.. nosa can be found on nearly every shower curtain and drain pipe around the world. Functions of Pseudomonas aeruginosa that were previously unknown have been identified, suggesting new avenues for drugs to treat serious lung infections caused by this bacterium. Researchers now have a better understanding of why Pseudomonas aeruginosa is naturally resistant to most antibiotics. As a result, they have new ideas on how to identify antibiotics that might circumvent some of the bacterium’s intrinsic drug resistance mechanisms. The bacterium was sequenced based on one particular organism, or isolate, that is the standard in laboratories.
Variations are now being examined that occur when the organism is taken from patients with cystic fibrosis. Scientists are looking for not only how Pseudomonas aeruginosa differs from patient to patient, but what happens to the organism inside the body. “We want to figure out what is different about those clinical isolates, and how these isolates change over time during chronic ingection” Olson, 142. With this information in hand, new windows of opportunity may arise, suggesting that certain biochemical pathways or proteins within Pseudomona aeruginosa are good targets for drug development. Pseudomonas aeruginosa is difficult to overcome with antibiotics even in patients with new infections. Over time, treatment becomes progressively more difficult; this is not unique to Pseudomonas aeruginosa.
Attempts to produce a vaccine for Pseudomonas aeruginosa have not resulted in a high level of protection against subsequent infections. Previous studies have focused on creating immunity against a single surface element of the bacterium. There is a study going on now that is testing the feasibility of using an oral dose of an intact but weakened or attenuated strain of Pseudomonas aeruginosa for vaccine development. This approach has been used in vaccine production in other diseases and has resulted in an immune response in the lung. Strains of Pseudomonas aeruginosa are being produced which must be supplied with certain amino acids for growth, and thus should be able to survive only under laboratory conditions. Plans are to feed these strains to mice to determine whether the bacteria can cause disease, how long the bacteria survive, and whether an immune response is generated in the lung. The long-term goal is to produce a safe vaccine for use in the individuals with cystic fibrosis.
Pseudomonas aeruginosa infection is also common among persons infected with HIV. Most of the patients who developed invasive Pseudomonas aeruginosa infections were severely immunocompromised, with a mean CD4+ cell count of 31/uL and a history of lung injury. These infections often occur at multiple sited, particularly the lungs and sinuses. Since the advent of the routine use of HAART (highly active antiretroviral therapy), there has been a striking decline in the incidence of invasive Pseudomonas aeruginosa disease. Scientists suggest that HAART may in fact restore humoral immunity. HIV positive adults often are plagued with severe pyrogenic infections that tend to recur.
In fact, recurrent bacterial pneumonia is considered an AIDS defining illness. Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella catarrhalis are the most frequently isolated pathogens. Pseudomonas aeruginosa infection is yet another complication of late stage HIV disease. Mortality from Pseudomonas aeruginosa infection in HIV positive patients is estimated at 22% to 36%. The literature reveals that neutropenia, indwelling catheters, and hospitalization may be associated with Pseudomonas aeruginosa infection, but traditional risk factors are not always present. Clinical records were reviewed of all patients with HIV infection seen at the outpatient clinic of the Hospital of Saint Raphael between January 1992 and January 1998 to identify patients who had invasive pseudomonal disease. Pseudomonas aeruginosa pneumonia was defined as the presence of a febrile (temperature greater than 38.3*C) respiratory illness, isolation of Pseudomonas aeruginosa as the sole pathogen from expectorated sputum, and evidence of infiltrate on chest radiograph. Bronchitis was defined as a productive cough.
Otitis media was defined as the presence of a bulging or inflamed tympanic membrane with purulent auditory canal drainage that grew Pseudomonas aeruginosa. Sinusitis was defined as a febrile illness, headache, sinus tenderness, and purulent nasal discharge that grew Pseudomonas aeruginosa. Bacteremia was defined as the isolation of Pseudomonas aeruginosa from one or more blood cultures from a patient with clinical signs of infection. The hospital microbiology laboratory processed all specimens. Blood samples were incubated in a Bac-T alert system. Expectorated sputum samples were inoculated onto blood MacConkey and chocolate agar, and nasal aspirates were inoculated onto chocolate plates. Antimicrobial susceptibilities were obtained using the Microscan walkaway system.
