No abstract

Mucoid Pseudomonas aeruginosa is isolated from most patients with cystic fibrosis, in whom it causes a chronic, incurable lung infection. Bronchopulmonary disease is the cause of death in 95% of patients with cystic fibrosis,'2 and mucoid P aeruginosa was cultured from 94% of Danish patients with cystic fibrosis at death.3 Typically the airways are colonised initially with non-mucoid strains of P aeruginosa" and after a variable period of colonisation, usually one to two years, mucoid strains emerge that produce large amounts of the extracellular polysaccharide alginate. Compared with non-mucoid strains, infection with mucoid P aeruginosa is associated with a poorer clinical state,6 lower pulmonary function,78 and greater risk of death.7Infection with mucoid strains was also associated with an increased humoral immune response to P aeruginosa.`0 An increased antibody response is associated with poorer pulmonary function7"' and the lung damage in cystic fibrosis is mediated by immune complexes.'213 This suggests that alginate is a virulence factor in chronic P aeruginosa pulmonary infection in cystic fibrosis.'4Our objective was to test the hypothesis that alginate producing, mucoid P aeruginosa is more virulent than non-mucoid strains. We studied 73 patients with cystic fibrosis classified according to their sputum bacteriology longitudinally and determined their antibody responses to P aeruginosa alginate and somatic antigens, lung function, and nutritional state for three years before and for up to 10 years after the onset of chronic P aeruginosa lung infection. Patients and methodsThe diagnosis of cystic fibrosis was based on repeatedly raised electrolyte concentrations in sweat and characteristic clinical features. The criteria for entry into the study were that the onset of chronic P aeruginosa infection was after 1975, that the patient had been followed up monthly at the Danish Cystic Fibrosis Centre at Rigshospitalet before the onset of infection, and that sputum bacteriology had been recorded for at least eight months of each year. Data were recorded prospectively and included forced vital capacity (FVC), height, weight, and sputum bacteriology. Since 1976 all patients with chronic P aeruginosa infection have been admitted to the centre every three months for intravenous courses of antipseudonomas chemotherapy.'5 BACTERIOLOGY The onset ofchronic P aeruginosa infection was defined as the time when P aeruginosa had been grown in consecutive monthly sputum cultures over six months.

Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospective double-blind placebo-controlled study of colistin inhalation. Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline. Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group (18 versus 11). Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score, maintenance of pulmonary function and inflammatory parameters. We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy.

This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia.

The optimized hip fracture program reduced the rate of in-hospital postoperative complications and mortality. Randomized clinical trials are needed to confirm these results and elucidate the elements of the program that have the greatest effect on clinical outcomes and mortality.