Pseudomonas Aeruginosa

Pseudomonas aeruginosa
Research Paper
Julie Johnson
Pseudomonas aeruginosa is a versatile gram negative bacterium that grows in soil, marshes, and coastal marine habitats, as well as on plant and animal tissues. People with cystic fibrosis, burn victims, individuals with cancer, and persons infected with HIV are particularly at risk of disease resulting from Pseudomonas aeruginosa.
Unlike many environmental bacteria, Pseudomonas aeruginosa has a remarkable capacity to cause disease in susceptible hosts. It has the ability to adapt to and thrive in many ecological niches, from water and soil to plant and animal tissues. The bacterium is capable of utilizing a wide range of organic compounds as food sources, thus giving it an exceptional ability to colonize ecological niches where nutrients are limited. Pseudomonas aeruginosa can produce a number of toxic proteins, which not only cause extensive tissue damage, but also interfere with the human immune systems defense mechanisms. These proteins range from potent toxins that enter and kill host cells at or near the site of colonization to degradative enzymes that permanently disrupt the cell membranes and connective tissues in various organs.
In people with cystic fibrosis the most serious complication is respiratory tract infection by the ubiquitous bacterium Pseudomonas aeruginosa. CF is one of the most common fatal genetic disorders in the United States, affecting about 30,000 individuals. A comparable number of people in Europe also have CF. It is most prevalent in the Caucasian population, occurring in one of every 3,300 live births. The gene involved in cystic fibrosis was identified in 1989. Located on human chromosome 7, it codes for a protein called the cystic fibrosis transmembrane conductance regulator (CFTR). This protein, normally produced in a number of tissues throughout the body, regulates the movement of salt and water in and out of these cells. The abnormality in the CFTR gene alters the CFTR protein in people with cystic fibrosis. As a result, one hallmark of CF is the presence of a thick mucus secretion which clogs the bronchial tubes in the lungs and plugs the exit passages from pancreas and intestines, leading to loss of function of these organs.
Progressive lung disease is the predominant cause of illness and death in people with CF. Mucus blocks the airway passages and results in a predisposition toward chronic bacterial infections. Although the genetic defect underlying CF has been characterized, exactly how and why individuals become infected with Pseudomonas is unknown. The lungs of most children with CF become colonized by Pseudomonas aeruginosa before their 10th birthday. Chronic infection with these bacteria reduces an individuals quality of life, causing acute symptoms of cough, sputum production, and inflammation, which causes repeated exacerbations or episodes of intense breathing problems. Eventually leading to scarring and destruction of lung tissue and, ultimately, death. While it is clear that antibiotic therapy directed against these organisms lengthens the life span of individuals with CF, increasing antibiotic resistance develops. Although antibiotics can decrease the frequency and duration of these attacks, the bacterium establishes a permanent residence and can never be completely eliminated from the lungs.
Management of cystic fibrosis lung disease requires a multipronged approach. Outpatient management of pulmonary exacerbation usually includes a combination of 2 IV antipseudomonal antibiotics (an aminoglycoside plus a beta-lactam), appropriate antimicrobial treatment, effective airway clearance, optimization of nutritional status, and anti-inflammatory therapies. Additionally, prevention of respiratory viral disease and avoidance of exposure to irritants, such as smoke, is recommended. Usual duration of therapy is 14 to 21 days, and clinical response is assessed by physical exam, pulmonary function tests, nutritional status, and exercise tolerance. Microbial eradication is not a therapeudic end point. Choice of antibiotics should be based on culture and sensitivity of the sputum. Emergence of antibiotic-resistant species, such as Pseudomonas aeruginosa, has required close monitoring of antibiotic susceptibility patterns and strict infection-control policies.
Administration of chronic intermittent inhaled antipseudomonal therapy (tobramycin solution for inhalation), over a 6 month period was shown to improve FEV by 11.9%, decrease the bacterial density, and reduce hospitalization in CF patients chronically infected with Pseudomonas aeruginosa. Following 92 weeks of therapy with inhaled tobramycin, the mean % change in FEV was 4.7% above baseline. There was no increase in the utilization of antipseudomonal therapy despite an increase in MIC at the end of 12 treatment cycles. Decreases in Pseudomonas aeruginosa tobramycin susceptibility