Aerosol Antibiotics Research Articles

Abstract 1281: Antibiotics aerosolization shrinks intratumoral Tregs and impairs lung tumor growth by perturbing the taxonomic structure of tumor-associated microbiota

Abstract The lung has been traditionally regarded as a sterile environment. Emerging evidence has overturned this belief unveiling the existence of a specific lung microbiota that plays a pivotal role in modulating lung immune tolerance. Recent research also sheds light on how the tissue microbiota is significantly altered by the presence of a growing tumor. Here, we investigated the compositional changes in lung-colonizing bacterial populations associated with the growth of LLC1 lung carcinoma cells in C57BL/6 mice, by analyzing the lung 16S rRNA profiling. While overall microbial diversity and structure were similar in tumor-bearing and healthy lungs, abundance analysis of amplicon sequence variants (ASVs) revealed that 48 ASVs were differentially modulated at significant level (FDR ≤ 0.05). Notably, local treatment with aerosolized vancomycin/neomycin antibiotics starting 4 days after tumor injection caused a different representation of 47 ASVs (FDR ≤ 0.05), mostly reducing those ASVs specifically emerging in the lung by the tumor growth, belonging to Bacterioidales, Clostridiales, Lactobacillales and Enterobacteriales. A different microbial composition was also suggested by the results of Partial Least Squares Discriminant Analysis (PLS-DA) that clustered lung tumor samples as saline or antibiotic-aerosolized. Based on the reported ability of some bacteria belonging to these orders to induce immunosuppressive cells in the gut, we examined the impact of antibiotic aerosol on tumor-associated Tregs in the lung. The presence of the tumor promoted the appearance of Tregs expressing CD69 and PD-1 activation markers, but vancomycin/neomycin aerosol treatment strongly dropped Treg frequency in tumor-bearing lungs, compared to saline. In a therapeutic setting, aerosolization of antibiotics starting 4 days after LLC1 tumor intravenous injection significantly reduced the number of lung metastases (p=0.0116). This effect was associated with an increased cytotoxic activity of immune infiltrating effector cells suggesting that the modulation of the lung microbiota impairs tumor growth and enhances antitumor immune response. Some cultivable bacterial strains, that were in agreement with metataxonomic profile results, were isolated from tumor-bearing lungs, but not from healthy lungs. Ongoing experiments suggest an effect of their in vivo transfer in the lung by aerosol on tumor growth and the ability to induce Treg expansion in vitro. Overall, this study unveils that the growth of the murine LLC1 tumor shapes the lung microbial composition by favoring the expansion of microbes with potential immunosuppressive activity eventually affecting the tumor progression. Moreover, our findings unravel the therapeutic potential of localized antibiotics to revert the immunosuppressive microenvironment by targeting tumor-associated bacteria. Citation Format: Giancarla Bernardo, Valentino Le Noci, Elena Montanari, Emerenziana Ottaviano, Giorgio Gargari, Elisa Borghi, Simone Guglielmetti, Federico Ambrogi, Tiziana Triulzi, Elda Tagliabue, Serenella M. Pupa, Michele Sommariva, Lucia Sfondrini. Antibiotics aerosolization shrinks intratumoral Tregs and impairs lung tumor growth by perturbing the taxonomic structure of tumor-associated microbiota [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1281.

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review.

Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure.

Correlation between Aerosol Therapy and Other Associated Factors in Early Childhood with Molar Incisor Hypomineralization.

The etiology of molar incisor hypomineralization (MIH) has been extensively explored. Recently, the effect of drugs used in aerosol therapy in childhood has been implicated as a possible factor in the development of MIH. A case-control study was conducted in children aged 6-13 years to determine the association between aerosol therapy and other factors in the development of MIH. A total of 200 children were examined for the presence of MIH according to the European Academy of Paediatric Dentistry (EAPD) criteria (2003). Their mothers or primary caregivers were interviewed regarding the preterm history and perinatal, and postnatal history of the child up to 3 years of life. The collected data were subjected to statistical analysis using descriptive and inferential analyses. The p-value ≤ 0.05 was considered statistically significant. Statistically significant association was observed between the development of MIH and exposure to aerosol therapy in childhood and the use of antibiotics before 1 year of life. Exposure to aerosol therapy and antibiotics before 1 year of age are risk factors in MIH. Children who had aerosol therapy and antibiotics are 2.01 times and 1.61 times more prone to MIH. Shinde MR, Winnier JJ. Correlation between Aerosol Therapy and Other Associated Factors in Early Childhood with Molar Incisor Hypomineralization. Int J Clin Pediatr Dent 2022;15(5):554-557.

