Pulmonary Colonization Research Articles

Pasteurella multocida Infections

Pasteurella multocida, a small, gram-negative coccobacillus , is part of the normal oral flora of many animals, including the dog and cat. P. multocida is the etiologic agent in a variety of infectious disease syndromes. We have reported 34 cases of infection caused by P. multocida and have reviewed the English literature. P. multocida infections may be divided into three broad groups: 1. Infections resulting from animal bites and scratches : The most common infections caused by P. multocida are local wound infections following animal bites or scratches . Cats are the source of infection in 60 to 80% of cases and dogs in the great majority of the remainder. Local infections are characterized by the rapid appearance of erythema, warmth, tenderness, and frequently purulent drainage. The most common local complications are abscess formation and tenosynovitis. Serious local complications include septic arthritis proximal to bites or scratches , osteomyelitis resulting from direct inoculation or extension of cellulitis, and the combination of septic arthritis and osteomyelitis, most commonly involving a finger or hand after a cat bite. 2. Isolation of P. multocida from the respiratory tract: The isolation of P. multocida from the respiratory tract must be interpreted differently than its isolation from other systemic sites. Most commonly P. multocida found in the respiratory tract is a commensal organism in patients with underlying pulmonary disease, but serious respiratory tract infections including pneumonia, empyema, and lung abscesses may develop. Most patients with respiratory tract colonization or infection have a history of animal exposure. 3. Other systemic infections: P. multocida is recognized as a pathogen in a variety of systemic infections including bacteremia, meningitis, brain abscess, spontaneous bacterial peritonitis, and intra-abdominal abscess. P. multocida often acts as an opportunistic pathogen with a predilection for causing bacteremia in patients with liver dysfunction, septic arthritis in damaged joints, meningitis in the very young or elderly, and pulmonary colonization or invasion in patients with underlying respiratory tract abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Forskolin: A potential antimetastatic agent

Forskolin, a diterpene from the roots of an Indian plant, Coleus forskohlii, is a potent platelet aggregation inhibitor and has been examined for its effects on (a) tumor-induced human platelet aggregation and (b) pulmonary tumor colonization in mice. These studies employed a subline of B16 murine melanoma, B16-F10 (highly metastatic to lungs). Forskolin (2 microM) strongly inhibits the melanoma cell-induced human platelet aggregation. A single dose of forskolin (82 micrograms/mouse) administered intraperitoneally 30 or 60 min prior to tail vein injection of cultured B16-F10 cells (2 or 3 X 10(5) cells/mouse) reduced tumor colonization in the lungs by more than 70%. Similar results were obtained in three separate experiments. These findings raise the possibility that forskolin could prove of value in the clinic for the prevention of cancer metastasis.

Catheter colonization and bacteremia with pulmonary and arterial catheters

We prospectively studied the incidence of catheter-related sepsis in 51 critically ill patients who underwent 52 arterial and 37 pulmonary artery catheterizations over a period of 3 months. Daily cultures of blood and catheter insertion site were done and the catheters were cultured semiquantitatively at the time of removal. Catheter colonization defined as growth of 15 or more colonies was observed with 9 (10%) catheters and bacteremia with 4 (4.5%) catheters. The skin cultures were positive in 56% of the colonized catheters compared with 11% of sterile catheters (p less than 0.01). The mean duration of catheterization of 3.8 days in colonized catheters was not different than 3.3 days in noncolonized catheters. Presence of concurrent infection and use of antibiotic did not change the rate of catheter colonization. Often, microorganisms other than those colonizing the catheter were recovered from blood. Femoral arterial catheterization appeared to be more often associated with colonization than radial catheters. It appears that the arterial and pulmonary artery catheter colonization occurs in about 10% of catheters and predisposes to catheter-related sepsis. Semiquantitative cultures of the catheter may aid in better documentation of catheter-induced sepsis.

