Mnlticentre evaluation of azithromycin in comparison with co-amoxiclav for the treatment of acute otitis media in children

A total of 389 children (age 0.6-10.2 years) with typical signs and symptoms of acute otitis media were randomized (1:1) to treatment with either azithromycin or co-amoxiclav. The dosage schedule for azithromycin was 10 mg/kg/day, in a single daily dose, administered for three days. Co-amoxiclav was given at a dose of 13.3 mg/kg (amoxycillin equivalent) tid for ten days. Patients were evaluated 4-6 days and 12-16 days after the start of therapy. A satisfactory clinical response was reported for 93.2% of the 192 evaluable azithromycin-treated patients (144 cured, 35 improved), and for 97.3% of the 189 evaluable co-amoxiclav-treated patients (148 cured, 36 improved). Six (3.0%) relapses occurred in the azithromycin group, and four (21%) in the co-amoxiclav treatment group, respectively. Side-effects were recorded in a significantly fewer number of the azithromycin patients (23 of 197; 11.7%) compared with the co-amoxiclav patients (43 of 192; 22.4%, P < 0.02). Adverse events were mainly gastrointestinal in nature, with diarrhoea the most frequent complaint (32 cases with co-amoxiclav; five with azithromycin; P < 0.001). One patient from each group discontinued therapy because of treatment-related adverse events. Laboratory analyses (mainly haematologjcal in nature) showed abnormalities in six of 100 azithromycin patients and ten of 101 co-amoxiclav patients. It was concluded that three-day, single-dose azithromycin and ten-day tid co-amoxiclav therapy have comparable clinical efficacy in paediatric patients with acute otitis media; however, there was a lower incidence of side effects in the azithromycin grou

Fibronectin-Cleaving Activity in Bronchial Secretions of Patients with Cystic Fibrosis

In cystic fibrosis, colonization of the airways with Pseudomonas aeruginosa follows colonization with Staphylococcus aureus and is related to accelerated deterioration of pulmonary function. Because P. aeruginosa adheres better to cell surfaces devoid of fibronectin, we searched for fibronectin-cleaving activity in bronchial secretions and saliva from 24 patients with cystic fibrosis who were followed up for 4.5 y and from two control groups. Proteolytic activity against 125I-labeled fibronectin wascontinuously present in cystic fibrosis bronchial secretions; significantly higher fibronectin-cleaving activity was found in older vs. younger patients, in patients with advanced disease stages determined by a five-stage scoring system, and in those colonized with P. aeruginosa. The fibronectin-cleaving activity was due to neutrophil elastase and cathepsin G. Cystic fibrosis bronchial secretions had proteolytic activity against surface fibronectin of airway mucosal cells. Thus fibronectin-cleaving activity of bronchial secretions rather than of saliva may favor P. aeruginosa colonization of the upper respiratory tract in individuals with cystic fibrosi

Affinity Constants of Naturally Acquired and Vaccine-Induced Anti-Pseudomonas aeruginosa Antibodies in Healthy Adults and Cystic Fibrosis Patients

Naturally acquired anti-Pseudomonas aeruginosa antibody fails to afford protection against repeated P. aeruginosa bronchopulmonary exacerbations in cystic fibrosis (CF) patients. In an effort to explain this phenomenon, the titer and affinity constants of serum anti-lipopolysaccharide (LPS) IgG were determined in five study groups: healthy adults before and after immunization with a polyvalent LPS-based vaccine, healthy noncolonized CF patients before and after immunization, nonimmunized CF patients with significantly elevated anti-LPS antibody titers without documented colonization, recently colonized CF patients before and after immunization, and nonimmunized CF patients chronically colonized with P. aeruginosa. Immunization elicited a significant rise in total anti-LPS immunoglobulin levels and affinity constants in both healthy adults and CF patients. Although chronically colonized patients had elevated levels of total anti-LPS antibody, these antibodies possessed affinities at least tOO-fold less than those of vaccine-induced antibodie

Levels of Free Granulocyte Elastase in Bronchial Secretions from Patients with Cystic Fibrosis: Effect of Antimicrobial Treatment Against Pseudomonas aeruginosa

