Authors: Hessel van der Weide & Jeffrey Ritsema (Erasmus MC, Rotterdam, The Netherlands)
Take a look behind the scenes of a recent Future Microbiology review, entitled: ‘Antibiotic-Nanomedicines – Facing The Challenge of Antibiotic-Resistant Respiratory Tract Infections’, as we ask the authors about the challenges in treating respiratory tract infections and how nanomedicines could help.
What inspired you to write this special report?
Our inspiration came from the research we have performed within the PneumoNP research consortium in which nanomedicines were combined with novel antimicrobial peptides and tested for efficacy against pneumonia caused by multidrug-resistant Klebsiella pneumoniae; an infection with high mortality rates caused by a bacterial species known for its extensive antibiotic resistance. While there are many excellent up-to-date reviews on both nanomedicine and antibiotic development, we were inspired to write a special report that focused on the application of antibiotic-nanomedicines for treating respiratory tract infections in the context of the current antibiotic crisis.
What are the main challenges for treating antibiotic-resistant respiratory tract infections?
The main challenges for the treatment of antibiotic-resistant respiratory tract infections is the continued spread of multidrug-resistant strains that are resistant to an ever-growing list of currently used antibiotics in the clinic, combined with diminishing returns in the last decades on discovering and developing new classes of antibiotics. Together, these forces work together to reduce the available pool of effective antibiotics to treat these infections, further complicating the treatment of a group of infections which already cause both high mortality and morbidity.
What are the recent treatment strategies?
Clinicians currently use ‘drugs of last resort’ in the case of multidrug-resistant respiratory tract infections. These are often older antibiotics which were not fully developed for the clinic or fell into disuse because of production issues or considerable side effects. Despite these disadvantages, such drugs of last resort represent the last viable solution for multidrug-resistant infections and are making a return to the clinical practice.
As few new antibiotic classes have been discovered and developed in the past decades, more attention is given to strategies to prevent or even revert the spread of antibiotic-resistance in pathogenic bacteria. Such strategies will be important for the stewardship of novel antibiotics so that these may remain effective for a longer period.
Despite these practices, the first cases of pan-resistant infections have been reported. In such cases, no effective antimicrobial treatment is available: there is nothing left to do for physicians other than providing patient care as best as possible.
How could nanomedicines help treat respiratory tract infections?
Healthcare professionals have the availability to treat pulmonary infectious diseases by targeting specific cells or regions of the lung, avoiding the lung’s clearance mechanisms and improving drug retention within the lung for longer periods. With this improved efficiency, nanoparticles allow for smaller total deliverable doses and a decrease in unwanted side-effects, thereby increasing clinical effectiveness and improving patient compliance.
What work are you hoping to do and what do you think needs to be done in this area?
Further investigation into the effect of nanomedicines’ physicochemical properties (e.g., size and composition of nanomedicines) on extending particle persistence in the lungs and on particle fate is necessary to aid the design of improved drug delivery systems and improve clinical efficiency.
Also, the complexity of the nanomedicines is a key factor in the ability of nanomedicines to be translated to the clinic, irrelevant of its therapeutic efficacy. The structural and physicochemical complexity of the formulation itself requires complex and/or laborious synthesis procedures that generally have limited clinical translation potential, as they can be quite problematic to pharmaceutically manufacture on a large scale. An essential requirement for improved clinical translation is to have access to nanomedicines that allow for production at large scalable quantities, can be consistently manufactured at the same high level of quality, and have batch-to-batch reproducibility within the set specifications.
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