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Established treatment regimens for the autosomal dominant hyperimmunoglobulin E syndrome, denominated Job syndrome, are lacking. Thus, Job syndrome still exerts a dramatic impact on patients’ quality of life. Our aim was to present safety and effectiveness of a regimen including co-trimoxazole, omalizumab and inhaled tobramycin in Job syndrome. A 26-year-old woman diagnosed with Job syndrome since infancy through sequencing revealing G342D mutation in STAT3 gene was initiated in the above mentioned treatment regimen; she was followed for 6 months, and to date, none recurrent pulmonary or skin infection was noticed. Furthermore, a considerable improvement in skin lesions was observed. A combination of anti-IgE and longitudinal use of inhaled antibiotics seems well-founded in Job syndrome.

OBJECTIVE Early antibiotic therapy has the potential to eradicate initial Pseudomonas aeruginosa infection and postpone chronic infection. There are limited data evaluating the efficacy and safety of inhaled tobramycin in patients with cystic fibrosis (CF) who are younger than 1 year. The objective of this study was to evaluate the effectiveness of inhaled tobramycin in early eradication of P aeruginosa in infants with CF. METHODS This retrospective study evaluated patients with CF younger than 1 year with first time infection with P aeruginosa. The primary outcome was the frequency of P aeruginosa eradication. Secondary outcomes were sustained culture negativity at 12 and 18 months and safety assessments. RESULTS Of 18 patients included in the study, 9 received inhaled tobramycin and an enteral fluoroquinolone and 9 received inhaled tobramycin alone. Microbiologic clearance of respiratory cultures was observed in 83% patients at end of therapy and 78% of patients at 1 month posttherapy. Eradication of P aeruginosa was observed in 56% of patients at 6 months posttreatment with sustained culture negativity observed in 39% of patients up to 18 months. CONCLUSIONS Inhaled-tobramycin therapy is effective in early eradication of P aeruginosa infection and is well tolerated in infants younger than 1 year.

Introduction: In recent years, administration of inhaled aminoglycosides has gained popularity in tracheostomy-dependent pediatric patients because of medication delivery to the target site of action while minimizing systemic absorption and adverse effects. A recent report of detectable serum tobramycin concentrations in critically ill children receiving inhaled tobramycin 300 mg every 12 h prompted our investigation in tracheostomy-dependent pediatric patients receiving inhaled tobramycin 80 mg every 8 h. Methods: Serum tobramycin trough concentrations were obtained from tracheostomy-dependent pediatric patients receiving treatment with inhaled tobramycin 80 mg every 8 h for the treatment of tracheitis. Patient data, including demographic data, medical history, renal function, and serum concentrations, were collected. Results: Twelve patients with a median age of 0.5 (0.3–6.1) years had serum tobramycin concentrations evaluated. Eleven of the 12 patients had undetectable trough concentrations (

Background Antimicrobial susceptibility testing (AST) is a cornerstone of infection management. Cystic fibrosis (CF) treatment guidelines recommend AST to select antimicrobial treatments for CF airway infection but its utility in this setting has never been objectively demonstrated. Methods We conducted a systematic review of primary published articles designed to address two PICO (patient, intervention, comparator, outcome) questions: 1) “For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection predictable from AST results available at treatment initiation?” and 2) “For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection affected by the method used to guide antimicrobial selection?” Relationships between AST results and clinical response (changes in pulmonary function, weight, signs and symptoms of respiratory tract infection, and time to next event) were assessed for each article and results were compared across articles when possible. Results Twenty-five articles describing the results of 20 separate studies, most of which described Pseudomonas aeruginosa treatment, were identified. Thirteen studies described pulmonary exacerbation (PEx) treatment and seven described ‘maintenance’ of chronic bacterial airways infection. In only three of 16 studies addressing PICO question #1 was there a suggestion that baseline bacterial isolate antimicrobial susceptibility was associated with clinical response to treatment. None of the four studies addressing PICO question #2 suggested that antimicrobial selection methods influenced clinical outcomes. Conclusions There is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment, suggesting a need for careful consideration of current AST use by the CF community.

