Citation: Cuevas Brun EH, “Enhancing Inhalation Therapy by Reintroducing Antibiotics Using Mesh Technology”. ONdrugDelivery Magazine, Issue 102 (Nov 2019), pp 26-28.
Edgar Hernan Cuevas Brun looks at how the administration of some old antibiotics could be a valuable response to fight infections.
“Clinicians around the world have started to reppraise the use of antibiotics that have not been used for a long time – colistin being one of them.”
The last three decades have seen a slow movement when it comes to the development of new antibiotics. Different reasons can be attributed, mostly involving regulations governing drug approval, market forces and scientific bottlenecks.1 As a result, a new antibiotic resistance era was confirmed in 2015, and it has not been brought under control so far. There is no doubt that there is a need for new antibiotics. However, in the meantime, clinicians around the world have started to reappraise the use of antibiotics that have not been used for a long time – colistin being one of them.2
REINTRODUCING COLISTIN
Colistin, also known as polymyxin E, is an antibiotic that belongs to the polymyxin class and is mostly effective against Gram-negative bacilli.3 It was discovered in 1949 and initially used in Japan, Europe and the US in the 1950s.4 Its usage was eventually reported to cause nephrotoxicity. Consequently, its application was largely reduced only 20 years after its discovery.
In recent years, colistin has regained the interest of clinicians and scientists alike, leading to the need for a deeper understanding of the pharmacodynamics, pharmacokinetics and toxicodynamics of this old antibiotic to properly set the right administration regimens.5,6
For patients suffering from cystic fibrosis, colistin has become an important tool to fight infections. At the same time, the critical practice guidelines from the Infectious Diseases Society of America and the American Thoracic Society have also cited the administration of inhaled colistin to treat ventilator-associated pneumonia.7 Nowadays, finding the most efficient and effective pathways to deliver colistin is undoubtedly a top priority for the reintroduction of this drug.
Figure 1: Pulmogine vibrating mesh nebuliser.
INHALATION THERAPY: MESH NEBULISERS
Inhalation therapy has mainly been associated with the treatment of respiratory diseases. Metered dose inhalers, dry powder inhalers and nebulisers are among the most commonly used devices to treat diseases that affect the respiratory system. Invented in the early 1990s, mesh nebulisers have gradually attracted pharmaceutical companies to evaluate the delivery of inhalation drugs. They are a type of nebuliser that has been praised for providing a better performance while improving conditions of usage.8,9
The Pulmogine vibrating mesh nebuliser (Figure 1), developed and manufactured by HCmed Innovations, aims to improve the efficiency of drug delivery. Pulmogine has been designed based on a customisable platform intended to improve diverse parameters. The tailoring features of Pulmogine provide it with an advantage when it comes to delivering a wide range of medications, including solutions, suspensions, biologics, high-viscosity drugs and antibiotics – the last one being of particular importance to treat infectious diseases in the lungs and under the scope of the study in this article.
“The tailoring features of Pulmogine provide it with an advantage when it comes to delivering a wide range of medications.”
DELIVERING ANTIBIOTICS
In order to further understand the capabilities of Pulmogine to deliver antibiotics, colistin was used to observe the performance of the mesh nebuliser. It had previously been reported that the optimal particle size for deposition in the lungs is between 1 and 5 μm.10
Different concentrations of colistin were aerosolised during the study to identify any meaningful variabilities. Nonetheless, it is relevant to point out that appropriate prescriptions are indispensable to effective treatment and also to avoid major side effects.
Throughout the series of tests, standard indicators were measured to examine aerosol characteristics. The conducted tests demonstrated that mass median diameter (MMD) remained between 3.578 and 3.996 μm even after quadrupling the initial concentration, while the fine particle fraction (FPF) remained above 58% at all times.
Moreover, the output rate was also seen to stay high, although there was a more considerable decrease when the concentration of colistin was increased. The summary of the mean values obtained from the tests performed with three devices is displayed in Table 1.
| Colistin Conc. (mg/mL) |
MMD (μm) |
FPF (%) |
Output Rate (mg/min) |
| 16.7 | 3.578 | 63.85 | 0.493 |
| 33.4 | 3.647 | 63.39 | 0.407 |
| 50.1 | 3.755 | 61.39 | 0.347 |
| 66.8 | 3.996 | 58.82 | 0.280 |
Table 1: Mean Pulmogine performance values when aerosolising different colistin concentrations.
CONCLUSION
Given recent concerns caused by antibiotic resistance, the administration of some old antibiotics has become a valuable response to fight infections. When it comes to respiratory infections, inhalation therapy can be used as a primary pathway of treatment by using new technologies that are able to increase the efficiency of drug delivery. The platform offered by Pulmogine is a clear example of advancements.
REFERENCES
- Wright G, “Something old, something new: revisiting natural products in antibiotic drug discovery”. Can J Microbiol, 2014, Vol 60 (3), pp 147-154.
- Jain R et al, “Multidrug-Resistant Acinetobacter Infections: An Emerging Challenge to Clinicians”. Annals of Pharmacotherapy, 2004, Vol 38 (9), pp 1449-1459.
- Caniaux I et al, “MCR: modern colistin resistance”. Eur J Clin Microbiol Infect Dis, 2017, Vol 36 (3), pp 415-420.
- Falagas M et al, “Colistin: The revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections”. Clin Infect Dis, 2005, Vol 40 (9), pp 1333-1342.
- Li J et al, “Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections”. The Lancet Infectious Diseases, 2006, Vol 6 (9), pp 589-601.
- Nation R et al, “Colistin in the 21st century”. Current Opinion in Infectious Diseases, 2009, Vol 22 (6), pp 535-543.
- Kalil A et al, “Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society”. Clinical Infectious Diseases, 2016, Vol 63 (5), pp e61-e111.
- Pritchard J et al, “Mesh nebulizers have become the first choice for new nebulized pharmaceutical drug developments”. Ther Deliv, 2018, Vol 9 (2), pp 121–136.
- Galindo-Filho V et al, “Radioaerosol Pulmonary Deposition Using Mesh and Jet Nebulizers During Noninvasive Ventilation in Healthy Subjects”. Respir Care, 2015, Vol 60 (9), pp 1238-1246.
- Pilcer G et al, “Correlations between cascade impactor analysis and laser diffraction techniques for the determination of the particle size of aerosolised powder formulations”. Int J Pharm, 2008, Vol 358 (1-2), pp 75-81.