Near Elimination of In Vitro Predicted Extrathoracic Aerosol Deposition in Children Using a Spray-Dried Antibiotic Formulation and Pediatric Air-Jet DPI.

This study evaluated the in vitro aerosol performance of a dry powder antibiotic product that combined a highly dispersible tobramycin powder with a previously optimized pediatric air-jet dry powder inhaler (DPI) across a subject age range of 2-10years. An excipient enhanced growth (EEG) formulation of the antibiotic tobramycin (Tobi) was prepared using a small particle spray drying technique that included mannitol as the hygroscopic excipient and trileucine as the dispersion enhancer. The Tobi-EEG formulation was aerosolized using a positive-pressure pediatric air-jet DPI that included a 3D rod array. Realistic in vitro experiments were conducted in representative airway models consistent with children in the age ranges of 2-3, 5-6 and 9-10years using oral or nose-to-lung administration, non-humidified or humidified airway conditions, and constant or age-specific air volumes. Across all conditions tested, mouth-throat depositional loss was < 1% and nose-throat depositional loss was < 3% of loaded dose. Lung delivery efficiency was in the range of 77.3-85.1% of loaded dose with minor variations based on subject age (~ 8% absolute difference), oral or nasal administration (< 2%), and delivered air volume (< 2%). Humidified airway conditions had an insignificant impact on extrathoracic depositional loss and significantly increased aerosol size at the exit of a representative lung chamber. In conclusion, the inhaled antibiotic product nearly eliminated extrathoracic depositional loss, demonstrated high efficiency nose-to-lung antibiotic aerosol delivery in pediatric airway models for the first time, and provided ~ 80% lung delivery efficiency with little variability across subject age and administered air volume.

Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery

Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIPs) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIPs was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2 μm; and >80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI). The MIPs released from the EEG aerosol had human airway mucus and CF sputum diffusion properties comparable to the suspension formulation. These properties make this formulation a promising pulmonary drug delivery system for CF lung infections.

Prospective Evaluation of Intensity of Symptoms, Therapeutic Procedures and Treatment in Palliative Care Patients in Nursing Homes.

The aim of the study is to evaluate the intensity of symptoms, and any treatment and therapeutic procedures received by advanced chronic patients in nursing homes. A multi-centre prospective study was conducted in six nursing homes for five months. A nurse trainer selected palliative care patients from whom the sample was randomly selected for inclusion. The Edmonton Symptoms Assessment Scale, therapeutic procedures, and treatment were evaluated. Parametric and non-parametric tests were used to evaluate month-to-month differences and differences between those who died and those who did not. A total of 107 residents were evaluated. At the end of the follow-up, 39 had (34.6%) died. All symptoms (p < 0.050) increased in intensity in the last week of life. Symptoms were more intense in those who had died at follow-up (p < 0.05). The use of aerosol sprays (p = 0.008), oxygen therapy (p < 0.001), opioids (p < 0.001), antibiotics (p = 0.004), and bronchodilators (p = 0.003) increased in the last week of life. Peripheral venous catheters (p = 0.022), corticoids (p = 0.007), antiemetics (p < 0.001), and antidepressants (p < 0.05) were used more in the patients who died. In conclusion, the use of therapeutic procedures (such as urinary catheters, peripheral venous catheter placement, and enteral feeding) and drugs (such as antibiotics, anxiolytics, and new antidepressant prescriptions) should be carefully considered in this clinical setting.

