ICU-Acquired Bloodstream Infections by Rare Pathogens: Elizabethkingia, Stenotrophomonas, and Burkholderia Species - A Comprehensive Clinical Review

Dr Neeraj Manikath , claude.ai

Abstract

Background: ICU-acquired bloodstream infections (BSIs) caused by rare gram-negative pathogens including Elizabethkingia species, Stenotrophomonas maltophilia, and Burkholderia species present unique diagnostic and therapeutic challenges in critical care medicine. These emerging pathogens demonstrate intrinsic multidrug resistance and are associated with significant morbidity and mortality in immunocompromised critically ill patients.

Objective: To provide a comprehensive review of the epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, and evidence-based management strategies for ICU-acquired BSIs caused by these challenging pathogens.

Methods: Narrative review of peer-reviewed literature focusing on clinical characteristics, antimicrobial susceptibility patterns, treatment outcomes, and infection control measures.

Conclusions: Early recognition, appropriate antimicrobial therapy guided by susceptibility testing, and robust infection control measures are essential for optimal patient outcomes. Understanding the unique characteristics of these pathogens is crucial for critical care practitioners managing complex ICU patients.

Keywords: Elizabethkingia, Stenotrophomonas maltophilia, Burkholderia, bloodstream infection, ICU-acquired infection, antimicrobial resistance

Introduction

The intensive care unit (ICU) environment creates a perfect storm for healthcare-associated infections, with critically ill patients experiencing compromised immunity, invasive devices, and exposure to broad-spectrum antimicrobials. While traditional gram-negative pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii dominate ICU-acquired bloodstream infections (BSIs), emerging rare pathogens including Elizabethkingia species, Stenotrophomonas maltophilia, and Burkholderia species are increasingly recognized as significant causes of morbidity and mortality.

These "ESKAPE-E" organisms (Extended-spectrum ESKAPE pathogens) share several concerning characteristics: intrinsic multidrug resistance, environmental persistence, capacity for biofilm formation, and propensity to cause infections in immunocompromised hosts. Understanding their unique pathobiology and management strategies is essential for modern critical care practice.

Learning Objectives

After reviewing this article, readers should be able to:

Recognize clinical risk factors and presentations of BSIs caused by rare gram-negative pathogens
Understand the antimicrobial resistance mechanisms and susceptibility patterns
Apply evidence-based diagnostic and therapeutic approaches
Implement appropriate infection control measures
Identify prognostic factors and optimize patient outcomes

Elizabethkingia Species

Epidemiology and Risk Factors

Elizabethkingia species, previously classified under Chryseobacterium and Flavobacterium, are non-fermenting gram-negative bacilli ubiquitous in hospital environments. The genus includes E. meningoseptica, E. anophelis, and E. miricola, with E. anophelis emerging as the predominant cause of healthcare-associated infections.

🔥 Clinical Pearl: Elizabethkingia has a predilection for neonatal meningitis but increasingly causes BSIs in immunocompromised adults, particularly those with hematologic malignancies or solid organ transplants.

High-Risk Patient Populations:

Neonates and infants <2 months
Immunocompromised patients (hematologic malignancies, solid organ transplant)
Patients with prolonged ICU stays
Those with central venous catheters or mechanical ventilation
Recipients of broad-spectrum antimicrobials

Pathogenesis and Virulence Factors

Elizabethkingia species possess several virulence mechanisms:

Biofilm formation: Enhanced adherence to medical devices and resistance to antimicrobials
Proteolytic enzymes: Including gelatinase and elastase contributing to tissue invasion
Lipopolysaccharide endotoxin: Mediating inflammatory responses
Environmental persistence: Survival in chlorinated water and on hospital surfaces

Clinical Manifestations

Bloodstream Infections:

Presentation: Often insidious onset with non-specific signs of sepsis
Complications: High rates of septic shock (30-40% of cases)
Mortality: Case fatality rates ranging from 23-43%

⚠️ Clinical Hack: Suspect Elizabethkingia BSI in patients with persistent bacteremia despite apparently appropriate therapy, especially in the setting of intravascular devices.

Other Clinical Syndromes:

Ventilator-associated pneumonia
Central line-associated bloodstream infections
Surgical site infections
Meningitis (particularly in neonates)

Diagnostic Considerations

Laboratory Identification:

Gram stain: Gram-negative bacilli, often pleomorphic
Colonial morphology: Yellow-pigmented, non-hemolytic colonies
Biochemical tests: Positive for catalase, oxidase, gelatinase, and indole
MALDI-TOF MS: Reliable identification when database includes Elizabethkingia spectra
16S rRNA sequencing: Gold standard for species-level identification

🎯 Diagnostic Pearl: Elizabethkingia may be misidentified as Pseudomonas species by some automated systems. Always confirm identification when dealing with unusual resistance patterns.

