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Background: Inhaled antibiotics are an important part of cystic fibrosis (CF) airway disease management and should be individualized to fit the microorganism and match patient needs. To investigate the implementation of personalized treatment, this study mapped the use of different types of inhaled antibiotics and adherence patterns. Methods: We performed individual structured interviews in a cross-sectional study at the CF Centre in Copenhagen, Denmark. Patients with CF older than 15 years attending clinical consultations were included. Clinical data were obtained from centralized databases. Results: Among 149 participants, 107 (72%) had indication for treatment with inhaled antibiotics. In this group, 97 (91%) reported the use of inhaled antibiotics within the last 12 months. Change from one inhaled antibiotic to another during that period was reported by 31 (29%), and 17 (25%) with Pseudomonas aeruginosa had used off-label antibiotics. Adherence to a minimum of one daily dose of antibiotic was reported by 78%, while adherence to all daily doses was 28 percentage points lower. Skipping inhalations was due to side effects and doubt about the effect in less than 5% of cases. Conclusion: Change of inhaled antibiotics and use of off-label antibiotics for inhalation were common and side effects were a rare cause of nonadherence. This suggests satisfactory implementation of the principle of tailored antibiotic inhalation prescription in the Copenhagen CF population. Adherence to at least one daily inhalation dose was markedly higher than adherence to multiple daily inhalations.

International guidelines have recommended the use of inhaled beta‐2 agonists and systemic corticosteroids (SCs) as the first‐line treatment for acute asthma. Objective To evaluate the evidence for the efficacy of inhaled corticosteroids (ICSs) in addition to SCs compared to SCs alone in children with acute asthma in the emergency department (ED) or during hospitalization. Data Sources Five electronic databases were searched. Study Selection All randomized clinical trials that compared ICS (via nebulizer or metered dose inhaler) plus SC (oral or parenteral) with placebo (or standard care) plus SC were included without language restriction. Data Extraction Two reviewers independently reviewed all the studies. The primary outcomes were hospital admission and hospital length of stay (LOS), and secondary outcomes were readmissions during follow‐up, ED‐LOS, lung function, asthma clinical score, oxygen saturation, and heart and respiratory rates. Results Nine studies (n = 1473) met the inclusion criteria. In all the studies, the ICS was budesonide. Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreased hospital LOS by more than 1 day (MD = −29.08 hours [−39.9 to −18.3]; I2 = 0%, P =

Background Revefenacin (TD-4208) is a potent, lung-selective, long-acting muscarinic antagonist currently in development as a once-daily nebulized therapy for chronic obstructive pulmonary disease (COPD). We evaluated the pharmacodynamics (bronchodilator activity), pharmacokinetics (PK) and safety of single- and multiple-dose administrations of revefenacin in two clinical trials (Study 0059 and Study 0091) in patients with moderate to severe COPD. Methods In Study 0059, 32 patients were randomized to receive a single dose of revefenacin (350 or 700 μg), active control ipratropium (500 μg) or placebo inhalation solution administered via standard jet nebulizer in a double-blind, crossover fashion. In Study 0091, 59 patients were randomized to receive once-daily inhalations of revefenacin (22, 44, 88, 175, 350 or 700 μg) or placebo for 7 days in a double-blind, incomplete block, five-way crossover design. The primary efficacy endpoint was change from baseline in peak (0–6 h) forced expiratory volume in 1 s (FEV1) in Study 0059, and trough FEV1 after the final dose (Day 7) in Study 0091. In both studies, secondary endpoints included area under the FEV1-time curve (FEV1 AUC) values from time 12–24 h post dose and FEV1 AUC values from time zero to 24 h post dose. Results Revefenacin demonstrated a rapid onset and sustained duration of bronchodilator action in both studies. In Study 0059, mean peak FEV1 was significantly higher (p < 0.001) for revefenacin and ipratropium compared to placebo, with differences of 176.8 mL for 350 μg revefenacin, 162.2 mL for 700 μg revefenacin and 190.6 mL for ipratropium. In Study 0091, mean trough FEV1 on Day 7 was significantly higher (p < 0.006) for all revefenacin doses compared to placebo, with differences ranging from 53.5 mL (22 μg dose) to 114.2 mL (175 μg dose). The results for the other spirometry endpoints were consistent with the primary endpoint for each study, demonstrating that the bronchodilator effect of revefenacin lasted more than 24 h following nebulized administration. Revefenacin was rapidly absorbed and extensively metabolized, followed by a slow apparent terminal elimination and minimal accumulation with repeated dosing. In both studies, adverse events were generally mild and occurred with similar frequencies in all groups, with no indication of significant systemic anti-muscarinic activity at any dose. Conclusions Following single or multiple nebulized-dose administration in patients with COPD, revefenacin demonstrates a rapid onset and sustained duration of bronchodilator effect over 24 h following once-daily administration, with a PK profile that is commensurate with low systemic exposure.

