Aerosolized Antibiotics

Restrepo, Marcos I.; Keyt, Holly; Reyes, Luis Felipe

doi:10.4187/respcare.04208

Cited by 34 publications

(30 citation statements)

References 56 publications

(83 reference statements)

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“…51 To reach the deep airways in sufficient concentrations, high, often toxic doses of drugs would need to be given systemically. The inhalation of antibacterial agents on the other hand allows higher concentrations to be deposited directly in the lungs so that pathogens are exposed to supralethal concentrations while minimizing potential systemic toxicity by limiting absorption and avoiding unfavorable PK/PD consequences, 52,53 Furthermore, pulmonary drug delivery allows targeting the drug delivery directly to lung both for local and systemic treatment 54 making it a suitable route of administration for both respiratory and bloodstream infections. …”

Section: Discussionmentioning

confidence: 99%

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Velikova

Mas

Miguel-Romero

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr−) permeability barrier for the HKAIs. The observed bactericidal activity against Gr− bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr− and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria.

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Section: Discussionmentioning

confidence: 99%

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Velikova

Mas

Miguel-Romero

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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“…It is hypothesized that aerosolized antibiotics could improve clinical outcomes based on the principle that antibiotics decrease bacterial density in the airways and therefore reduce inflammation and lung damage [15]. In addition to this, according to Wang et al early treatment with inhaled antibiotics for A. xylosoxidans may prevent or postpone chronic infection and, as a result, clinical deterioration in patients with cystic fibrosis [16].…”

Section: Discussionmentioning

confidence: 99%

“…Their results are in line with experience with Pseudomonas aeruginosa, where randomized trials have shown efficacy of inhaled antibiotics in the absence of concurrent systemic therapy. Further studies should focus on treatment outcomes different from FEV 1 and number of exacerbations such as survival, bacterial eradication, quality of life, decrease of sputum bacterial load and decrease of local inflammation to assess efficacy of aerosolized imipenem [15].…”

Section: Discussionmentioning

confidence: 99%

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Experience with Aerosolized Imipenem in Patients with Cystic Fibrosis and Achromobacter xylosoxidans

Marcos¹,

Espinosa²,

Pérez³

et al. 2017

J Infect Dis Ther

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Achromobacter xylosoxidans is a gram negative non-fermentative rod that infects adult cystic fibrosis patients with moderate to severe lung compromise. Its clinical implications are still to be determined. The aim of this study was to analyze the impact of inhaled imipenem on forced expired volume in 1 sec (FEV 1 ) and number of exacerbations in adult cystic fibrosis patients. Patients colonized by A. xylosoxidans with more than two intravenous antibiotic cycles and/or ≥ 5% FEV 1 impairment during the last year were included.We included six patients with a mean age of 24.8 years. At the beginning of treatment FEV 1 was 1.18 l (52%) with a mean of 3.4 exacerbations in the previous 12 months and 2.24 (p=0.04) the following 12 months. There was a significant difference between the initial FEV 1 value and three months after treatment (p=0.005).

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“…Its use has now extended to prevention and treatment of VAP, ventilator associated tracheobronchitis, bronchiectasis [15]. Few antibiotic formulations for the nebulized route are studied and approved [13].…”

Section: Declaration By Authormentioning

confidence: 99%

Study of the disposition of nebulized tobramycin

Dhanani¹

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BackgroundVentilator associated pneumonia occurs commonly in critically ill patients. Despite recommended antibiotic therapy, outcomes remain poor. Inadequate antibiotic concentrations at the site of action, the interstitial space fluid, could be one of the reasons. Whilst the risk of causing systemic side effects limits the ability to use increasing doses of parenteral therapy, the subtherapeutic concentrations commonly associated with current regimens could lead to emergence of drug resistant organisms. This, and the drying up of the antibiotic pipeline, have led to a renewed interest in the investigation of alternative drug delivery to maximise drug effects.Nebulized therapy is one such therapy and has been used successfully for many respiratory diseases. Nebulized antibiotic therapy for lung infections whilst not novel, has been used increasingly worldwide with the aim of improving patient outcomes, particularly in the context of drug resistant pathogens. However, understanding and applying key pharmacokinetic principles is important for effective antibiotic therapy. A number of factors affect nebulized drug delivery in mechanically ventilated patients and for nebulized antibiotics, there is a paucity of robust data. Moreover, the current methods to study the pharmacokinetics of aerosolized antibiotics have critical limitations. Pseudomonas aeruginosa is a common cause of, both hospital and ventilator-associated pneumonia. Tobramycin, an aminoglycoside, is an effective antibiotic to treat infections caused by this pathogen. High-dose parenteral tobramycin therapy is not able to be used to treat lung infections caused by P. aeruginosa due to the likelihood severe side effects. Nebulized tobramycin might be a valid application for critically ill patients with ventilator-associated pneumonia given the supportive data from cystic fibrosis patients and patients with bronchiectasis, although the dose and frequency, type of formulation (nebulized, dry powder), position of the nebulizer in the circuit for optimal therapy in this population is unclear.Therefore, the primary aim of this Thesis was to describe current knowledge of factors affecting nebulized tobramycin delivery with mechanical ventilation. Using a suite of in V Publications during candidature

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Aerosolized Antibiotics

Cited by 34 publications

References 56 publications

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Experience with Aerosolized Imipenem in Patients with Cystic Fibrosis and Achromobacter xylosoxidans

Study of the disposition of nebulized tobramycin

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