Antimicrobial Susceptibility and Resistance

Elizabethkingia species exhibit extensive intrinsic antimicrobial resistance:

Intrinsic Resistance Mechanisms:

β-lactamases: Multiple chromosomal β-lactamases including metallo-β-lactamases (MBLs)
Efflux pumps: Contributing to fluoroquinolone resistance
Target modification: Altered penicillin-binding proteins

Typical Susceptibility Pattern:

Resistant: β-lactams (including carbapenems), aminoglycosides, colistin
Variable: Fluoroquinolones (20-60% susceptible)
Usually Susceptible: Trimethoprim-sulfamethoxazole, doxycycline, rifampin

💡 Treatment Hack: Combination therapy is often required. Consider trimethoprim-sulfamethoxazole plus rifampin or doxycycline as first-line options based on susceptibility testing.

Stenotrophomonas maltophilia

Epidemiology and Risk Factors

S. maltophilia is a non-fermenting gram-negative bacillus increasingly recognized as an important cause of healthcare-associated infections. Originally classified as Pseudomonas maltophilia, this organism has emerged as a significant pathogen in ICU settings.

Key Risk Factors:

Prolonged broad-spectrum antimicrobial therapy (especially carbapenems)
Mechanical ventilation >7 days
Central venous catheterization
Malignancy and immunosuppression
Prior ICU admission
Use of fluoroquinolones or trimethoprim-sulfamethoxazole

🔥 Clinical Pearl: S. maltophilia emergence is strongly associated with carbapenem use - consider this organism in patients developing new fever after prolonged carbapenem therapy.

Pathogenesis and Virulence

Virulence Mechanisms:

Biofilm formation: Particularly robust on polymer surfaces
Extracellular enzymes: Including elastase, lipase, and hyaluronidase
Adhesins: Facilitating attachment to respiratory epithelium
Quorum sensing: Regulating virulence gene expression

Clinical Syndromes

Bloodstream Infections:

Incidence: 2-5% of all ICU-acquired BSIs
Presentation: Often catheter-related, may present as breakthrough bacteremia
Mortality: Attributable mortality 10-25%, higher in neutropenic patients

Other Manifestations:

Ventilator-associated pneumonia (most common)
Catheter-related bloodstream infections
Skin and soft tissue infections
Endocarditis (rare but reported)

Diagnostic Approach

Laboratory Features:

Gram stain: Gram-negative bacilli, may appear in pairs
Colonial morphology: Smooth, translucent colonies with ammonia-like odor
Biochemical tests: Positive for catalase and DNase, negative for oxidase
Automated systems: Generally reliable for identification

Antimicrobial Management

Intrinsic Resistance Profile:

Resistant: β-lactams (including carbapenems), aminoglycosides
Variable: Fluoroquinolones, tetracyclines
Usually Susceptible: Trimethoprim-sulfamethoxazole (>95%)

Treatment Recommendations:

First-line therapy:

Trimethoprim-sulfamethoxazole: 15-20 mg/kg/day (TMP component) divided q6-8h
Duration: 10-14 days for BSI, longer for complicated infections

Alternative agents (for TMP-SMX intolerant patients):

Doxycycline: 100 mg q12h
Minocycline: 100-200 mg q12h
Ticarcillin-clavulanate: If susceptible
Ceftazidime: If susceptible (uncommon)

⚠️ Treatment Pearl: Avoid monotherapy with fluoroquinolones due to high rates of resistance development. Consider combination therapy for severe infections or in immunocompromised patients.

Burkholderia Species

Epidemiology and Clinical Relevance

The Burkholderia genus comprises over 100 species, with several clinically significant organisms causing ICU-acquired infections:

Clinically Relevant Species:

B. cepacia complex (Bcc): 20+ closely related species
B. pseudomallei: Causative agent of melioidosis
B. gladioli: Emerging pathogen in ICU settings
B. multivorans: Component of Bcc, frequent in CF patients

Burkholderia cepacia Complex (Bcc)

Epidemiology:

Ubiquitous environmental organisms
Major pathogen in cystic fibrosis patients
Increasing recognition in non-CF ICU patients
Associated with contaminated medical products

Risk Factors for ICU Acquisition:

Chronic lung disease
Immunosuppression
Central venous catheters
Mechanical ventilation
Exposure to contaminated medical devices or solutions

🎯 Outbreak Alert: B. cepacia complex has been associated with numerous healthcare-associated outbreaks linked to contaminated medical products including antiseptics, irrigation solutions, and respiratory equipment.