Hypertonic saline enhances the efficacy of aerosolized gentamicin against Pseudomonas aeruginosa

Aerosol inhalation is a promising strategy for the delivery of antibiotic agents. The efficacy of antibiotic treatment by aerosol inhalation is reduced by the formation of microbial biofilms in the respiratory system and excessive airway mucus build-up. Various approaches have been taken in order to overcome this barrier. In this in vitro study, we used hypertonic saline (7%, by weight), a low cost Food and Drug Administration-approved reagent, as an aerosol carrier to study its effects with the antibiotic, gentamicin, on the most common respiratory opportunistic pathogen, Pseudomonas aeruginosa, present in the mucus. The results indicated that the hypertonic saline aerosol containing gentamicin, a low cost antibiotic, significantly eliminated biofilm growth by ~3-fold, compared to the regular saline aerosol containing gentamicin. In addition to enhancing the penetration efficiency of drug molecules by 70%, bacterial motility also decreased (~50%) after treatment with aerosolised hypertonic saline. In conclusion, our results demonstrate that hypertonic saline can significantly enhance the efficacy of antibiotic aerosols, which may contribute to the current use of inhaled therapeutic compounds.

Development of levofloxacin-loaded PLGA microspheres of suitable properties for sustained pulmonary release

Aerosol antibiotics are an interesting alternative to oral or intravenous therapy in Cystic Fibrosis lung infections. Levofloxacin (LVX) inhaled solution is already an effective option. In this study, the aim was the development of LVX-loaded PLGA microspheres (MS) for pulmonary administration as a dry powder. MS were prepared, for the first time, by a modified double emulsion solvent evaporation method with premix membrane homogenization. Aqueous phases were saturated with LVX and a fatty acid (lauric acid) was added to avoid the drug escaping from the organic phase. MS were characterized in terms of size, drug content, morphology and in vitro release properties. X-ray diffraction, Fourier-transform infrared spectroscopy, differential and gravimetric thermal analysis, and cytotoxicity analyses were performed. Results showed this new method increased the drug loading while maintaining an adequate (∼5 µm) particle size and controlled release. Compared to a solution for inhalation, these properties combined with the dry-powder nature of these MS will improve patient compliance. The incorporation of lauric acid was not advantageous because the particle size was higher and no improvements concerning the sustained release occurred. LVX was molecularly dispersed in the matrix, or it was in amorphous state, as confirmed by the physico-chemical analyses. Calu-3 cell viability assays demonstrated no cytotoxicity for these MS, making them a promising system for LVX pulmonary delivery.

Understanding Treatment Adherence With the Health Belief Model in Children With Cystic Fibrosis.

Children's health beliefs are significantly related to their adherence; however, pediatric literature has rarely tested health-related theories as a whole. The goal of the present study was to evaluate the use of the health belief model (HBM) in understanding children's adherence, both globally and to individual treatment components. Thirty-three patient-parent dyads completed questionnaires regarding health beliefs and adherence to medical regimens. Multiple linear regressions found a significant relationship among the HBM variables and reports of global adherence for children and parents. For children, the HBM variables were significantly related to adherence to aerosol medications, aerosol antibiotics, metered dose inhalers, and vitamins. For parents, the HBM variables were significantly related to children's adherence to airway clearance, oral antibiotics, and vitamins. Paired sample t tests found children and parents had significantly discrepant heath beliefs. These findings provide further support for the HBM in evaluating pediatric adherence, with evidence that barriers and cues to action may be targets for early intervention. Future research using this model to identify a comprehensive way to assess, understand, and elicit change in the adherence to medical regimens for youth with chronic illness would be beneficial.

An Update on Aerosolized Antibiotics for Treating Hospital-Acquired and Ventilator-Associated Pneumonia in Adults.