Background Asthma is characterized by airways narrowing and airflow limitation. The conventional therapy for asthma exacerbation is usually efficient but sometimes patients not respond to it, consequently; other additive drugs may be used as magnesium sulfate(MgSO 4 ) either intravenously or by nebulization. Objective To compare the bronchodilator effect of MgSO 4 via intravenous injection and nebulization in controlling asthma exacerbation. Methods 40 patients with asthma exacerbation were equally and randomly enrolled in two groups. One group received nebulized MgSO 4 (A), and the other group received intravenous MgSO 4 (B). Results Improvement was higher in group B than in group A but without significant change in PEFR also there was no high significant difference in the two group parameters after MgSO 4 treatment. Complications were few and manageable in both groups. Conclusion Intravenous MgSO 4 is effective affordable and cheap drug for asthma exacerbation management with good response while nebulized MgSO 4 didn’t give the aimed response in these patients.

To determine by experimentation whether micafungin and anidulafungin possess physicochemical properties suitable for nebulization.PH, osmolality, viscosity, density and chloride content were determined by pH monitoring, osmometry, viscometry, densitometry and potentiometry in two samples of different concentrations, 5 and 10 mg/mL each echinocandin. Results: The results obtained for micafungin solution were: pH 5.80 (0.14), osmolality 293.33 (1.53) mOsm/kg, chloride content 134.67 (0.58) mmol/L and density 1,009.4 (0,1) kg/m3; while for 10 mg/mL solution: osmolality 342.00 (1.00) mOsm/kg, chloride content 139.67 (0.58) mmol/L and density 1,014.5 (0.2) kg/m3. The results obtained for 5 mg/mL anidulafungin were: pH 4.22 (0.01), osmolality 464.67 (2.52) mOsm/kg, chloride content 137.00 (0.00) mmol/L and density 1,016.5 (0,2) kg/m3; while for 10 mg/mL solution: osmolality 656.33 (1.15) mOsm/kg, chloride content 132.00 (0.00) mmol/L and density 1,029.8 (0.4) kg/m3. Conclusions: PH, osmolality, chloride content and density values proved to be suitable for proper tolerability by nebulization.Objetivo: Determinar experimentalmente si micafungina y nidulafungina poseen propiedades fisicoquímicas adecuadas para su nebulización.Método: Se determinó el pH, la osmolalidad, la viscosidad, la densidad y el contenido en cloruros mediante pH-metría, osmometría, viscosimetría, densitometría y potenciometría, respectivamente, en dos muestras de diferente concentración, 5 y 10 mg/ml, de cada equinocandina.Resultados: Para la solución de micafungina 5 mg/ml los resultados obtenidos fueron: pH 5,80 (0,14), osmolalidad 293,33 (1,53) mOsm/kg, contenido en cloruros 134,67 (0,58) mmol/l y densidad 1.009,4 (0,1) kg/m3; y para la solución de 10 mg/ml: osmolalidad 342,00 (1,00) mOsm/kg, contenido en cloruros 139,67 (0,58) mmol/l y densidad 1.014,5 (0,2) kg/m3. Para la solución de anidulafungina 5 mg/ml los resultados obtenidos fueron: pH 4,22 (0,01), osmolalidad 464,67 (2,52) mOsm/kg, contenido en cloruros 137,00 (0,00) mmol/l y densidad 1.016,5 (0,2) kg/m3; y para la solución de 10 mg/ml: osmolalidad 656,33 (1,15) mOsm/kg, contenido en cloruros 132,00 (0,00) mmol/l y densidad 1.029,8 (0,4) kg/m3. Conclusiones: Los valores de pH, osmolalidad, contenido en cloruros y densidad resultaron adecuados para una correcta tolerabilidad ediante nebulización.

