Tim Jensen

Management of Pseudomonas Aeruginosa Lung Infection in Danish Cystic Fibrosis Patients

ABSTRACT. The annual mortality rate of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection at the Danish CF‐centre ranged from 10 to 20% in the years 1970–1975. In this period the patients received antipseudomonal chemotherapy only during acute exacerbations of infection. From 1976 99 patients acquired chronic P. aeruginosa infection and were given regular and intensive antipseudomonal treatment 3–4 times per year. The patients were followed for 612 patient‐years; 7 died and the 10‐year survival rate after onset of P. aeruginosa infection was 90%±4%. The annual mortality rate is now 1–2%. Although precipitating antibodies against P. aeruginosa increased significantly, pulmonary function did not deteriorate with duration of infection. Cross‐infection between patients caused an increased incidence of chronic P. aeruginosa infection which was reduced by hygienic measures.

Effect of oral N-acetylcysteine administration on human blood neutrophil and monocyte function

N‐acetylcysteine (NAC) is known to be a scavenger of free oxygen radicals, and recent in vitro studies have demonstrated that it is also able to inhibit leukocyte function. The clinical significance of these effects is, however, not known. In this study we have measured the effect on human blood neutrophil and monocyte function of a single 400 mg dose of NAC administered orally. Administration of NAC to ten healthy volunteers resulted in significant reduction of neutrophil chemiluminescence response following activation by opsonized zymozan as compared to four non‐treated persons acting as controls. No effect was observed on the chemotaxis of either cell type or on monocyte chemiluminescence response. These findings suggest that NAC may be beneficial in clinical conditions like cystic fibrosis, where tissue damage may be a consequence of the effects of increased release of toxic oxygen radicals and proteolytic enzymes.

Does Centralized Treatment of Cystic Fibrosis Increase the Risk of Pseudomonas aeruginosa Infection

ABSTRACT. Two hundred and forty Danish patients with cystic fibrosis (97% of the total CF population in Denmark) participated in a point‐prevalence study of Pseudomonas aeruginosa infection. One hundred and ninety‐two patients were treated at the Danish CF centre and 48 patients were treated in other places. The age distribution was significantly different as no patients older than 19 years were found in the non‐centre group. Pathogenic bacteria were isolated from the sputum of 96% of the patients. P. aeruginosa was more prevalent in patients from the centre, whereas Staphylococcus aureus was more prevalent in the non‐centre group. No difference in serogroup and phage pattern of P. aeruginosa was found. There was a tendency that non‐centre treated patients acquired chronic broncho‐pulmonary P. aeruginosa infection later, but at the age of 16 years 90% of all patients will be chronically infected. Chronic P. aeruginosa infection was significantly more common in the age group 10‐14 years at the centre than outside the centre. It is not possible to prevent chronic P. aeruginosa infection in CF patients treated in small groups and because of the better prognosis of centralized treatment the latter must be recommended.

Mucosal immunity to Pseudomonas aeruginosa alginate in cystic fibrosis.

Patients with cystic fibrosis commonly acquire chronic pulmonary infection with alginate‐producing Pseudomonas aemginosa. The infection remains localized at the mucosal surfaces of the airways. Using enzyme‐linked immunosorbent assays immunoglobulin concentrations and titers of specific antibodies to purified P. aeruginosa alginate and to P. aemginosa sonicated antigens were measured in tears, saliva, sputum and serum. CF patients had significantly higher concentrations of IgG, IgA and SIgA in serum and saliva than controls. They also had significantly higher levels of specific antibodies to alginate and sonicated antigen in secretions and serum. Local production of IgA, IgG and IgM antibodies to P. aeruginosa was demonstrated. Only a minor proportion of specific IgA antibodies were present as secretory IgA in tears, saliva and sputum. The ratio of alginate‐specific SIgA to specific monomeric IgA in sputum was significantly lower than the similar ratio in saliva, whereas the same ratio for specific P. aeruginosa sonicate antigens was found in saliva and sputum.

