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Pseudomonas Infection - Comprehensive Notes (2nd Year MBBS Microbiology)

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Definition

• Name derivation: "pseudes" (false) + "monas" (a unit) - refers to how pairs of cells resemble a single cell on Gram stain
• "aeruginosa" - full of copper rust or green (refers to blue + yellow pigments that appear green)

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Morphology and General Properties

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Epidemiology / Habitat

• Environmental reservoir: Soil, water, decaying organic matter, vegetation - ubiquitous in nature
• Hospital reservoirs (moist): Sinks, toilets, floor mops, cut flowers, food, humidifiers, ventilator circuits, dialysis equipment, respiratory therapy equipment, contact lens solutions, even some disinfectants
• Colonization rate: 2-10% of throat/stool in healthy persons; much higher in hospitalized patients
• High-risk groups:
  • Neutropenic/immunocompromised patients
  • Cystic fibrosis (CF) patients
  • Extensive burn patients
  • Patients on broad-spectrum antibiotics
  • Hematologic malignancy patients
  • Diabetics (especially malignant otitis externa)
  • IV drug abusers (endocarditis)

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Virulence Factors

1. Adhesins (Surface Structures)

2. Secreted Toxins and Enzymes

3. Type III Secretion System (T3SS)

• A molecular "syringe" that directly injects effector proteins (ExoS, ExoT, ExoU) into host cells
• Bypasses extracellular immune defenses
• Expressed by the vast majority of P. aeruginosa strains
• Associated with more severe, invasive disease

4. Antibiotic Resistance

• Intrinsic resistance: Outer membrane porins are relatively impermeable (unlike Enterobacteriaceae), limiting antibiotic entry
• Acquired resistance: Horizontal gene transfer of resistance genes
• Adaptive resistance: Upregulation of efflux pumps; biofilm formation
• Resistant to most penicillins, cephalosporins (except certain anti-pseudomonal ones), and many other classes

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Pathogenesis

1. A break in first-line defenses (e.g., wound, burn) or a bypass (contaminated IV line, endotracheal tube)
2. A compromised host (immunosuppression, neutropenia)

1. Colonization/Attachment: Pili, flagella, and alginate slime mediate adherence to epithelial cells via sialic acid and N-acetylglucosamine receptors. Attachment is favored by loss of surface fibronectin (which normally blocks binding) - explains why debilitated patients are predisposed.
2. Local tissue invasion: Exotoxin A, elastases, phospholipase C, and alkaline protease degrade host proteins, lipids, and extracellular matrix. This allows acquisition of nutrients and local spread.
3. Systemic spread: Elastase and ExoS mediate destruction of blood vessel walls (histological hallmark: hemorrhagic vascular destruction). Organisms enter the bloodstream → bacteremia.
4. Toxin-mediated damage:
   • ExoA shuts down protein synthesis in host cells
   • ExoS/T injected into cells cause cytoskeletal disruption and apoptosis
   • Pyocyanin impairs mucociliary clearance
   • Elastase destroys elastin in lungs and blood vessels
5. Biofilm formation (especially in CF): Mucoid mutants overproduce alginate, forming a thick biofilm that is essentially impossible to eradicate with antibiotics.

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Clinical Manifestations / Symptoms

A. Respiratory Tract Infections

• Pneumonia: Particularly in ventilated patients (VAP - Ventilator-Associated Pneumonia); also in CF patients
• In CF: chronic colonization → mucoid biofilm formation → progressive pulmonary destruction → leading cause of morbidity and death in CF
• Presents with fever, productive cough, purulent/green sputum, dyspnea, chest pain

B. Urinary Tract Infections (UTI)

• Typically nosocomial, associated with catheterization or urological procedures
• Complicated UTI, often with antibiotic-resistant strains

C. Skin and Soft Tissue Infections

• Burn wound infections: Most feared complication of burns; can progress to bacteremia and sepsis
• Ecthyma gangrenosum: Pathognomonic skin lesion of Pseudomonas bacteremia - starts as erythematous papule/vesicle → becomes hemorrhagic → black necrotic ulcer; due to direct vascular invasion by organism
• Folliculitis: "Hot tub folliculitis" - pruritic erythematous papules/pustules after exposure to contaminated water; self-limiting
• Wound infections: Post-surgical, post-traumatic

D. Ear Infections

• Otitis externa ("swimmer's ear"): Common, localized, managed with topical antibiotics
• Malignant (necrotizing) otitis externa: Seen in diabetics and elderly; invades underlying tissues and bone (osteomyelitis of temporal bone); damages cranial nerves (especially VII); life-threatening; requires aggressive IV antibiotics ± surgery

E. Eye Infections

• Keratitis: Usually following corneal trauma (contact lens abrasion) + contaminated solutions; can destroy cornea within 24-48 hours
• Conjunctivitis, endophthalmitis (post-trauma or surgery)

