What are Klebsiella pneumoniae, Enterobacter cloacae, and Citrobacter freundii?

Klebsiella pneumoniae, Enterobacter cloacae, and Citrobacter freundii: Gram-Negative Pathogens of Clinical Significance

Klebsiella pneumoniae, Enterobacter cloacae, and Citrobacter freundii are clinically significant gram-negative bacteria belonging to the Enterobacteriaceae family that can cause serious infections with high morbidity and mortality, particularly in healthcare settings. These organisms share common characteristics but differ in their specific virulence factors and resistance patterns.

Common Characteristics

• Taxonomy: All three belong to the Enterobacteriaceae family of gram-negative, facultative anaerobic bacilli 1, 2
• Habitat: Primarily found in the gastrointestinal tract and can colonize the human gut 2
• Clinical significance: Important causes of healthcare-associated infections, particularly in immunocompromised patients 1
• Resistance mechanisms: All three can develop antimicrobial resistance through various mechanisms, including extended-spectrum β-lactamase (ESBL) production 1

Klebsiella pneumoniae

Microbiological Characteristics

• Gram-negative, encapsulated, non-motile bacillus
• Most clinically significant species of the Klebsiella genus 2
• Characterized by a prominent polysaccharide capsule that contributes to its virulence 3, 4

Clinical Significance

• Causes a wide range of infections including:
  • Pneumonia (particularly in alcoholics and diabetics)
  • Urinary tract infections
  • Bloodstream infections
  • Liver abscesses (especially hypervirulent strains)
  • Wound infections 3, 5
• Accounts for a significant proportion of hospital-acquired infections 6
• Hypervirulent strains can cause severe community-acquired infections even in healthy individuals 3, 4

Resistance Mechanisms

• Produces ESBLs that confer resistance to many β-lactam antibiotics 1
• Can develop carbapenem resistance through production of carbapenemases (KPC) 2
• Infections with ESBL-producing K. pneumoniae are associated with higher treatment failure rates (35% vs. 15%) and increased healthcare costs ($66,590 vs. $22,231) 1

Enterobacter cloacae

Microbiological Characteristics

• Gram-negative, motile bacillus
• Contains chromosomal AmpC β-lactamase that is inducible 1

Clinical Significance

• Causes various nosocomial infections, particularly:
  • Ventilator-associated pneumonia (VAP)
  • Urinary tract infections
  • Surgical site infections
  • Bloodstream infections 7
• VAP caused by E. cloacae has high mortality (24%), particularly in women and patients with translaryngeal tubes 7
• Risk factors include mechanical ventilation, prior surgical procedures, and immunodeficiency 7

Resistance Mechanisms

• Possesses inducible AmpC β-lactamase that can be hyperexpressed by mutation, conferring resistance to many β-lactams 1
• Can acquire plasmid-mediated resistance such as ESBL production 1

Citrobacter freundii

Microbiological Characteristics

• Gram-negative, motile bacillus
• Contains chromosomal AmpC β-lactamase similar to Enterobacter species 1

Clinical Significance

• Causes various infections including:
  • Urinary tract infections
  • Intra-abdominal infections
  • Bloodstream infections
  • Wound infections 1, 8
• Often implicated in complicated intra-abdominal infections (cIAI) 8
• Less common than Klebsiella and Enterobacter in clinical settings but still significant

Resistance Mechanisms

• Possesses inducible AmpC β-lactamase similar to Enterobacter species 1
• Can develop resistance to multiple antibiotics through various mechanisms

Treatment Considerations

Antibiotic Options

• For susceptible strains: third or fourth-generation cephalosporins, fluoroquinolones, or aminoglycosides 1
• For ESBL-producing strains: carbapenems are often the drugs of choice 2
• For carbapenem-resistant strains: limited options include:
  • Tigecycline (active against many resistant gram-negative bacteria) 9
  • Avibactam combinations (ceftazidime-avibactam has activity against KPC-producing Klebsiella) 8
  • Polymyxins (colistin) as a last resort 1

Treatment Challenges

• Increasing prevalence of multidrug-resistant strains limits therapeutic options 1, 2
• Infections with resistant strains are associated with higher mortality and healthcare costs 1
• The emergence of carbapenemase-producing strains is particularly concerning 1

Prevention and Control

• Implement strict infection control measures, including hand hygiene and contact precautions 1
• Judicious use of antibiotics to prevent further resistance development 1
• Active surveillance in healthcare settings to detect and isolate carriers of resistant strains 1
• For catheter-related bloodstream infections caused by these organisms, catheter removal is often necessary 1

Clinical Pitfalls to Avoid

1. Underestimating virulence: Particularly with hypervirulent K. pneumoniae strains that can cause severe infections even in healthy individuals 3

2. Inappropriate empiric therapy: Failing to consider local resistance patterns when initiating empiric therapy can lead to treatment failure 1

3. Delayed source control: For intra-abdominal infections and other collections, antibiotic therapy alone is often insufficient without adequate source control 1

4. Overlooking colonization vs. infection: Distinguishing between colonization and true infection is crucial to avoid unnecessary antibiotic use 1

5. Ignoring emerging resistance: Regular monitoring of susceptibility patterns is essential as resistance mechanisms continue to evolve 2