Revefenacin is a novel once‐daily, lung‐selective, long‐acting muscarinic antagonist developed as a nebulized inhalation solution for the maintenance treatment of chronic obstructive pulmonary disease. In a randomized, 4‐way crossover study, healthy subjects received a single inhaled dose of revefenacin 175 µg (therapeutic dose), revefenacin 700 µg (supratherapeutic dose), and placebo via standard jet nebulizer, and a single oral dose of moxifloxacin 400 mg (open‐label) in separate treatment periods. Electrocardiograms were recorded, and pharmacokinetic samples were collected serially after dosing. The primary end point was the placebo‐corrected change from baseline QT interval corrected for heart rate using Fridericia's formula, analyzed at each postdose time. Concentration‐QTc modeling was also performed. Following administration of revefenacin 175 and 700 µg, placebo‐corrected change from baseline QTcF (ΔΔQTcF) values were close to 0 at all times, with the largest mean ΔΔQTcF of 1.0 millisecond (95% confidence interval [CI], −1.2 to 3.1 milliseconds) 8 hours postdose and 1.0 millisecond (95%CI, −1.1 to 3.1 milliseconds) 1 hour postdose after inhalation of revefenacin 175 and 700 µg, respectively. Revefenacin did not have a clinically meaningful effect on heart rate (within ±5 beats per minute of placebo), or PR and QRS intervals (within ±3 and ±1 milliseconds of placebo, respectively). Using concentration‐QTc modeling, an effect of revefenacin > 10 milliseconds can be excluded within the observed plasma concentration range of up to ≈3 ng/mL. Both doses of revefenacin were well tolerated. These results demonstrate that revefenacin does not prolong the QT interval.

Introduction Gastric overdistension by mask ventilation during induction of anesthesia in congenital diaphragmatic hernia (CDH) repair may worsen hypoxemia. Topical airway anesthesia may improve the intubating conditions during sevoflurane induction without muscle relaxation. The present study was designed to evaluate the effect of nebulized lidocaine and fentanyl on the intubating conditions without muscle relaxation during sevoflurane induction of anesthesia in infants undergoing CDH repair. The secondary aim was studying hemodynamic changes during induction. Patients and methods Forty patients scheduled for (CDH) repair were randomly selected and blindly categorized to the following: Nebulizer group: Nebulized solution of 4 mg kg −1 lidocaine 1% plus 2 μg kg −1 fentanyl, Control group: Nebulized solution of comparable volume/weight normal saline 0.9%. Nebulizer of either solution was applied 15 min before sevoflurane induction. Results Heart rate (HR) and mean arterial blood pressure (mABP) statistically significantly increased in the control group following intubation and for 2 min regarding HR and for 5 min regarding mABP in comparison with the base line and relative to the nebulizer group. There was a statistical significant improvement regarding the intubation conditions in the nebulizer group relative to the control group ( p ⩽ 0.001). The same was noticed regarding the intubation time and the number of intubation attempts ( p ⩽ 0.001). Conclusions Premedication of infants undergoing CDH repair with nebulized solution containing 4 mg kg − 1 lidocaine 1% plus 2 μg kg − 1 fentanyl improves the intubating conditions under inhalational sevoflurane induction without muscle relaxation. The studied combination can suppress patients’ hemodynamic changes to intubation.