F. Bacteremia and Septicemia

• Most common sources: lower respiratory tract, UTI, skin/soft tissue (especially burn wounds)
• Clinically indistinguishable from other Gram-negative bacteremia initially
• Higher mortality than most Gram-negative bacteremias due to: immunocompromised host, antibiotic resistance, inherent virulence
• May present with ecthyma gangrenosum (pathognomonic)

G. Endocarditis

• Rare; primarily in IV drug abusers (contaminated needles/paraphernalia)
• Tricuspid valve most commonly involved
• Chronic course; better prognosis than left-sided valve involvement

H. Other Infections

• Meningitis/CNS: Post-neurosurgical procedures
• Osteomyelitis: Especially in IV drug abusers and diabetic foot
• Gastrointestinal infections: Rare; necrotizing enterocolitis in neonates
• Septic arthritis

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Suppurative Complications

1. Lung abscess / empyema - from severe pneumonia
2. Bacteremia / septicemia - spread from primary focus
3. Septic shock - from overwhelming bacteremia (endotoxin-mediated)
4. Ecthyma gangrenosum - vascular invasion causing skin necrosis
5. Endophthalmitis - from keratitis progression (can lead to blindness)
6. Malignant otitis externa with osteomyelitis - bone destruction
7. Osteomyelitis and septic arthritis - from hematogenous seeding or direct inoculation
8. Endocarditis - especially tricuspid valve in IV drug users
9. Meningitis / brain abscess - from neurosurgical or hematogenous spread
10. Multi-organ failure - from uncontrolled sepsis

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Non-Suppurative Complications

1. Immune complex deposition: In chronic Pseudomonas infection (especially in CF lungs), antibodies form against LasA and LasB elastases → immune complexes deposit in infected tissues → chronic inflammation and tissue injury
2. Reactive arthritis: Rare, following Pseudomonas bacteremia
3. Chronic pulmonary destruction in CF: Progressive fibrosis and bronchiectasis driven partly by immune-mediated inflammation against persistent Pseudomonas antigens
4. Systemic inflammatory response syndrome (SIRS): Cytokine storm from LPS (endotoxin) triggering TNF-α, IL-1, IL-6 cascade

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Laboratory Diagnosis

1. Specimen Collection

• Based on site of infection: sputum, BAL, wound swab, urine (midstream or catheter), blood (for bacteremia), CSF, eye swab, ear swab

2. Direct Microscopy (Gram Stain)

• Gram-negative rods, arranged singly or in pairs
• Mucoid capsule may be visible in CF patients (slime around organisms)
• Pus cells (neutrophils) in most infections

3. Culture

• Grows on all common media: Blood agar, MacConkey agar, nutrient agar
• Selective media: Cetrimide agar (contains cetrimide as selective agent - inhibits other organisms)

• Blood agar: Large, spreading, β-hemolytic colonies; metallic sheen; fringed/irregular edges; characteristic fruity/grape-like odor (due to aminoacetophenone)
• MacConkey agar: Non-lactose fermenting (pale/colorless) colonies
• Pigments: Produces diffusible pigments that color the medium
  • Pyocyanin (blue) - produced ONLY by P. aeruginosa
  • Pyoverdin/fluorescein (yellow-green, fluorescent under UV)
  • Together they produce a characteristic blue-green color on plates
  • Other pigments: pyorubin (reddish-brown), pyomelanin (brown-black)

4. Biochemical Identification

5. Antibiotic Sensitivity Testing

• Essential due to multiple resistance patterns
• Methods: Kirby-Bauer disc diffusion, MIC determination (broth microdilution)
• Test against: piperacillin-tazobactam, ceftazidime, cefepime, carbapenems (imipenem/meropenem), aminoglycosides (amikacin/gentamicin/tobramycin), fluoroquinolones (ciprofloxacin), colistin

6. Serology

• Not routinely used for diagnosis
• Anti-elastase (anti-LasA, anti-LasB) antibodies may be detected in chronic CF infections
• Useful for monitoring chronic pulmonary infection in CF patients

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Treatment

General Principles

• Pseudomonas is intrinsically resistant to many antibiotics (due to restricted outer membrane permeability, efflux pumps)
• Monotherapy is generally ineffective and can rapidly select resistant mutants
• Combination therapy (aminoglycoside + anti-pseudomonal β-lactam) is the standard approach for serious infections

Drug Classes Active Against Pseudomonas

Recommended Regimens by Infection Type

Why Monotherapy Fails

• Intrinsic resistance: restricted porin permeability blocks antibiotic entry
• Efflux pumps (MexAB-OprM, MexXY-OprM) actively export antibiotics
• β-lactamase production (AmpC, OXA, MBL types)
• Biofilm formation reduces antibiotic penetration by 100-1000x

Prevention and Control

• Strict infection-control measures in hospitals: prevent contamination of sterile equipment
• Avoid unnecessary broad-spectrum antibiotic use (prevents selection of resistant strains)
• Adequate hand hygiene, sterilization of respiratory therapy equipment
• Maintain sterility of IV lines, urinary catheters
• For CF: inhaled tobramycin (TOBI) prophylaxis to slow respiratory deterioration

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Summary Table (Quick Recall for Exams)

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