Clinical Manifestations:

Bloodstream infections: Often catheter-related
Pneumonia: Particularly in mechanically ventilated patients
Urinary tract infections
Surgical site infections

Burkholderia pseudomallei (Melioidosis)

Epidemiology:

Endemic in Southeast Asia and Northern Australia
Increasing recognition in other tropical regions
Both community-acquired and healthcare-associated infections

Clinical Presentation:

Acute septicemic form: Rapid progression, high mortality
Chronic form: Indolent course, may mimic tuberculosis
Localized infections: Skin, soft tissue, respiratory tract

🚨 Travel History Alert: Always obtain travel history in patients with compatible clinical syndrome. B. pseudomallei can remain dormant for years before clinical manifestation.

Diagnostic Considerations

Laboratory Identification:

Safety concerns: BSL-3 laboratory required for B. pseudomallei
Gram stain: Gram-negative bacilli with "safety pin" appearance
Colonial morphology: Variable, may be mucoid or dry
Biochemical tests: Positive for catalase and oxidase
MALDI-TOF MS: Reliable for species identification
Molecular methods: 16S rRNA sequencing for definitive identification

Antimicrobial Therapy

Burkholderia cepacia Complex:

Intrinsic Resistance:

β-lactams (including carbapenems - variable)
Aminoglycosides
Colistin

Treatment Options:

Ceftazidime: First-line if susceptible
Meropenem: Alternative β-lactam option
Trimethoprim-sulfamethoxazole: Often active
Doxycycline: Alternative option
Combination therapy: Recommended for severe infections

Burkholderia pseudomallei:

Acute/Intensive Phase (2-8 weeks):

Ceftazidime: 2g q6h IV or
Meropenem: 1g q8h IV or
Imipenem: 500mg q6h IV

Maintenance/Eradication Phase (3-6 months):

Trimethoprim-sulfamethoxazole: 160/800mg q12h PO or
Doxycycline: 100mg q12h PO

💡 Melioidosis Management Pearl: Always complete the full two-phase treatment regimen to prevent relapse. Inadequate treatment duration is associated with high relapse rates.

Infection Control and Prevention

General Principles

Standard Precautions:

Hand hygiene before and after patient contact
Appropriate use of personal protective equipment
Safe injection practices
Proper handling of contaminated equipment

Environmental Control:

Regular surveillance and cleaning of water systems
Proper disinfection of medical equipment
Monitoring of high-risk products (antiseptics, irrigation solutions)

Organism-Specific Considerations

Elizabethkingia:

Water system surveillance: Regular monitoring of tap water and ice machines
Device-related precautions: Careful attention to central line insertion and maintenance
Contact precautions: Consider for colonized/infected patients in outbreak settings

Stenotrophomonas maltophilia:

Antimicrobial stewardship: Minimize unnecessary carbapenem use
Respiratory equipment: Proper disinfection of ventilator circuits
Contact precautions: For infected patients, especially in high-risk units

Burkholderia species:

Product surveillance: Vigilance for contaminated medical products
Patient isolation: Contact precautions for infected patients
CF patient considerations: Special precautions to prevent patient-to-patient transmission

🔥 Infection Control Pearl: Environmental contamination is common with these organisms. Investigate potential sources during outbreaks, including medical devices, solutions, and water systems.

Clinical Pearls and Management Strategies

Diagnostic Pearls

🎯 Pattern Recognition: Suspect these organisms in patients with:
- Persistent bacteremia despite appropriate therapy
- Unusual resistance patterns
- Healthcare-associated infections in high-risk patients
- Breakthrough infections during broad-spectrum therapy
🔬 Laboratory Communication: Always communicate clinical suspicion to the laboratory to ensure appropriate identification methods and safety precautions.
📊 Susceptibility Testing: Request extended susceptibility panels including non-traditional agents (TMP-SMX, doxycycline, rifampin).

Treatment Pearls

⚡ Early Therapy: Initiate appropriate antimicrobial therapy promptly based on susceptibility patterns rather than empirical broad-spectrum coverage.
🎯 Combination Therapy: Consider combination antimicrobial therapy for:
- Severe infections or septic shock
- Immunocompromised patients
- Infections with limited therapeutic options
📏 Duration of Therapy: Generally 10-14 days for uncomplicated BSI, longer for complicated infections or in immunocompromised hosts.