Summary Introduction Aerosolized tobramycin is a standard of care for chronic Pseudomonas aeruginosa (Pa) infection in patients with cystic fibrosis (CF). Objectives The long-term safety and efficacy of intermittent (28-day “on”/“off” cycles) inhaled tobramycin nebulization solution 300 mg/4 ml (TNS4, Bramitob®/Bethkis®) was assessed over 56 weeks in CF patients aged ≥6 years having baseline 1 sec forced expiratory volume (FEV1) 40–80% predicted. Methods Patients were initially randomized in an 8-week open-label trial (core phase) to compare TNS4 (N = 159) and tobramycin 300 mg/5 ml (TNS5, TOBI®) (N = 165). A subset of patients continued in a 48-week, single-arm extension receiving TNS4 only. The primary endpoint of the core phase was to demonstrate the non-inferiority of TNS4 compared to TNS5 in terms of absolute change from baseline to week 4 in FEV1 % predicted. The assessment of long-term safety was the primary purpose of the extension phase. Throughout all phases of the study, microbiological assessments, adverse events, and audiometry findings were also evaluated. Results In the core phase (N = 321), FEV1 (% predicted) increased from baseline (absolute change) following a single on-treatment cycle for both TNS4 (7.0%) and TNS5 (7.5%) and the non-inferiority between treatments was met [difference between treatments of −0.5 (95% CI: −2.6; 1.6)]. These improvements were maintained throughout the extension phase (N = 209), ranging throughout the study between 5.1% (95% CI: 3.2; 6.9) and 8.1% (95% CI: 6.8; 9.4) compared to baseline. Pa sputum count reductions ranged between 0.6 (95% CI: 0.2; 0.9) to 2.3 (95% CI: 2.0; 2.6) log10 CFU/g throughout the 56 weeks. No remarkable safety issues were identified throughout both study phases, with similar percentages of patients reporting adverse events in the two treatment groups during the 8-week core phase [TNS4 (31.4%); TNS5 (28.0%)]. Conclusions Overall, TNS4 demonstrated short-term clinical benefits similar to TNS5 which were maintained during the long-term use of TNS4 and was also associated with a favorable tolerability profile. Pediatr Pulmonol. 2014; 49:1076–1089. © 2014 Wiley Periodicals, Inc.

The KDIGO guidelines for acute kidney injury (AKI) are designed to assist health-care providers around the world in managing patients with AKI. Clinical guidelines are intended to help the clinician make an informed decision based on review of the currently available evidence. Due to the generic nature of guidelines, it is sometimes difficult to translate a guideline for a particular individual patient who may have specific clinical circumstances. To illustrate this point, we have discussed the interpretation of the KDIGO guideline in patients who have subtleties in their clinical presentation, which may make treatment decisions less than straightforward.

Objective To examine cystic fibrosis (CF) physician adherence to the 2007 CF Foundation (CFF) Pulmonary Guidelines for Chronic Medications. Specifically adherence and barriers to prescribing level A medication recommendations (i.e., inhaled tobramycin and dornase alfa) and level B medication recommendations (i.e., macrolide antibiotics and hypertonic saline) were studied. Methods During Spring 2010, the CFF emailed survey invitations to directors of 136 accredited CF care centers treating 50+ CF patients. Directors were asked to forward the invitations to their physician colleagues. One hundred thirty-three surveys were included in the analyses, representing 92 centers. Barriers were conceptualized based on Cabana et al.'s framework for adherence to guidelines. Adherence was assessed via a case vignette. Results Logistic regression analysis revealed that higher outcome expectancy (OR = 1.099, CI 1.010–1.196) and fewer environmental/system barriers (OR = 1.484, CI 1.158–1.902) were significantly associated with Vignette Adherence. A trend for an association between Familiarity and Vignette Adherence (OR = 1.642, CI 0.953–2.828) was evident, while no demographic variables were significantly associated with Vignette Adherence. Conclusion Targeting outcome expectancy and external barriers with multifaceted, ongoing interventions may improve guideline adherence. Pulmonologists are clearly looking for empirical evidence that these medications benefit their patients over the long-term and offset patient treatment burden with improved health. Pediatr Pulmonol. 2012; 47:434–440. © 2012 Wiley Periodicals, Inc.

BackgroundReducing nebulisation times for tobramycin solution for inhalation in cystic fibrosis (CF) may improve compliance.MethodsIn this single-dose, open-label, two-way crossover study, 13 subjects (7 CF, 6 healthy) were randomised to receive tobramycin via eFlow rapid or LC Plus jet nebuliser. Drug deposition in the lung using gamma scintigraphic imaging, nebulisation times, pharmacokinetics, and safety were evaluated.ResultsIn CF patients, whole-lung deposition was 40% less with the eFlow rapid compared with LC Plus nebulisers was (8.9±0.8%, and 15.1±6.0%, p>0.05). Nebulisation time was shorter with eFlow rapid compared to LC Plus (7.0min versus 20.0min, p

Background Patients with cystic fibrosis spend as much 30 min a day inhaling tobramycin. Could a new rapid system deposit the equivalent amount of tobramycin faster? Methods Six healthy adult males inhaled 5 ml (300 mg) of tobramycin from a breath enhanced nebulizer and either 125 mg (n = 3) or 150 mg (n = 3) from a vibrating membrane system with a large or small aerosol mixing chamber respectively. A radiolabel was added to the solution and shown to “track” with the tobramycin. Imaging was done with a dual headed gamma camera. Because the radiolabel will be cleared by mucociliary action during administration, algorithms were developed to allow the comparison of a slower system to a faster one. Results Both formulations were well tolerated. The lung deposition was 16.6 ± 3.2% (mean ± SD) of the charge dose delivered in 10.9 ± 1.0 min for the breath enhanced nebulizer versus 32.0 ± 5.1% delivered in 2.5 ± 0.4 min from the vibrating membrane system. The absolute pulmonary delivery of tobramycin was 49.9 ± 9.6 versus 43.9 ± 4.8 mg for the two systems respectively, differences that were statistically significant (pair t-test) but unlikely to be clinically significant. There was a similar deposition of tobramycin for the 125 and 150 mg dose. Conclusions It is possible to deliver an equivalent amount of tobramycin in a shorter period of time with the new vibrating membrane system and a more concentrated formulation. These data will allow the design of a comparison in patients with CF. Pediatr Pulmonol. 2008; 43:753–759. © 2008 Wiley-Liss, Inc.

