Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa. The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. A pilot study of low-dose erythromycin in bronchiectasis. Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study. Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis.
The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes. Bronchiectasis is a chronic pulmonary process characterized by recurrent respiratory infections leading to destruction of airways secondary to inflammation. We investigated whether the addition of 6-months' twice-weekly azithromycin to the existing treatment regimen in patients with pulmonary bronchiectasis decreased the number of exacerbations and improved pulmonary function compared with a similar period of time without concurrent azithromycin.
                Thirty patients with high-resolution computed tomography scan-confirmed bronchiectasis were to be recruited. In random order, patients received usual medications for 6 months, and usual medications plus oral azithromycin 500mg twice weekly for 6 months. Patients receiving azithromycin first had a 1-month washout period prior to entering the second phase. Patients recorded weekly peak flow (PF) measurements. Pulmonary function tests (PFTs), 24-hour sputum volume, and needs for intervention with medication or ancillary support were collected at baseline and every 3 months. Exacerbation incidence and sputum volume measurements were compared from baseline to the end of each study phase.
                Twelve patients were enrolled; 11 were included in the analysis. Owing to randomization, most patients received the azithromycin first, which was fairly well tolerated. PFTs did not change significantly during either study phase and PFs appeared to remain stable during azithromycin therapy and throughout the subsequent control phase. Azithromycin significantly decreased the incidence of exacerbations compared with usual medications (5 vs 16; p = 0.019). Mean 24-hour sputum volume significantly decreased (15% [p = 0.005]) during the active treatment phase, and remained decreased during the control phase (p = 0.028). Subjectively, patients reported increased energy and quality of life while receiving treatment with azithromycin.
                The addition of twice-weekly azithromycin significantly decreased the incidence of exacerbation and 24-hour sputum volume and may have stabilized the PFTs and PFs in this 11-patient pilot study. The results of this study justify further investigation of adding azithromycin to the treatment regimens of patients with bronchiectasis for its disease-modifying effects. Non-cystic fibrosis (CF) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to worsening lung function and increased morbidity and mortality.
                To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity.
                A double-blind, placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles, each for 6 months, with a one-month washout period. The number of exacerbations, number of hospital admissions, number of hospital admission days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity, density of PA in sputum, emergence of bacterial resistance, and emergence of other opportunistic bacteria were recorded.
                The number of admissions and days of admission (mean +/- SD) during the tobramycin period (0.15 +/- 0.37 and 2.05 +/- 5.03) were lower than those during the placebo period (0.75 +/-1.16 and 12.65 +/- 21.8) (p < 0.047). A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle (p = 0.038). No significant differences were observed in the number of exacerbations, antibiotic use, pulmonary function, and quality of life. The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not with detectable ototoxicity or nephrotoxicity.
                Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum. Nevertheless, pulmonary function and quality of life are not improved, and the risk of bronchospasm is appreciable. Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis. Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study. Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed. The pretreatment characteristics of the two groups were similar. Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02). Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment. The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group. There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp. in sputum between exacerbations was similar in the two groups. Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment. Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group. Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity. We conducted a placebo-controlled, double-blind, randomized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or placebo (n = 37), which was self-administered twice daily for 4 wk and followed by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated in 35% of TSI patients but was detected in all placebo patients. Investigators indicated that 62% of TSI patients showed an improved medical condition compared with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1 to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups (p = 0.41). More TSI-treated patients than placebo patients reported increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms did not limit therapy. Additional study is warranted to further evaluate TSI in bronchiectasis patients. Increased airway responsiveness (AR) is frequently associated with bronchiectasis. Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities. This study was designed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR. Twenty five children with bronchiectasis, who had an increased AR (defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) <25 mg x mL(-1) evaluated by the dosimeter method), were randomized, double-blind into two parallel groups. Thirteen of the children were treated with roxithromycin (4 mg x kg(-1) b.i.d.) for 12 weeks and 12 received placebo. FEV1, sputum purulence and leucocyte scores were assessed every 3 weeks. To estimate AR, high-dose methacholine challenge tests were performed before and after treatment. On the dose-response curve to methacholine, PD20 and maximal response (two indices of AR) were measured. Changes in FEV1 were not observed during the course of the study in both groups. A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group. After 12 weeks of roxithromycin therapy, the geometric mean (range of 1 SD) of provocative cumulative dose producing a 20% fall in FEV1 (PD20) increased significantly (p<0.01) to 169.2 (83.2-344.2) breath units (BU) (1 BU denotes one inhalation of 1 mg x mL(-1) methacholine) and the mean+/-SD of maximal response decreased significantly (p<0.01) to 32.5+/-6.8%, as compared with the initial values (PD20 87.1 (47.3-160.4) BU; maximal response 40.9+/-7.4%). No significant changes in either parameter were observed in the placebo group. Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness. Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact. The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF).
                To evaluate the effects of a macrolide antibiotic [clarithromycin (CAM)] on the process of inflammation [by measuring IL-8, TNF-alpha, IL-10 levels and cell profiles in bronchoalveolar lavage (BAL) fluid], pulmonary function and sputum production in children with steady-state bronchiectasis, secondary to causes other than CF or primary immunodeficiencies.
                Seventeen patients randomized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only.
                Compared with the control group, the treatment group showed a significant decrease in IL-8 levels, total cell count, neutrophil ratios in BAL fluid and daily sputum production at the end of the third month. There was also a significant increase in the treatment group's BAL fluid macrophage ratios. The differences in pulmonary function test parameters were not significant.
                Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs. No corresponding clinical improvement could be shown but although this is possible with long-term use, trial validation is necessary.
The evidence available shows a small benefit for the use of prolonged antibiotics in the treatment of bronchiectasis. This review is limited by the diversity of the trials. Further randomised controlled trials with adequate power and standardised end points are required.