Diseases
P. aeruginosa causes infections (e.g., sepsis, pneumonia, and urinary tract infections) primarily in patients with extensive anti biotic exposure and underlying chronic illnesses. It also causes chronic lower respiratory tract infections in patients with cystic fibrosis, wound infections (cellulitis) in burn patients (Figure 1), and malignant otitis externa in diabetic patients. It is the a common cause of ventilator-associated pneumonia.
Fig1. Cellulitis caused by Pseudomonas aeruginosa. Note the blue-green color of the pus in the burn wound infection. (Used with permission from Dr. Robert L. Sheridan.)
Burkholderia cepacia and Stenotrophomonas maltophilia also cause these infections, but much less frequently. Burkholderia pseudomallei, the cause of melioidosis.
Important Properties
Pseudomonads are gram-negative rods that resemble the members of the Enterobacteriaceae but differ in that they are strict aerobes (i.e., they derive their energy only by oxidation of sugars rather than by fermentation). Because they do not ferment glucose, they are called nonfermenters, in contrast to the members of the Enterobacteriaceae, which do ferment glucose. Oxidation involves electron transport by cytochrome c (i.e., they are oxidase-positive).
Pseudomonads are able to grow in water containing only traces of nutrients (e.g., tap water), and this favors their persistence in the hospital environment. P. aeruginosa and B. cepacia have a remarkable ability to withstand disinfectants; this accounts in part for their role in hospital-acquired infections. They have been found growing in hexachlorophene-containing soap solutions, in antiseptics, and in detergents.
P. aeruginosa produces two pigments useful in clinical and laboratory diagnosis: (1) pyocyanin, which can color the pus in a wound blue and (2) pyoverdin (fluorescein), a yellow green pigment that fluoresces under ultraviolet light, a property that can be used in the early detection of skin infection in burn patients. In the laboratory, these pigments diffuse into the agar, imparting a blue-green color that is useful in identification. P aeruginosa is the only species of Pseudomonas that synthesizes pyocyanin (Figure 2).
Fig2. Pseudomonas aeruginosa—blue-green pigment. Blue-green pigment (pyocyanin) produced by P. aeruginosa diffuses into the agar. (Used with permission from Professor Shirley Lowe, University of California, San Francisco School of Medicine.)
Strains of P. aeruginosa isolated from cystic fibrosis patients have a prominent slime layer (glycocalyx), which gives their colonies a very mucoid appearance. The slime layer mediates adherence of the organism to mucous membranes of the respiratory tract and prevents antibody from binding to the organism.
Pathogenesis & Epidemiology
P. aeruginosa is found chiefly in soil and water, although approximately 10% of people carry it in the normal flora of the colon. It is found on the skin in moist areas and can colonize the upper respiratory tract of hospitalized patients. Its ability to grow in simple aqueous solutions has resulted in contamination of respiratory therapy and anesthesia equipment, intravenous fluids, and even distilled water.
P. aeruginosa is primarily an opportunistic pathogen that causes infections in hospitalized patients (e.g., those with extensive burns), in whom the skin host defenses are destroyed; in those with chronic respiratory disease (e.g., cystic fibrosis), in whom the normal clearance mechanisms are impaired; in those who are immunosuppressed; in those with neutrophil counts of less than 500/μL; and in those with indwelling catheters. It causes 10% to 20% of hospital-acquired infections and, in many hospitals, is the most common cause of gram-negative nosocomial pneumonia, especially ventilator-associated pneumonia.
Pathogenesis is based on multiple virulence factors: endo toxin, exotoxins, and enzymes. Its endotoxin, like that of other gram-negative bacteria, causes the symptoms of sepsis and septic shock. The best known of the exotoxins is exotoxin A, which causes tissue necrosis. It inhibits eukaryotic protein synthesis by the same mechanism as diphtheria exotoxin, namely, ADP ribosylation of elongation factor-2. It also produces enzymes, such as elastase and proteases, that are histotoxic and facilitate invasion of the organism into the bloodstream. Pyocyanin dam ages the cilia and mucosal cells of the respiratory tract.
Strains of P. aeruginosa that have a “type III secretion system” are significantly more virulent than those that do not. This secretion system transfers the exotoxin from the bacterium directly into the adjacent human cell, which allows the toxin to avoid neutralizing antibody. Type III secretion systems are mediated by transport pumps in the bacterial cell membrane. Of the four exoenzymes known to be transported by this secretion system, Exo S is the one most clearly associated with virulence. Exo S has several modes of action, the most important of which is ADP-ribosylation of a Ras protein, leading to damage to the cytoskeleton.
Clinical Findings
P. aeruginosa can cause infections virtually anywhere in the body, but urinary tract infections, pneumonia (especially in cystic fibrosis patients), and wound infections (especially burns) (see Figure 1) predominate. It is an important cause of hospital-acquired pneumonia, especially in those undergoing mechanical ventilation (ventilator-associated pneumonia). From these sites, the organism can enter the blood, causing sepsis. The bacteria can spread to the skin, where they cause black, necrotic lesions called ecthyma gangrenosum (Figure 3). Patients with P. aeruginosa sepsis have a mortality rate of greater than 50%. It is an important cause of endocarditis in intravenous drug users.
Fig3. Ecthyma gangrenosum. Necrotic skin lesion caused by Pseudomonas aeruginosa. (Reproduced with permission from Wolff K, Johnson R, Saavedra A: Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 8th ed. New York, NY: McGraw Hill; 2017.)
Severe external otitis (malignant otitis externa) and other skin lesions (e.g., folliculitis) occur in users of swimming pools and hot tubs (hot tub folliculitis) in which the chlorination is inadequate. P. aeruginosa is the most common cause of osteo myelitis of the foot in those who sustain puncture wounds through the soles of gym shoes. Corneal infections caused by P. aeruginosa are seen in contact lens users.
In addition to P. aeruginosa, Stenotrophomonas and Burkholderia also cause chronic lung infections in patients with cystic fibrosis.
Laboratory Diagnosis
P. aeruginosa grows as non–lactose-fermenting (colorless) colonies on MacConkey’s or EMB agar. It is oxidase-positive. A typical metallic sheen of the growth on TSI agar, coupled with the blue-green pigment on ordinary nutrient agar (see Figure 2), and a fruity aroma are sufficient to make a presumptive diagnosis. The diagnosis is confirmed by biochemical reactions. Identification for epidemiologic purposes is done by bacteriophage or pyocin[1] typing.
Treatment
Because P. aeruginosa is resistant to many antibiotics, treatment must be tailored to the sensitivity of each isolate and monitored frequently; resistant strains can emerge during therapy. The treatments of choice include an antipseudomonal penicillin (e.g., piperacillin/tazobactam), a cephalosporin with anti-pseudomonal activity like ceftazidime or cefepime or a carbapenem like imipenem or meropenem (ertapenem is not active against pseudomonas).
Prevention
Prevention of P. aeruginosa infections involves keeping neutrophil counts above 500/μL, removing indwelling catheters promptly, taking special care of burned skin, and taking other similar measures to limit infection in patients with reduced host defenses.
[1] A pyocin is a type of bacteriocin produced by P. aeruginosa. Different strains produce various pyocins, which can serve to distinguish the organisms.