Lectin Agglutinability of Mammary Tumours with Differing Metastatic Colonisation Potentials

A new fully quantitative method for assessment of lectin agglutinability has been used in this investigation to compare the surface composition of cells from tumours with high and low pulmonary colonisation potential. As in our previous work, we have used only primary (i.e., naturally-occurring) mammary tumours in mice. It was found that agglutinability with the lectins Concanavalin-A and Wheatgerm agglutinin bore no relationship to the pulmonary colonisation potential of the primary mammary tumour. However, cells from disaggregated secondary deposits of tumours which manifested high colonisation potential were consistently less agglutinable than the cells of the primary tumours from which they were derived.

Macrophage content and colony-forming potential in mouse mammary carcinomas.

The macrophage content of cell suspensions from naturally occurring mouse tumours has been assessed by the Fc-mediated phagocytosis assay, and the results compared with the individual tumour's capacity for spontaneous metastasis and with its pulmonary colonization potential after i.v. inoculation. It was found that these tumours differ in their properties from the transplantable fibrosarcomas studied previously by other investigators, in that the macrophage content of all the tumours was uniformly low, ranging from 2 to 9% (mean 4.2 +/- 1.8%) and there was no inverse correlation with frequency of spontaneous metastasis, which was low. When the tumours were inoculated i.v. there was also no correlation with colony-forming capability, which varied greatly between tumours. Lung secondary deposits contained 1.7-6% macrophages (mean 4.4 +/- 0.6%) with a lower phagocytic activity for antibody-coated red cells than in the primary tumour.

1215 ASPERGILLOSIS AND ATOPY IN CYSTIC FIBROSIS (CF)

There is an increased incidence of antibodies to Aspergillus (Asp.) antigens in the serum of patients with CF. Forty-six CF patients of varying clinical severity(age 5-46yrs.)were studied for evidence of:(1)respiratory colonization with Asp, (2)bronchopulmonary allergic aspergillosis (BPAA), and (3) atopy.Asp. was cultured from sputums of 46%(21/46) of patients. A laboratory isolation rate of 6.5%(20/305) was found in respiratory specimens of non-CF patients (p<0.001).Hyphae were seen on sputum smears from 95% of culture-positive CF patients. 61% of culture-positive and 39% of all CF patients had serum precipitins to Asp. in contrast to only 2.2%(1/45) asthmatic controls.Two (2/46) CF patients developed definite evidence of BPAA with (1)wheezing, (2)lung infiltrates,(3)Asp. on sputum culture & smear, (4)positive immediate skin test,(5)elevated serum IgE, & (6)IgE antibodies to Asp. fumigatus by RAST. An additional CF patient with BPAA proven 2 yrs. before was controlled with prednisone during the study period. Six more patients had elevated Asp. RAST. Four fulfilled 4 criteria for BPAA.IgE was elevated in 19% of CF. Type I sensitivity to≥2pollens was found in 22%; to Asp. in 39%; & to ≥3 molds in 39%. Mold-sensitive patients were older & had more severe disease.Significant pulmonary colonization with Asp. occurs in CF. CF patients are at risk to develop BPAA. The respiratory tract is a significant route of sensitization to Asp. and other molds in these patients.

815 CONCOMITANT LOSS OF MUCOID TRAIT AND ANTIBIOTIC RESISTANCE IN PSEUDOMONAS AERUGINOSA STRAINS FROM CYSTIC FIBROSIS PATIENTS

