What is the management of Pseudomonas aeruginosa infections?

Pseudomonas aeruginosa: Essential Information for NEET PG

Microbiological Characteristics

Pseudomonas aeruginosa is a Gram-negative, aerobic, rod-shaped bacterium that is ubiquitous in the environment, particularly in water reservoirs. 1

• It is an opportunistic pathogen that rarely colonizes healthy individuals transiently 1
• The organism possesses a large genome with impressive genetic flexibility, allowing it to survive in diverse environments 2
• It grows well on standard laboratory media including 5% sheep blood agar and chocolate agar 1
• Selective media such as cetrimide agar facilitates isolation from other bacterial species 1
• Plates are incubated at 35°C in 5% CO₂ atmosphere for 24 hours 1
• Identification is based on characteristic colony morphology and standard microbiological methods 1

Clinical Significance and High-Risk Populations

P. aeruginosa is one of the most important healthcare-associated pathogens causing significant morbidity and mortality, particularly in immunocompromised patients. 3

Major Risk Groups:

• Cystic fibrosis patients - P. aeruginosa is the most frequent pathogen isolated, with 29.8% of patients aged 2-5 years and 81.3% aged 26-30 years infected 1
• Patients with severe burns 1
• Cancer patients, especially those with neutropenia 4
• Patients with chronic obstructive pulmonary disease (COPD), particularly those with FEV₁ <30% 1
• Patients requiring mechanical ventilation 1
• Immunocompromised hosts including those with paraplegia 1

Risk Factors for P. aeruginosa Infection

P. aeruginosa should be considered when at least two of the following risk factors are present: 1

1. Recent hospitalization 1
2. Frequent antibiotic use (>4 courses per year) or recent antibiotic administration within the last 3 months 1
3. Severe underlying disease (FEV₁ <30-35% in COPD patients) 1
4. Oral corticosteroid use (>10 mg prednisolone daily in the last 2 weeks) 1
5. Previous isolation of P. aeruginosa or known colonization 1

Common Clinical Manifestations

Healthcare-Associated Infections:

• Nosocomial pneumonia - particularly in ventilated patients 5
• Bloodstream infections - may present with ecthyma gangrenosum (pathognomonic skin lesions) 6
• Urinary tract infections - especially in catheterized patients 7
• Burn wound infections - requiring specialized multidisciplinary management 6

Community-Acquired Infections:

• Hot tub folliculitis - from contaminated water exposure 6
• External otitis (swimmer's ear) 6
• Green nail syndrome 6
• Toe web infections 6
• Skin and soft tissue infections - particularly in diabetic and immunocompromised patients 6

Virulence Factors (High-Yield for Exams)

P. aeruginosa produces multiple virulence factors that enable tissue damage and immune evasion: 3, 8

• Lipopolysaccharide (LPS) - endotoxin component
• Quorum sensing systems - coordinate virulence gene expression
• Six type secretion systems - deliver toxins into host cells
• Biofilm formation - protects from antibiotics and immune clearance 8
• Exotoxin A - inhibits protein synthesis
• Pyocyanin - blue-green pigment causing oxidative damage 8
• Proteases and elastases - tissue destruction
• Alginate production - mucoid phenotype in chronic infections 1
• Pili and flagella - motility and adherence 8

Antibiotic Resistance Patterns

P. aeruginosa has high intrinsic resistance and readily develops acquired resistance during treatment, making it a major therapeutic challenge. 1

Resistance Mechanisms:

• Intrinsic resistance to multiple antibiotic classes 2
• Acquired resistance develops rapidly, especially to carbapenems 7
• Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains are increasingly common 1
• Difficult-to-treat resistance (DTR-PA) defined as non-susceptibility to all first-line agents including ceftazidime, cefepime, piperacillin-tazobactam, aztreonam, carbapenems, and fluoroquinolones 1

First-Line Antibiotic Treatment

For Susceptible Strains:

Piperacillin-tazobactam is the preferred first-line agent for P. aeruginosa susceptible to standard antibiotics. 9, 5

• Standard dosing: 3.375-4.5g IV every 6 hours 9, 5
• For nosocomial pneumonia: 4.5g IV every 6 hours plus an aminoglycoside 5
• Treatment duration typically 7-14 days 5

Alternative First-Line Options:

• Ceftazidime 2g IV every 8 hours - third-generation cephalosporin with antipseudomonal activity 9
• Cefepime 2g IV every 8-12 hours - fourth-generation cephalosporin 9
• Carbapenems (imipenem, meropenem, doripenem) - but NOT ertapenem which lacks antipseudomonal activity 9
• Fluoroquinolones (ciprofloxacin or levofloxacin 750mg) - particularly for combination therapy 9, 7

Treatment of Difficult-to-Treat Resistant (DTR-PA) Strains

For invasive infections caused by DTR-PA, novel β-lactam/β-lactamase inhibitor combinations are the first-line options. 1

Preferred Agents:

• Ceftolozane-tazobactam 1.5-3g IV every 8 hours 1, 9
• Ceftazidime-avibactam 2.5g IV every 8 hours 1, 9

Alternative Options:

• Imipenem-cilastatin-relebactam 1.25g IV every 6 hours 1, 9
• Cefiderocol - novel siderophore cephalosporin 1
• Colistin-based therapy - reserved for extensively resistant strains 1

Combination Therapy Considerations

Combination therapy should not be routine but may be considered on a case-by-case basis, especially in severe infections or suspected resistant strains. 1, 9

• For nosocomial pneumonia with P. aeruginosa risk factors: antipseudomonal β-lactam PLUS either aminoglycoside or fluoroquinolone 9, 5
• Fosfomycin as companion agent may be considered in combination regimens 1
• Monotherapy with highly active β-lactam is generally preferred for susceptible isolates 1, 9
• Aminoglycoside should be continued if P. aeruginosa is isolated from nosocomial pneumonia patients 5

Infection Control Measures

Strict infection control is essential to prevent transmission in healthcare settings. 1

Key Interventions:

• Hand hygiene with alcohol-based hand rub before and after all patient contacts 1
• Patient isolation in single rooms for colonized/infected patients 1
• Cohorting of patients and staff with same MDR strains 1
• Environmental cleaning and disinfection of surfaces, medical equipment, nebulizers 1
• Decontamination of water reservoirs including sinks, toilets, dental tubing 1
• Active surveillance cultures at hospital admission followed by contact precautions 1
• Separation of CF patients with and without P. aeruginosa to limit cross-infection 1

Important Clinical Pearls for NEET PG

• Small colony variants may only grow after 48 hours and can be overlooked in routine diagnostics 1
• Different morphotypes (mucoid, smooth, rough) from a single patient usually belong to a single genotype 1
• Serological tests (ELISA, RIA) help distinguish early colonization from chronic infection in non-expectorating patients 1
• Strain changes of H. influenzae, S. pneumoniae, and M. catarrhalis (but NOT P. aeruginosa) are associated with COPD exacerbations 1
• Prolonged or continuous infusions of β-lactams may improve outcomes in critically ill patients 9
• Ertapenem lacks antipseudomonal activity and should never be used for P. aeruginosa 9
• Resistance can develop rapidly during treatment, particularly to carbapenems and fluoroquinolones 7, 2