Large amounts of free granulocyte elastase (GE), an enzyme capable of mediating airway damage, have been found in bronchial secretions of patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. This finding indicates an imbalance between GE and its antiproteases, α1-proteinase inhibitor (α1-PI) and bronchial mucosal inhibitor (BMI), in the airways of these individuals. The effect of intravenous antimicrobial treatment against P. aeruginosa on activity and concentration of GE, BMI, and α1-PI was evaluated in 30 treatment courses of 20 patients with cystic fibrosis. Although sputum volume and level of immunoreactive GE decreased and concentrations of α1-PI and BMI increased significantly (P < .05), a high level of free GE persisted. No active α1-PI and BMI were detectable after treatment. High levels of GE correlated with a poor pulmonary condition (rs = .98, P < .001). In vitro, elastolytic activity of bronchial secretions from patients with cystic fibrosis was significantly inhibited by eglin C and an oxidation-resistant variant of α1-PI, both compounds currently produced by recombinant DNA technolog

Immunization of Noncolonized Cystic Fibrosis Patients against Pseudomonas aeruginosa

The long-term safety and immunogenicity of a polyvalent Pseudomonas aeruginosa conjugate vaccine was evaluated in 30 noncolonized cystic fibrosis patients. Four doses were administered over 3 years, and patients were followed for a mean of 38 months. No acute or long-term adverse effects were noted. Immunization engendered a significant antibody response to all vaccine components. A decline in titers during year 3 of observation was associated with a marked rise in the isolation of P. aeruginosa. This organism was isolated repeatedly from the respiratory tract of 4 patients and only once from 7 patients. The remaining patients were repeatedly culture-negative. Only 1 patient showed clinical deterioration associated with multiple isolations of P. aeruginos

Matrix Metalloproteinase (MMP)-8 and MMP-9 in Cerebrospinal Fluid during Bacterial Meningitis: Association with Blood-Brain Barrier Damage and Neurological Sequelae

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF speci-mens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P <.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P <.001) and tumor necrosis factor-α (P =.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequela

Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae

Genome-Wide Mutagenesis of Xanthomonas axonopodis pv. citri Reveals Novel Genetic Determinants and Regulation Mechanisms of Biofilm Formation

Xanthomonas axonopodis pv. citri (Xac) causes citrus canker disease, a major threat to citrus production worldwide. Accumulating evidence suggests that the formation of biofilms on citrus leaves plays an important role in the epiphytic survival of this pathogen prior to the development of canker disease. However, the process of Xac biofilm formation is poorly understood. Here, we report a genome-scale study of Xac biofilm formation in which we identified 92 genes, including 33 novel genes involved in biofilm formation and 7 previously characterized genes, colR, fhaB, fliC, galU, gumD, wxacO, and rbfC, known to be important for Xac biofilm formation. In addition, 52 other genes with defined or putative functions in biofilm formation were identified, even though they had not previously reported been to be associated with biofilm formation. The 92 genes were isolated from 292 biofilm-defective mutants following a screen of a transposon insertion library containing 22,000 Xac strain 306 mutants. Further analyses indicated that 16 of the novel genes are involved in the production of extracellular polysaccharide (EPS) and/or lipopolysaccharide (LPS), 7 genes are involved in signaling and regulatory pathways, and 5 genes have unknown roles in biofilm formation. Furthermore, two novel genes, XAC0482, encoding a haloacid dehalogenase-like phosphatase, and XAC0494 (designated as rbfS), encoding a two-component sensor protein, were confirmed to be biofilm-related genes through complementation assays. Our data demonstrate that the formation of mature biofilm requires EPS, LPS, both flagellum-dependent and flagellum-independent cell motility, secreted proteins and extracellular DNA. Additionally, multiple signaling pathways are involved in Xac biofilm formation. This work is the first report on a genome-wide scale of the genetic processes of biofilm formation in plant pathogenic bacteria. The report provides significant new information about the genetic determinants and regulatory mechanism of biofilm formation

Testing the Effect of Relative Pollen Productivity on the REVEALS Model : A Validated Reconstruction of Europe-Wide Holocene Vegetation

Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1° × 1°) over the Holocene (last 11.7 ka BP) using the 'Regional Estimates of VEgetation Abundance from Large Sites' (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity