Mucoid Pseudomonas Aeruginosa Research Articles

Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype.

Whether allelic variants of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) independently contribute to pulmonary outcome in CF patients has not been resolved. We used both cross-sectional and mixed-model longitudinal analyses of data from CF patients that were at least 12 years old to determine the influence on pulmonary function (percent predicted forced expiratory volume [FEV(1)]) of the CFTR gene genotype, gender, mucoid Pseudomonas aeruginosa (MPA) infection status, presence of total opsonic antibody to MPA, and, separately, the opsonic antibody activity specific to the mucoid exopolysaccharide (MEP) surface antigen. Two different factors were independently associated with the lack of MPA infection: a high level of MEP-specific opsonic activity (MSOA), implicating an immunologically based mechanism of resistance to infection, and a lack of any type of opsonic antibody to MPA, indicative of no significant exposure or infection. This latter phenotype was found in a subset of CF patients who carried at least one uncommon CFTR gene allele suggestive of a genetic basis for resistance to infection in this group of older CF patients. For CF patients in whom both CFTR gene alleles were identified by screening for the 12 most common variants (75% of alleles), cross-sectional analysis showed that MPA infection was best correlated with lower percent predicted FEV(1), while genotype (two versus one DeltaF508 CFTR gene allele) and a low level of MSOA were associated with increased risk of infection. A mixed-model analysis of longitudinal spirometric measurements that considered multiple risk factors to derive regression equations was used to determine which clinical parameters had the greatest effect on the annual rate of decline in percent predicted FEV(1). This analysis showed that the CFTR gene genotype only modestly modified the constant (y intercept) of the derived equations, while gender and MPA infection status had the largest effects on annual rates of decline in percent predicted FEV(1). These results indicate that the CFTR genotype is usually not a primary determinant of pulmonary function in most CF patients, but gender and MPA infection status are. Infection status is potentially influenced by both immunologic (a high level of MSOA) and genetic factors, such as carriage of a CFTR gene allele that leads to a diagnosis of CF but still confers resistance to infection that is comparable to that of the wild-type CFTR gene.

Long term follow up of changes in FEV1 and treatment intensity during Pseudomonas aeruginosacolonisation in patients with cystic fibrosis

BACKGROUNDColonisation with Pseudomonas aeruginosa (PA) is a striking feature of lung involvement in cystic fibrosis. To identify the clinical consequences of the different steps of colonisation with PA under a...

Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection

The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed ( n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients.

Chemotherapy of chronic infections with mucoid Pseudomonas aeruginosa in lower airways of patients with cystic fibrosis.

The bacteriological effect of chemotherapy against Pseudomonas aeruginosa (Ps.ae.) in lungs of patients with cystic fibrosis is reviewed. During a 5-year period 49 children and adults were treated with 190 courses of different antibiotics. The mucoid strains of Ps.ae. disappeared in 72.0% of the courses in which a combination of tobramycin and carbenicillin was employed. Tobramycin given alone had only bacteriological effect in 26.6% of the courses. Colimycin alone or in combination with carbenicillin had no effect. In 18 patients who received subsequent courses of tobramycin and combination of tobramycin and carbenicillin a significant difference in favour of the combination therapy was found, also in cases with many precipitins against Ps.ae. in serum. In 74.5% of the initially successful courses the patients were recolonized with Ps.ae. within 1 month. No nephrotoxic or ototoxic side effects were demonstrated in spite of the high doses of tobramycin (10 mg/kg/24 h) emmployed and the repeated courses.