Nebulised Antibiotics Research Articles

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma. They also confirm that the alveolar-capillary membrane, either normal or injured by the infectious process, restricts the penetration of intravenous aminoglycosides in the infected lung parenchyma, precluding a bactericidal effect at the site of infection. However, injury of the alveolar-capillary membrane promotes the systemic diffusion of nebulized aminoglycosides. Based on experimental data obtained in animals with inoculation pneumonia, it challenges the classical belief that nebulization protects against systemic toxicity. Loss of lung aeration decreases the lung penetration of nebulized aminoglycosides. Nevertheless, lung tissue concentrations measured in non-aerated lung regions with severe and extended pneumonia are most often greater than 5 times the MICs, resulting in a bactericidal effect followed by a progressive pulmonary reaeration. It is likely that the penetration into the consolidated lung, results from the bronchial diffusion of nebulized aminoglycosides toward adjacent non-aerated infected alveolar spaces and their penetration into mechanical ventilation-induced intraparenchymal pseudocysts and distended bronchioles. In animals receiving nebulized aminoglycosides, epithelial lining fluid concentrations grossly overestimate lung interstitial fluid concentrations because of the bronchial contamination of the distal tip of the bronchoscope during the bronchoalveolar procedures. Lung microdialysis is the only technique able to accurately assess lung pharmacokinetics in animals with inoculation pneumonia treated by nebulized aminoglycosides. In 2024, the European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia (ENAVAP) called for the creation of an international research network for Lung Microdialysis applied to Nebulized Antibiotics (LUMINA) to promote multicentered, experimental, randomized, and controlled studies addressing lung pharmacokinetics of intravenous vs. nebulized antibiotics, using different dosing and ventilator settings.

Patient attitudes to nebulised antibiotics in the treatment of bronchiectasis: a mixed-methods study.

Regular daily nebulised antibiotics are widely used in managing bronchiectasis. This patient population typically has severe bronchiectasis requiring multiple other medications. Given that little is known about patients' views and preferences for such therapies, this was the focus of our study. To explore patient lived-experience using nebulised antibiotics, focus groups and semi-structured interviews were conducted with patients and carers; these were audio-recorded and transcribed to enable thematic analysis. QSR NVivo software facilitated data management. The themes developed from the qualitative data analysis were then used to co-design a questionnaire to capture attitudes and preferences towards nebulised therapy. Questionnaires were completed by patients and statistical analysis was performed. Ethical approval was obtained (13/WS/0036). The study's focus groups comprised 13 patients and carers, and 101 patients completed the questionnaire. Patients described nebulised therapy as an imposition on their daily routine, in turn affecting reported rates of adherence. Results demonstrated that 10% of all patients using nebulised antibiotics found these hard/very hard to administer. Further, 53% of participants strongly agreed/agreed that they would prefer an antibiotic delivered by an inhaler over a nebuliser, if it were as effective at preventing exacerbations. Notably, only 10% of participants wished to remain on nebulised therapy. Inhaled antibiotics delivered via dry powder devices were deemed quicker and easier to use by patients. Providing they were at least as effective as current nebulised treatments, patients deemed inhaled antibiotics to be a preferable treatment option.

An observational study of Pseudomonas aeruginosa in adult long-term ventilation.

