Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy

Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B. H.

doi:10.1016/j.xphs.2016.02.007

Cited by 16 publications

(4 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, all spray–dried powders used in this study are inhalable, since a FPF value above 30% is an index of robust aerosol performance [ 16 ]. Notably, PMB–SD possesses a significantly higher respirable fraction compared to CIP–SD ( Figure 6 ), while they have similar geometric particle sizes and size distributions ( Table 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…Drug pairs with synergistic effects can afford an amplified antibacterial effect compared to single used antibiotics, enhancing bacteria kill rate and narrowing the time window of the resistant development [ 13 ]. A polymyxin–based combination treatment has been considered as a promising treatment option against MDR A. baumannii [ 15 , 16 , 17 ]. In a clinical study, a synergistic effect was observed when polymyxin B was combined with levofloxacin, tobramycin and meropenem to treat MDR A. baumannii infections [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Drug Combination of Ciprofloxacin and Polymyxin B for the Treatment of Multidrug–Resistant Acinetobacter baumannii Infections: A Drug Pair Limiting the Development of Resistance

et al. 2023

View full text Add to dashboard Cite

Polymyxins are considered as last–resort antibiotics to treat infections caused by Acinetobacter baumannii. However, there are increasing reports of resistance in A. baumannii to polymyxins. In this study, inhalable combinational dry powders consisting of ciprofloxacin (CIP) and polymyxin B (PMB) were prepared by spray–drying. The obtained powders were characterized with respect to the particle properties, solid state, in vitro dissolution and in vitro aerosol performance. The antibacterial effect of the combination dry powders against multidrug–resistant A. baumannii was assessed in a time–kill study. Mutants from the time–kill study were further investigated by population analysis profiling, minimum inhibitory concentration testing, and genomic comparisons. Inhalable dry powders consisting of CIP, PMB and their combination showed a fine particle fraction above 30%, an index of robust aerosol performance of inhaled dry powder formulations in the literature. The combination of CIP and PMB exhibited a synergistic antibacterial effect against A. baumannii and suppressed the development of CIP and PMB resistance. Genome analyses revealed only a few genetic differences of 3–6 SNPs between mutants and the progenitor isolate. This study suggests that inhalable spray–dried powders composed of the combination of CIP and PMB is promising for the treatment of respiratory infections caused by A. baumannii, and this combination can enhance the killing efficiency and suppress the development of drug resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drug Combination of Ciprofloxacin and Polymyxin B for the Treatment of Multidrug–Resistant Acinetobacter baumannii Infections: A Drug Pair Limiting the Development of Resistance

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Further investigation of co-formulated spray-dried ciprofloxacin combination powders has identified that a ciprofloxacin /gatifloxacin /ambroxol powder (formulated with L-leucine) demonstrated an improvement in synergistic formulation with increased antimicrobial efficacy against Pa than the binary mixture [157]. Combination powders of spray-dried colistin/crystalline rifapentine [158] and ternary combinations of colistin/meropenem/tigecycline/rifampicin (3 drugs per powder) have demonstrated synergistic activities in in vitro bacterial models [159]. Translation into pre-clinical studies will be of great interest to identify the efficacy of the treatment in the living host.…”

Section: Future Directions 51 Combination Therapiesmentioning

confidence: 99%

Antimicrobial Molecules in the Lung: Formulation Challenges and Future Directions for Innovation

Woods

Rahman

2018

Future Med. Chem.

View full text Add to dashboard Cite

Inhaled antimicrobials have been extremely beneficial in treating respiratory infections, particularly chronic infections in a lung with cystic fibrosis. The pulmonary delivery of antibiotics has been demonstrated to improve treatment efficacy, reduce systemic side effects and, critically, reduce drug exposure to commensal bacteria compared with systemic administration, reducing selective pressure for antimicrobial resistance. This review will explore the specific challenges of pulmonary delivery of a number of differing antimicrobial molecules, and the formulation and technological approaches that have been used to overcome these difficulties. It will also explore the future challenges being faced in the development of inhaled products and respiratory infection treatment, and identify future directions of innovation, with a particular focus on respiratory infections caused by multiple drug-resistant pathogens.

show abstract

“…The literature evidence has shown the potential of ternary combinations of polymyxin B, carbapenem (or its family antibiotics) and rifampicin for rapid killing against pan-drug resistant (PDR) A. baumannii (Yoon et al, 2004), K. pneumoniae (Diep et al, 2017) and P. aeruginosa (Urban et al, 2010). Thus far there has been one attempt to develop DPI formulations of ternary antibiotic combinations (Lee et al, 2016). However, the effects of each component and surface composition on the aerosol performance at elevated humid conditions were not been investigated; this is important as the latter has been demonstrated to critically affect the aerosol stability of DPIs containing hygroscopic compounds such as colistin (Zhou et al, 2014a;Zhou et al, 2016;Zhou et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effects of the antibiotic component on in-vitro bacterial killing, physico-chemical properties, aerosolization and dissolution of a ternary-combinational inhalation powder formulation of antibiotics for pan-drug resistant Gram-negative lung infections

Mangal

Huang

Shetty

et al. 2019

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Combinational antibiotic formulations have emerged as an important strategy to combat antibiotic resistance. The main objective of this study was to examine effects of individual components on the antimicrobial activity, physico-chemical properties, aerosolization and dissolution of powder aerosol formulations when three synergistic drugs were co-spray dried. A ternary dry powder formulation consisting of meropenem (75.5 %w/w), colistin (15.1 %w/w) and rifampicin (9.4 %w/w) at the selected ratio was produced by spray drying. The ternary formulation was characterized for in-vitro antibacterial activity, physico-chemical properties, surface composition, aerosol performance and dissolution. All of the formulations demonstrated excellent aerosolization behavior achieving a fine particle fraction of >70%, which was substantially higher than those for the Meropenem-SD and Colistin-Meropenem formulations. The results indicated that rifampicin controlled the surface morphology of the ternary and binary combination formulations resulting in the formation of highly corrugated particles. Advanced characterization of surface composition by XPS supported the hypothesis that rifampicin was enriched on the surface of the combination powder formulations. All spray-dried formulations were amorphous and absorbed substantial amount of water at the elevated humidity. Storage at the elevated humidity caused a substantial decline in aerosolization performance for the Meropenem-SD and Colistin-Meropenem, which was attributed to increased inter-particulate capillary forces or particle fusion. In contrast, the ternary combination and binary Meropenem-Rifampicin formulations showed no change in *

show abstract

Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy

Cited by 16 publications

References 74 publications

Drug Combination of Ciprofloxacin and Polymyxin B for the Treatment of Multidrug–Resistant Acinetobacter baumannii Infections: A Drug Pair Limiting the Development of Resistance

Drug Combination of Ciprofloxacin and Polymyxin B for the Treatment of Multidrug–Resistant Acinetobacter baumannii Infections: A Drug Pair Limiting the Development of Resistance

Antimicrobial Molecules in the Lung: Formulation Challenges and Future Directions for Innovation

Effects of the antibiotic component on in-vitro bacterial killing, physico-chemical properties, aerosolization and dissolution of a ternary-combinational inhalation powder formulation of antibiotics for pan-drug resistant Gram-negative lung infections

Contact Info

Product

Resources

About