73 Real world evidence on inhaled tobramycin use in CF patients: analysis of the RAMQ data (Canada) J. Lachaine1, M.-E. Lapierre2, C. Beauchemin2, G. Angyalosi3, M.-M. Balp3, F. Calado3, L. Debonnett4, J. Desforges5, A. Sagkriotis3. 1University of Montreal, Faculty of Pharmacy, Montreal, Canada; 2University of Montreal, Montreal, Canada; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Pharmaceuticals Corporation, New York City, United States; 5Novartis Pharmaceuticals Canada Inc., Dorval, Canada

73 Real world evidence on inhaled tobramycin use in CF patients: analysis of the RAMQ data (Canada) J. Lachaine1, M.-E. Lapierre2, C. Beauchemin2, G. Angyalosi3, M.-M. Balp3, F. Calado3, L. Debonnett4, J. Desforges5, A. Sagkriotis3. 1University of Montreal, Faculty of Pharmacy, Montreal, Canada; 2University of Montreal, Montreal, Canada; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Pharmaceuticals Corporation, New York City, United States; 5Novartis Pharmaceuticals Canada Inc., Dorval, Canada

year. Data are presented as Median (Interquartile Range) and 2-tailed, Wilcoxon signed-rank tests were used to compare parameters. Results: 11 patients [Median Age: 30 (19–61)] years, had 6-month data available. All patients tolerated the treatment well. The results are shown in the table below. Conclusions: Our experience and this data suggests a significant clinical benefit in the short term in a select group of acutely deteriorating adult CF patients and we continue to monitor its effects over the longer term.

Objectives Allergic Bronchopulmonary Aspergillosis syndrome (ABPAs) occurs in 10 to 15% of the CF patients. We intend to study facilitators and consequences of ABPAs in P. aeruginosa (Ps) colonized CF patients. Methods Sixty four ABPAs and Ps colonized patients matched for age and gender were compared to 128 controls. FEV1, FVC, infectious exacerbations and BMI were studied 10 years before until 10 years after the index year. Results On the index year no differences were found for BMI, FVC and FEV1. Patients with ABPAs have a higher prevalence of CFRD and significantly more were on treatment with inhaled corticosteroids, RhDnase, azithromycin and inhaled tobramycin. Cumulative values (FEV1, FVC, days of IV antibiotics) over the period before the index year were similar, over the 10 years period after the index year significantly lower values for FEV1 (p Significantly more patients with ABPAs had at least one positive culture for A. fumigatus (p Conclusion In chronic Ps colonized CF patients lower lung function values are not a facilitating factor for ABPAs. Inhaled corticosteroids, RhDnase, azithromycin and inhaled tobramycin were significantly more prevalent in the ABPA group. ABPAs patients needed significantly more antibiotics, in contrast with controls, after than before the index year.

It is well-known that inhaled tobramycin is safe and effective for the treatment of Pseudomonas lung infections.[1][1] The majority of investigations of inhaled tobramycin have involved patients with cystic fibrosis. Inhalation of tobramycin delivers the drug directly to the site of infection in the

Background Several guidelines on infection control and treatment of infection exist for cystic fibrosis (CF) caregivers, although the extent of implementation is variable. Methods Adherence to European Consensus Guidelines for CF was studied by sending surveys to named healthcare professionals in 487 European CF centres/units. Qualitative data analysis was performed. Results A total of 177/547 (32%) surveys were returned. Infection control policies were implemented by most (77%) respondents. Separation of patients with Burkholderia cepacia was more common in adults (95%) than children (9%), and was implemented by 53% of respondents for Pseudomonas aeruginosa . Nebulised colistin plus oral ciprofloxacin was the most common (43%) therapy for P. aeruginosa infection. First infections of P. aeruginosa were usually treated with inhaled tobramycin; 41% of repondents did not intervene until lung function deteriorated. Most exacerbations were treated for less than the recommended period. Conclusions European Consensus Guidelines are widely adhered to. Areas for improvement include: initiating therapy for exacerbations early, separating infected patients and optimising duration of antibiotic therapy.

BackgroundInhaled tobramycin therapy has been shown to be efficacious in clinical trials for the eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis (CF). However, the effectiveness of different regimens in eradicating P. aeruginosa and preventing the development of chronic infection in actual clinical settings has yet to be determined.MethodsThis was an observational study of children (

De mauvaises conditions de prelevement de sang au bout du doigt chez un enfant entrainent des concentrations excessivement elevees de Tobramycine. Le prelevement par voie intraveineuse et en prenant des precautions pour empecher l'exposition de la peau au medicament permettent de trouver des concentrations valables