Background and aim. In the last decade a significant increase of nebulized medication usage has been documented in Romania. Authors are aiming to describe parental and physician’s change of perspective regarding nebulized medication in the new era of online communication and education. Material and methods. Two different questionnaires were posted in a large and representative group (more than 60,000 followers) of Romanian parents and physicians, Virtual Children’s Hospital („Spitalul Virtual de Copii”). Results. More than 4,000 answers were submitted. 94.4% responders confirmed using at least once wetnebulized medication in children. A particular aspect documented was dexamethasone off-label usage via nebulizer in 67.8% children. Additional 7% of responders confirmed that they received an indication to nebulize a normal saline suspension with dexamethasone phosphate for parenteral usage, but they didn’t follow the indication and used an approved treatment. Conclusions. Upon our knowledge this is the first large study on nebulized dexamethasone in Romanian literature. 95% of Romanian children receive nebulized medication. Nebulizer is regarded by parents as a simple and friendly tool that can solve virtually all issues related to airway diseases in our country. 75% of children that received nebulized medication had a prescription for off-label use of dexamethasone.

There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs of 16 mg/liter and 64 mg/liter) and Klebsiella pneumoniae (MICs of 2 mg/liter and 64 mg/liter) using a dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations of 300 mg/liter amikacin and/or 1,200 mg/liter fosfomycin as a 12-hourly dosing regimens were used. Quantitative cultures were performed to describe changes in concentrations of the total and resistant bacterial populations. The targeted starting inoculum was 10 8 CFU/ml for both strains. We observed that neither amikacin nor fosfomycin monotherapy was bactericidal against P. aeruginosa while both were associated with rapid amplification of resistant P. aeruginosa strains (about 10 8 to 10 9 CFU/ml within 24 to 48 h). For K. pneumoniae , amikacin but not fosfomycin was bactericidal. When both drugs were combined, a rapid killing was observed for P. aeruginosa and K. pneumoniae (6-log kill within 24 h). Furthermore, the combination of amikacin and fosfomycin effectively suppressed growth of resistant strains of P. aeruginosa and K. pneumoniae . In conclusion, the combination of amikacin and fosfomycin was effective at maximizing bacterial killing and suppressing emergence of resistance against these clinical isolates.

Background: Ventilator-associated pneumonia (VAP) due to multidrug-resistant organisms (MDROs) is associated with a significant mortality in the Intensive Care Unit (ICU). The aim of this study was to compare the efficacy and safety of extended infusion of meropenem and nebulized amikacin on VAP caused by Gram-negative MDRO versus intravenous (IV) meropenem and amikacin alone. Methodology: A randomized nonblinded controlled trial was performed on ninety patients with VAP. Patients were randomized into three equal groups: Group I received IV amikacin 20 mg/kg/24 h and meropenem 2 g over 30 min/8 h. Group II received the same as Group I in addition to nebulized amikacin 25 mg/kg/day every 8 h. Group III received IV amikacin 20 mg/kg/24 h, nebulized amikacin 25 mg/kg/day every 8 h, and meropenem 2 g diluted in 240 ml normal saline over 3 h/8 h. The primary outcome was the clinical outcome of VAP. Secondary outcomes were microbiological outcome, VAP-related mortality, duration of MV, ICU stay, and nephrotoxicity. Results: Group II and Group III compared to Group I showed higher incidence of clinical cure (53.33% in Group II and 66.67% in Group III vs. 26.67% in Group I, P = 0.007). Group II compared to Group I showed significant reduction in ventilator days (5.32 ± 1.86 vs. 7.3 ± 2.1 days, respectively, P < 0.001) and reduction in ICU days (11.87 ± 2.6 vs. 15.3 ± 3.1 days, respectively, P < 0.001). Group III compared to Group II showed significant reduction in ventilator days (4.22 ± 1.32 vs. 5.32 ± 1.86, respectively, P = 0.011) and highly significant reduction in ICU days (9.21 ± 1.17 vs. 11.87 ± 2.6, respectively, P < 0.001). All groups were comparable as regards nephrotoxicity or mortality. Conclusions: Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.

