Pseudomonas

Pseudomonas is a non-lactose-fermenting, gram-negative bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas has a sweet, grape-like odor. The most clinically relevant species is Pseudomonas aeruginosa (P. aeruginosa), which has a wide array of clinical manifestations from benign diseases, such as swimmer’s ear and “hot tub” folliculitis, to disseminated bacteremia and osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis. Risk factors for infections include: neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia, cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis, asplenia Asplenia Asplenia is the absence of splenic tissue or function and can stem from several factors ranging from congenital to iatrogenic. There is a distinction between anatomic asplenia, which is due to the surgical removal of the spleen, and functional asplenia, which is due to a condition that leads to splenic atrophy, infarct, congestion, or infiltrative disease. Asplenia, burn injuries, and indwelling catheters/endotracheal intubation. Management is primarily with piperacillin/tazobactam.

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Classification

Gram negative bacteria classification flowchart

Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
Most bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

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General Characteristics

  • Gram-negative bacilli
  • Encapsulated
  • Motile: 1–3 motile flagella
  • Obligate aerobe
  • Oxidase positive
  • Catalase positive
  • Non-lactose fermenting
  • Produces a blue-green pigment: due to pyocyanin and fluorescein production
  • Produces a characteristic fruity, grape-like odor
  • Clinically relevant species: Pseudomonas aeruginosa (P. aeruginosa)
Pseudomonas aeruginosa bacteria

Photograph depicts the colonial growth pattern displayed by Pseudomonas aeruginosa bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview.

Image: “6688” by the CDC/Dr. Theo Hawkins. License: Public domain.

Pathogenesis

Reservoir and transmission

Reservoir: 

  • Ubiquitous in the environment
  • Moist reservoirs: 
    • Sinks
    • Respiratory and dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Overview and Types of Dialysis equipment

Transmission:

  • Person-to-person transmission from infected reservoirs

Risk factors

  • Neutropenia
  • Burn injuries
  • Asplenia
  • Cystic fibrosis
  • Endotracheal intubation
  • Chronic, indwelling catheters

Pathogenesis of P. aeruginosa 

Table: Virulence factors
Virulence factor Effect
Polysaccharide capsule
  • Antiphagocytic
  • Adherence to tracheal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
  • Aids in prolonged colonization/biofilm production
Pili
  • Adherence to respiratory epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
Phospholipase C
  • Degrades cell membranes
Exotoxin A
  • Ribosylates and inactivates EF-2, which causes cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death
Pyocyanin
  • Mediates tissue damage through production of reactive oxygen species
Type III secretion system
  • Facilitates direct delivery of toxins to host cell
In vivo biofilm formation
  • Allows organism to persist in airways of patients with cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
ꞵ-lactamase and efflux pumps
  • Contributes to multi-drug resistance
Mechanisms of pathogenesis pseudomonas aeruginosa

Mechanisms of pathogenesis of Pseudomonas aeruginosa

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Diseases Caused by P. aeruginosa 

Table: Diseases caused by P. aeruginosa
Type of condition Characteristics
Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract infection
  • Especially in patients with indwelling catheters
  • Common cause of nosocomial UTIs
Burn wound infections Associated with burn injuries, causing:
  • Vascular damage
  • Tissue necrosis
  • Bacteremia
  • Ear infections Otitis externa Otitis externa Otitis externa (also known as external otitis or swimmer's ear) is an infection of the external auditory canal that is most often caused by acute bacterial infection and is frequently associated with hot, humid weather and water exposure. Patients commonly present with ear pain, pruritus, discharge, and hearing loss. Otitis Externa:
    • Benign, but painful
    • Often associated with swimmers (“swimmer’s ear”)
    Malignant external otitis:
    • Pain, swelling, and purulent discharge from the external auditory canal
    • May lead to:
      • Cranial nerve damage
      • Bacteremia
      • Sepsis
    Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin infections Ecthyma gangrenosum:
    • Rapidly progressive, focal, black, necrotic skin lesions
    • Associated with neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia
    “Hot tub” folliculitis:
    • Infection in regions of apocrine sweat glands (external ear, areola, nipple)
    • Named as such due to the source of infection, which is often from pools/hot tubs
    Pulmonary infections
    • Causes nosocomial pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia and ventilator-associated pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Most common cause of chronic pulmonary infection in patients with cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
    Eye infections Occurs in contact lens wearers or minor eye trauma:
    • Corneal ulcers
    • Keratitis
    Disseminated infections Occurs in immunocompromised hosts:
    • Transplant patients
    • Neutropenic patients
    Osteomyelitis
    • Often in patients with IV drug use or diabetes 
    • Associated with puncture wounds
    Sites of pseudomonas infection

    Diagram of common sites of Pseudomonas infection

    Image by Lecturio.

    Antimicrobials

    Treatment

    • P. aeruginosa has varying resistance to antibiotics:
      • Multi-drug resistant: resistant to at least 1 agent in > 3 antibiotic categories
      • Extensively drug resistant: resistant to at least 1 agent in all but 2 antibiotic categories
      • Pan-drug resistant: resistant to all antibiotic categories
    • Antibiotic choice is tailored to local resistance patterns (combination antibiotic therapy): 
      • 1st line: 
        • Combination penicillin/beta-lactamase inhibitors (piperacillin/tazobactam)
        • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with "cef-" or "ceph-." Cephalosporins (ceftazidime)
        • Monobactam ( aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam)
        • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones (ciprofloxacin) (only oral)
        • Carbapenems (meropenem)
      • Multi-drug-resistant strains are treated with newly developed antibiotics:
        • Beta-lactam-beta-lactamase inhibitor combinations (ceftolozane/tazobactam) 
        • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with "cef-" or "ceph-." Cephalosporins (cefiderocol)
        • Carbapenem Carbapenem The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam-beta-lactamase combination (imipenem-cilastatin-relebactam)
        • Polymyxins
      • Adjunct antibiotics: aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides (tobramycin, gentamicin, amikacin)

    Prevention

    • Hygiene within the hospital:
      • Use of appropriate sterile technique
      • Careful cleaning of communal sinks and showers
    • Periodic monitoring, replacement, and cleaning of:
      • Respiratory support equipment
      • Intravenous (IV) lines (especially long-term lines)
      • Catheters 

    Mnemonic

    To help remember the many clinically relevant facts about Pseudomonas, use the mnemonic “PSEUDOMONAS”:

    • Pneumonia, pyocyanin
    • Sepsis
    • Ecthyma gangrenosum
    • UTIs
    • Diabetes, drug use
    • Osteomyelitis 
    • Mucoid, polysaccharide capsule
    • Otitis externa (“swimmer’s ear”)
    • Nosocomial infections (catheters, endotracheal tubes)
    • Exotoxin A
    • Skin infections (“hot tub” folliculitis and burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns)

    References

    1. Riedel, S., & Hobden, J.A. (2019). In Riedel S, Morse SA, et al (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed.)
    2. Hohmann, E.L., & Portnoy, D.A. (2018). In Jameson JL, et al (Eds.), Harrison’s Principles of Internal Medicine (20th ed. Vol 2, pp. 2676–2683).
    3. Baron, S. (1996). Medical microbiology. University of Texas Medical Branch at Galveston. https://www.ncbi.nlm.nih.gov/books/NBK7627/

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