A significant percentage of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have poor outcomes with intravenous antibiotics. It is not clear if adding aerosolized antibiotics improves treatment. This review is an update on using aerosolized antibiotics for treating HAP/VAP in adults. PubMed search using the terms "aerosolized antibiotics pneumonia," "nebulized antibiotics pneumonia," and "inhaled antibiotics pneumonia." Reference lists from identified articles were also searched. Clinical studies of aerosolized antibiotics for treating HAP/VAP in adults from July 2010 to March 2017. This article updates a previous review on this topic written in mid-2010. The size and quality of studies have improved dramatically in the recent time period compared to previous studies. However, there still are not large randomized controlled trials available. Colistin and aminoglycosides were the most commonly studied agents, and the most common pathogens were Pseudomonas and Acinetobacter. The clinical efficacy of adding aerosolized antibiotics was mixed. Approximately half of the studies showed better outcomes, and none showed worse outcomes. Aerosolized antibiotics appear to be relatively safe, though pulmonary adverse events can occur. Attention to proper administration technique in mechanically ventilated patients is required, including the use of vibrating plate nebulizers. Adding aerosolized antibiotics to intravenous antibiotics may improve the outcomes of adult patients with HAP/VAP in some settings. It seems reasonable to add aerosolized antibiotics in patients with multidrug-resistant organisms or who appear to be failing therapy. Clinicians should pay attention to potential adverse events and proper administration technique.

Study of ventilator-associated tracheobronchitis in respiratory ICU patients and the impact of aerosolized antibiotics on their outcome

Lower respiratory tract infections in intubated patients include ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia. Aerosol delivery to intubated patients has improved with advances in techniques and with the development of newer aerosol generators. The aim of the current study was to assess VAT and study the effect of aerosolized antibiotics (AAs) as an adjuvant to systemic antibiotic (SA) on outcome in VAT patients over 18 months, starting from December 2013, who were admitted to the respiratory ICU of Ain Shams University Hospital. Seventy-four patients out of 104 mechanically ventilated patients admitted to the respiratory ICU were subjected to serial mini-BAL sputum sampling from the first day of mechanical ventilation (MV). Thirty-two patients who developed VAT were divided into two groups: group I (13 VAT patients who received AAs in the form of ceftazidime 500 mg/12 h+amikacin 400 mg/12 h added to the SA) and group II (10 VAT patients who received only SA). The current study included only those patients whose relatives agreed to share in the study. All patients were subjected to daily assessment for signs of respiratory tract infection and to twice weekly chest radiography, leukocytic count evaluation, and microbiological assessment using mini-BAL. VAT incidence was found to be 22.1%. Eighty percent of patients who received AAs showed clinical improvement in the form of significant decrease in temperature, amount of sputum, and leukocytic count, and significant increase in PaO2/FiO2 ratio, in comparison with 30% in the SA group. The incidence of VAT was found to be 22.1%, and was mainly caused by Gram-negative bacteria. AAs adjuvant to SA were effective in rapid resolution of signs of respiratory infection, in causing decreased bacterial load, reduced bacterial resistance, reduced progression of VAT to ventilator-associated pneumonia, reduced days of SA use, decreasedMVdays and ICU stay days, and probably reduced cost of ICU admission, but did not affect mortality.

Should Aerosolized Antibiotics Be Used to Treat Ventilator-Associated Pneumonia?

In patients with ventilator-associated pneumonia, systemic use of antibiotics is the cornerstone of medical management. Supplemental use of aerosolized antibiotics with intravenous antibiotics in both experimental and clinical studies has been shown to have the following pharmacologic benefits: (1) aerosolized antibiotics reach the infected lung parenchyma without crossing the pulmonary alveolar capillary barrier; (2) aerosolized antibiotics increase anti-bacterial efficacy through increased local antibiotic concentration; and (3) aerosolized antibiotics decrease systemic toxicity. These benefits may be particularly beneficial to treat pneumonia caused by multidrug-resistant pathogens. Clinical data on the benefits of aerosolized antibiotics are more limited. Studies to date have not clearly shown improvements in time to extubation, mortality, or other patient-centered outcomes. At present, amikacin, colistin, and ceftazidime are the most frequently used and studied aerosolized antibiotics. This review summarizes the characteristics of aerosolized antibiotics, reviews the advantages and disadvantages of using aerosolized antibiotics, and calls for future investigations based on animal study data.

Effects of Emulsion Composition on Pulmonary Tobramycin Delivery During Antibacterial Perfluorocarbon Ventilation.

