Moonah et al., 2013; Seydel et al., 2000).

Pyogenic Liver Abscess

Pyogenic liver abscess occurs whenever the initial inflammatory response fails to clear an infectious insult to the liver. Pyogenic liver abscesses are usually classified by presumed route of hepatic invasion: (1) biliary tree, (2) portal vein, (3) hepatic artery, (4) direct extension, and (5) penetrating trauma.

Microbiology

Amebic Liver Abscess

Although E. histolytica is the only species of Entamoeba known to cause invasive infections, certain strains may be more proficient at causing liver disease (Ali et al., 2007; Haghighi et al., 2002; Zaki et al., 2002). Ali and colleagues analyzed paired isolates from patients with concurrent amebic liver abscesses and intestinal infection and found discordant genotypes, suggesting either genetic reorganization during invasion or that only a subset of strains is capable of metastasizing to the liver (Ali et al., 2003).

Pyogenic Liver Abscess

The microbiology of pyogenic liver abscess is complex. Abscess cultures are positive in 80% to 90% of cases. Anaerobic organisms are recovered 15% to 30% of the time. Many liver abscesses are polymicrobial, with estimates ranging from 20% to 50% (Brook and Frazier, 1998).

Table 2: Microbiology of Liver Abscess

Type of Organism	Common (>10%)	Uncommon (1%–10%)
Gram-negative	Escherichia coli, Klebsiella spp.	Pseudomonas, Proteus, Enterobacter, Citrobacter, Serratia
Gram-positive	Streptococcus (anginosus group), Enterococcus spp., Other viridans group streptococci	Staphylococcus aureus, β-Hemolytic streptococci
Anaerobic	Bacteroides spp.	Fusobacterium, Anaerobic streptococci, Clostridium spp., Lactobacilli

Epidemic Klebsiella pneumoniae Pyogenic Liver Abscess

In the mid-1980s, investigators in Taiwan first noted a distinctive syndrome of monomicrobial K. pneumoniae pyogenic liver abscess in individuals who were often diabetic but had no biliary tract disorders (Chang and Chou, 2000; Liu et al., 1986; Wang et al., 1998b). Subsequently, community-acquired K. pneumoniae liver abscess has become a major health problem in parts of Asia, accounting for 80% of all cases of pyogenic liver abscess (Fang et al., 2007; Tsai et al., 2008), and has been reported in North America, Europe, Africa, and Australia (Chung et al., 2007; Foo et al., 2010; Lederman and Crum, 2005; Lee et al., 2008; McCabe et al., 2013; Moore et al., 2013; Rahimian et al., 2004; Siu et al., 2012).

Figure 9: Hypervirulent *Klebsiella pneumoniae* — the mucoid “string test” phenotype characteristic of hypermucoviscous strains associated with community-acquired liver abscess.

Convergent Drug-Resistant Strains

Hypermucoviscous strains of K. pneumoniae are typically highly drug sensitive, unlike classic health care–associated strains. However, convergent strains that are both hypermucoviscous and multidrug resistant (MDR) or extensively drug resistant (XDR) can emerge, posing a serious public health challenge (Gu et al., 2018).

Infections are primarily caused by capsular serotypes K1 or K2. A 25-kb chromosomal element containing 20 open reading frames directs K1 capsular polysaccharide synthesis (CPS). Mutagenesis of the cps gene, magA (mucoviscosity-associated gene A), abolishes hypermucoviscosity and increases sensitivity to phagocytosis (Chuang et al., 2006; Fang et al., 2004; Struve et al., 2005; Yu et al., 2007).

Clinical Manifestations

Amebic Liver Abscess

Patients with amebic liver abscess typically present with fever and a dull, aching pain localizing to the right upper quadrant. Only 15% to 35% of patients present with concurrent gastrointestinal symptoms. Symptoms are acute (<2 weeks’ duration) in about two-thirds of cases but can develop months to years after travel to an endemic area. The presentation is indistinguishable from pyogenic liver abscess on clinical grounds; epidemiologic risk factors (corticosteroid use, male sex) are of paramount importance.

Pyogenic Liver Abscess

Only 1 patient in 10 presents with the classic triad of fever, jaundice, and right upper quadrant tenderness. Fever is common, often without localizing signs but with a general failure to thrive, including malaise, fatigue, anorexia, or weight loss.