The unusual frequency of pulmonary colonization of cystic fibrosis patients by mucoid (mu+) strains of P. aeruginosa suggests a special relationship between these strains and the pulmonary milieu of CF patients. To better characterize the control of slime production, we isolated P. aeruginosa from sputum cultures of CF patients collected during respiratory therapy. 16 of 19 patients yielded P. aeruginosa which was identified by the API method with growth at 41° and on Pseudomonas isolation agar. Mu+ strains were isolated from 13 of 16 pattents; 11 of 16 had both mu+ and nonmucoid (mu−) strains. All 13 mu+ strains were unstable in nutrient broth, producing mu− variants at characterisic frequencies ranging from 1-97% of c.f.u. in 24 hours. Mu− segregation frequency is medium-and temperature-dependent. The low frequency (<1×10-5) of reversion of mu− to mu+ suggests inherited loss of the capacity to produce slime. 2 of 13 mu+ strains showed concomitant loss of slime production and selected anti-biotic resistance on Mueller-Hinton agar. Each of 10 independently derived mu−clones from VLO-1 became bactrim sensitive; MIC by the agar dilution method for trimethoprim and sulfamethoxazole were respectively 64 and 160μg/ml for VLO-lmu+ vs 8 and 40μg/ml for VLO-1mu−. Strain TWH-1mu− showed a similar increase in sensitivity to chloramphenicol. This suggests that slime production is encoded by a plasmid which also specifies resistance to certain antibiotics.

Adult mice as a model for early onset group B streptococcal disease

The intravenous inoculation of adult mice with virulent group B streptococci serotype Ia resulted in fulminating sepsis with extensive colonization of the lungs and kidneys. The time course of the infection lasting 24 to 40 h, extensive pulmonary colonization, and resistance of the type Ia organism to phagocytosis in the absence of specific antibody suggest that mice are an appropriate model for the study of early onset streptococcal infection of human neonates.

Aspergillus antibody in patients with cystic fibrosis.

The respiratory flora of patients with cystic fibrosis (CF) frequently includes Aspergillus, and 30% of their serum samples have been observed to contain precipitating antibody to this fungus. Serum from 61 CF patients, 60 healthy persons, and three patients with CF and allergic bronchopulmonary aspergillosis was studied, using a quantitative assay for antibody to A fumigatus. Although CF patients had significantly higher levels of Aspergillus antibody, some antibody was found in all serum samples from normal individuals. Binding was immunologically specific for A fumigatus. Serum IgE levels and dermal reactivity to Aspergillus were similar in both CF and normal subjects. Increased levels of Aspergillus antibody in CF patients probably reflect pulmonary colonization, which only rarely causes infection or sensitization.

Pseudomonas aeruginosa: immune status in patients with cystic fibrosis.

In order to have a better understanding of the clinical significance of Pseudomonas aeruginosa, circulating and secretory antibodies were measured. Of 100 patients diagnosed as having cystic fibrosis (CF) and an atypical mucoid P. aeruginosa cultured from their sputum, each possessed serum precipitins. These immunoprecipitates, however, were not detected in the sera of 40 CF patients, some of whom were chronically ill with pulmonary colonization by typically rough-smooth strains of P. aeruginosa. The sera of 46 CF patients and 27 CF patient parents not colonized by P. aeruginosa were negative for the precipitins. The sera from 15 of 45 chronically ill patients not having CF, however, but harboring P. aeruginosa, also possessed serum precipitins. The sera from 85 subjects not having CF and not clinically infected with P. aeruginosa were negative for precipitins. Serum hemagglutination titers as high as 1:4096 were measured in older CF patients having advanced pulmonary disease and who were infected with mucoid P. aeruginosa. Salivary titers ranged from 1:8 to 1:64. Increased levels of both circulating and secretory antibodies of the immunoglobulin A and G classes were demonstrated in patients with CF. Once a patient with CF becomes colonized with P. aeruginosa a process of conversion from the rough and smooth forms to the mucoid form is almost inevitable. Although the mucoid form predominates in the sputum, intermediates of the various colony types are often present. Serum precipitins were demonstrable only after the appearance of mucoid strains in the sputum of patients with CF. Although antibiotics tend to reduce the number of mucoid microorganisms, they are rarely, if ever, eradicated from these patients' lungs. Recurrent episodes of servere pulmonary infection and the evidence of increasing antibody formation to mucoid strains indicates the invasiveness of these particular strains.