The effectiveness of inhaled aerosolized antibiotics is limited by poor ventilation of infected airways. Pulmonary delivery of antibiotics emulsified within liquid perfluorocarbon [antibacterial perfluorocarbon ventilation (APV)] may solve this problem through better airway penetration and improved spatial uniformity. However, little work has been done to explore emulsion formulation and the corresponding effects on drug delivery during APV. This study investigated the effects of emulsion formulation on emulsion stability and the pharmacokinetics of antibiotic delivery via APV. Gravity-driven phase separation was examined in vitro by measuring emulsion tobramycin concentrations at varying heights within a column of emulsion over 4 hours for varying values of fluorosurfactant concentration (Cfs = 5-48 mg/mL H2O). Serum and pulmonary tobramycin concentrations in rats were then evaluated following pulmonary tobramycin delivery via aerosol or APV utilizing sufficiently stable emulsions of varying aqueous volume percentage (Vaq = 1%-5%), aqueous tobramycin concentration (Ct = 20-100 mg/mL), and Cfs (15 and 48 mg/mL H2O). In vitro assessment showed sufficient spatial and temporal uniformity of tobramycin dispersion within emulsion for Cfs ≥15 mg/mL H2O, while lower Cfs values showed insufficient emulsification even immediately following preparation. APV with stable emulsion formulations resulted in 5-22 times greater pulmonary tobramycin concentrations at 4 hours post-delivery relative to aerosolized delivery. Concentrations increased with emulsion formulations utilizing increased Vaq (with decreased Ct) and, to a lesser extent, increased Cfs. The emulsion stability necessary for effective delivery is retained at Cfs values as low as 15 mg/mL H2O. Additionally, the pulmonary retention of antibiotic delivered via APV is significantly greater than that of aerosolized delivery and can be most effectively increased by increasing Vaq and decreasing Ct. APV has been further proven as an effective means of pulmonary drug delivery with the potential to significantly improve antibiotic therapy for lung disease patients.

Inhaled ceftazidime and amikacin versus inhaled colistin in the treatment of gram negative ventilator associated pneumonia

Aerosol antibiotics administration offers the theoretical advantages of achieving high drug concentrations at the infection site and low systemic absorption.

Long-term safety and efficacy of tobramycin in the management of cystic fibrosis.

Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene whose mortality is conditioned by a progressive decline in lung function. Bacterial infections play a key role in this decline. Chronic bacterial infection in CF patients varies over time and the presence of Pseudomonas aeruginosa in sputum is a marker of poor prognosis. P. aeruginosa is eradicated from the airways using inhaled antibiotics administered in various formulations and devices. Antipseudomonal antibiotics have extended the survival of CF patients to 40 years. Tobramycin is a bactericidal aminoglycoside antibiotic with demonstrated activity against gram-negative microorganisms. Initially, the drug was administered as an inhaled parenteral solution. Subsequently, a specific tobramycin inhalation solution was developed. PulmoSphere™ technology enables dry tobramycin powder to be formulated for inhalation (tobramycin inhalation powder) using a small and portable capsule-based breath-activated device (T-326). Chronic colonization by P. aeruginosa is the main indication for aerosol antibiotic therapy. The American Cystic Fibrosis Foundation, European guidelines, and Spanish consensus guidelines provide different recommendations for eradication.

Reduction of Bacterial Resistance with Inhaled Antibiotics in the Intensive Care Unit