Medical records of patients who met the criteria for Pseudomonas aeruginosa pneumonia, sinusitis, and otitis media were reviewed. Paying close attention to the following variables: age, gender, race, self-reported risk of HIV acquisition, CD4+ cell count, previous opportunistic infections, antiviral therapy, use of Pneumocystic carinii pneumonia prophylaxis, prior pulmonary infection, signs and symptoms of disease on presentation, therapeutic interventions, and clinical outcome, including death. Specific antiviral regimens varied, most subjects were on a regimen that included one or two reverse transcriptase inhibitors. Of the two patients who developed invasive Pseudomonas aeruginosa infections following the routine use of HAART, one was receiving a three-drug regimen, including a protease inhibitor, and the other did not comply with his antiviral therapy. Pseudomonas aeruginosa is an important cause of recurrent, community-acquired sinopulmonary disease among HIV infected patients, even in the absence of traditional risk factors.
Several studies delineating the potential risks of pseudomonal infection in the HIV population have found corticosteroid use, recent antibiotic exposure, PCP prophylaxis with TMP-SMX, prior hospitalization, and neutropenia to be predictive of Pseudomonas aeruginosa infection. The profound immunosuppression inherent in advanced HIV disease may in fact be the most important risk factor for Pseudomonas aeruginosa infection. Patients with pseudomonal disease were severely immunocompromised and suffered from frequent opportunistic infections. Cell-mediated immunity is thought to play a vital role in defending against Pseudomonas aeruginosa infection. Therefore, it is not surprising that the loss of functionally active T cells that occurs with progressive HIV infection was an important predisposing factor for pseudomonal disease. Many patients with pseudomonal disease, including the two in whom infections developed hollowing the initiation of HAART, had suffered previous pulmonary infections.
This suggests that chronic lung damage resulting from recurrent bacterial pneumonias and other opportunistic infections may predispose a patient to subsequent pseudomonal disease. Recurrent bacterial lung infections, combined with defective humoral immunity, may contribute to the development of bronchiectasis in HIV infected patients. The destructive nature of Pseudomonas aeruginosa in particular may make patients vulnerable to bronchiectasis and lead to persistent bacterial colonization and relapsing pneumonia. Pseudomonas aeruginosa produces an elastase that destroys the Pis that are normally present in the bronchial tree and cleaves IgG, necessary for opsonization. In addition, Pseudomonas aeruginosa releases endotoxin and results in a polyclonal increase in immunoglobulins that are deposited as immune complexes, causing further lung damage.
Precisely how HAART affects this cascade of damage remains to be elucidated. Defective humoral immunity is another possible contributing factor in the development of Pseudomonas aeruginosa infections in patients with HIV. Although hypergammaglobulinemia occurs commonly in patients with HIV disease, it selectively involves IgG subclasses 1 and 3, with relative deficiencies of IgG2 and IgG4. Adequate opsonization of encapsulated organisms requires antibody to polysaccharide antigen, which consists primarily of IgG2. In addition, it has been shown that most HIV infected patients with Pseudomonas aeruginosa bacteria were unable to mount a specific IgG response to lipopolysaccharide immunotypes despite the presence of hypergammaglobulinemia.
Defective chemotaxis, abnormal neutrophil degranulation, and impaired antibody response to new antigens have all been seen in patients with AIDS. Pseudomonas aeruginosa pneumonia and sinusitis frequently occurs together in AIDS patients. In general, HIV infected patients are at increased risk for sinus infections, especially when theCD4+ cell count falls below 200/uL. In addition to the immunologic deficits associated with HIV infection, local factors may predispose the patient to sinus disease. Persistent bacterial colonization along with the loss of mucosal integrity from smoking or cocaine use may predispose a patient to recurrent bouts of sinusitis.
In addition, prior sinusitis and impaired sinus drainage, possibly from lymphoid hyperplasia, may be risk factors for recurrent disease. How HAART will affect the incidence of pseudomonal infections is still not clear. A correlation between viral load and risk of opportunistic infections has been established, and there has been a decline in AIDS related morbidity and mortality in patients treated with aggressive anti-viral regimens. Most of the observed changes in immune competence relate to cellular immunity rather then humoral immunity. Thus, based on experiments, there is an anticipation of a decline in the incidence of sinopulmonary disease caused by Pseudomonas aeruginosa. Prospective studies are necessary to determine whether the patients with newly diagnosed HIV infection who have pulmonary damage will develop pseudomonal disease and to better define the changing epidemiology, optimal treatment strategies, and the role of adjunctive immunotherapies.
Now that scientists have completed the genome sequence genetic map of Pseudomonas aeruginosa, it may lead to potential new treatments for patients with cystic fibrosis, patients with HIV, and others who develop this type of infection. This map of the genome provides scientists with a powerful tool that opens up new doors to develop innovative therapies that will make a difference in many lives. Medicine.