IntroductionPseudomonas aeruginosa increases morbidity and mortality in respiratory disease. To date the long-term ventilation population does not have clear guidelines regarding its management.MethodWe undertook a retrospective observational study in a regional long-term ventilation population (837 patients). We defined the primary outcome as P. aeruginosa isolation. In addition positive cultures for copathogens (Serratia, Proteus species, Stenotrophomonas, Burkholderia cepacia complex and nontuberculous mycobacteria) were recorded. Logistic regression and odds ratios were calculated.Results17.6% of the cohort isolated P. aeruginosa, and this pathogen was cultured more frequently in patients with a tracheostomy (logistic regression coefficient 2.90, p≤0.0001) and cystic fibrosis/bronchiectasis (logistic regression coefficient 2.48, p≤0.0001). 6.3% of patients were ventilated via tracheostomy. In the P. aeruginosa positive cohort 46.9% of patients were treated with a long-term macrolide, 36.7% received a nebulised antibiotic and 21.1% received both. Tracheostomised P. aeruginosa positive patients received a nebulised antibiotic more frequently (OR 2.63, 95% CI 1.23–5.64, p=0.013). Copathogens were isolated in 33.3% of the P. aeruginosa cohort. In this cohort patients with a tracheostomy grew a copathogen more frequently than those without (OR 2.75, 95% CI 1.28–5.90).ConclusionsP. aeruginosa isolation is common within the adult long-term ventilation population and is significantly associated with tracheostomy, cystic fibrosis and bronchiectasis. Further research and international guidelines are needed to establish the prognostic impact of P. aeruginosa and to guide on antimicrobial management. The increased risk of P. aeruginosa should be considered when contemplating long-term ventilation via tracheostomy.

The effect of nebulized antibiotics in children with tracheostomy

IntroductionChildren with tracheostomy have an increased risk of bacterial colonization and infection of the lower respiratory tracts. This study aimed to investigate the effects of nebulized antibiotics on the bacterial load, the need for oral antibiotics, the number of hospitalizations, and the length of stay in the intensive care unit in tracheotomised children with persistent colonization. MethodsChildren with tracheostomy and persistent bacterial colonization who were started on nebulized antibiotic therapy after a lower respiratory tract infection were included in the study. Nebulized gentamicin or colistin were used according to the results of the tracheal aspirate cultures. Demographic and clinic characteristics were recorded from one year prior until one year after initiation of nebulized antibiotic treatment. ResultsNebulized antibiotic treatment was initiated in 22 patients. Nebulized gentamicin was administered to 14 patients (63.6%) and colistin to 8 patients (36.4%). The median duration of treatment was 3 months (range 2–5 months). Following nebulized antibiotic treatment, median number of hospitalizations decreased from 2 (range 1.0–3.5) to 1 (range 0.0–1.5) (p = 0.04). The median length of stay in the intensive care unit reduced significantly from 89.5 days (range 43.0–82.5) to 25 days (range 7.75–62.75) after starting nebulized antibiotics (p = 0.028). Following nebulized antibiotic treatment median bacterial colony count also decreased (from 105 CFU/ml (range 105-106) to 6 × 104 CFU/ml (range 104-105); p = 0.003). There were no significant side effects during nebulized antibiotic therapy. ConclusionsThe use of nebulized antibiotics reduced the number of hospitalizations, length of stay in the intensive care unit, and bacterial load in tracheotomised children with persistent airway colonization without significant side effects. The use of nebulized antibiotics showed a statistically significant decrease in the measures studied. Use of nebulized antibiotics may help to decrease the health care burden of these children, families and health care system. Further studies are needed to determine the indications and optimal duration of long-term nebulized antibiotic treatment in children with tracheostomy.

Nebulized antibiotics for ventilator-associated pneumonia: methodological framework for future multicenter randomized controlled trials.

Although experimental evidence supports the use of nebulized antibiotics in ventilator-associated pneumonia (VAP), two recent multicenter randomized controlled trials (RCTs) have failed to demonstrate any benefit in VAP caused by Gram-negative bacteria (GNB). This review examines the methodological requirements concerning future RCTs. High doses of nebulized antibiotics are required to reach the infected lung parenchyma. Breath-synchronized nebulizers do not allow delivery of high doses. Mesh nebulizers perform better than jet nebulizers. Epithelial lining fluid concentrations do not reflect interstitial lung concentrations in patients receiving nebulized antibiotics. Specific ventilator settings for optimizing lung deposition require sedation to avoid patient's asynchrony with the ventilator. Future RCTs should compare a 3-5 day nebulization of amikacin or colistimethate sodium (CMS) to a 7-day intravenous administration of a new cephalosporine/ß-lactamase inhibitor. Inclusion criteria should be a VAP or ventilator-associated tracheobronchitis caused by documented extensive-drug or pandrug resistant GNB. If the GNB remains susceptible to aminoglycosides, nebulized amikacin should be administered at a dose of 40 mg/kg/day. If resistant to aminoglycosides, nebulized CMS should be administered at a dose of 15 millions international units (IU)/day. In VAP caused by pandrug-resistant GNB, 15 millions IU/day nebulized CMS (substitution therapy) should be compared with a 9 millions IU/day intravenous CMS.