Multidrug-resistant organisms (MDRO) are the dominant airway pathogens in the intensive care unit (ICU) and present a major treatment challenge to intensivists. Aerosolized antibiotics (AA) result in airway concentrations of drug 100-fold greater than the minimal inhibitory concentration of most bacteria including MDRO. These levels, without systemic toxicity, may eradicate MDRO and reduce the pressure for selection of new resistant organisms. To determine if AA effectively eradicate MDRO in the intubated patient without promoting new resistance. In a double-blind placebo-controlled study, critically ill intubated patients were randomized if they exhibited signs of respiratory infection (purulent secretions and Clinical Pulmonary Infection Score ≥6). Using a well-characterized aerosol delivery system, AA or saline placebo was given for 14 days or until extubation. The responsible clinician determined administration of systemic antibiotics for ventilator-associated pneumonia and any other infection. AA eradicated 26 of 27 organisms present at randomization compared with 2 of 23 organisms with placebo (P < 0.0001). AA eradicated the original resistant organism on culture and Gram stain at end of treatment in 14 out of 16 patients compared with 1 of 11 for placebo (P < 0.001). New drug resistance to AA was not seen. Compared with AA, resistance to systemic antibiotics significantly increased in placebo patients (P = 0.03). Compared with placebo, AA significantly reduced Clinical Pulmonary Infection Score (mean ± SEM, 9.3 ± 2.7 to 5.3 ± 2.6 vs. 8.0 ± 23 to 8.6 ± 2.10; P = 0.0008). In chronically intubated critically ill patients, AA successfully eradicated existing MDRO organisms and reduced the pressure from systemic agents for new respiratory resistance. Clinical trial registered with www.clinicaltrials.gov (NCT 01878643).

Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study

RationaleIn cystic fibrosis (CF), the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa. Pathogens subsequently descend to the lower airways, with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease. Unlike conventional aerosols, vibrating aerosols applied with the PARI Sinus™ nebulizer deposit drugs into the paranasal sinuses. This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage.ObjectivesTo evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability.MethodsPatients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days, with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline.ResultsNine patients participated, six initially receiving tobramycin and three placebo. Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine. P. aeruginosa quantity decreased in four of six (67%) patients given tobramycin, compared with zero of three given placebo (non-significant). SNOT-20 scores were significantly lower in the tobramycin than in the placebo group (P=0.033).ConclusionSinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.

Clinical experimentation with aerosol antibiotics: current and future methods of administration [Corrigendum

Clinical experimentation with aerosol antibiotics: current and future methods of administration [Corrigendum] Throughout the paper Microsprayer should have been cited as MicroSprayer® Aerosolizer (Penn-Century, Inc., Wyndmoor, PA, USA). On page 1127 and 1128 the paragraph on Azithromycin should not have been included in the paper.

Clinical experimentation with aerosol antibiotics: current and future methods of administration

Currently almost all antibiotics are administered by the intravenous route. Since several systems and situations require more efficient methods of administration, investigation and experimentation in drug design has produced local treatment modalities. Administration of antibiotics in aerosol form is one of the treatment methods of increasing interest. As the field of drug nanotechnology grows, new molecules have been produced and combined with aerosol production systems. In the current review, we discuss the efficiency of aerosol antibiotic studies along with aerosol production systems. The different parts of the aerosol antibiotic methodology are presented. Additionally, information regarding the drug molecules used is presented and future applications of this method are discussed.

Internal mouthpiece designs as a future perspective for enhanced aerosol deposition. Comparative results for aerosol chemotherapy and aerosol antibiotics

In an effort to identify factors producing a finest mist from Jet-Nebulizers we designed 2 mouthpieces with 4 different internal designs and 1-3 compartments. Ten different drugs previous used with their "ideal" combination of jet-nebulizer, residual-cup and loading were used. For each drug the mass median aerodynamic diameter size had been established along with their "ideal" combination. For both mouthpiece, drug was the most important factor due the high F-values (Flarge=251.7, p<0.001 and Fsmall=60.1, p<0.001) produced. The design affected the droplet size but only for large mouthpiece (Flarge=5.99, p=0.001, Fsmall=1.72, p=0.178). Cross designs create the smallest droplets (2.271) so differing from the other designs whose mean droplets were greater and equal ranging between 2.39 and 2.447. The number of compartments in the two devices regarding the 10 drugs was found not statistically significant (p-values 0.768 and 0.532 respectively). Interaction effects between drugs and design were statistically significant for both devices (Flarge=8.87, p<0.001, Fsmall=5.33, p<0.001). Based on our experiment we conclude that further improvement of the drugs intended for aerosol production is needed. In addition, the mouthpiece design and size play an important role in further enhancing the fine mist production and therefore further experimentation is needed.