James E. Pennington

Pseudomonas pneumonia: A retrospective study of 36 cases

Abstract The clinical course in 36 cases of Pseudomonas pneumonia collected over a 15 year period (1956 to 1970) at the Clinical Center of the National Institutes of Health were reviewed to identify factors which increased the risk of infection and affected prognosis. In all cases, the patients had a serious underlying disease which predisposed to infection, and the majority had neoplastic diseases, particularly acute leukemia; cardiac or pulmonary diseases were less frequent. Pseudomonas related mortality was 81 per cent and was not influenced by type of antibiotic therapy or by the year of occurrence. Many patients were neutropenic, usually subsequent to cytotoxic chemotherapy, and frequently had been treated with steroids or antibiotics just prior to the development of pneumonia. Adequate numbers of circulating granulocytes were essential to survival. No patient with a positive blood culture survived. Possibilities for new means of prevention and treatment of Pseudomonas pneumonia are discussed.

USE OF A PSEUDOMONAS AERUGINOSA VACCINE IN PATIENTS WITH ACUTE LEUKEMIA AND CYSTIC FIBROSIS

A heptavalent lipopolysaccharide Pseudomonas vaccine was evaluated in 22 patients with acute leukemia and 12 patients with cystic fibrosis during an 18 month interval at the Clinical Center of the National Institutes of Health. Of the 34 patients, 32 had an excellent serum hemagglutinating (HA) antibody response to immunization. In comparison to the patients with cystic fibrosis, the patients with leukemia had a smaller HA antibody response, which lasted a shorter period of time, and also experienced greater toxicity from the vaccine. The mixing of adrenal corticosteroids with vaccine greatly decreased side reactions among the patients with leukemia without significantly inhibiting antibody production. Previous antineoplastic chemotherapy had little influence on antibody response in patients with leukemia, with the exception of methortrexate. Vaccinated patients with leukemia had 1 Pseudomonas infection of 14 bacterial or fungal infections, whereas 2 pseudomonas infections of 5 bacterial or fungal infections occurred in a control group of 20 patients with acute leukemia. Of the 12 patients with cystic fibrosis, 4 had a Pseudomonas infection after vaccination.

Pseudomonas aeruginosa Infections: Persisting Problems and Current Research to Find New Therapies

Despite the availability of specific antibiotics, Pseudomonas aeruginosa bacteria still cause troublesome infections in patients with a variety of illnesses: extensive thermal injury, leukopenia from antineoplastic chemotherapy and other forms of immunosuppressive treatment, chronic pulmonary disease such as cystic fibrosis, or intravenous narcotic use. The use of antibiotics has improved the prognosis of pseudomonas infections considerably. However, patients with marginal or defective host immunity may need more extensive therapy to master the infection. By evaluating additional modalities of treatment such as granulocyte replacement, improved usage of antibiotics, and active (prophylaxis) or passive antibody administration, the optimal combination may be found.

Granulocyte transfusion therapy of experimental Pseudomonas pneumonia

Pseudomonas pneumonia was produced in dogs with radiation-induced leukopenia. Treatment of this infection with either gentamicin alone or gentamicin plus daily granulocyte transfusion was compared in a randomized controlled trail. The dogs receiving granulocytes plus gentamicin survived significantly longer than those treated with gentamicin alone (P < 0.05). The Pseudomonas immunotype which was inoculated into the dogs were recovered at autopsy from none of the granulocyte-transfused dogs, whereas seven or eight of the dogs treated with gentamicin alone had the inoculated Pseudomonas immunotype in the area of induced pneumonia at autopsy. As measured by the limulus test, the granulocyte-transfused dogs also did not have endotoxemia as frequently as the dogs given only gentamicin (P < 0.05). This controlled study establishes that transfused granulocytes can favorably alter the course of experimental Pseudomonas pneumonia and suggests that granulocyte transfusion may be a useful therapy in serious bacterial infections of leukopenic subjects.

Tobramycin in Bronchial Secretions

The penetration of tobramycin sulfate (nebramycin factor 6) into normal lower respiratory tract secretions was studied in a dog model. After a 1.7 mg/kg intravenous dose of tobramycin, the antibiotic was detected promptly in bronchial secretions, but the peak bronchial secretion concentration was not usually reached until 2 h after injection (mean level 1.15 μg/ml). The maximum tobramycin concentration in bronchial fluids was equal to the mean inhibitory concentrations that have been reported for about 80% of Pseudomonas isolates.

Intranasal administration of a Pseudomonas lipopolysaccharide vaccine in cystic fibrosis patients.

A purified lipopolysaccharide Pseudomonas aeruginosa vaccine was administered via intranasal spray to cystic fibrosis patients in an attempt to induce development of local antibody without the side effects associated with parenteral administration of the vaccine. Although slight increases in serum antibody titers were noted, there was no appreciable change in specific antibody levels in parotid saliva or sputum following intranasal administration of the vaccine.

5-Fluorocytosine and Amphotericin B in Bronchial Secretions

The penetration into and clearance from bronchial secretions of 5-fluorocytosine and amphotericin B were studied in a dog model. After a single intravenous dose of 35 mg/kg, 5-fluorocytosine intrabronchial concentrations were greater than the minimal inhibitory concentration for 80 to 90% of Candida species. These inhibitory concentrations persisted up to 3 h. In contrast, amphotericin B in intravenous doses of 0.6 and 1.2 mg/kg penetrated the blood-bronchus barrier poorly.