Comparative lung distribution of radiolabeled tobramycin between nebulized and intravenous administration in a mechanically-ventilated ovine model, an observational study.

BackgroundVentilator-associated pneumonia is common and is treated using nebulized antibiotics. Although adequate pulmonary biodistribution is important for antibiotic effect, there is a lack of data for both intravenous (IV) and nebulized antibiotic administration during mechanical ventilation. ObjectiveTo describe the comparative pulmonary regional distribution of IV and nebulized technetium-99m-labeled tobramycin (99mTc-tobramycin) 400 mg in a mechanically-ventilated ovine model. MethodsThe study was performed in a mechanically-ventilated ovine model. 99mTc-tobramycin 400 mg was obtained using a radiolabeling process. Computed tomography (CT) was performed. Ten sheep were given 99mTc-tobramycin 400 mg via either an IV (five sheep) or nebulized (five sheep) route. Planar images (dorsal, ventral, left lateral and right lateral) were obtained using a gamma camera. Blood samples were obtained every 15 min for 1 h (4 time points) and lung, liver, both kidney, and urine samples were obtained post-mortem. ResultsTen sheep were anesthetized and mechanically ventilated. Whole-lung deposition of nebulized 99mTc-tobramycin 400 mg was significantly lower than with IV (8.8% vs. 57.1%, P<0.001). For both administration routes, there was significantly lower deposition in upper lung zones compared with the rest of the lungs. Dorsal deposition was significantly higher with nebulized 99mTc-tobramycin 400 mg compared with IV (68.9% vs. 58.9%, P=0.003). Lung concentrations of 99mTc-tobramycin were higher with IV compared with nebulized administration. There were significantly higher concentrations of 99mTc-tobramycin in blood, liver and urine with IV administration compared with nebulized. ConclusionsNebulization resulted in lower whole and regional lung deposition of 99mTc-tobramycin compared with IV administration and appeared to be associated with low blood and extra-pulmonary organ concentrations.

Management of initial colonisations with Burkholderia species in France, with retrospective analysis in five cystic fibrosis Centres: a pilot study

BackgroundWhereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome.MethodsWe performed a retrospective review of the primary colonisations (PC), defined as newly positive sputum cultures, observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected.ResultsSeventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher forced expiratory volume in 1 second and forced vital capacity at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. The management of PC was shown to be heterogeneous, thus impairing the statistical power of our study. Large prospective studies are needed to define whom to treat, when, and how.ConclusionsPending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia 1 month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of intravenous beta-lactam + oral or intravenous fluoroquinolone + inhaled aminoglycoside.

How should we treat acinetobacter pneumonia?

