Search

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.

BackgroundInhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa. However, TIP/S effect on the CF sputum microbiome has not been explored. We hypothesised that TIP/S has additional ‘off-target’ effects beyond merely P. aeruginosa and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response.MethodsWe drew sputum samples from a prospectively collected biobank. Patients were included if they had one sputum sample in the 18 months before and after TIP/S. Bacterial 16S rRNA gene profiling was used to characterise the sputum microbiome.ResultsForty-one patients met our inclusion criteria and 151 sputum samples were assessed. At baseline, median age was 30.4 years (IQR 24.2–35.2) and forced expiratory volume in 1 (FEV1) second was 57% predicted (IQR 44–74). Nineteen patients were defined a priori as responders having no net decrease in FEV1 in the year following TIP/S. No significant changes were observed in key microbiome metrics of alpha (within-sample) or beta (between-sample) diversity for samples collected before and after TIP/S. However, significant beta-diversity (Bray-Curtis) differences were noted at baseline between patients based on response status. Notably, responders were observed to have a higher abundance of Staphylococcus in pretherapy baseline samples.ConclusionsOur longitudinal study demonstrates that the sputum microbiome of patients with CF is relatively stable following inhaled tobramycin over many months. Intriguingly, our findings suggest that baseline microbiome may associate with patient response to TIP/S—suggesting the sputum microbiome could be used to personalise therapy.

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 (

61-year-old man, with a history of years of unknown etiology bronchiectasis, with chronic bronchial infection by Burkholderia multivorans, who received treatment with a double lung transplant on 08/20/2020. Persistent positive cultures of Burkholderia multivorans after transplant in respiratory samples was observed, and treatment with inhaled tobramycin 300 mg/12 hours was started. One month after treatment, a significant worsening of renal function was observed, which was already altered, and toxic levels of tobramycin were measured in blood samples 12 hours after the last inhaled administration. After stopping treatment, kidney function returned to its baseline values.

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.

The aim of this study was to investigate efficacy and safety of early supplemental administration of inhaled tobramycin for prevention and treatment of hospital-acquired pneumonia (HAP) in patients with severe multiple trauma. Methods. Fifty four patients with severe multiple trauma were divided into 2 groups: the study group (n = 27) who took inhaled tobramycin added to systemic antibiotics and the control group (n = 27) who took standard systemic antibacterial treatment. Baselines characteristics did not differ between the groups. The patients' status was assessed daily using APACHE II and CPIS scales. Results. Frequency of HP in the study group was as twice as rare compared to the controls with correspondent reduction in days in ICU. The groups did not differ in mechanical ventilation parameters and frequency of sepsis. CPIS and APACHE II scores did not increase in the inhaled tobramycin group whereas CPIS total score increased and APACHE II score did not improve in the control group. To the 5 th day, significant between-group difference was found in CPIS (p = 0.0028) and APACHE-II (р = 0.0004). Conclusion. Early administration of inhaled tobramycin 600 mg daily added to the standard systemic antibacterial therapy is safe and effective in prevention and treatment of HAP in patients with severe multiple trauma. Such therapy decreased frequency of pulmonary infectious complications and significantly reduced duration of treatment in ICU.

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.

Background CFF practice guidelines recommend patients ≥age 6 use dornase alfa and hypertonic saline daily, and those ≥age 6 colonized with Pseudomonas aeruginosa use inhaled tobramycin and oral azithromycin to improve lung function and reduce pulmonary exacerbations. A decline in FEV1 was noted in our 2008 CF Center Report. We hypothesized that increasing adherence to prescribing guidelines for these pulmonary medications would improve mean FEV1. Methods This was a quality improvement project completed at a US CF center. CFF practice guidelines were reviewed with the center physicians. Patients were identified that were eligible to receive recommended therapies and it was determined whether they were prescribed the therapies. Baseline FEV1 data was collected. Adherence rates and FEV1 were followed quarterly for 1 year. Providers received a quarterly report card with adherence rates, mean FEV1 compared to colleagues, and a list of eligible patients that were not prescribed recommended therapies. Results Ninety-two patients were included. At baseline, the overall adherence rate was 59%. Overall adherence increased quarterly (P =

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.

Inhaled tobramycin solution is indicated for use in the management of Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Concerns have been raised regarding increasing off-label use of inhaled tobramycin, particularly for the management of COPD. We conducted an 8-year repeated cross-sectional study examining the indication for prescription claims for inhaled tobramycin in Ontario paid for by the Public Drug Benefit Program, which covers all Ontario residents with financial needs or aged 65 and older. Inhaled tobramycin prescription claims increased approximately 3 times greater from 86 prescriptions in the second quarter of 2007 to 261 prescriptions in the first quarter of 2015. Approximately half of all prescriptions (range: 46-65%) per quarter were dispensed to patients with CF. A large proportion of prescriptions (range: 31-36%) were dispensed to individuals who did not have a diagnosis of CF but had a diagnosis of COPD. In 2014, there were 324 unique users of inhaled tobramycin solution in the Ontario Public Drug Program (OPDP). Only half of users (54%; n=163) had a diagnosis of CF. Our study found increasing prescriptions of inhaled tobramycin from 2007 to 2015 in the OPDP with approximately half of these claims being for off-label use, mostly among patients with COPD.

Many new therapies are emerging for the treatment of CF. In the last 2 years, six agents have been approved by the Food and Drug Administration (FDA) and four agents have given an opinion in favor of granting a marketing authorization by the European Medicines Agency (EMA) representing dramatic results from decades of investment in basic and clinical science. In this month's journal, Assael and colleagues present data from a phase 3 open-label, randomized, parallel-group, active-comparator non-inferiority trial comparing aztreonam for inhalation solution (AZLI) and inhaled tobramycin nebulizer solution (TNS)...

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.

Background Aerosolized tobramycin inhalation solution (TIS) may be absorbed and result in measurable serum concentrations. We assessed the significance of TIS dosing in the latter portion of the IV dosing interval on the calculation of pharmacokinetic (PK) parameters and dosing. Methods Twenty adult CF patients admitted to the hospital for treatment of a pulmonary exacerbation were enrolled. PK parameters of tobramycin were calculated before and after introduction of TIS, which was given 5–9h after the IV dose. Results Nine patients had a clinically significant change in tobramycin trough concentration. Fourteen patients had a reduced calculated elimination rate constant after TIS administration, which may be misinterpreted as a decreased clearance of IV tobramycin. Conclusion Trough tobramycin concentrations were significantly influenced in some CF patients (45%), suggesting that timing of the inhaled dose should be considered when interpreting PK measures of IV tobramycin dosing.

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.

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 (