Increased IgG2 and IgG3 Concentration Is Associated with Advanced Pseudomonas Aeruginosa Infection and Poor Pulmonary Function in Cystic Fibrosis

ABSTRACT. The concentrations of IgG subclass immunoglobulins were determined by radial immunodiffusion in serum from 126 patients with cystic fibrosis (CF). The results were compared to values from age‐matched healthy children and adults and correlated to patients age, duration of chronic Pseudomonas aeruginosa infection and lung function parameters. Fifty‐two percent of the patients had an elevated concentration of at least one of the IgG subclasses; IgG1 28%, IgG2 16%, IgG3 18% and IgG4 48%. There was significant correlation between elevated serum levels of IgG2, and to a lesser extent IgG3, with decreased lung function (for FEV1; p=0.0001, and p=0.001 respectively) and high levels of antipseudomonas precipitins (p=0.008, and p=0.002). A similar correlation was not found for IgG1 and IgG4. IgG subclasses vary in their ability to promote phagocytosis and to activate complement and it is possible that individual differences in the IgG subclass pattern could explain the variable course of this disease.

Is the arterial switch operation still a challenge in small centers

OBJECTIVE In the last years, major changes as regards timing for operation, surgical technique, and perioperative care determined a great improvement in the arterial switch operation (ASO) allowing excellent mid-term results in a few leading centers. This stimulated the widespread adoption of ASO as procedure of choice for transposition of the great arteries (TGA), even in small institutions. We reviewed our early experience with ASO in an attempt to evaluate its safety in a small center. METHODS Since April 1992, 39 consecutive patients underwent TGA repair by ASO in our department. There were 27 patients with simple TGA, 8 with TGA and VSD and 4 with Taussig-Bing heart and aortic coarctation. Median age and weight at operation were 7 days and 3.5 kg, respectively. Neonatal repair was performed in 34 patients. In accordance with the Planché coronary classification, type I was encountered in 21 patients, type II in 4 and type III in 14. Several modifications of the original technique were used, mainly regarding coronary relocation, pulmonary artery reconstruction and approaches for associated VSD closure and aortic arch repair. RESULTS Early mortality was 2.6% (n = 1), the only operative death being related to unsatisfactory coronary relocation. Since modified ultrafiltration was adopted, mean ICU stay decreased from 5 +/- 4 days (n = 21) to 2 +/- 1 days (n = 17) (P < 0.05). Three patients required reoperation for residual ASD and/or VSD closure. There were no late deaths. After a mean follow-up of 26 +/- 15 months all survivors are thriving and are currently asymptomatic. CONCLUSIONS Although this series is rather small, most of the major coronary anomalies and complex anatomic associations were encountered. This experience suggests that neonatal repair of TGA by ASO can be safely accomplished even in small centers. Modified ultrafiltration appears to improve the early outcome of neonates undergoing ASO.

Fluoroquinolones in the Treatment of Cystic Fibrosis

SummaryCystic fibrosis patients suffer from recurrent and chronic lung infections mainly caused by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The fluoroquinolones, notably ciprofloxacin and ofloxacin, represent an important addition to the therapy of P. aeruginosa infections. They offer the possibility of effective oral treatment for early colonisation as well as chronic infections, even in children. They are associated with only few and mild adverse effects. Development of resistance represents an increasing problem.

Comparison of Amoxycillin/Clavulanate with Amoxycillin in Children and Adults with Chronic Obstructive Pulmonary Disease and Infection with Haemophilus influenzae

71 children and adults (median age 7 years) with chronic obstructive pulmonary disease in which ampicillin-sensitive Haemophilus influenzae were isolated from lower airway secretions were included in a single-blind study comparing amoxycillin/clavulanate and amoxycillin alone. The dosage of amoxycillin was 50 mg/kg/day given together with probenecid and divided in 3 doses. Duration of treatment was 14 days. Clinical and bacteriological examinations were performed at study entry and again immediately after the treatment period. A late bacteriological follow-up 1.5 months after entry was performed. 65 patients were eligible for analysis of clinical outcome, and no difference between the groups was found. Side-effects were mild at a frequency of 3% for either preparation. In terms of eradication of the initially isolated H. influenzae amoxycillin/clavulanate tended to be better than amoxycillin, although the difference was not significant (70% and 57%, respectively). In a subset of 33 patients with polymicrobial flora amoxycillin/clavulanate was significantly more effective than amoxycillin. However, amoxycillin/clavulanate did not significantly reduce the emergency of beta-lactamase producing H. influenzae during treatment, and thus offers no advantage over amoxycillin in patients with amoxycillin-sensitive H. influenzae. The combination should be reserved to patients with either polymicrobial flora or ampicillin-resistant H. influenzae.