To describe recent data about Acinetobacter baumannii pneumonia epidemiology and the therapeutic options including adjunctive nebulized therapy. A. baumannii is a major cause of nosocomial pneumonia in certain geographic areas affecting mainly debilitated patients, with prolonged hospitalization and broad-spectrum antimicrobials. Inappropriate empirical treatment has clearly been associated with increased mortality in A. baumannii pneumonia. Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are the antimicrobials with the greatest level of in-vitro activity. Colistin is the antimicrobial most widely used although polymyxin B is associated with less renal toxicity. It is clear that lung concentrations of polymyxins are suboptimal in a substantial proportion of patients. This issue has justified the use of combination therapy or adjunctive nebulized antibiotics. Current evidence does not allow us to recommend combination therapy for A. baumannii pneumonia. Regarding nebulized antibiotics, it seems reasonable to use in patients who are nonresponsive to systemic antibiotics or A. baumannii isolates with colistin minimum inhibitory concentrations close to the susceptibility breakpoints. Cefiderocol, a novel cephalosporin active against A. baumannii, may represent an attractive therapeutic option if ongoing clinical trials confirm preliminary results. The optimal treatment for multidrug-resistant A. baumannii pneumonia has not been established. New therapeutic options are urgently needed. Well designed, randomized controlled trials must been conducted to comprehensively evaluate the effectiveness and safety of nebulized antibiotics for the treatment of A. baumannii pneumonia.

The Efficacy and Safety of using Nebulized Antibiotics in Treatment of Ventilator-Associated Pneumonia

Development of ventilator- associated pneumonia [VAP] is associated with high morbidity and mortality rates. VAP mortality ranges between 5.8% and 27% [1]. Routine administration of intravenous antibiotics does not reach a bactericidal concentration in lung tissues. intravenous antibiotics are mainly detected in respiratory segments of lungs, but not in sputum [2].This study was conducted on 60 patients who were admitted to critical care department at Benha University Hospital and diagnosed with Ventilator Associated Pneumonia [VAP]. patients were divided into two groups: Group A included 30 patients have received only systemic antibiotics and Group B included 30 patients have received systemic and nebulized antibiotics. In this study the clearance of organism, resistance, superinfection and combined [resistance and super infection] were significantly different in group A vs.B .There was significant decrease regarding creatinine level in group B vs. A .There were significant reduction in duration of MV and length of ICU stay in group B vs. A.Nebulized Amikacin plus ceftazidime are effective in the treatment of VAP.

191 The potential use of dual nebulised antibiotics for the treatment of pulmonary exacerbations among adults with cystic fibrosis and chronic P. aeruginosa infection

191 The potential use of dual nebulised antibiotics for the treatment of pulmonary exacerbations among adults with cystic fibrosis and chronic P. aeruginosa infection

Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients

Nebulized antibiotics have an established role in patients with cystic fibrosis or bronchiectasis. Their potential benefit to treat respiratory infections in mechanically ventilated patients is receiving increasing interest. In this consensus statement of the European Society of Clinical Microbiology and Infectious Diseases, the body of evidence of the therapeutic utility of aerosolized antibiotics in mechanically ventilated patients was reviewed and resulted in the following recommendations: Vibrating-mesh nebulizers should be preferred to jet or ultrasonic nebulizers. To decrease turbulence and limit circuit and tracheobronchial deposition, we recommend: (a) the use of specifically designed respiratory circuits avoiding sharp angles and characterized by smooth inner surfaces, (b) the use of specific ventilator settings during nebulization including use of a volume controlled mode using constant inspiratory flow, tidal volume 8 mL/kg, respiratory frequency 12 to 15 bpm, inspiratory:expiratory ratio 50%, inspiratory pause 20% and positive end-expiratory pressure 5 to 10 cm H2O and (c) the administration of a short-acting sedative agent if coordination between the patient and the ventilator is not obtained, to avoid patient's flow triggering and episodes of peak decelerating inspiratory flow. A filter should be inserted on the expiratory limb to protect the ventilator flow device and changed between each nebulization to avoid expiratory flow obstruction. A heat and moisture exchanger and/or conventional heated humidifier should be stopped during the nebulization period to avoid a massive loss of aerosolized particles through trapping and condensation. If these technical requirements are not followed, there is a high risk of treatment failure and adverse events in mechanically ventilated patients receiving nebulized antibiotics for pneumonia.

Oral anti-pseudomonal antibiotics for cystic fibrosis.

Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review. To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016. Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment. Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information. We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the included trials reported significantly better lung function when treating a pulmonary exacerbation with ciprofloxacin when compared with intravenous treatment; however, our analysis did not confirm this finding. We found no evidence of difference between oral anti-pseudomonal antibiotics and other treatments regarding adverse events or development of antibiotic resistance, but trials were not adequately powered to detect this. None of the studies had a low risk of bias from blinding which may have an impact particularly on subjective outcomes such as quality of life. The risk of bias for other criteria could not be clearly stated across the studies. We found no conclusive evidence that an oral anti-pseudomonal antibiotic regimen is more or less effective than an alternative treatment for either pulmonary exacerbations or long-term treatment of chronic infection with P. aeruginosa. Until results of adequately-powered future trials are available, treatment needs to be selected on a pragmatic basis, based upon any available non-randomised evidence, the clinical circumstances of the individual, the known effectiveness of drugs against local strains and upon individual preference.

Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient.

Gram-negative pneumonia in patients who are intubated and mechanically ventilated is associated with increased morbidity and mortality as well as higher healthcare costs compared with those who do not have the disease. Intravenous antibiotics are currently the standard of care for pneumonia; however, increasing rates of multidrug resistance and limited penetration of some classes of antimicrobials into the lungs reduce the effectiveness of this treatment option, and current clinical cure rates are variable, while recurrence rates remain high. Inhaled antibiotics may have the potential to improve outcomes in this patient population, but their use is currently restricted by a lack of specifically formulated solutions for inhalation and a limited number of devices designed for the nebulization of antibiotics. In this article, we review the challenges clinicians face in the treatment of pneumonia and discuss the characteristics that would constitute an ideal inhaled drug/device combination. We also review inhaled antibiotic options currently in development for the treatment of pneumonia in patients who are intubated and mechanically ventilated.

Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis.

Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.Date of last search of Cochrane trials register: 27 July 2015. Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. The authors assessed studies for eligibility and risk of bias and extracted data. We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life. The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment.

Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. OBJECTIVES: To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.Date of last search of Cochrane trials register: 27 July 2015. SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and risk of bias and extracted data. MAIN RESULTS: We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life. AUTHORS' CONCLUSIONS: The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment.

319 Nebulised temocillin for prophylaxis against Burkholderia vietnamiensis in an adult with cystic fibrosis

Objectives To illustrate the use of nebulised temocillin for prophylaxis in CF and chronic Burkholderia infection in a 29-year-old male. Methods Retrospective data collection from medical notes, included spirometry, CRP, frequency of IV antibiotics (14-day courses), and symptomatology. Data was collected for pre and post temocillin periods. Results Baseline spirometry: FEV1 66% pred., FVC 89% pred. Between ages 23 and 27 years, he had 2 courses of IV antibiotics yearly for exacerbations. FEV1 fell to a minimum of 55% pred., and CRP ( 100 on 3 occasions), and worsened spirometry (minimum FEV1 37% pred. and FVC 40% pred.). Worsening symptoms were recorded. Following onset of nebulised temocillin alternate months (7 months), frequency of IV antibiotics decreased to 4 courses (3 courses whilst off temocillin). Maximum CRP 42, and minimum FEV1 50% pred., significant symptom improvement was reported. Continuous nebulised temocillin was then started. No IV antibiotics were given in the following 4-month period. Conclusion Temocillin is a narrow spectrum penicillin stable to most β-lactamases and ESBLs. It demonstrates in vitro activity against B. cepacia . It does not induce β-lactamase production. Clinical data suggests benefit of IV temocillin for CF patients with B. cepacia . This case illustrates that temocillin may be a well tolerated and effective nebulised antibiotic for CF patients with Burkholderia .

Paranasal sinus pathogens in children with cystic fibrosis: Do they relate to lower respiratory tract pathogens and is eradication successful?