Table 3: Signs and Symptoms of Liver Abscess

Feature	Amebic Liver Abscess	Pyogenic Liver Abscess
Epidemiology
Male-to-female ratio	5–18	1–2.4
Age (years)	30–40	50–60
Duration (days)	<14 (≈ 75% of cases)	5–26
Mortality (%)	10–25	0–5
Symptoms and Signs (Approximate % of Cases)
Fever	80	80
Weight loss	40	30
Abdominal pain	80	55
Diarrhea	15–35	10–20
Cough	10	5–10
Jaundice	10–15	10–25
Right upper quadrant tenderness	75	25–55
Laboratory Tests (Approximate % of Cases)
Leukocytosis	80	75
Elevated alkaline phosphatase	80	65
Solitary lesion	70	70

Diagnosis

The diagnosis of liver abscess should be suspected in all patients with fever, leukocytosis, and a space-occupying liver lesion. Leukocytosis is present in most patients. An elevated alkaline phosphatase concentration is the most frequently abnormal liver function test, occurring in about two-thirds of patients, but a normal value does not exclude the diagnosis.

Prognostic Markers

A hemoglobin concentration of less than 10 g/dL and a blood urea nitrogen concentration greater than 28 mg/dL were independent predictors of mortality in patients found to have pyogenic liver abscess (odds ratios of 13 and 14, respectively) (Chen et al., 2009).

Imaging

Once the diagnosis is suspected, radiographic imaging studies are essential. Ultrasonography has a sensitivity of 70% to 90%. Contrast-enhanced CT scanning has improved sensitivity (≈ 95%) and is superior for guiding complex drainage procedures (Halvorsen et al., 1984).

Amebic Serology

Serum amebic serology by enzyme immunoassay has a sensitivity of about 65% to 92% and is highly specific for E. histolytica infection (Haque et al., 1995). Although serology can be negative during acute presentation (symptom duration <2 weeks), a repeat serology determination is usually positive (Blessmann et al., 2003; Haque et al., 2000; Stanley et al., 1991; Tanyuksel and Petri, 2003).

Therapy

Amebic Liver Abscess

Amebic liver abscess can almost always be treated with medical therapy alone. Metronidazole (750 mg three times daily) is typically given for 7 to 10 days. An alternative is tinidazole (2 g daily for 3 days). Other nitroimidazoles with extended half-lives include secnidazole and ornidazole.

Luminal Treatment

Patients frequently remain colonized with E. histolytica despite nitroimidazole treatment and should be treated with paromomycin, a nonabsorbable aminoglycoside with E. histolytica activity, to eliminate this condition (Blessmann and Tannich, 2002; Irusen et al., 1992).

Uncomplicated amebic liver abscess does not require drainage. Percutaneous image-guided aspiration has replaced surgical drainage when drainage is needed, such as when there is no response to appropriate therapy, uncertainty about the diagnosis, exclusion of pyogenic liver abscess, or bacterial superinfection.

Pyogenic Liver Abscess

Unlike amebic liver abscess, pyogenic liver abscesses usually require drainage in addition to antibiotic therapy. Percutaneous catheter drainage is the preferred primary therapy, with success rates of 69% to 90%.

Table 4: Antibiotic Therapy for Pyogenic Hepatic Abscess. ^a Metronidazole or tinidazole should be included for presumptive therapy of amebic abscess if suspected.

Type of Therapy	Agents
Monotherapy
β-Lactam–β-lactamase inhibitor combination	Piperacillin-tazobactam
Carbapenem	Imipenem-cilastin, meropenem, ertapenem
Combination Therapy
Cephalosporin-based	Third- or fourth-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, cefepime) plus metronidazole
Fluoroquinolone-based	Fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) plus metronidazole

Antibiotic Duration

To date, no randomized clinical trials have evaluated the optimal duration of antibiotic treatment for pyogenic liver abscess. A meta-analysis of 16 studies reported treatment durations as long as 68.9 days and a pooled mean treatment duration of 32.7 days (Cai et al., 2015). Some studies have reported successful treatment with less than 4 to 6 weeks of therapy. Historically, parenteral antibiotics for 2 to 3 weeks followed by oral agents to complete 4 to 6 weeks total has been the standard approach.

Infection of the Biliary System

Infections of the biliary tract, including the common bile duct and gallbladder, are most often associated with obstruction to the flow of bile. In the United States, gallstones are common and most often asymptomatic.

Cholecystitis

Cholecystitis is inflammation and bacterial infection of the gallbladder, usually resulting from obstruction by gallstones. Acalculous cholecystitis involves a similar inflammatory process without stones and is more common in critically ill patients, carrying a higher mortality rate. Treatment consists of cholecystectomy combined with antibiotic therapy.

Cholangitis

Cholangitis is infection of the bile ducts, representing a life-threatening emergency that requires urgent biliary decompression. The classic presentation is the Charcot triad of fever, jaundice, and right upper quadrant pain. The Reynolds pentad adds hypotension and altered mental status, indicating progression to sepsis. Mortality ranges from 5–10% with treatment to up to 90% without surgical and antibiotic intervention.

Biliary Drainage Procedures

Biliary decompression is the cornerstone of management for cholangitis and should be performed urgently. The two main approaches are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic drainage.

