Inhaled Liposomal Antimicrobial Delivery in Lung Infections
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REVIEW ARTICLE
Inhaled Liposomal Antimicrobial Delivery in Lung Infections Matteo Bassetti1,2 · Antonio Vena1 · Alessandro Russo3 · Maddalena Peghin4
© The Author(s) 2020
Abstract The management of difficult-to-treat acute and chronic respiratory infections (infections in cystic fibrosis, non-cystic fibrosis bronchiectasis, immunocompromised and mechanically ventilated patients) and difficult-to-treat pathogens (including multidrug-resistant strains) has become a challenge in clinical practice. The arsenal of conventional antibiotic drugs can be limited by tissue penetration, toxicities, or increasing antibiotic resistance. Inhaled antimicrobials are an interesting therapeutic approach for optimizing the management of respiratory infections. Due to extensive developments in liposome technology, a number of inhaled liposome-based antibiotic and antifungal formulations are available for human use and many products are undergoing clinical trials. Liposomes are biocompatible, biodegradable, and nontoxic vesicles able to encapsulate and carry antimicrobials, enhancing the therapeutic index of various agents and retention at the desired target within the lung. Liposomes reduce drug toxicity and improve tolerability, leading to better compliance and to decreased respiratory side effects. The aim of this article was to provide an up-to-date overview of nebulized liposomal antimicrobials for lung infections (with a special focus on liposomal amikacin, tobramycin, ciprofloxacin, and amphotericin B for inhalation), discussing the feasibility and therapeutic potential of these new strategies of preventing and treating bacteria, mycobacterial and fungal infections.
1 Introduction Over recent years, there has been a worldwide increase in the prevalence of multidrug-resistant (MDR) and difficultto-treat pathogens [1, 2]. This issue has forced clinicians to rediscover old drugs with suboptimal pharmacokinetics and toxicity issues and has resulted in significant research efforts, with few new molecules proposed for use in clinical practice. In addition, alternative novel therapies have been developed including monoclonal antibodies, vaccines, stem cells, bacteriophages, and liposomes [3]. Lung infections include a challenging spectrum of clinical conditions, ranging from acute to chronic infections, and new therapeutic * Matteo Bassetti [email protected] 1
Infectious Diseases Unit, Ospedale Policlinico San Martino, IRCCS, Genoa, Italy
2
Department of Health Sciences, University of Genoa, Genoa, Italy
3
Division of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
4
Infectious Diseases Clinic, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy
approaches are warranted for optimizing treatment in difficult-to-treat infections, cystic fibrosis (CF), non-cystic fibrosis bronchiectasis (NCFB), and immunocompromised and mechanically ventilated patients. Liposomes are safe and suitable carriers for
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