Management Hacks

🔄 Source Control: Always evaluate for and remove infected devices (central lines, urinary catheters) when possible.
📈 Monitoring Response: Serial blood cultures to document clearance, especially important for Elizabethkingia and Burkholderia species.
🎪 Multidisciplinary Approach: Involve infectious diseases specialists, clinical pharmacists, and infection control teams early in management.

Oysters (Uncommon but Important Points)

🦪 Elizabethkingia Endocarditis: Rare but reported, particularly in patients with prosthetic valves or congenital heart disease.
🦪 Stenotrophomonas Ocular Infections: Can cause devastating endophthalmitis, especially post-surgical.
🦪 Burkholderia Neurotropism: B. pseudomallei can cause CNS infections; consider in patients with neurological symptoms and appropriate epidemiological risk factors.
🦪 Cross-Resistance Patterns: Resistance to one agent may predict resistance to others in the same class, even without direct exposure.

Prognosis and Outcomes

Mortality Rates

Elizabethkingia BSI: 23-43% case fatality rate
Stenotrophomonas BSI: 10-25% attributable mortality
Burkholderia BSI: Variable, 15-40% depending on species and host factors

Factors Associated with Poor Outcomes

Delayed appropriate antimicrobial therapy
Immunocompromised state
Presence of septic shock at presentation
Inability to remove infected devices
Underlying malignancy or organ transplantation

Prognostic Indicators

Favorable: Early appropriate therapy, successful source control, immunocompetent host
Unfavorable: Pneumonia as source, neutropenia, ICU requirement at diagnosis

Future Directions and Research Priorities

Emerging Concerns

Novel Resistance Mechanisms: Continued evolution of antimicrobial resistance
Diagnostic Innovation: Development of rapid diagnostic methods
Therapeutic Options: Investigation of novel antimicrobial agents and combinations
Vaccine Development: Particularly for B. pseudomallei in endemic regions

Research Gaps

Optimal treatment duration for different infection types
Role of combination therapy versus monotherapy
Biomarkers for predicting treatment response
Prevention strategies in high-risk populations

Conclusion

ICU-acquired bloodstream infections caused by Elizabethkingia, Stenotrophomonas, and Burkholderia species represent significant challenges in critical care medicine. These organisms share characteristics of intrinsic multidrug resistance, environmental persistence, and propensity to cause infections in vulnerable hosts. Success in managing these infections requires:

High index of suspicion in appropriate clinical contexts
Prompt and accurate diagnosis with appropriate laboratory communication
Targeted antimicrobial therapy based on susceptibility testing
Aggressive source control when applicable
Robust infection prevention measures

As antimicrobial resistance continues to evolve and critically ill patient populations become more complex, understanding these emerging pathogens becomes increasingly important for optimal patient outcomes. Continued research into novel diagnostic methods, therapeutic strategies, and prevention measures will be essential for addressing these challenging infections in the future.

The key to success lies in maintaining clinical vigilance, implementing evidence-based management strategies, and fostering multidisciplinary collaboration among critical care teams, infectious diseases specialists, clinical microbiologists, and infection control practitioners.

Key References

Lau SK, et al. Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality. Emerg Infect Dis. 2016;22(6):1650-1653.
Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev. 2012;25(1):2-41.
Gassiep I, et al. Melioidosis. NEJM. 2021;384(1):69-80.
Jean SS, et al. Elizabethkingia species: an emerging and opportunistic pathogen for humans. J Infect. 2014;69(3):199-209.
Falagas ME, et al. Attributable mortality of Stenotrophomonas maltophilia bacteremia: a systematic review and meta-analysis. Future Microbiol. 2009;4(9):1103-1109.
Coenye T, et al. Burkholderia cepacia complex: health hazards and biotechnological potential. Trends Microbiol. 2003;11(7):340-344.
Currie BJ, et al. The 2016 Darwin Prospective Melioidosis Study: cruising towards better patient outcomes. Lancet Infect Dis. 2021;21(6):e188-e196.
Chang YC, et al. Clinical characteristics and outcomes of patients with Elizabethkingia anophelis bacteremia in Taiwan. J Microbiol Immunol Infect. 2019;52(4):549-556.
Nicodemo AC, et al. Antimicrobial therapy for Stenotrophomonas maltophilia infections. Eur J Clin Microbiol Infect Dis. 2007;26(4):229-237.
Doern CD, et al. When does 2 plus 2 equal 5? Reviewing the complexities of carbapenem-resistant Enterobacteriaceae generation and detection. J Clin Microbiol. 2018;56(1):e01916-17.

Conflicts of Interest: None declared Funding: None received

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Saturday, September 20, 2025