(a) ERCP — endoscopic approach for biliary drainage and stone removal

Antibiotic Therapy for Biliary Tract Infections

The choice of antibiotic for biliary tract infections must take into account the ability of the agent to achieve adequate concentrations in bile. The antibiotic bile/serum concentration ratio (ABSCR) provides a useful guide to drug selection.

Table 5: Antibiotic Bile/Serum Concentration Ratios (ABSCR). Source: Ansaloni et al. PMID 27307785.

Good Penetration (ABSCR ≥1)	ABSCR	Low Penetration (ABSCR <1)	ABSCR
Piperacillin/tazobactam	4.8	Ceftriaxone	0.75
Tigecycline	>10	Cefotaxime	0.23
Amoxicillin/clavulanate	1.1	Meropenem	0.38
Ciprofloxacin	>5	Ceftazidime	0.18
Ampicillin/sulbactam	2.4	Vancomycin	0.41
Cefepime	2.04	Amikacin	0.54
Levofloxacin	1.6	Gentamicin	0.30
Penicillin G	>5
Imipenem	1.01

Mild–Moderate Severity (Community-Acquired, No Prior Biliary Instrumentation)

For community-acquired cholecystitis and cholangitis in patients without prior biliary instrumentation and low resistance risk, the following regimens are recommended:

Table 6: Antibiotic Regimens for Mild–Moderate Biliary Tract Infections

Regimen	Agents
3rd-generation cephalosporin	Ceftriaxone, cefotaxime
2nd-generation cephalosporin	Cefuroxime
1st-generation cephalosporin	Cefazolin (cholecystitis only)
Fluoroquinolone	Ciprofloxacin, levofloxacin (if local resistance permits)
β-Lactam/β-lactamase inhibitor	Amoxicillin/clavulanate

Anaerobic Coverage

Anaerobic coverage is not required for mild–moderate biliary tract infections unless the patient has a bilioenteric anastomosis or prior biliary intervention.

Severe or Healthcare-Associated Biliary Tract Infections

For Grade III cholangitis, healthcare-acquired infections, patients with prior biliary instrumentation, or those at high resistance risk, broader empiric therapy is warranted:

Table 7: Antibiotic Regimens for Severe/Healthcare-Associated Biliary Tract Infections (Solomkin et al., 2010)

Regimen	Agents
Carbapenem	Imipenem/cilastatin, meropenem, ertapenem
β-Lactam/β-lactamase inhibitor	Piperacillin/tazobactam
Fluoroquinolone + anaerobic cover	Ciprofloxacin or levofloxacin + metronidazole

Additional Considerations for Severe Biliary Infections

Add vancomycin if MRSA risk is present (prior MRSA colonization, healthcare-associated infection). Add fluconazole if Candida risk is elevated (immunosuppressed patients, prolonged prior antibiotic exposure). Fluoroquinolone-based regimens should be adjusted for local antibiogram data, as E. coli fluoroquinolone resistance exceeds 10% in many centers.

Summary Comparison Tables

Comparing Hepato-Biliary Infections

Table 8: Summary Comparison of Appendicitis, Amebic Liver Abscess, and Pyogenic Liver Abscess

	Appendicitis	Amebic Abscess	Pyogenic Abscess
Peak age	15–25 years	30–40 years	50–60 years
Cause	Obstruction/dysbiosis	E. histolytica	Biliary/polymicrobial
Diagnosis	CT	Serology + imaging	Culture + imaging
Treatment	Surgery or antibiotics	Metronidazole	Drainage + antibiotics

Comparing Cholecystitis and Cholangitis

Table 9: Comparison of Cholecystitis and Cholangitis

	Cholecystitis	Cholangitis
Structure involved	Gallbladder	Bile ducts
Cause	Gallstone obstruction; acalculous in critically ill	Biliary obstruction (stones, stricture, malignancy)
Clinical features	Fever, RUQ pain, Murphy’s sign	Charcot triad (fever, jaundice, RUQ pain); Reynolds pentad if septic
Urgency	Urgent (elective if mild)	Medical emergency — biliary decompression within 24–48 h
Diagnosis	Ultrasound ± CT	Clinical + ultrasound/MRCP/CT
Microbiology	E. coli, Klebsiella, Enterococcus	Same + anaerobes if bilioenteric anastomosis
Source control	Cholecystectomy (laparoscopic preferred)	ERCP or percutaneous transhepatic drainage
Antibiotics — mild	Cefazolin, ceftriaxone, amoxicillin/clavulanate	3rd-gen cephalosporin, fluoroquinolone
Antibiotics — severe	Piperacillin/tazobactam, carbapenem	Piperacillin/tazobactam, carbapenem ± vancomycin
Mortality	<1% (calculous); higher in acalculous	5–10% treated; up to 90% without decompression

Key Distinction

Both cholecystitis and cholangitis share biliary obstruction as the primary driver. The critical distinction is urgency: cholangitis mandates emergent decompression, while cholecystitis management can be staged based on severity.

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