BackgroundThe study aims were to assess the association of microflora between the paranasal sinus and the lower airways of children attending a regional paediatric cystic fibrosis centre and to determine the performance of an eradication treatment protocol for positive paranasal sinus samples. MethodPaired nasal lavage and lower airway samples (cough swabs or sputum) were taken from 54 children with cystic fibrosis (median age 11years). Positive paranasal sinus samples received eradication treatment, using oral and sinonasal nebulised antibiotics. ResultsA correlation between paranasal sinus and lower airways was detected in 33/54 paired timed samples (p<0.02). Of 4/54 children who reported sinus symptoms, only 2 had paranasal sinus positive samples. 28 positive nasal lavage samples cultured 8 Pseudomonas aeruginosa (PA), 8 Staphylococcus aureus (SA) and 12 other bacterial pathogens. Eradication using sinonasal nebulised antibiotics and oral antibiotics showed a success of 14/21 (67%) treated paranasal sinus positive samples at 1month & 3months after treatment. Success rate was 75% in the PA group and 71% in the SA group. Ongoing monitoring with nasal lavage will continue. ConclusionThere was agreement between pathogens or lack of them found in the paranasal sinus and lower airways. Paranasal infection is often asymptomatic in children with cystic fibrosis. The eradication protocol for paranasal sinus pathogens had a good success rate.

The Cost Effectiveness of Dry Powder Antibiotics for the Treatment of Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonasaeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance. Our objective was to evaluate the cost effectiveness of (i) colistimethate sodium dry powder for inhalation (DPI) and (ii) tobramycin DPI versus nebulised tobramycin for the treatment of chronic P.aeruginosa lung infection in patients with CF from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). We developed a state transition model based on transitions between three strata of lung function measured in terms of forced expiratory volume in 1 second (FEV1) % predicted. Additional health states representing post-lung transplantation and dead are also modelled. The model structure was informed by systematic reviews of evidence concerning the plausibility of potential relationships between intermediate endpoints and final outcomes. The model assumes that treatment impacts on FEV1 trajectory, which manifest as changes in health-related quality of life. No survival benefit is assumed due to the absence of robust quantifiable evidence. Model parameters were informed by patient-level and aggregate data from two randomised controlled trials together with the best available evidence from the literature. Resource use and costs associated with drug acquisition, the management of exacerbations and reduced nebuliser maintenance were drawn from reference sources and expert opinion. Costs were valued at 2011/2012 prices. Costs and health outcomes were discounted at a rate of 3.5%. Simple and probabilistic sensitivity analyses were undertaken, including additional analyses of Patient Access Scheme (PAS) price discounts offered by the manufacturers of both DPI products. Colistimethate sodium DPI is expected to produce fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Based on its list price, colistimethate sodium DPI is expected to be dominated by nebulised tobramycin. When the PAS is incorporated, the incremental cost-effectiveness ratio (ICER) for colistimethate sodium DPI versus nebulised tobramycin is expected to be approximately £288,600 saved per QALY lost. Based on its current list price, the ICER for tobramycin DPI versus nebulised tobramycin is expected to be approximately £124,000 per QALY gained. When the proposed PAS is included, tobramycin DPI is expected to dominate nebulised tobramycin. Under their list prices, neither DPI product is likely to represent good value for money for the NHS given current cost-effectiveness thresholds. The PAS discounts have a significant impact upon the economic attractiveness of both DPI products compared against nebulised tobramycin. The clinical effectiveness and cost effectiveness of the DPIs against other nebulised antibiotics, such as aztreonam and inhaled colistimethate sodium, remains unclear.

P109 Do specialist non-CF bronchiectasis clinics improve quality of care?

IntroductionNon Cystic Fibrosis (CF) Bronchiectasis is increasingly recognised as a major cause of respiratory morbidity in the UK. Previous BTS audits have shown poor adherence to the 2010 BTS guidelines...

PRS38 - The Cost-Effectiveness of Dry Powder Antibiotics for the Treatment of Pseudomonas Aeruginosa in Patients with Cystic Fibrosis

Background Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonas aeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance.