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Background: A protocol was established for ventilator-associated tracheitis or pneumonia using inhaled tobramycin 300 mg every 12 hours in mechanically ventilated children via a vibrating mesh nebulizer, 30 cm from the endotracheal tube in the inspiratory loop of the mechanical ventilator., Objectives: The primary objective was to determine the incidence of detectable tobramycin trough concentrations >0.5 µg/mL. Secondary objectives included a comparison of clinical characteristics between those with and without detectable concentrations and identification of patients with acute kidney injury (AKI) as defined by the Kidney Diseases Improving Global Outcomes (KDIGO) criteria., Methods: This was a single-center retrospective study of critically ill children <18 years without cystic fibrosis receiving inhaled tobramycin between July 1, 2016, and August 31, 2021. Data collection included demographics, tobramycin regimen, and renal function. Analysis was performed using SAS 9.4, with a P -value <0.05, and a multivariable regression model was performed to identify factors for detectable concentrations and AKI., Results: Forty-four patients (66 courses) were included, with an overall age of 0.83 years. Thirty (68%) patients had detectable concentrations and 9 (20.5%) developed AKI. No significant differences in demographics, diagnosis, mechanical ventilation settings, and number of nephrotoxins were noted between those with and without detectable concentrations or AKI. Multivariable regressions did not identify factors associated with detectable concentrations or AKI., Conclusion and Relevance: Detectable concentrations occurred with the majority of courses, with AKI associated with approximately one-fourth of courses. Clinicians should consider utilizing trough monitoring for all mechanically ventilated critically ill children receiving inhaled tobramycin., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

There is no effective chronic suppressive therapy Burkholderia cepacia complex infection in cystic fibrosis (CF) patients. This was a pilot, open-label clinical trial of tobramycin inhalation powder (TIP) delivered via Podhaler twice daily for 28 days in adults and children with CF and chronic B. cepacia complex infection in Toronto, Canada. A total of 10 subjects (4 pediatric, 6 adult patients) were treated. There was a mean drop of 1.4 log (CFU/ml) in sputum bacterial density (p = 0.01) and sputum IL-8 levels decreased significantly after 28 days of TIP (p = 0.04). The mean relative change in FEV 1 (L) from Day 0 to Day 28 of TIP administration was a 4.6% increase but this was not statistically significant. The majority of patients (70%) had no or mild adverse events. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Pseudomonas aeruginosa (Pa) is the predominant organism infecting the airways of patients with cystic fibrosis (CF). This organism has an armamentarium of survival mechanisms that allows it to survive in the CF airway. Since colonization and chronic infection with Pa is associated with poorer lung function and increased morbidity and mortality, therapies that can prevent infection could significantly improve the lives of patients with CF. Numerous studies have examined the effects of treatment on the eradication of Pa as a means to ameliorate disease. This article outlines the pathophysiology and clinical implication of Pa acquisition, and reviews the existing treatment regimens aimed at early eradication of Pa in patients with CF. [Copyright &y& Elsevier]

Introduction: In aim to achieve better infection control and possible eradication of the pathogens involved in chronic infections of patients with cystic fibrosis (CF) scientists have developed a new way to administer antimicrobials - inhalation. The first and so far the only available inhalable antimicrobial in Bulgaria is inhaled tobramycin (TOBI), introduced in 2009.We aimed to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients before and after initiation of TOBI in the regular treatment regimen. Methodology: We have determined the minimal inhibitory concentration (MIC) of 17 antimicrobials by the E-test (LIOFILCHEM) in sputa samples of 118 CF patients for the period of 2005-2014. The results were interpreted according to the annual Clinical and Laboratory Standards Institute guidelines. Results: In the sputa of 70 patients a total of 102 P. aeruginosa isolates were found. Sixty-eight out of 102 (66.7%) were susceptible to all studied antimicrobials. We divided the isolates in two chronological groups: those collected before the introduction of TOBI as a regular treatment in 2009 and those collected after 2009. A significant reduction (p < 0,001-0,02) in susceptibility for the strains after 2009 was noted towards piperacillin (100% vs 50%), ceftazidime (100%/77.3%), cefepime (97.9%/68.2%), amikacin (100%/63.6%), gentamicin (95.7%/40.9%), tobramycin (93.6%/59.1%) and ciprofloxacin (93.6%/45.5%). Conclusion: The introduction of inhaled tobramycin as a regular therapy for CF patients in Bulgaria lead to a significant change in antimicrobial susceptibility of CF P. aeruginosa. [ABSTRACT FROM AUTHOR]

Abstract: European consensus guidelines recommend nebulised antibiotics for maintenance therapy in patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Two formulations of tobramycin for inhalation are available in Europe (Tobi®; Novartis AG, Switzerland; Bramitob®; Chiesi Farmaceutici S.p.A., Italy). Data from a series of randomised controlled studies in patients with mild-to-moderate cystic fibrosis and chronic P. aeruginosa infection show that both Tobi® and Bramitob® significantly improve lung function and reduce the density of P. aeruginosa in sputum. Bacterial resistance may develop but does not seem to be clinically important. Other benefits, such as improved patient nutritional status and reductions in the need for hospitalisation, antipseudomonal antibiotics and productivity losses have also been documented with Tobi® and Bramitob®. Both formulations of inhaled tobramycin are well tolerated with no evidence of renal or ototoxicity. Improved patient compliance may be achieved through reducing nebulisation time, either by using Bramitob®, which is formulated in a smaller volume than Tobi®, or with new generation nebulisers. In conclusion, inhaled tobramycin not only improves lung function in patients with cystic fibrosis, but also offers other benefits which have implications for healthcare costs and patient quality of life. [Copyright &y& Elsevier]

Abstract: Background: The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood. Purpose: The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture. Methods: The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1–12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15–20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1787 were enrolled in the cohort study. Conclusions: These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the airways of young children with CF. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]