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PubMedDate not supplied

Pseudomonas respiratory infection in cystic fibrosis: a possible defect in opsonic IgG antibody?

Chronic Pseudomonas aeruginosa infections of the respiratory tract of people with cystic fibrosis (CF) usually are impossible to eradicate and greatly influence their health and longevity. General mechanisms of host defense are not impaired in this disease, except that serum does not support optimal phagocytosis of pseudomonas bacteria by alveolar macrophages and lung ciliary clearance is diminished, perhaps because of the accumulation of tenacious, purulent secretions in bronchiectatic airways and not by a defect in cilia structure or inhibitors of ciliary function. To investigate the defect in phagocytosis, we postulated that opsonic antibody might not be functioning well. Samples of purified IgG antibody against the typical strain of mucoid pseudomonas were prepared on immunoadsorbents, using CF sera and normal sera from volunteers previously immunized with a pseudomonas vaccine. CF IgG opsonin was found to agglutinate and coat well pseudomonas, but not to adhere or attach well to the surface of human alveolar macrophages, hence a defect in the function of the Fc portion of IgG was noted. In extending this analysis to CF lung secretions obtained by bronchoalveolar lavage, IgG antibody was purified exactly as from serum. Although this IgG had good agglutinating activity, much of it was fragmented (5 S size) and found to lack its Fc portion. It was evident that proteolytic enzymes in the purulent lavage secretions could cleave IgG. This activity was localized to a metallo-proteinase elaborated by the mucoid strain of pseudomonas. Thus, CF IgG may have reduced opsonic antibody function because of a molecular change in the Fc portion; this defect is magnified in the infected CF lung where a bacterial protease can actually fragment IgG and further impair its opsonic activity which is already marginal.

Cystic Fibrosis↗
PubMed1976

Effects of zinc sulfate on Pseudomonas aeruginosa infections and protease in rabbit corneas.

Zinc ions were shown to reversibly inhibit the activity of Pseudomonas protease. Zinc sulfate was more effective topically in preventing corneal perforations by this enzyme than either cysteine or edetate disodium (Na2 EDTA). The reversibility of the enzyme inactivation by zinc sulfate and its efficacy in preventing perforations were used to estimate the duration of the enzyme activity in the cornea. The protease was found to retain its activity in the rabbit cornea for up to two days after intrastromal injection. The extent of corneal destruction in rabbit corneas infected with live Pseudomonas cells was significantly greater in eyes treated with zinc sulfate than in controls, precluding its use in a clinical setting.

Animals↗
PubMed1999

Efficacy of locally delivered polyclonal immunoglobulin against Pseudomonas aeruginosa infection in a murine burn wound model.

The leading cause of morbidity and mortality in severe burn wound patients is infection. Treatment of burn wound infection is complicated by the emergence of antibiotic resistant organisms. A potential therapeutic alternative to antibiotic drugs is the local administration of polyclonal antibodies, termed passive local immunotherapy (PLI), directly to the burned tissue. A mouse burn wound infection model to simulate full thickness burn wound infection was used to evaluate the efficacy of passive local immunotherapy as a viable prophylactic or therapeutic agent. Pooled human immunoglobulins (IgG), delivered locally to the site of infection, are shown to be more effective at preventing fatal burn wound sepsis than treatment by intravenous infusion of IgG. A single 10 mg dose of human IgG administered locally to the burned, infected tissue site, either 24 hours prior to bacterial challenge, or within 3 hours after bacterial challenge, enhanced animal survival significantly (P < 0.001 and P < 0.05 respectively) compared to control animals. In addition, reduced levels of bacteria were found in local and systemic tissues of IgG-treated mice compared to control mice (P < 0.05). These data support the local use of polyclonal immunoglobulin preparations as an efficacious and cost effective means to prevent and treat burn wound infections.

Animals↗
PubMed2000

[Pretreatment of acid-induced lung injury with specific neutrophil elastase inhibitor ONO-5046 did not exasperate the subsequent bacterial lung infection by Pseudomonas aeruginosa].

Patients with acid lung injuries are at high risk for bacterial pulmonary infections which commonly occur several days after the acid aspiration. We reported that a specific neutrophil elastase inhibitor ONO-5046 inhibited the multi-organ injury caused by acid-instillation into the lung. In this study, we evaluated the effect of ONO-5046 on lung infection by Pseudomonas aeruginosa (PAO-1:Ps.) following acid-induced lung injury in rat lungs. Animals received 0.2 ml of hydrochloric acid (pH = 1) into the right lungs. Pretreated animals were administered ONO-5046 (30 mg.kg-1) i.v. 15 min. before acid instillation. Other groups received vehicle (saline). Twenty four hours later, they were instilled with 0.1 ml of Ps. 1 x 10(8) cfu into the left lungs. Four hours after bacterial challenge, the animals were deeply anesthetized and killed. Bronchoalveolar lavage was done on each lung separately to evaluate neutrophil elastase activity, neutrophil number and protein permeability of lung endothelium and epithelium. The numbers of Ps. in the lungs were measured. In the Ps.-instilled lung, the number of Ps. or the protein permeability was not increased with ONO-5046 pretreatment compared with those in the untreated group. Pretreatment inhibited the exasperation of the protein permeability indirectly caused by Ps. infection in the acid-instilled lung. It was indicated that ONO-5046 could inhibit the indirect lung injury caused by acid-instillation into the lung without aggravating the subsequent bacterial infection.

Animals↗
PubMedDate not supplied

Current approach to prevention and treatment of Pseudomonas aeruginosa infections in burned patients.

The extensively burned or severely injured patient is at increased risk of wound infection as well as of infection of other organs as a result of various degrees of impairment of host defense mechanisms. The incidence of burn wound and other infections increases as the severity of injury increases. The ease with which gram-negative, opportunistic organisms, especially Pseudomonas aeruginosa of either endogenous or exogenous origin, can colonize and invade the immunosuppressed patient demands an active infection-surveillance program. Topical therapy for burn wounds with any of three available agents has significantly reduced the occurrence of invasive pseudomonas burn-wound sepsis, but none of the agents sterilize the burn wound, and the microbial flora of the burns of any given patient may escape from control and invade viable tissue. Clinical identification and biopsy confirmation of invasive burn-wound sepsis necessitates changes in both wound and general care, with surgical and antibiotic treatment guided by the extent and depth of wound invasion. Immunologic prophylaxis and treatment of pseudomonas infections, although attractive, remain of unverified clinical effectiveness. Effective treatment of pseudomonas septicemia secondary to invasive burn-wound sepsis and of pseudomonas infections in other organs is dependent on early diagnosis, appropriate antibiotic therapy guided by sensitivity testing, and adequate surgical intervention when required.

Animals↗