What are the common sources of bacterial sepsis in patients with high-grade non-Hodgkin's lymphoma?

Common Sources of Bacterial Sepsis in High-Grade Non-Hodgkin's Lymphoma

Patients with high-grade non-Hodgkin's lymphoma are at significant risk for bacterial sepsis from multiple sources, with respiratory tract infections being the most common source, followed by bloodstream infections, gastrointestinal infections, and genitourinary tract infections. 1

Primary Sources of Infection

Respiratory Tract

• Lower respiratory tract infections represent the most common source (41.2%) of nosocomial infections in NHL patients 1
• Endobronchial tumor involvement may cause recurrent postobstructive pneumonias 2
• Common respiratory pathogens include Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus 1, 3

Bloodstream

• Bloodstream infections are a significant source of sepsis in NHL patients 3
• Gram-negative organisms and Staphylococcus aureus cause 83% of documented infections in NHL patients 3
• Pseudomonas aeruginosa is a major cause of bacteremia in these patients 3

Gastrointestinal Tract

• Alimentary canal infections are common in NHL patients 3
• Direct tumor invasion through colonic mucosa can lead to local abscess formation and sepsis by enteric flora 2
• Clostridium difficile colitis is a significant concern in heavily treated patients 2

Genitourinary Tract

• Urinary tract infections are common in NHL patients 1
• Abdominal tumors may obstruct the genitourinary tract, predisposing patients to pyelonephritis 2

Catheter-Related Infections

• Device-related infections are particularly frequent in immunocompromised patients 2
• Any artificial device (e.g., venous catheter) should be carefully checked for signs of infection 2

Risk Factors for Sepsis in NHL

Disease-Related Factors

• Bone marrow involvement significantly increases infection risk 1
• Advanced clinical stage (III, IV) is an independent risk factor for nosocomial infection 1
• Tumor necrosis can form a nidus for infection 2
• Hematologic malignancies may cause leukopenia from marrow infiltration 2

Treatment-Related Factors

• Neutropenia (neutrophil count <0.5×10^9/L) is a major independent risk factor for infection 1, 3
• Most infections occur following the first (39%) or second (18%) cycle of chemotherapy 4
• Longer hospital stays increase infection risk 1
• Multiple prior chemotherapy regimens significantly increase infection risk 2

Common Pathogens

Bacterial Pathogens

• Gram-negative bacteria account for 52.1% of infections, with Gram-positive bacteria causing 28.2% 1
• Key gram-negative pathogens include Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli 1, 3
• Staphylococcus aureus is a significant gram-positive pathogen 1, 3
• Extended-spectrum β-lactamase (ESBL) producing organisms are common (36.4% of Klebsiella pneumoniae and 22.2% of E. coli) 1

Fungal Pathogens

• Fungal infections account for approximately 19.7% of infections in NHL patients 1
• Candida albicans is the predominant fungal pathogen 1

Management Approach

Initial Assessment

• Obtain at least 2 sets of blood cultures before starting antimicrobial therapy 5
• Perform appropriate imaging studies promptly to identify the source of infection 5
• Administer effective intravenous antimicrobials within the first hour of recognition of septic shock 2, 5

Source Control

• Rapidly identify and address the anatomical source of infection within 12 hours of diagnosis 5, 6
• Remove potentially infected intravascular access devices promptly after establishing alternative access 5

Antimicrobial Therapy

• Initial empiric anti-infective therapy should include one or more drugs active against all likely pathogens 2
• Consider combination therapy for neutropenic patients with severe sepsis 2
• For Pseudomonas aeruginosa bacteremia, use combination therapy with an extended-spectrum β-lactam and either an aminoglycoside or a fluoroquinolone 2
• Reassess antimicrobial regimen daily for potential de-escalation 2, 5
• Duration of therapy typically 7-10 days; longer courses may be needed for patients with slow clinical response, undrainable foci of infection, or neutropenia 2

Prevention Strategies

• Consider antimicrobial prophylaxis in high-risk patients 2
• Consider PCP prophylaxis in patients receiving corticosteroids equivalent to prednisone 20 mg/day for ≥4 weeks 2
• Monitor for neutropenia regularly during chemotherapy 1

Prognosis

• Poor prognosis is associated with infections in granulocytopenic patients with stable or falling granulocyte counts, infection at multiple sites, and bacteremia 3
• Infection remains a leading cause of death (33%) in NHL patients despite advances in therapy and supportive care 7