Pseudomonas aeruginosa: characteristics, pathogenesis, and clinical significance

Psuedomonas Aeruginosa

Pseudomonas aeruginosa

Epidemiology

The Gram-negative, motile, rod-shaped bacterium Pseudomonas aeruginosa is an opportunistic killer that takes advantage of people suffering from medical problems (Van Delden and Iglewski, 1998).For this reason, P. aeruginosa is one of the most common nosocomial infection that occurs in hospitals. P. aeruginosa is responsible for causing 16% of pneumonia cases, 12% of urinary tract infections, 10% of bloodstream infections, and 8% of surgical infections due to hospital care. Patients who are immune-compromised are also susceptible to P. aeruginosa infections, such as patients undergoing chemotherapy, suffering from HIV / AIDS, recovering in burn units, and suffering from cystic fibrosis. With death rates ranging from 30 to 60% for these patients, P. aeruginosa is considered to be a significant threat to patient health.

Ecology

P. aeruginosa can switch between a free-swimming planktonic form and colonies enclosed within slime-protected biofilms attached to surfaces (Baltch and Smith, 1994, p. 1). The planktonic form is susceptible to all forms of bactericidal agents, including antibiotics, but when encased within the biofilm (mucoid form) the bacterium can survive many of these agents, in addition to environmental predators.

P. aeruginosa is almost ubiquitous in the environment, but pathogenic concentrations can be found wherever humans and livestock are found (Botzenhart and Doring, 1993, p. 3-6). Water sources are particularly susceptible to contamination, including plumbing fixtures, swimming pools, and saunas. It can be found in bodies of water contaminated with human waste, including ocean bays, rivers, and lakes. Nursing homes, hospitals, intensive care units, medical clinics, and dental clinics are frequently found to be reservoirs of P. aeruginosa.

Surprisingly though, healthy humans are not considered to be a natural habitat for P. aeruginosa. When the fecal matter from healthy people was examined, only 1.2% to 2.3% contained this bacterium. In contrast, P. aeruginosa is able to grow on stainless steel or in highly pure water. This suggests P. aeruginosa cannot withstand an assault from a healthy immune system.

Pathogenesis

For P. aeruginosa to cause disease, the normal barriers to entry must be compromised (Van Delden and Iglewski, 1998). A compromised immune system, a break in an epithelial barrier due to trauma, disease, or surgery, or the insertion of a medical device like a catheter, can create an opportunity for colonization by P. aeruginosa.

Once colonized, the bacterium will attach to surfaces through adhesion molecules (Van Delden and Iglewski, 1998). This can happen through type 4 pili, through non-pilus mechanisms which are not well-known, or through the adhesin properties of the flagella structure. The attachment to epithelia surfaces is considered irreversible.

The planktonic form of P. aeruginosa is generally susceptible to first line antibiotic treatments, so this course of disease, though acute, is curable once diagnosed (Hurley, Camara, and Smyth, 2012). The disease course will vary depending on the health condition of the person exposed and the concentration of bacteria, since healthy individuals are almost invariably immune to the planktonic form of P. aeruginosa and biofilms cannot form. However, established biofilms are generally considered resistant to all antibiotics and even hydrogen peroxide. When biofilms are found to be contaminating inserted medical devices, such as catheters, they must be scraped off.

Once attached to an epithelial surface, the bacterium begins to produce small signaling molecules (Hurley, Camara, and Smyth, 2012). If enough bacteria have attached in the same location, the concentration of these molecules become sufficient to turn on genes producing virulence factors. This sensing process is called quorum sensing. The virulence factors are responsible for causing the disease and the most common are exotoxin A, exoenzyme S, phospholipas C, rhamnolipid, and a number of proteases. The result is the local destruction of tissue and immune suppression (Van Delden and Iglewski, 1998).

There is also considerable phenotypic variation between P. aeruginosa strains, resulting in considerable variability in susceptibility to medical interventions (Hurley, Camara, and Smyth, 2012). P. aeruginosa is also capable of rapid adaptation, including the development antibiotic resistance within the same individual. When encased in a biofilm, the metabolic activity can slow to the point that even if antibiotics penetrate, a viable inner core of bacteria remain that can resume normal metabolic activity once the antibiotic treatment has ceased. In other words, P. aeruginosa is capable of entering a state equivalent to mammalian hibernation in the presence of bactericidal agents and reemerging once the threat has passed.

Signs and Symptoms

The development of an acute P. aeruginosa infection results in signs and symptoms similar to infections with other gram negative bacteria (Baltch and Smith, 1994, p. 101-104, 137-138). Most patients will present with a moderate to high fever and 50% will be hypotensive. Skin manifestations may be present and include papules, blisters, diffuse rash, and ecthyma gangresnosum (flat, ulcerating pustules). Patients may appear sleepy and confused, sweating, agitated, or weak. It is important to note, however, that symptoms will vary depending on the tissues and organs primarily affected. For example, patients suffering from infective endocarditis will present with leukocytosis, anemia, thrombocytopenia, and azotemia, in 40%, 60%, 30%, and 40-50% of patients, respectively, and two thirds of these patients will have an abnormal X-ray.

The most common locations for P. aeruginosa infections are the blood, heart, lungs, urinary tract, central nervous system, bones and joints, skin and soft tissues, eyes, ears, and gut (Baltch and Smith, 1994). The lungs are particularly susceptible in patients suffering from cystic fibrosis.

Diagnosis

A definitive diagnosis of a P. aeruginosa infection depends on the results of laboratory tests (Baltch and Smith, 1994, p. 104). For example, if an adult patient undergoing chemotherapy for colon cancer presents with a fever and chills, and bacteremia is suspected, then blood samples are cultured. Preferably, two to three blood samples, separated by about an hour, are taken before the patient is started on antibiotics (Vandepitte et al., 2003, p. 20-23). If the patient is already on antibiotics, the anticoagulant sodium polyanethol sulfonate can be added to the blood sample. The blood sample, typically 10 ml, is then diluted with 100 ml of blood broth to dilute any antibiotics and phagocytic immune cells. This is added to culture bottle and incubated for 7 or more days.

If growth is observed, then a sample is taken and examined under a microscope and tested with a Gram stain (Vandepitte et al., 2003, p. 23-25). Gram-negative, rod shaped microorganisms, such as P. aeruginosa (Figure 1) would be streaked onto blood agar, MacConkey agar, Kligler iron agar, motility indole-urease (MIU) medium, and Simmons citrate agar. P. aeruginosa should grow well on blood agar. Positive identification begins by picking a colony and culturing it on cetrimide agar supplemented with nalidixic acid (Hawkey and Kerr, 2004, p. 338). This growth media is selective for P. aeruginosa. Positive cultures are blue/green under normal light, or rarely pink/maroon. Under ultraviolet light, the cultures will fluoresce yellow. The initial identification of the species by culture is usually confirmed through one or more typing methods, which can distinguish between different strains of P. aeruginosa (Botzenhart and Doring, 1993, p. 8). The most common typing method for P. aeruginosa is serotyping, which involves the use of antisera to identify different strains of P. aeruginosa (Hawkey and Kerr, 2004, p. 344-345).