β2-agonists have questionable symptomatic effect in infants with acute bronchiolitis, whereas inhaled, nebulized racemic adrenaline, commonly used in Norway, appears (clinically) to be effective. Limited lung function observations during acute bronchiolitis exists, and less for assessing possible effects inhaled adrenaline.In this preliminary study, tidal flow-volume loops were measured in 16 infants with acute bronchiolitis and seven healthy controls (mean age 7·9 and 4·4 months, respectively), with repeated measurements 15 min after inhaled nebulized racemic adrenaline (4 mg diluted in 2 ml saline) in nine bronchiolitis patients.The ratio of time to reach peak tidal expiratory flow to total expiratory time (tPTEF/tE) was significantly reduced in children with acute bronchiolitis (mean, 95% CI) (0·08, 0·05–0·10) compared to controls (0·31, 0·18–0·43), with significant improvement after inhaled racemic adrenaline 0·19 (0·13–0·25), parallel with significant clinical improvement.Lung function (tPTEF/tE) was reduced in infants with acute bronchiolitis and improved significantly after inhaled racemic adrenaline. Inhaled racemic adrenaline is potentially an important alternative for treating infants with acute bronchiolitis.

Background: The efficacy of steroid administration in the prevention of postextubation complications in critical care remains controversial. The purpose of this study was to determine whether administration of nebulized budesonide in critically ill patients reduces the occurrence of postextubation airway complications. Materials and Methods: This was a prospective, randomized, double-blind, placebo-controlled study.We prospectively followed up 70 adult patients in the intensive care unit who were intubated for more than 48 h. Patients received either nebulized budesonide (1 mg every 12 h; n = 35) or placebo (normal saline; n = 35) until 48 h after extubation. Then, the postextubation complications were assessed and recorded within 48 h of extubation. Results: The incidence of respiratory distress was lower in budesonide group (8.6% vs. 31.4%, P = 0.017). Reintubation with mechanical support was necessary in 8.6% (3.35) of patients in the budesonide group and 31.4% (11.35) of patients in the placebo group (P = 0.017). Conclusion: Nebulized budesonide after extubation is effective in reducing the incidence of reintubation and respiratory distress in adult patients.

Repeated bouts of acute and chronic lung infections are responsible for progressive pulmonary function decline in individuals with cystic fibrosis (CF), ultimately leading to respiratory failure and death. Pseudomonas aeruginosa is the archetypical CF pathogen, causes chronic infection in 70% of individuals, and is associated with an accelerated clinical decline. The management of P. aeruginosa in CF has been revolutionized with the development and widespread use of inhaled antibiotics. Aerosol delivery of antimicrobial compounds in CF enables extremely high concentrations of antibiotics to be reached directly at the site of infection potentially overcoming adaptive resistance and avoiding the potential for cumulative systemic toxicities. Tobramycin inhalation powder (TIP) represents the first dry powder inhaled (DPI) antibiotic available for use in CF. DPIs are notable for a markedly reduced time for administration, ease of portability, and increased compliance. TIP has been developed as a therapeutic alternative to tobramycin inhalation solution (TIS), the standard of care for the past 20 years within CF. Relative to TIS 300 mg nebulized twice daily in on-and-off cycles of 28 days duration, TIP 112 mg twice daily via the T-326 inhaler administered on the same schedule is associated with marked time savings, increased patient satisfaction, and comparable clinical end points. TIP represents an innovative treatment strategy for those individuals with CF and holds the promise of increased patient compliance and thus the potential for improved clinical outcomes.